Limited research has focused on the clinical features of sudden sensorineural hearing loss (SSNHL) in pediatric patients. This study is aimed to investigate the relationship between clinical features and the baseline hearing severity and outcomes of SSNHL in the pediatric population.We conducted a bi-center retrospective observational study in 145 SSNHL patients aged no more than 18 years who were recruited between November 2013 and October 2022. Data extracted from medical records, audiograms, complete blood count (CBC) and coagulation tests have been assessed for the relationship with the severity  and outcomes .P = 0.004) and a higher platelet-to-lymphocyte ratio (PLR) (P = 0.041) were found in the patient group with profound initial hearing than in the less severe group. Vertigo  and lymphocyte count  showed significant associations with the threshold of the initial hearing. In the multivariate logistic model, the probability of recovery was higher for patients with ascending and flat audiograms compared to those with descending audiograms . Patients with tinnitus had a 3.2-fold increase in the probability of recovery , while the baseline hearing threshold  and duration to the onset of therapy  were negatively associated with the odds of recovery.A lower lymphocyte count (The present study showed that accompanying tinnitus, the severity of initial hearing loss, the time elapse and the audiogram configuration might be related to the prognosis of pediatric SSNHL. Meanwhile, the presence of vertigo, lower lymphocytes and higher PLR were associated with worse severity. Sudden sensorineural hearing loss (SSNHL) is an urgent otologic condition that should be managed promptly. The frequency of SSNHL in adults is expected to range from 5 to 27 cases per 100,000 per year . NeverthTo date, there have been a limited number of studies focusing on pediatric patients with SSNHL. It is probably due to the low prevalence. It is common knowledge that children are not “small” adults. Thus, accurately describing the symptoms and relevant medical history is not easy for them. Hearing loss, especially unilateral hearing loss, is sometimes a less perceptible symptom. Thus, it can be difficult to clarify whether a child's hearing loss occurs “suddenly” or in the long run. Another unanswered question is whether SSNHL in children is the same as that observed in adults. Previous study found differences with respect to the recovery rate and audiogram configuration between adult and pediatric patients with SSNHL , 7. HoweAmong the existing studies on pediatric SSNHL, there were some inadequacies. First, the small sample size reduced the power of the statistical analysis. Second, most of the previous studies were conducted in a single center, which made them more susceptible to bias; and third, the statistical methods used were commonly limited to univariate analysis, which was not able to exclude confounding factors to identify adequately independent correlations.In the present study, we analyzed the clinical parameters associated with the severity and prognosis of SSNHL in children and developed interpretable prognostic prediction models to improve counseling.We conducted a retrospective analysis of pediatric patients with SSNHL aged ≤ 18 years who consecutively visited two Chinese tertiary centers  between November 2013 and October 2022. All the patients underwent a comprehensive clinical assessment, including a neurotological physical examination, audiometry, and imaging. The follow-up visit was conducted in person at the hospital, and 145 patients  were included in the study . We utilThe participants enrolled were assessed using pure-tone audiometry. Pure-tone air and bone conduction thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz were examined based on the standard audiometric methodology. The average baseline hearing threshold was calculated at the affected frequencies of air conduction (frequencies with hearing loss >20 dB HL). The severity of initial hearing loss was classified as follows: mild hearing loss: 20–40 dB HL; moderate hearing loss: 41–60 dB HL; severe hearing loss: 61–80 dB HL; and profound hearing loss: >80 dB HL. We categorized the configurations of the audiogram into four types as described in our earlier study : ascendiU-test, Fischer's exact test, and the Student's t-test, between the two subgroups. The Kruskal–Wallis test was applied to the ordinal variables for the group comparison. In addition, post-hoc pair-wise comparisons were used where there were more than two subgroups. The “glm” package was used to fit multivariate models to explore the factors that affected either the initial hearing or the hearing outcomes. The multivariate linear regression included the baseline hearing threshold as the response variable. Based on the variables having significance in the comparison between groups, the presence of vertigo, the lymphocyte count, and the monocyte count should be incorporated into the model. However, the analysis (Pearson correlation coefficient) revealed a significant linear correlation between the lymphocyte count, the monocyte count, and PLR. Furthermore, when these variables were included in the model, high variance inflation factor (VIF) values were observed. Therefore, we only chose the lymphocyte count to avoid potential collinearity. To analyze factors affecting hearing outcomes, a binomial categorical variable (recovery vs. non-recovery) and a continuous variable  were utilized as dependent variables. Significant variables from the univariate analysis for hearing recovery were included in the multivariate linear and logistic regression models, adjusted for age, sex, and time to the onset of therapy. To include nominal variables in the linear regression, a dummy variable was developed with a value of 1 if the case matched the description and 0 otherwise. Regression coefficients, standard regression coefficients, 95% confidence intervals, and odds ratios were calculated using regression models. All analyses were conducted using RStudio  and R (http://www.R-project.org). A two-sided p-value of < 0.05 was deemed statistically significant.We analyzed the initial severity of hearing loss and hearing outcomes based on Siegel's criterion. The patients with an average baseline hearing threshold graded as profound (>80 dB HL) were allocated to the profound group, whereas those with less severe baseline hearing were assigned to the not profound group. According to Siegel's criterion, patients whose hearing outcomes were classified as CR or PR were allocated to the recovery group, and the remaining patients were assigned to the non-recovery group. The Shapiro–Wilk test was used to determine if a continuous variable was normally distributed. Continuous data with a normal distribution were given as the mean and standard deviation, whereas non-normal data were presented as the median and interquartile range. The frequency and proportion were used to characterize nominal variables. Subgrouping comparisons were performed using appropriate statistical tests, such as the Mann–Whitney ‘P = 0.021). Regarding the configurations of the initial audiogram, the flat configuration was the most common , and a significant difference in the initial hearing was detected among groups (P = 0.001). Eighty-one patients had complete blood count (CBC) test results, and 83 patients had coagulation factor test findings. The study found that patients with profound initial hearing loss had a significantly lower absolute lymphocyte count compared to those without . The patients in the profound group had a higher level of PLR and a lower level of monocytes than their counterparts with less severe hearing loss.P = 0.044) . The configurations of the audiograms were significantly different across the groups (P = < 0.001). Patients with cophosis figures had significantly different recovery than those with descending (P = 0.020), ascending (P < 0.001), and flat figures (P < 0.001). Patients with descending figures had significantly different recovery than those with ascending (P = 0.011) and flat figures (P = 0.038) after post-hoc comparison. The thresholds for the initial and final hearing comparison, sorted by the initial configuration, are shown in P = < 0.001; descending: P = < 0.001; flat: P = < 0.001). A worse final hearing was found in patients with descending figures than with ascending (P = < 0.001) and flat (P = 0.016) figures, respectively. The threshold for a final hearing with ascending figures was similarly lower than for that with the flat figure (P = 0.019). No statistical difference was found in complete blood cell and coagulation test biomarkers across the recovery group and the non-recovery group.= 0.044) . There wP = 0.007), lymphocyte count  (P = 0.001), baseline hearing , and configurations . The odds of recovery were 3.2 times higher for patients with tinnitus than for those without tinnitus . The threshold for baseline hearing  and the onset of therapy  were negatively associated with the odds of recovery. To predict the hearing outcomes of pediatric patients with SSNHL, a nomogram was established by incorporating the following parameters: tinnitus, the onset of therapy, baseline hearing, and configuration  , and indurations . In the urations , the patguration .The present bi-center study found some predictive factors of hearing outcomes in pediatric patients with SSNHL, including tinnitus, the time elapsed from the onset of the symptoms to the commencement of the treatment, initial audiogram configuration, and hearing levels. We observed a higher proportion of accompanying vertigo, a greater degree of inflammatory biomarkers (lower the concentration of lymphocytes. and a higher level of PLR), and worse hearing outcomes  in patients with more severe initial hearing loss. Meanwhile, according to the multivariate linear regression model, we developed a nomograph as a simple predictive tool for the final hearing threshold.The coexisting symptoms of vertigo 29–56%) and tinnitus (41–90%) were frequently observed in adult patients with SSNHL , 20. The% and tinIn terms of audiograms, we observed that patients with ascending and flat configurations had lower thresholds for the final hearing and greater recovery odds than patients with descending figures; these findings were consistent with the conclusions drawn by Qian et al.  and ChenThis study's results found that the lymphocyte count correlated with the initial hearing thresholds, with a marginally higher value in patients who recovered. Although a low lymphocyte count was identified as a risk factor and a poor prognostic factor in adults , 14, recIn the current study, we observed that among the ears studied, 36.7% had profound initial hearing, and among these ears, 45.3% showed no improvement. The findings were similar to the conclusion drawn by a recent meta-analysis , with 36To the best of our knowledge, our study on SSNHL in children is one of the largest of its kind, with a sample size of 145 patients. Furthermore, we conducted a bi-center investigation, which increases the representativeness of the target population and reduces individual bias compared to single-center studies. Nonetheless, there are several drawbacks. First, because of the respective research design, it was impossible to confirm causal relationships between the investigated factors and the severity or outcomes. Second, the investigation was exploratory without a scientistic hypothesis or pivot statistical estimate—no sample size calculation to ensure a significant statistical power. Meanwhile, due to the low prevalence of SSNHL in children, only a portion of the patients had complete blood counts and coagulation tests available. Third, only the total lymphocyte count was determined; no subtype analysis was performed. Therefore, further research is warranted to focus on the potential biomarkers in children to demonstrate whether these biomarkers differ from those in adults.In conclusion, it was an exploratory study on pediatric patients with SSNHL. Some factors, including accompanying tinnitus, the severity of the initial hearing loss, the onset of therapy, and the configuration of audiograms, might be related to the prognosis of pediatric patients with SSNHL. Meanwhile, the incidence of vertigo, lower lymphocytes, and higher PLR were associated with poor hearing severity. Further research is needed to establish a more accurate understanding of the relationship between pediatric SSNHL and its underlying mechanisms, given the diversity of clinical trials involving adults and children.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China and Ethics Committee, The First People's Hospital of Foshan, Foshan, PR China. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.DB contributed to the study design, data analysis, and manuscript writing. YL and XZ contributed to the study design, data collection and analysis, and manuscript writing. ZD and DD contributed to the data analysis, collection, and holding. All authors contributed to the article and approved the submitted version.


