Hearing loss is defined as the partial or total reduction in auditory acuity. Hearing loss can cause detrimental effects on speech, language, developmental, educational, and cognitive outcomes in children. This study aimed to find out the prevalence of hearing loss among children visiting the Department of Otolaryngology and HNS of a tertiary care centre.A descriptive cross-sectional study was conducted among children aged 5-19 years visiting the outpatient Department of Otolaryngology and HNS between 1 January 2022 and 31 December 2022 after obtaining ethical approval. All the patients who underwent pure tone evaluation were included in the study. A convenience sampling technique was used. The point estimate was calculated at a 95% Confidence Interval.Among 3051 children, 328 (10.75%)  had hearing loss. Among children with hearing loss, 170 (51.83%) of children were female. The mean age of children with hearing loss was 13.31±3.39 years. The mean pure tone average among 452 ears with hearing loss was 44.60±17.71 dB. The commonest degree of hearing loss was mild hearing loss 266 (58.85%), and the commonest type was conductive hearing loss 310 (68.58%). Among children with hearing loss, 124 (37.80%) had bilateral hearing loss.The prevalence of hearing loss among children visiting the Department of Otolaryngology and HNS was found to be lower than similar studies done in similar settings. The estimated prevalence of hearing impairment in the 1990s in children aged 5-15 years was 8.32%, while a study from 2015 to 2019 among school-aged children in Nepal showed 5.73% had hearing impairment.This study aimed to find out the prevalence of hearing loss among children visiting Department of Otolaryngology and HNS of a tertiary care centre.A descriptive cross-sectional study was conducted among children aged 5 to 19 years visiting the Outpatient Department of Otolaryngology and HNS at the Audiology Unit of the Hospital for Children, Eye, ENT, and Rehabilitation Services (CHEERS), Lokanthali, Bhaktapur, Nepal. The ethical approval was taken from the Ethical Review Board of Nepal Health Research Council (Reference number: 3792). The records of children patients visiting the audiology unit for hearing evaluation following referral from the otolaryngology outpatient clinic between 1 January 2022 to 31 December 2022 were collected from 1 August 2023 to 31 August 2023. All the patients who underwent pure tone evaluation were included in the study. The record review permission was taken from CHEERS. The records available at the Audiology Unit were selected for the study. A convenience sampling method was used. The sample size was estimated using the following formula:Where,n = minimum required sample sizeZ = 1.96 at a 95% Confidence Interval (CI)p = prevalence taken as 50% for maximum sample size calculationq = 1-pe = margin of error, 2%The calculated sample size was 2401. However, 3,051 children were included in the study.6All children with complaints or suspicion of hearing loss are sent for hearing tests using pure tone audiometry (PTA). PTA procedure was accomplished in a double-walled, sound-treated audiometric booth, using a two-channel calibrated clinical audiometer (Maico-42) and a supra-aural headphone (Telephonics TDH-49P). Pure tone thresholds were obtained at six-octave band frequencies from 250-8000 Hz, using a 10 decibel (dB) up and 5 dB down regimen according to the modified Hughson-Westlake method.6 The three types of hearing loss were categorized according to the auditory system affected. The conductive type of hearing loss has damage in the external ear and middle ear, the sensorineural type has damage in the inner ear, and the mixed type of hearing loss has damage in the external or middle ear and the inner ear.6The degree of hearing loss in this study refers to the severity of hearing loss. It has been categorized into different levels based on the dB range of hearing loss in relation to normal hearing. Mild, moderate, moderately severe, severe, and profound hearing loss was defined as hearing loss between 26 to 40 dB, 41 to 55 dB, 56 to 70 dB, 71 to 90 dB, and more than 90 dB, respectively.The record review proforma was developed from the literature review and the advice of fellow otolaryngology-HNS Surgeons, Consultant Audiologists, and Public Health experts.The data collected were entered in Microsoft Excel 2019 and analyzed using IBM SPSS Statistics version 26.0. The point estimate was calculated at 95% CI.Among 3051 children, 328 (10.75%)  had hearing loss. Among 328 patients, 124 (37.80%) had bilateral hearing loss. The mean pure tone average among 452 ears with hearing loss was 44.60±17.71 dB. Similarly, the pure tone average in 267 right ears with hearing loss was 44.27±17.14 dB, and in 185 left ears with hearing loss was 45.08±18.55 dB. Among the children with hearing loss, the commonest degree