Background: Undiagnosed neonatal hearing loss causes severe language, cognitive, and behavioral problems in children. Sick newborns who spend 48 hours in the neonatal intensive care unit (NICU) have a 10- to 20-fold increased risk of permanent hearing loss. The aim of this study is to identify hearing impairment in high-risk sick newborns who spend at least 48 hours in the NICU.Methods: The present prospective observational study was conducted at a single center. All sick neonates admitted to the NICU for a minimum of 48 hours at the JK Lon Hospital, Zanana Hospital, and Mahila Chikitsalaya, Sawai Man Singh (SMS) Medical College, Jaipur, Rajasthan, India, from June 2017 to May 2018 were considered eligible for the study. The primary outcome was the assessment of hearing loss of high-risk newborns using otoacoustic emissions at the time of discharge, six weeks of age, and automated auditory brainstem response (AABR) at three months of chronological age. The secondary outcome was to analyze the association of hearing loss with different risk factors in high-risk neonates.Results: A total of 150 infants who had one or more risk factors were studied, 60 were female and 90 were male. No statistically significant difference in hearing loss was observed based on birth weight, sex, and gestational age. The first distortion-product otoacoustic emission (DPOAE) screening was done on infants at the time of discharge from the NICU. Eighty-three infants (55.33%) had “refer” on the first DPOAE and the remaining 67 (44.67%) were passed results at the time of discharge. At six weeks of life, on repeat screening with a second DPOAE test, 36% "refer" on the first screen had a "refer" result on the second DPOAE. However, 4.4% "pass" on the first screen turned out to be "refer" on the second screen. These 33 infants who had "refer" results on the second screen were subjected to testing. At 10 weeks of life, AABR was performed on 33 infants. Eleven infants out of 33 had sensorineural hearing loss (SNHL) on AABR. Hearing impairment with the DPOAE test was observed with risk factors neonatal hyperbilirubinemia (NHH), hypoxic ischemic encephalopathy (HIE), and very low birth weight (VLBW) and was statistically significant among all risk factors. But, no such association (between hearing impairment and risk factors) was observed with the AABR test. In our study, we found that the duration of mechanical ventilation in mean days 7.67±6.24 had statistically significant SNHL compared to the lesser duration of mechanical ventilation (p<0.001).Conclusion: Two-stage DPOAE done prior to AABR is helpful in the early detection of hearing loss. Early recognition of hearing loss (HL) and timely intervention is essential to prevent adverse speech and language outcomes due to permanent congenital or acquired HL in the neonatal period ,2. The fIn 2006, the National Program for Prevention and Control of Hearing Loss was launched in India .Automated auditory brainstem response (AABR) and otoacoustic emission (OAE) tests are the best methods of hearing assessment among diagnostic methods because of their specificity and sensitivity. OAE assesses the function of the outer hair cells of the cochlea  and is used in assessing cochlear diseases, such as exposure to viruses, noise, and ototoxic substances . OAEs arThis prospective observational, single-center study was conducted from June 2017 to May 2018 in the NICU of J.K. Lon Hospital, Zanana Hospital, and Mahila Chikitsalaya, Sawai Man Singh (SMS) Medical College, Jaipur, Rajasthan, India. All sick newborns ≥28 weeks of gestational age who remained in the NICU for at least 48 hours were considered eligible for the study. The following neonates were excluded from the study: newborns who stayed in the NICU for <48 hours; newborns <28 weeks of gestational age; newborns with defects of auricles, auditory canal, or other life-threatening anomalies; neonates who died or did not complete all phases of the study; or parents who refused consent. Informed written consent for the study was obtained from the parent for enrollment in the study after explaining the purpose of the study. They were also provided with a participant information sheet. The Institute Research Review Board of SMS Medical College and the attached hospital  approved the study. A routine otorhinolaryngologic examination of all participants was carried out, which consisted of an inspection of the pre-aural, pinna, and post-aural regions in the ear, nose, and throat department. Occluding wax or debris was gently removed using a cotton-tipped swab. A detailed history, complete clinical examination, and general examination were carried out, and potential risk factors were identified. Neonates underwent hearing assessment at the time of discharge using the DPOAE test. The machine used for this test was the “Echo Screen UC-232 S/N: 251430” by Natus Europe GmbH . Otoacoustic emission probe calibration was carried out daily to ensure the infants were screened with a functioning probe. During the measurement, two pure tone stimuli (f1 and f2), where f2 was higher than f1, were presented with an f1/f2 ratio of approximately 1.22 (range 1.21-1.23) to obtain a robust DPOAE response in human ears [Testing was done while the infant was naturally sleeping or alert and calm or under sedation (20 mg/kg of triclofos given), as the results of OAE are not affected by sedation. The test results were displayed on the screening unit as a "pass" or a "refer.” This was recorded in the book of vaccination and the newborn medical record. The results of OAE were interpreted according to the Rhode Island criteria: (1) pass: response is 3 dB or more in at least four frequency bands  and (2) “refer”: no response is present in any frequency band . An infaThe sample size was calculated at a 95% confidence level, assuming first-stage failure by OAE in 6.1% of high-risk neonates as per the results of the reference article. At the absolute allowable error of 4% (precision), a minimum of 138 high-risk neonates are required as a sample size, which is further enhanced and rounded off to 150 patients expecting 10% dropout/loss to follow-up/attrition. Figure Study outcomes across major risk factors for HL are summarized in Tables This prospective observational cohort study was performed to assess HL in sick infants by using DPOAE at discharge and at six weeks of age, followed by AABR performed at 14 weeks of age in those DPOAE failing (refer) at six weeks of age. In our study, 7.33% of infants had SNHL. In contrast to our study, other previously published studies had 2%-6.5% SNHL, but these studies were performed either in high-risk neonates or healthy and high-risk neonates -18.Gouri et al. studied hearing assessment on healthy and sick newborns with "AABR after transient-evoked otoacoustic emissions (TEOAE)," where 137 out of 415 newborns required NICU admission . Stadio In contrast, in our study, we found 1%-1.5% more SNHL that could have been missed by two-step hearing screening. In our study, we found VLBW infants, amikacin, HIE, and neonatal hyperbilirubinemia (NNH) required for exchange transfusion caused more hearing impairment  than other diseases during DPOAE screening. However, on testing with AABR, no such association was seen. In our study, we found that those infants who had MV for a mean of 7.67±6.24 days had SNHL compared to those who had MV for a lesser duration and had no HL. Pourarian et al. found that oxygen therapy and the use of antibiotics were statistically significant compared to other risk factors including the risk factor "duration of MV of more than five days" . On the Limitation of studyThe study incorporated fewer risk factors as compared to the factors suggested by the Joint Commission on Infant Hearing (JCIH). Moreover, this is a single-center study, and it is advocated that such type of trials should be conducted in other centers for better availability of results. Additionally, we have a smaller sample size, and a much larger sample size may reveal better results. Furthermore, a significant analysis of hearing screening would require studies with larger sample sizes. Our 100% follow-up is the strength of our study. For early detection of HL, "two-stage DPOAE preceded by AABR" can be successfully implemented as a newborn hearing screening program in a hospital setting. Minimizing mechanical ventilation may improve HL in sick newborns.


Using data collected from hearing aid users’ own hearing aids could improve the customization of hearing aid processing for different users based on the auditory environments they encounter in daily life. Prior studies characterizing hearing aid users’ auditory environments have focused on mean sound pressure levels and proportions of environments based on classifications. In this study, we extend these approaches by introducing entropy to quantify the diversity of auditory environments hearing aid users encounter.Participants from 4 groups  wore research hearing aids and completed ecological momentary assessments on a smartphone for 1 week. The smartphone was programmed to sample the processing state (input sound pressure level and environment classification) of the hearing aids every 10 min and deliver an ecological momentary assessment every 40 min. Entropy values for sound pressure levels, environment classifications, and ecological momentary assessment responses were calculated for each participant to quantify the diversity of auditory environments encountered over the course of the week. Entropy values between groups were compared. Group differences in entropy were compared to prior work reporting differences in mean sound pressure levels and proportions of environment classifications. Group differences in entropy measured objectively from the hearing aid data were also compared to differences in entropy measured from the self-report ecological momentary assessment data.Auditory environment diversity, quantified using entropy from the hearing aid data, was significantly higher for younger listeners than older listeners. Entropy measured using ecological momentary assessment was also significantly higher for younger listeners than older listeners.Using entropy, we show that younger listeners experience a greater diversity of auditory environments than older listeners. Alignment of group entropy differences with differences in sound pressure levels and hearing aid feature activation previously reported, along with alignment with ecological momentary response entropy, suggests that entropy is a valid and useful metric. We conclude that entropy is a simple and intuitive way to measure auditory environment diversity using hearing aid data. Recent years have seen a growing interest in understanding the soundscapes or auditory environments that listeners, and specifically hearing aid users, encounter in daily life . UnderstTo that end, this study presents an analysis of the data described in . The purdiversity among those groups by quantifying diversity using entropy of measurements collected from the participants’ hearing aids. To further validate the use of entropy as a measure of auditory environment diversity, entropy measured from hearing aid data will be compared to self-report data from ecological momentary assessments . Entropy measures how diverse some system or parameter is as a function of its predictability. That is, the more predictable a system is—or the less often and the less drastically it changes—the less diverse it is and thus the less entropy it has  as well as entropy from EMA responses were computed for each participant. Entropy was compared among groups and data types. Methods and findings from this study can inform future investigations of auditory environment diversity and its relationship to clinical practice and audiologic outcomes.This study aims to investigate differences in auditory environment y it has . Entropyy it has ,10. Ghozy it has  used enty it has  proposedy it has  first shy it has . The autThe dataset from  was usedParticipants wore Starkey Halo 2 i2400 receiver-in-the-canal hearing aids with research firmware for one week. Participants were asked to wear the hearing aids for 12–16 h per day. For participants with normal hearing, the hearing aids were set to have zero gain in all channels. For participants with hearing loss, the hearing aids were set to match the gain-frequency response of the participant’s own hearing aids using real-ear measures. For a complete description of the fitting process, see .Participants also carried a smartphone connected to the hearing aids via Bluetooth. Throughout the week, data from the hearing aid was sent to and stored on the smartphone. Data included the sound level of the environment and the environment classifier as well as the processing state of the hearing aid. Due to the power limitations of the hearing aids and the smartphone, data was collected by sampling the hearing aid data, rather than collecting it continuously. Every 10 min, the system attempted to collect data for one minute at a sampling rate of 2 Hz. Every 40 min, the system attempted to collect data for 5 min at a sampling rate of 2 Hz. The purpose of the longer sampling period every 40 min was because every 40 min the smartphone delivered an EMA which asked participants to report on the auditory environment and their experience. EMAs were delivered to participants using the AudioSense+ app . ParticiAuditory environments were quantified using two indicators, measured by the hearing aids: SPLs and environment classifier. To calculate SPL for each sampling period, all 24 channels of the hearing aids recorded the input level to that channel every 2 sec. Frequency-specific transforms were used to estimate the free-field level at each ear to account for microphone location effects. Then, microphone and pre-amp gain corrections were applied. These values were converted to dB full scale (FS) and summed. Finally, a correction factor was applied to provide an estimate of the SPL at each sample. For this study, the median value of these measurements within each sampling period for each hearing aid was calculated and the values for each hearing aid were averaged to give a single SPL value for each sampling period. The hearing aids also returned a classifier of the environment for each sample: quiet, speech, noise, music, machine, or wind. The exact nature of how the hearing aids make decisions on the environment classification is proprietary and could involve hundreds of parameters. However, the common approach is to train an algorithm using known environments and allow the algorithm to determine what acoustic features are best associated with each class and then use these features to make decisions about novel environments H(x)=ronments ,12. Thusx is the time series of SPLs and i is the SPL bin) and multiplied by the log10 of that probability. These values were summed and multiplied by x is the time series of environment classifications and i is the classifier). These values were then multiplied by the log10 of the values, summed, and multiplied by SPL and environment classification entropy per subject were calculated using data from the hearing aids. SPL entropy quantifies the overall predictability or diversity of a participant’s SPLs across the entire week. The more diverse the participant’s SPLs, the less predictable the participant’s SPLs and the higher the overall entropy. SPL entropy for each participant was calculated from the time series of SPL values where each value is the median SPL in each sample across the entire week. The distributions of SPLs were discretized into 3 dB bins from 43 dB SPL to 109 dB SPL (based on the observed range of SPLs encountered by participants). The same number of bins (23), size (3 dB), and bin edges were used for each subject. To calculate entropy, the probabilities of SPLs falling into each bin were calculated . Group differences were analyzed using one-way Analysis of Variance (ANOVA). When appropriate, significant omnibus statistics were followed with a priori pairwise comparisons with Tukey Hearing aid data was collected from a total of 46 participants across the 4 groups. Participants per group and summary statistics for each group are given in A total of 8,292 data points from the hearing aids (SPLs and matched environment classifications) were analyzed: 1,654 for YNH-U, 2,117 for OHL-U, and 1,802 for YNH-R, 2,719 for OHL-R. The YNH showed lower numbers of data points than the OHL groups, likely because the sample size was slightly smaller for the YNH groups. However, the number of samples per participant did not differ significantly between groups . On average, each participant completed 8.3 EMA surveys per day . Number of EMA surveys completed per group did not differ with the exception that the YNH-R group completed fewer EMA surveys than the OHL-R group (EMA entropy differences between all groups followed a similar pattern as SPL entropy . EMA entPearson’s product-moment correlations were used to assess the relationship among the 3 entropy values. Correlation coefficients and 95% confidence interval estimates are shown in This study aimed to use a novel metric—entropy—to quantify auditory environment diversity using SPL and environment classification data from hearing aids. We showed that entropy could be calculated in a straightforward manner from hearing aid data. The study then aimed to validate the use of entropy, calculated from hearing aid data, as a measure of auditory environment diversity by comparing SPL and environment class entropy between younger and older listeners from an urban and rural area and comparing these entropy differences to differences in entropy on EMA. SPL and environment class entropy was significantly higher for the YNH than the OHL participants, with the largest differences were observed between the YNH-U and OHL-R groups. Similarly, the YNH participants had significantly higher EMA entropy than the OHL participants. Finally, this study aimed to compare entropy measured objectively from hearing aid data to entropy measured from EMA, a self-report measure. Significant, moderate correlations were observed between SPL and environment class entropy and between SPL and EMA entropy, providing further evidence for the validity of entropy as a measure of auditory environment diversity. Taken together, the findings from this study suggest that younger listeners encounter a greater diversity of auditory environments than older listeners, that this diversity can be captured using hearing aid data and measured using entropy, and that entropy calculated using objective hearing aid data broadly corresponds with entropy measured from self-report EMA data.Findings in the present study are broadly consistent with the findings in , where yauditory environment diversity is not necessarily related to environment diversity. Thus, hearing aids, because they collect acoustic data specifically, provide a more sensitive measure of auditory environments that broader metrics like GPS tracking.Quantifying auditory environments via entropy with hearing aid data has some advantages over other approaches. Because data is collected frequently, it may be more sensitive to detecting auditory environment differences than other approaches. For example, as reported in , no diffA simple, intuitive, and theoretically meaningful measure of auditory environment diversity such as entropy has many potential applications. Hearing aids users who encounter greater auditory environment diversity may benefit from more advanced hearing aid technologies such as a more detailed environment classification taxonomy, faster feature activation of adaptation, more user control, GPS-tagged features, feature parameters that learn from the environment and user input, or other algorithms that take into account less predictable inputs ,5,6. BecThis re-analysis had three key limitations that should be noted. First, absolute entropy values are not meaningful. What the actual entropy values are depends on the parameter and the study design. It is not possible to compare absolute entropy values across studies. Second, there is no ground truth for auditory environment diversity. We do not have a way to validate the entropy value by comparing it to the “true” auditory environment diversity of each participant. We validate entropy as a measure of auditory environment diversity by comparing entropy to other measures of diversity and by comparing various methods of measuring entropy. Third, this study relied on a relatively small sample from only two geographic areas. We did not attempt to collect data about all factors that might affect auditory environment diversity, such as cultural, socioeconomic, or other demographic factors. The bias in auditory environments of this sample relative to the population is unknown, and the effects of age and location on auditory environment entropy may be moderated by additional factors not accounted for in this study.Entropy, calculated using hearing aid data such as SPL and environment classification, is an intuitive, simple, and theoretically meaningful way to estimate the diversity of auditory environments encountered by listeners. SPL and environment class entropy are consistent with other measures of auditory environment diversity as well as entropy calculated using self-report on EMA, suggesting that entropy may be a valid measure of auditory environment diversity. Entropy could be a useful metric for a hearing aid to determine the auditory environment diversity of a user and make processing changes based on individual users’ auditory environment diversity.


We investigated the clinicopathological features and prognoses of the new molecularly defined entities in latest edition of the World Health Organization (WHO) classification of sinonasal carcinoma (SNC)Integrated data were combined into an individual patient data (IPD) meta-analysis.IDH2-mutant, 41 NUT carcinoma, 187 SWI/SNF loss, and 25 triple negative SNCs  for analyses. Compared to other molecular groups, NUT carcinoma was associated with a younger age at presentation and an inferior disease-specific survival. Among SNCs with SWI/SNF inactivation, SMARCB1-deficient tumors presented later in life and were associated with a higher rate of radiotherapy administration. SMARCA4-deficiency was mostly found in teratocarcinosarcoma while SMARCB1-deficient tumors were associated with undifferentiated carcinoma and non-keratinizing squamous cell carcinoma.We included 61 studies with 278 SNCs including 25 Our study facilitates our current understanding of this developing molecular-defined spectrum of tumors and their prognoses. In the previous editions of the World Health Organization (WHO) Classification, sinonasal malignancies were mainly classified as conventional squamous cell carcinoma (SCC), non-keratinizing SCC, intestinal-type adenocarcinoma (ITAC), non-ITAC, neuroendocrine carcinoma (NEC), poorly differentiated carcinoma (PDCA), sinonasal undifferentiated carcinoma (SNUC), and other rare subtypes . The 202versions .SMARCB1- and SMARCA4-deficient sinonasal carcinoma  AND (carcinoma OR cancer) AND (SMARCB1 OR SMARCB-1 OR SMARCB 1 OR INI1 OR INI 1 OR INI-1 OR SMARCA4 OR SMARCA-4 OR SMARCA 4 OR BRG1 OR BRG-1 OR BRG 1 OR SWI/SNF OR NUT OR isocitrate OR IDH1/2 OR IDH2). We carefully reviewed the reference list of potential articles to avoid missing important data. This study protocol strictly followed the recommendations of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement .SMARCB1-deficient, SMARCA4-deficient, NUT midline, and IDH2-mutant carcinoma of the sinonasal tract. We excluded studies if they are (i) reviews, (ii) conference abstracts or conference papers, (iii) books, (iv) without IPD, and (iv) duplicated data.For abstract screening, two independent teams  reviewed the titles and abstracts of included articles. Studies were included if they are observational studies and report individual patient data (IPD) of Following this step, two independent teams read all full texts of potential studies and extracted data into a standardized worksheet. The following data were collected: author names, institution, city, country, publication year, number of patients, age, gender, clinicopathological information , treatments administered, progression-free survival (PFS), and disease-specific survival (DSS).SWI/SNF loss, NUT carcinoma, IDH2-mutant, and those without SWI/INF deficiency, NUTM1 fusion, and IDH2 mutation (triple negative group). We excluded cases that were absent the NUTM1 rearrangement and SWI/SNF loss but missing information on IDH2 status. For SWI/INF-deficient tumors, we also compared the SMARCB1-deficient versus SMARCA4-deficient carcinomas. We used Chi-squared and Fisher’s exact test for comparison of categorical variables while t-test, Wilcoxon rank sum test, or analysis of variance (ANOVA) were utilized for continuous covariates, if applicable. The R program  was used for statistical analyses.We divided data into four main groups: IDH2-mutant, 41 NUT carcinoma, 187 SWI/SNF loss, and 25 triple negative SNCs. Among NUT carcinoma, BRD4:NUTM1 was the most common variant and only one case harbored BRD3:NUTM1 rearrangement. The R172 variant was the most predominant IDH2-mutant genotype. Regarding SNCs with inactivation of one of the SWI/SNF complex genes, SMARCB1-deficient carcinoma was the most frequent subtype followed by SMARCA4-deficient tumors. Loss of SMARCA1, SMARCA5, and SMARCE1 were also found in one SNC case each. IDH2 mutations, NUTM1 rearrangement, and inactivation of SWI/SNF complex were mutually exclusive with each other.After merging search results from three electronic databases and removing the duplicates, we had 340 studies for title and abstract screening. Following this step, 84 articles were selected for full-text reading. Sixty-one of them met inclusion criteria corresponding to 278 SNCs which were included for analysis , 11–66 Figure 1IDH2-mutant, SWI/SNF loss, and triple negative groups, NUT carcinoma presented a significantly younger age (p < 0.001). Most IDH2-mutant SNCs were originally diagnosed as SNUC whereas the diagnosis of NUT carcinoma is usually more straightforward. SWI/SNF-loss SNCs were commonly misdiagnosed as SNUC, SCC, or TCS. Lymph node metastases were generally uncommon in SNCs whereas distant metastases were more frequently observed among all molecular groups.Regarding treatments, SWI/SNF-loss SNCs were less likely to receive radiotherapy as compared to other groups (p = 0.020). The rate of nodal metastasis, distant metastasis, surgical resection, and chemotherapy administration were statistically comparable between the four groups.SMARCA4-deficient versus SMARCB1-deficient SNCs . A subset of SMARCA4-deficient SNCs had overlapping histopathological findings with TCS whereas SMARCB1-deficient were distributed in more diverse histological diagnoses. Radiotherapy administration was more commonly used for SMARCB1-deficient tumors.We also sought to investigate the similarities and differences between ent SNCs Table 2.IDH2-mutant SNCs as compared to other groups. No IDH2-mutant SNCs metastasized to lung and most of these tumors had a metastatic preference to liver and other rare organs  (Bone and lung were the two most common metastatic sites for SNCs. We found significant different metastatic patterns of astinum) Table 3.IDH2-mutant and triple negative SNCs have a more favorable DSS compared to NUT carcinoma (p = 0.014) (SMARCA4-deficient versus SMARCB1- deficient SNCs (SNCs were associated with high-risk for local relapse and tumor progression during follow-up. We could not calculate and compare the PFS between the molecular groups due to high rate of missing data. Kaplan-Meier analyses demonstrated that ent SNCs Table 4.IDH2-mutant, NUT midline, and SWI/SNF-deficient SNCs were categorized as SNUC, PDCA, TCS, or NEC (NUT midline, SMARCA4-deficient, and SMARCB1-deficient SNCs have been recognized as separate entities. Given their distinct clinicopathological features and prognoses as compared to IDH2-wild type tumors (IDH2-mutant SNCs may nevertheless be regarded as a distinct molecular group in future WHO editions. Because of the rarity of SNCs, most data were presented as case reports or small- to medium-sized case series. The clinicopathological features and prognostic outcomes of new molecular groups of SNCs have been described. However, it is still controversial as to how these tumors are different from each other and in how clinicians can better assess patient outcomes. In this study, we integrated IPD of published studies into a meta-analysis to improve the statistical implication compared to cohort studies with limited sample size.In recent years, new molecular profiles of SNCs have been further clarified and novel molecular groups have been incorporated into the latest WHO classification of SNCs –6. Prior, or NEC , 5, 33. e tumors , IDH2-muIDH2-mutant SNCs were most likely to metastasize to liver and other rare organs compared to other groups. Like prior studies, our meta-analysis demonstrated improved survival of IDH2-mutant SNCs as compared to those without these mutations (IDH1/2 mutations in gliomas, chondrosarcoma, and cholangiocarcinoma have similarly been established (IDH2 mutation in SNCs provides a promising opportunity for targeted therapy with IDH inhibitors. Most IDH2-mutant SNCs occur in codon 172 and can be diagnosed by immunohistochemistry assay which is an accessible, rapid, and inexpensive method (Our results showed that these tumors were uniformly high-grade and distributed in diverse histopathological spectrums with SNUC and PDCA being the most common variants. All molecular groups of SNCs had a relatively considerable risk for tumor metastases to distant organs with bone and lung being the most common sites. We found that utations , 6, 8. Tablished –70. The e method .NUTM1 gene (This meta-analysis also highlighted that SNCs usually present at older age except for NUT carcinoma, which is more commonly seen in young adults and pediatric patients. NUT carcinoma is exceedingly rare, typically occurs in the midline structures, and histopathologically resembles PDCA. This tumor is characterized by a chromosomal rearrangement involving TM1 gene . The avaTM1 gene  and our SMARCB1 and SMARCA4 being the most common variants. It is still poorly understood regarding how these subtypes are different from each other. SMARCB1-loss SNC is associated with rhabdoid differentiation in SNUC (SMARCB1-deficient SNCs occur at a significantly older age and more likely to have radiotherapy administration in comparison to SMARCA4-deficient tumors. From our analysis, the DSS of these two new SNC entities were comparable. With the use of immunohistochemistry, it is easier to recognize these two rare entities and separate them from other sinonasal PDCAs.The most common genetically defined group of SNCs involves the SWI/SNF complex genes with loss of  in SNUC , which i in SNUC  and SNCsDEK::AFF2-rearranged non-keratinizing SCC and TP53-mutant ITAC due to limited data. In addition, we could not compare the effectiveness of treatment modalities in each molecularly defined SNC subgroup due to missing data. Finally, we could not assess PFS, an important prognostic value due to missing data in most included studies. Future large multicenter prospective studies are essential to validate the results of this study.This study is the first meta-analysis comparing the new molecular groups of SNCs in the new edition of WHO classification. It helps summarize and facilitate our current understanding about the clinicopathological behaviors and prognoses of these aggressive tumors. However, there are certain limitations. First, all included studies are retrospective cohort studies or case reports/series leading to inevitable selection bias. Next, we could not include other recently described molecular entities such as In summary, the evolution of molecular pathology alongside standard immunohistochemistry enables us to recognize and accurately diagnose novel molecular entities of SNCs. These tumors have distinct clinicopathological profiles and prognoses and should be distinguished from other SNCs to better understand their unique natural histories and treatment implications.HV: conceptualization, data curation, formal analysis, investigation, methodology, project administration, software, validation, writing original, review, and editing. TL: data curation, formal analysis, investigation, methodology, review, and editing. TTBL: data curation, formal analysis, investigation, methodology, review, and editing. HL: data curation, formal analysis, investigation, methodology, review, and editing. EE-R: data curation, formal analysis, investigation, methodology, review, and editing. KM: data curation, formal analysis, investigation, methodology, review, and editing. ID: conceptualization, project administration, validation, review, editing, and supervisions. All authors contributed to the article and approved the submitted version.


Hearing is essential to the formation of social relationships and is the principal afferent of social life. Yet hearing loss, which is one of the most prevalent forms of sensory disability worldwide and is critical for social development, has received little attention from the social interventionalist perspective. The purpose of this mini-review is to describe the basic neurobiological principles of hearing and to explore the reciprocal relationships between social support, hearing loss, and its psychosocial comorbidities. We also discuss the role of social enrichment in sensorineural recovery and identify open questions within the fields of hearing physiology and social networks. Throughout human history, communication has played a central role in shaping our social world. Language enabled our ancestors to share information and coordinate activities to facilitate social cohesion. As societies advanced, language became more complex, allowing for the transmission of ideas across generations and the construction of collective identities . Across Hearing plays multiple essential roles in shaping our social interactions. First, hearing is essential for afferent and efferent functions of language. Auditory input in early childhood drives the maturation of white matter microstructure in brain areas related to speech comprehension and production. Moreover, hearing continues to be important throughout life for features of communication such as speech enunciation . Second,Hearing loss, therefore, has multifold effects on social connectedness, yet has received little attention from the social interventionalist perspective. Hearing loss is a highly prevalent sensory disability affecting nearly 470 million people worldwide, and this number is expected to grow to 900 million by 2050 as our population continues to age . IndividJust as hearing loss may shape one’s social world, the social environment may in turn influence individuals’ experiences with hearing loss . IndividSound is a pressure transduction wave that is converted from a mechanical stimulus into an electrical stimulus by the ear. Sound waves are transduced into vibrations, starting with the tympanic membrane of the external ear and the ossicles of the middle ear. These vibrations are transmitted to the inner ear via the oval window, which generates a fluid wave within the endolymph-filled cochlea. This fluid wave bends tip links of stereocilia and opens mechanically gated ion channels on hair cells, the sensorineural tissue lining the cochlea. Surrounding potassium-rich endolymph depolarizes the hair cells and generates action potentials, which are transmitted via the auditory nerve to the brainstem and auditory cortex. Hair cells are organized tonotopically along the length of the cochlea, and the location of activation corresponds to the perceived frequency of sound .Disruptions to the conductive apparatus, including the tympanic membrane, ossicles, or bony labyrinth, result in conductive hearing loss. Disruptions to the sensorineural tissue, including hair cells within the cochlea or the auditory nerve, result in sensorineural hearing loss. Hearing loss involving both mechanisms is characterized as mixed hearing loss .Etiologies of hearing loss are multifold. Up to 50% of cases have a known genetic etiology. Genetic causes of hearing loss may present in childhood , with progressive onset into late adulthood , or during varied points in an individual’s lifetime  . GeneticRehabilitation options vary by the mechanism of hearing loss. Patients may benefit from amplification of sound through hearing aids, or from assisted listening devices such as loops, FM, infrared, or signaling systems . CochleaThe neurobiology of hearing is intrinsically coupled to communication. Language involves shared attention to detect, discriminate, and extract meaning from vocalizations, which requires auditory processing . ElectroOne of the earliest explanations of language acquisition is B. F. Skinner’s Behaviorist theory. Behaviorists view language as a product of imitation and reinforcement: successful associations of words are positively reinforced with reward . Noam ChNeuroanatomy studies suggest that the auditory cortex may play a central role in multimodal social processing. Functional magnetic resonance imaging (fMRI) identifies connections from the primary auditory cortex to limbic/paralimbic, visual, somatosensory, and motor regions - many of which participate in emotional processing and reinforcement of motor sequences . These mGiven the importance of auditory processing, hearing loss is important to address in early childhood as its presentation may influence linguistic and social development. Several studies, summarized in Children aged 1 to 5 years who have not yet received cochlear implants or are newly implanted have been shown to adopt different emotional regulation behaviors compared to hearing children. This difference may be in part due to absent pitch information required for detecting voice emotion . InteresChildren with hearing loss may also face increased psychosocial difficulties, such as behavioral dysregulation and social isolation, in settings with hearing children . A clustSome studies suggest that psychosocial difficulties may be related to adolescents’ ability to communicate with parents, peers, and other members of their social environment, beyond just sensory discrimination or linguistic ability . Polat . ReceptiAdult-onset hearing loss is associated with various social and cognitive challenges that may increase morbidity in older adults. Hearing loss later in life may result in isolation from social settings, including group dining and places of employment, and contribute to strain within interpersonal relationships . ImpaireIn elderly patients, hearing loss can have significant consequences with compounded morbidity. A recent meta-analysis found that hearing loss was associated with cognitive decline, including Alzheimer’s disease and dementia . Though While hearing loss in adulthood can have wide-ranging psychosocial consequences, adults with robust support networks show significantly fewer adverse outcomes and some pro-social benefits . Dunn etAn individual’s social environment may influence his or her response to hearing loss interventions. One such example is recovery of sensory function after cochlear implantation.Neural plasticity is essential for recovery from sensory disability. This principle is highlighted in models of rehabilitation after acute neurological injury, such as stroke. Following the onset of stroke, activation of plasticity-responsive sensory inputs is necessary to restore multimodal function. Environmental enrichment has been shown to improve recovery of sensory function after acute neurological injury . EnvironEffective response to cochlear implantation similarly requires neural plasticity within primary auditory and associative cortices. This idea is highlighted by differences in functional imaging studies in congenitally deaf and post-lingually deafened cochlear implant users. For instance, post-lingually deafened patients show tonotopic reorganization of the auditory cortex toward newly perceived frequencies following cochlear implant activation . This reGiven the varied etiologies of hearing loss, it is important that social interventions are tailored to the unique needs of each group. For young children with hearing loss, early intervention is critical to attain near-normal language abilities. Various social determinants of health, such as race, insurance status, or residency in a rural area, may delay diagnosis of hearing loss and receipt of cochlear implantation services. Interventions must address geographic and socioeconomic barriers . For pedDHH children may face challenges in environments with hearing children, and adverse outcomes can be mitigated with robust peer and familial support networks. Parental support and closeness of social networks in school are associated with improved quality of life in children with hearing loss . Of chilAdult-onset hearing loss can be challenging as patients may struggle to adapt to new communication strategies and may regard changing social dynamics with frustration or shame . A surveCochlear implant users with similar performance metrics may experience different degrees of cognitive load, which can drive social avoidance. Pupillometry is a growing area of study that assesses listening effort in adult cochlear implant recipients, where pupil diameter may distinguish tasks that are more or less effortful . Other pTo better understand the social dynamics of patients with hearing loss, it is important explore new methods of acquiring social data beyond self-report . WearablHearing plays an important role throughout life in language development, communication, and forming relationships. Hearing loss may contribute to adverse psychosocial outcomes early in life and morbidity in adulthood. Several factors protect against adverse outcomes related to hearing loss, including early intervention, perceived support, and closely knit social networks . Social AP and AD conceived of the review. All authors contributed to the outline and literature review. AP, NJ, MK, and AD participated in manuscript writing. All authors performed revisions and approved the final submission.


The disorder known as angio-invasive mucormycosis is characterized by tissue necrosis and infarction. The Mucorales order of saprophytic fungi is responsiblefor its development. It is unclear how widespread mucormycosis is in India due to a lack of population-based investigations. Diabetes mellitus is the risk factorthat occurs the most frequently, followed by solid organ transplant and hematological cancer. The present study has been carried out to assess the knowledgeregarding mucormycosis among nursing students from Nootan College of Nursing, Visnagar, Gujarat. For this we have selected 100 students by using the probabilitysampling technique. Structured questions were used to assess the knowledge of nursing students regarding mucormycosis. The Score was categorized as poor, averageand good. The results show that 45(45%) of the nursing students having poor knowledge, 35(35%) of them were having average knowledge, 20(20%) of them were havinggood knowledge. There is an association between gender, program and their level of knowledge. Most of the students having poor knowledge regarding mucormycosisand we need to create awareness regarding mucormycosis to Nursing students. A group of filamentous moulds belonging to the order Mucorales are responsible for the infection known as mucormycosis. Food contamination, spore inhalationinto the nose or lungs, or inoculation into broken skin or wounds can all cause infections. . MucormyApophysomyces elegans, Rhizopus homothallicus, Mucor irregularis,and Thamnostylum Lucknowense. Uncommon pathogens like these are also being documented [Over the past few decades, India has recorded an increasing number of cases of mucormycosis. Indian mucormycosis has a few distinctive characteristics. Themost common symptom is a rhino-orbito-cerebral presentation linked to uncontrolled diabetes. A new clinical entity called isolated renal mucormycosis has beenidentified. Emerging species in this area include cumented . With thcumented .Numeroucumented . Normal cumented . Due to cumented .This study used a quantitative research approach and a survey research design. A simple random sample technique was used to choose 100 nursing students whosatisfied the study's inclusion criteria from Nootan College of Nursing in Visnagar. The study tool is divided into two parts. Demographic variables wereassessed by structured interview it contains Age (In year), Programme, Gender, Knowledge regarding mucormycosis and Source of information regarding mucormycosisand Level of knowledge was assessed by using self-structured questionnaires. It compromised 25 multiple choice questions in a single correct answer. Every correctanswer was awarded one score and every incorrect was awarded as 0 score. The maximum score on knowledge was 25 and minimum score was zero. Formal administrativepermission to conduct study was obtained from Nootan College of Nursing, Visnagar. The nature, purpose and aim of the study were explained to the nursing students.Self-Structured tool was given to selected samples. The average time taken by nursing students to fill the questionnaire was 10-15 minutes.A prospective study of 38 patients who were diagnosed with mucormycosis in a specialized care center between January 2010 and June 2011 was conducted. Thecases' involvement site, underlying illness, isolated fungus species, susceptibility pattern to antifungal medications, and therapeutic results were all examined.72% of the patients were men, with a mean age of 40-43. Rhino-orbital mucormycosis was the most prevalent manifestation (61.5%), followed by cutaneous signs(31%), gastrointestinal symptoms (5%), and pulmonary (2.5%). The significant risk factor for rhino-orbito-cerebral presentation was diabetes mellitus (56%) [The estimated incidence of mucormycosis is 0.14 instances per 1000 persons in India, which is around 70 times higher than the expected incidence ofmucormycosis worldwide. 82 cases of mucormycosis were discovered out of the 6365 samples that were collected for mycological culture and examination withinthe designated time period. Out of these, there were 56 male patients and 27 female patients. The most frequent presentations were rhino-orbito-cerebral (37),cutaneous (25), pulmonary (14), oral cavity involvement (4), and gastrointestinal (2) . A totalData shows that the majority of nursing Indian students in the state of Gujarat knew little about mucormycosis, so it is important to create an effectiveteaching strategy at colleges that includes training.


Hypothesizing that the ospC operator may bind a regulatory factor, DNA affinity pulldown was performed and identified binding by the Gac protein. Gac is encoded by the C-terminal domain of the gyrA open reading frame from an internal promoter, ribosome-binding site, and initiation codon. Our analyses determined that Gac exhibits a greater affinity for ospC operator and promoter DNAs than for other tested borrelial sequences. In vitro and in vivo analyses demonstrated that Gac is a transcriptional repressor of ospC. These results constitute a substantial advance to our understanding of the mechanisms by which the Lyme disease spirochete controls production of OspC.The OspC outer-surface lipoprotein is essential for the Lyme disease spirochete’s initial phase of vertebrate infection. Bacteria within the midguts of unfed ticks do not express OspC but produce high levels when ticks begin to ingest blood. Lyme disease spirochetes cease production of OspC within 1 to 2 weeks of vertebrate infection, and bacteria that fail to downregulate OspC are cleared by host antibodies. Thus, tight regulation of OspC levels is critical for survival of Lyme borreliae and, therefore, an attractive target for development of novel treatment strategies. Previous studies determined that a DNA region 5′ of the IMPORTANCEBorrelia burgdorferisensu lato requires its surface-exposed OspC protein in order to establish infection in humans and other vertebrate hosts. Bacteria that either do not produce OspC during transmission or fail to repress OspC after infection is established are rapidly cleared by the host. Herein, we identified a borrelial protein, Gac, that exhibits preferential affinity to the ospC promoter and 5′ adjacent DNA. A combination of biochemical analyses and investigations of genetically manipulated bacteria demonstrated that Gac is a transcriptional repressor of ospC. This is a substantial advance toward understanding how the Lyme disease spirochete controls production of the essential OspC virulence factor and identifies a novel target for preventative and curative therapies. Borrelia burgdorferisensu lato, requires its OspC protein during the initial stages of vertebrate infection, and mutant bacteria that cannot produce this outer surface-exposed lipoprotein are unable to initiate infection in vertebrates , 45B. buequences . Howeversequence  46). B.. B.B. bu repeats  p repeat . All ospirection . The retB. burgdorferisensu stricto type strain, B31-MI-16, was cultured to mid-exponential phase at 35°C. That condition was adopted based on our previous characterization of the B. burgdorferierp operons, whose expression is also responsive to culture temperature, in which we found that the erp repressing and activating proteins were all adequately expressed when cultured at 35°C . The strain Ip89 sequence was used for these analyses under the hypothesis that a protein that binds to the 11-bp repeated sequence would have an overall greater affinity for the 7 direct repeats of Ip89 as opposed to the smaller number of separated repeats of B31 . These results indicate that Gac binds to the B31 ospC operator with a greater affinity than to the flaB, ospAB, or pCR2.1 competitor sequences but has a lower affinity for the B31 ospC operator than for the Ip89 ospC operator.Similar EMSAs and densitometric analyses were performed with labeled B31 ospC operator from strain B31 as the EMSA probe, truncated segments of that DNA region were used as competitors to narrow down the sequences that bound Gac  (CKO-1 complemented with wild-type gac), and strain NGR (an isogenic wild-type gac clone) were cultured to mid-exponential phase at 23°C and then diluted into fresh media and incubated to mid-exponential phase at 35°C  , consistent with Gac being a repressor of OspC synthesis. Levels of OspC in those two strains were not significantly different at 35°C, ranging between 0.92 to 1.4 times more OspC in CKO-1 than in NGR . Complementation of CKO-1 with a wild-type gac gene on pBLS820 did not fully restore OspC levels to those of wild-type bacteria. However, complementation reduced levels of OspC by 1.6- to 6.9-times at 23°C and by 1.2- to 4.3-times at 35°C. No significant differences were observed between the complemented strain and NGR at 23°C or shifted to 34°C . These results suggest that relief of Gac repression is a major contributor to the induction of OspC.To assess the effects of Gac in live  at 35°C , 32. Imm< 0.001) . HoweverB. burgdorferi strains NGR and CKO-1 were next transformed with plasmids that carry transcriptional fusions between B31 ospC operator/promoter sequences and gfp. Plasmid pBLS761 carries the same operator/promoter sequence that was used as the EMSA probe in the above-described studies, while pBLS764 lacks the DNA 5′ of the ospC promoter. Each transformant was cultured at 35°C to mid-exponential phase, and then bacterial GFP content was assessed by flow cytometry , which lacks the duce GFP . In contospC is induced in B. burgdorferi cultured at 35°C, we assessed ospC and gyrA and gac transcript levels over time in cultures of wild-type B. burgdorferi  results for each pair. Since the 5′ primers detected mRNA that only encoded gyrA, whereas the 3′ primers detected both gyrA and gac mRNAs, the relative concentration of gac mRNA was approximated by subtracting the results of 5′ qRT-PCR from results with the 3′ primer set. The concentration of Gac-encoding transcript was greatest during lag and early exponential phases and then declined as the cultures matured and entered stationary phase. Those changes were opposite of ospC and are consistent with the above-described results that indicate Gac is a repressor of ospC.Since gdorferi . Levels Borrelia species contain both circular and linear DNAs, and there is considerable interest in the mechanisms by which the spirochetes maintain linear replicons . We are currently examining whether these might be the hypothesized “factor X” antirepressor.Deletion of the cription –44. Thusn by Gac . On the B. burgdorferi DNA gyrase function by addition of coumermycin resulted in increased production of OspC protein  is unique to B. burgdorferi. The possibility that gyrA can encode two distinct proteins has never been addressed for the vast majority of other bacterial species. It would be worth examining other gyrA genes for the presence of potential ribosome binding sites and start codons near the beginning of the C-terminal domain.At this time, it is not known whether production of a separate Gac protein from the 3′ end of the B. burgdorferi Gac has elevated affinity for ospC operator/promoter DNAs. Gac repressed ospC transcription in vitro and in live spirochetes. Levels of ospC and gac transcripts changed in opposite directions during cultivation, consistent with ospC repression by Gac. Analyses of mutants indicate that the ospC operator is required to alleviate Gac repression of the ospC promoter, implying that one or more additional factors interact with the ospC operator to prevent repression by Gac. The Gac protein also bound with elevated affinity to an lp17 telomere, suggesting that it may play a role in linear DNA maintenance. Our observations, and those of others  and the ribosome binding site from AGGAGG to AGAAGA. The mutant does not produce a Gac protein, although it does produce normal levels of GyrA   by cloning the aterial) . B. burgospC promoter and operator in a transcriptional fusion with gfp. Plasmid pBLS764 is identical to pBLS761 except that it lacks the ospC operator. Both are based on pBLS740, which was produced for this work by cloning the gfp gene of pBLS590 between the BamHI and HindIII sites of vector pKFSS1 , NGR(pBLS764), CKO-1(pBLS761), and CKO-1(pBLS764). Two of our previously-described B. burgdorferi strains were used as GFP expression controls as follows: KS10, which carries a promoterless gfp on pBLS590, and KS20, which carries the constitutively expressed minimal erpAB promoter driving gfp on pBLS599 . Bacteria were harvested by centrifugation, washed with phosphate-buffered saline (PBS), and resuspended in a minimal volume of 50 mM Tris (pH = 7.6), 10 mM EDTA, and 10% (w/vol) sucrose. The suspension was frozen in a dry ice/ethanol bath and then allowed to thaw in an ice-water bath. NaCl, dithiothreitol, and lysozyme were added to final concentrations of 140 mM, 1 mM, and 0.4 mg/mL, respectively, and incubated on ice for 5 min. The cell mixture was subjected to four additional freeze-thaw cycles. Cellular debris was pelleted by centrifugation, and the supernatant was aliquoted and stored at −80°C . Protein-nucleic acid mixtures were then loaded into either 6% or 10% Novex Tris-borate-EDTA (TBE) gels (Thermo Fisher). Gels were prerun for at least 30 min at 100 V in 0.5× TBE buffer before sample loading. Following the addition of the samples, electrophoresis was conducted for up to 1.5 h at 100 V.B. garinii Ip89 DNA, from 5′ of the ospC operator through the ospC promoter, was amplified from genomic DNA (gDNA) by PCR with oligonucleotide primers 1021 and 1022 (see Table S1). The resulting amplicon was cloned into pCR2.1 (Invitrogen) to create pBLS756. Fluorescently tagged IP89 ospC operator was produced by PCR of pBLS756 using IRDye800-tagged M13-reverse and unlabeled M13-forward primers (Table S1). The probe was incubated with cleared borrelial cytoplasmic extract in EMSA buffer for 15 min at room temperature with 10 ng poly-dI-dC, then subjected to electrophoresis. These exploratory EMSAs were performed twice.Initially, a fragment of ospC operator/promoter probes, and unlabeled DNA competitors. Unless noted otherwise, all EMSAs were performed a minimum of three times.Other EMSAs used purified recombinant Gac protein, labeled E. coli TOP-10. The amplicon was completely sequenced on both strands to ensure fidelity. Fluorescently tagged telomere probe was produced by PCR using IRDye800-tagged M13-reverse and unlabeled M13-forward primers.In addition, a subtelomeric sequence of strain B31 lp17 was amplified from total genomic DNA by PCR with oligonucleotides TL16h and TL16g as previously described . The resDensitometric analyses of EMSAs were performed using Image Lab 6.1 (Bio-Rad) software. Lanes and bands were added manually and subsequently analyzed to generate the lane percentage totals for each band in a lane. Protein-DNA shifts were considered as the entire region above the free DNA in each lane. The free DNA was determined for each lane by analyzing the band percentage values. For each EMSA, the free DNA percentage values for all lanes were normalized to the probe-only control band percentage value. This set the free DNA percentage of the probe-only control as equal to 100%. The normalized free DNA values were then subtracted from 100% to calculate the percent shifted DNA in each lane. Fold changes in DNA binding of EMSA competition assays were calculated by dividing the percent shifted in competition lanes by the percent shifted of the protein-probe only lane.ospC operator DNA were purified from B31-MI-16 cytoplasmic extracts as previously described (7 bacteria/mL) culture were harvested, washed, and frozen at −80°C. Bacterial pellets were then thawed on ice and subjected to three additional rounds of freezing at −80°C/thawing on ice. Bacterial lysates were resuspended in a minimal volume of BS/THES buffer . THES buffer consists of 50 mM Tri HCl (pH 7.5), 10 mM EDTA, 20% sucrose (w/vol), 140 mM NaCl, 0.7% (vol/vol) Protease Inhibitor Cocktail II (Sigma), and 0.1% (vol/vol) Phosphatase Inhibitor Cocktail II (Sigma). BS buffer consists of 50 mM HEPES (pH = 7.5), 25 mM CaCl2, 250 mM KCl, and 60% (vol/vol) glycerol. Suspended bacteria were lysed by sonication on ice. Cellular debris was pelleted by centrifugation, and the supernatant was divided into aliquots.Proteins that bind escribed . BrieflyB. garinii Ip89 ospC operator/promoter sequence, was used as a template to produce a biotin-tagged amplicon by PCR with biotin-tagged M13-reverse and unlabeled M13-forward primers (see Table S1). The probe was incubated with cleared borrelial cytoplasmic extract in EMSA buffer for 15 min at room temperature with 10 ng poly-dI-dC and then subjected to electrophoresis. The bait DNA was bound to streptavidin Dynal beads (Invitrogen) and then washed with BS/THES buffer. Cytoplasmic extracts were incubated with the DNA-bound beads and washed extensively with BS/THES. Bound proteins were eluted by washing with buffer containing increasing NaCl concentrations to 0.2, 0.3, 0.5, 0.75, and 1.0 M. Fractions were analyzed by SDS-PAGE, and proteins were stained with SYPRO Ruby . A protein band that eluted at 0.3 and 0.5 M NaCl was cut out. The samples were treated with trypsin and assayed by liquid chromatography with tandem mass spectrometry (LC-MS-MS) at the University of Kentucky Proteomics Core. Results were compared with the B. burgdorferi strain B31-MI sequence  for 1 h at 37°C. Bacteria were collected by centrifugation, and the pellet was frozen at −80°C. The bacterial pellet was then thawed on ice, resuspended in phosphate-buffered saline (PBS) containing 10 mM imidazole, and bacteria lysed by sonication. The sonicate was subjected to centrifugation and then recombinant protein purified from the soluble fraction using HisPur Ni-nitrilotriacetic acid (Ni-NTA) columns (Thermo Scientific). Purified proteins were dialyzed against EMSA buffer. Protein concentrations were determined by Bradford assay and purity assessed by SDS-PAGE with Coomassie brilliant blue staining.The B31 t tests were conducted to compare between strains, and paired t tests were used to compare within the same strain using GraphPad Prism .Cultures of strains NGR, CKO-1, and CKO-1(pBLS820) were harvested at mid-exponential phase by centrifugation and then split into aliquots for immunoblot assays and RNA extraction. Pellets for immunoblot assays were frozen at −80°C, subsequently thawed at room temperature, resuspended in 10% SDS, boiled for 5 min, and vigorously vortexed. The resulting lysates were stored at 4°C. Prior to electrophoresis, samples were preheated to 42° before adding to 2× sodium dodecyl sulfate (SDS)-PAGE loading dye . Separation by SDS-polyacrylamide gel electrophoresis was followed by electrotransfer to nitrocellulose membranes and blocking with 5% nonfat dried milk in Tris-buffered saline-Tween 20 . The membranes were then incubated with murine monoclonal antibodies directed against FlaB or OspC , 80. AftospC promoter::gfp reporter constructs was assayed essentially as we previously described (7 bacteria/mL) in BSK-II broth at 35°C. Bacteria were collected by centrifugation, washed twice with phosphate-buffered saline (PBS), and then resuspended in PBS at concentrations of approximately 106 bacteria/mL. Aliquots of each bacterial suspension were analyzed using a FACSymphony flow cytometer , with excitation and detection wavelengths of 488 and 530 nm, respectively. Approximately 100,000 events were measured for each flow cytometry analysis.Transcriptional activity of escribed . BrieflyB. burgdorferi was cultured at 35°C, and 2-mL aliquots of bacteria were taken 1-, 3-, 5-, 7-, 9-, and 11-days postinoculation. Bacteria were pelleted and then washed two times with PBS and frozen at −80°C. Frozen pellets were later resuspended in 60°C TRIzol (Thermo Fisher), and RNA was extracted using Qiagen Mini RNA kits. Residual genomic DNA was depleted using on-column Turbo DNase (Thermo Fisher). The quality (RNA integrity number [RIN] > 7) and quantity of the RNA were determined using an Agilent 2100 Bioanalyzer and Agilent 6000 Nano chips. Purified RNA stocks were stored at −80°C.qC values were normalized to ftsK, a gene whose expression is stable across different growth phases . The cDNA stocks were diluted 1:100 into nuclease-free water for use as template. Quantitative PCR was carried out using iTaq Universal SYBR green supermix (Bio-Rad) and a Bio-Rad CFX96 Touch real-time PCR thermocycler. For all reactions, cycles involved melting at 95°C for 10 s, annealing at 55°C for 10 s, and extension at 72°C for 30 s. Each run was performed with technical triplicates of each reaction as well as no-template control reactions that lacked template. Melting curves were performed with each run to validate production of specific amplicons. Every reaction was tested with a reverse transcriptase negative template to validate the absence of contaminating gDNA. h phases , using ton 2−ΔCq .


Quickly intensifying tropical cyclones (TCs) are exceptionally hazardous for Atlantic coastlines. An analysis of observed maximum changes in wind speed for Atlantic TCs from 1971 to 2020 indicates that TC intensification rates have already changed as anthropogenic greenhouse gas emissions have warmed the planet and oceans. Mean maximum TC intensification rates are up to 28.7% greater in a modern era (2001–2020) compared to a historical era (1971–1990). In the modern era, it is about as likely for TCs to intensify by at least 50 kts in 24 h, and more likely for TCs to intensify by at least 20 kts within 24 h than it was for TCs to intensify by these amounts in 36 h in the historical era. Finally, the number of TCs that intensify from a Category 1 hurricane (or weaker) into a major hurricane within 36 h has more than doubled in the modern era relative to the historical era. Significance tests suggest that it would have been statistically impossible to observe the number of TCs that intensified in this way during the modern era if rates of intensification had not changed from the historical era. From 2012 to 2022, over 160 “billion-dollar” weather and climate disasters impacted the U.S; 24 of these events were TCs, including the six costliest disasters on record during this time5. Many of the most damaging TCs to impact the U.S. in recent years have been notable for the speed at which they have intensified. For instance, Hurricane Maria (2017), the climate disaster with the highest death toll since 1980, and the 4th highest economic cost in the last four decades, strengthened from a tropical storm to a Category 5 hurricane on the Saffir-Simpson scale in just over 48 hours7. Hurricanes Harvey (2017), Ian (2022), Sandy (2012), Ida (2021), and Irma (2017), the five other costliest U.S. weather and climate disasters in the last decade, all similarly strengthened rapidly, with most evolving from tropical storms to major hurricanes  in under three days12.Tropical cyclones (TCs) are the most damaging natural hazard to regularly impact the U.S. Atlantic and Gulf coasts16. These warm waters serve as a critical energy source for the strengthening storms which act as heat engines, transporting excess warmth from the oceans and atmosphere in the tropics to higher latitudes17. As anthropogenic emissions have warmed the planet, the world's oceans have warmed at the surface, where average temperatures have increased ~ 0.88 °C from 1850–1900 to 2011–202018. The rate at which ocean surfaces have warmed has also accelerated, with 0.60 °C of this warming occurring since 198018. Considering the role of warm upper ocean water and SSTs in the fastest TC intensification rates16, it is reasonable to expect that we may observe an increase in TC intensification rates that coincides with warming ocean temperatures in recent decades24. Given the highly-damaging nature of many TCs that intensify rapidly, and the operational and forecasting challenges posed by TCs that intensify most quickly26, there is an urgent need to better understand how intensification rates of TCs may already have changed in a warming climate.The fastest TC intensification rates often occur in areas of unusually warm upper ocean and sea surface temperatures (SSTs)34. For example, Ref.33 examined intensification trends in landfalling TCs in East and Southeast Asia, and found that a 12–15% increase in the intensity of such storms at landfall was primarily due to an increase in the rate at which they intensified. In the Atlantic basin, multiple studies have sought to understand how TC intensification rates have changed near major coastlines. For instance, Ref.22 found that there was an increased likelihood for TCs to intensify quickly near the U.S. coast during times when basin-wide conditions were generally less favorable for such intensification events. Also focusing on intensification near U.S. coastlines, Ref.28 found that although the mean 24-h intensification rate of TCs increased by 1.2 kts/6 h near the U.S. Atlantic coast from 1979 to 2018, no similar increase was observed along the U.S. Gulf coast. Using a similar focus region, Ref.32 found that, when considering U.S. landfalling TCs, there was a tendency for TCs that intensified rapidly in the 24 h prior to landfall to decay more slowly after landfall.Various past studies have sought to understand how rapid intensification of TCs may evolve in a warmer climate, including work focused on understanding how intensification events that occur within certain regions or fall above a certain threshold may change over time27 notes that in the central and eastern tropical Atlantic, the 95th percentile of 24-h TC intensity changes increased at 3.8 kts per decade from 1986 to 2015. Using the same threshold of the 95th percentile of 24-h intensity changes to define rapid intensification, Ref.30 suggest that it is possible to detect an anthropogenic-related increase in Atlantic TC rapid intensification rates. Adopting a slightly different threshold of 30 kts/24 h to define rapid intensification, Ref.29 identify no trend in TC rapid intensification tied to warming from 1950 to 2014, but do note key spatial and temporal patterns in rapid intensification events in the Atlantic.Elsewhere in the Atlantic, Ref.This study adds to the considerable previous research efforts described above by developing a broader assessment of overall basin-wide changes in the magnitude of peak Atlantic TC intensification rates. This work focuses on the Atlantic basin as a whole, rather than a subset of storms that occur in a specific portion of the basin. Furthermore, no arbitrary thresholds of intensification are used in this study to classify a TC rapid intensification event—instead, the work fills a key knowledge gap by assessing overall changes to the peak intensification rates achieved by all TCs across 12-, 24- and 36-h windows during the 5 decades spanning from 1971 to 2020. Results indicate broad increases to observed TC intensification rates over the past 50 years. These findings illustrate a vital need to not only work towards climate mitigation to limit future warming and thus additional changes in TC intensification rates, but also for emergency preparedness plans and resilience measures that will allow our coastlines to adapt to TCs that have already begun to exhibit increased rates of strengthening.35 are considered for a historical era (1971–1990), an intermediate era (1986–2005), and a modern era (2001–2020). The intermediate era contains five years of data that overlap with each of the historical and modern eras. Furthermore, the intermediate era ends in 2005, after which the Stepped Frequency Microwave Radiometer was installed on all National Oceanic and Atmospheric Administration hurricane research aircraft to help improve measurements and data collection related to maximum TC wind speeds36. The intermediate era is therefore useful for illustrating the temporal progression of TC intensification rates across the past 50 years, including across time periods that rely upon various instrumentation and data collection methods.Changes to the observed maximum intensification rates of TCs from the Atlantic hurricane best track database (HURDAT2)Maximum intensification rates are calculated for 12-h, 24-h, and 36-h windows along each track. The maximum intensification value of each TC for a particular window is defined as the greatest increase in wind speed across any window of that length during the lifetime of the storm see “” sectionDistributions of observed maximum intensification rates across 12-, 24-, and 36-h windows show increasing intensification rates from the historical to the modern era  to 45.0 kts (intermediate) to 52.5 kts , while the probability of such an intensification rate occurring within 36 h grows from 7.6% in the historical era to 14.5% in the modern era (becoming ~ 1.9 times more likely). Both of these increases are significant for a 90% credible interval  in the chance of such intensification happening within both 24 h  and 36 h  into a major hurricane  within either 24 or 36 h compared to their historical counterparts  to observe the number of intensification events that result in TCs intensifying similarly in the intermediate era, and statistically impossible (0% chance) to observe the numbers of intensification events that result in TCs intensifying similarly in the modern era for all time windows. Assuming the observed rates of intensification events that cause TCs to transition from a weak TC into a major hurricane for the intermediate era, there is only a 2.1% chance of the total observed number of modern intensification events occurring for a 12-h window, and less than a 0.25% chance of the observed number of modern intensification events occurring for a 24-h window (0.22%) or 36-h window (0.20%).28. There is also a decrease in the likelihood of TCs intensifying most quickly in an area just east of the Caribbean Sea, though this decrease appears to be driven by a single slow-moving TC track in the historical era with multiple maximum intensification points that occurred in this region  in the modern era compared to the historical era  or more likely (20 kts) to do so within 24 h in the intermediate and modern eras than to do so within 36 h in the historical era. These findings align well with previous studies that have suggested a shortening of the TC life cycle corresponding to changing intensification and weakening rates of TCs as the planet has warmed34.Exceedance probabilities of TC intensification rates indicate that it has become statistically more likely in recent decades for TCs to strengthen at an accelerated pace Fig. . The lik4 h Fig. , a thresIncreased TC intensification rates have also resulted in a growing number of peak intensification events that result in TCs strengthening from weak TCs into major TCs in a short amount of time in the modern era compared to the historical or intermediate eras Fig. . When co51. The vulnerability of these coastlines to such storms was exemplified by landfalls of particularly destructive TCs in this region in 2020, including Hurricane Eta52 and Hurricane Iota53, both of which quickly intensified into major hurricanes during the month of November as they approached the coast of Nicaragua54. Elsewhere, TCs that intensify at their fastest rate over the central part of the basin could be particularly dangerous for communities along the U.S. East coast—an area already threatened by other evolving TC hazards in a warming world, such as slower moving TCs and changing TC tracks57.In the modern era, it becomes more common for TCs to intensify most quickly in the southern Caribbean Sea , the central Atlantic (east of the U.S. Southeast coast), and the southeast Atlantic (off the west coast of Africa) compared to the historical era Fig. , Fig. S242, or changes in the most extreme intensification rates31. Analyses presented here expand our understanding of changing TC intensification rates by performing a broad assessment of observed variations in overall maximum intensification rates for Atlantic TCs during the satellite era. Findings illustrate that it is possible to detect significant changes over the past 50 years to both the magnitude and locations of peak intensification rates of TCs in the Atlantic.In a warming world, we expect changes to TC intensities, including the total number of very intense TCs58, and the vast majority of the most intense TCs undergo rapid intensification at some point in their lifecycle45. Because rapid intensification is often difficult to predict and forecast, quickly intensifying TCs can create communication and preparedness challenges for coastal communities in the storm’s path26. Results presented here suggest that the overall frequency and magnitude of quickly intensifying TC events have already increased for the Atlantic basin as the planet and our oceans have warmed over the past 50 years. Furthermore, the locations at which such intensification events occur have also varied. These changes may reasonably be expected to further amplify the substantial hazard and challenge that quickly intensifying TCs present to coastal communities. Findings presented here thus emphasize not only a need to curb greenhouse gas emissions and limit future warming, thereby limiting future increases to the rates at which TCs strengthen, but also a need for coastal planning and communication measures that will allow vulnerable communities to prepare for the changing hazard presented by quickly intensifying TC events.Historically, the most damaging TC events have been dominated by the most intense TCs to impact our coastlines35, comprised of “best track” data from the National Hurricane Center, which is updated regularly to include new TC events and any changes to the historical record based on retrospective reviews of the data. The HURDAT2 database includes a variety of variables describing each TC at 6-h intervals along the TC track, including the date, time, key points along the TC track , status of the system, latitude, longitude, maximum sustained wind, minimum pressure, radii of 34-kt, 50-kt, and 64-kt winds, and the radius of maximum wind35. Analyses presented in this work primarily use the TC maximum wind speed, along with variables to describe when (date/time) and where (latitude/longitude) the maximum increases in wind speed occurred along the TC track.Data used for this analysis are from the open-access HURDAT2 database62. To avoid the impact of these two major discontinuities related to technological innovation and observation capabilities, analyses presented here focus only on records beginning in 1971 or later.Although the data contained within the HURDAT2 database begin in 1851, there are known discontinuities within TC records contained in the HURDAT2 database, including the introduction of aircraft measurements (1944) and the introduction of satellites (for which records were not available for the full Atlantic basin until the late 1960s)Maximum intensification rates are measured by maximum increases in wind speeds for each Atlantic TC from 1971 to 2020 across 12-h, 24-h, and 36-h windows. These maximum changes in wind speed are found by calculating wind speed differences at each 6-h time step along the TC track where possible. Equation  with replacement to generate n new sample datasets that are equal in length to the original64. For Fig. It is worth noting that although maximum wind speeds are provided at 5-kt intervals within the HURDAT2 best track data, some results presented here are assessed as significant even when changes from one era to another are less than 5 kts. For instance, there is a significant increase in the mean maximum intensification rates for a 24-h window from the historical 17.7 kts) to the modern era (22.5 kts) of 4.8 kts (Fig. 7.7 kts t65.Heatmaps are used to visualize variations in the pre-intensification and post-intensification Saffir–Simpson category of TCs from the historical to the modern era Fig. . These h57. Units of densities shown on the maps in Fig. 66.Density difference maps showing spatial shifts in the locations at which TCs intensify most quickly are generated using a kernel density estimate in both the modern and historical eras Fig. , and theSupplementary Figures.


Hearing loss is a common concern in patients with intellectual and developmental disabilities (IDD), and early detection and intervention are crucial to prevent negative impacts on communication, cognition, socialization, safety, and mental health. Despite a lack of the literature specifically focused on hearing loss in adults with IDD, there is a substantial body of research demonstrating the prevalence of hearing loss in this population. This literature review examines the diagnosis and management of hearing loss in adult patients with IDD, with a focus on primary care considerations. Primary care providers must be aware of the unique needs and presentations of patients with IDD to ensure appropriate screening and treatment. This review highlights the importance of early detection and intervention, as well as the need for further research to guide clinical practice in this patient population. Intellectual and developmental disabilities are defined as limitations originating before the age of 22 in the domains of intellectual function, which includes learning, reasoning, and problem solving, as well as in adaptive behavior, which includes conceptual, social, and practical skills . These dA substantial body of the literature highlights the prevalence of hearing loss in patients with IDD, ranging from 24% , dependiHearing loss can be divided into three primary categories, namely, conductive hearing loss (CHL), sensorineural hearing loss (SNHL), and mixed hearing loss. SNHL is the most common type of hearing loss in the general population and is due to pathologies of the cochlea, auditory, nerve, or the central nervous system, including presbycusis, congenital syndromes, infections, ototoxicity, and trauma. In a study of 106,369 athletes aged 8–70 in the International Special Olympics between 2007 and 2017, 26.9% failed hearing screenings via distortion product otoacoustic emissions (DPOAE), tympanometry, and PTA, 67.8% of which were found to have undiagnosed SNHL . VariousIn contrast, CHL is due to any defect from the external ear through the ossicles impeding sound transmission to the cochlea, most commonly including cerumen impaction but also tympanic membrane perforation, otosclerosis, cholesteatomas, and chronic otitis media with effusion . In the There is a general lack of information and evidence concerning hearing screening guidelines for patients with IDD . Early aIn addition to a thorough physical exam, there are various screening tests that can be performed in the primary care setting with the appropriate technology. Subjective screening methods include pure tone audiometry (PTA) and speech audiometry, whereas objective tests include tympanometry, the otoacoustic emission test (OAE), and auditory brainstem response (ABR) testing. Pure tone audiometry is a standard tool for diagnosis and characterization of hearing loss performed by primary care providers and audiologists. Typically, various frequencies are delivered to the patient via headphones (air conduction) and via a bone oscillator (bone conduction). The patient is instructed to give a signal, such as pressing a button, when the sound is heard . SimilarDepending on the level of cognitive delay, these subjective diagnostic tools can be challenging and necessitate ABR testing as an alternative or supplemental objective test . During These subjective and objective methods for hearing loss screening present various challenges for patients with IDD. Patients may have difficulty communicating their experiences or understanding instructions related to the hearing screen, thus necessitating more objective measures . PatientTo overcome these challenges, it is important to first introduce the test in a way that will reduce anxiety and ensure trust between the patient and the health care provider . It may Compared to the general population, there is an increased prevalence of cerumen impaction in patients with IDD . PracticA recent systematic review examining appropriate management of OME in children with DS reported persisting clinical equipoise on the subject. Some studies that were included recommended conservative management in place of pressure equalizing tube placement (PET) in refractory or complicated cases, while other studies reported significant benefits including reduced complication rates with earlier PET placement in patients with down syndrome and OME. In the cases of PET failure, hearing aids may be a good alternative option . As OME Mixed success has been reported for hearing aids in patients with IDD primarily due to differing levels of disabilities. A pilot study conducted interviews with 16 adults with IDD before and 6 months after hearing aid fitting and reported improvements in distinction of sounds, auditory localization, and detection of sounds . Close cBone-anchored hearing aid (BAHA) placement can serve as an alternative to conventional air-conduction hearing aids in the general population as well as in patients with IDD, especially with conductive hearing loss. A case control study that observed 22 adult patients with IDD and conductive or mixed hearing loss found that after bone-anchored hearing aid placement, patients reported benefits not only in listening and learning capacities but also especially in user comfort and reduction of ear infections, as compared to conventional air-conduction hearing aids .Overall, variations exist in the outcomes of cochlear implants, depending on the type and level of IDD and assessment is often difficult due to poor speech perception and language skills. However, a substantial body of evidence supports the use of cochlear implants for SNHL in patients with IDD, often after failed treatment attempts with hearing aids for adults, particularly those with progressive hearing loss. Benefits in speech perception, speech intelligibility, and language development exist after cochlear implantation in patients across the age spectrum with IDD , 39, oftOne 2018 study explored the benefits of speech therapy in 36 adult patients with IDD via two 3-month periods of weekly 30-minute sessions dedicated to articulation training and listening skills, with a 3-month interval in between . The stuThe diagnosis, treatment, and management of hearing loss in patients with IDD present unique challenges due to impairments in multiple domains. Primary care providers must make special considerations with this patient population, as their presentations and needs may vary in comparison to the general population. However, there are many diagnostic tools and management options available, many of which overlap with conventional care methods that allow providers to deliver optimal care to patients with IDD and hearing loss. Many of the studies presented include pediatric data, largely due to the limited number of studies; however, early identification and treatment of hearing loss in children in the primary care setting are uniquely vital for positive longitudinal patient outcomes. Furthermore, much of the data presented from pediatric studies may be extrapolated to adult populations with IDD.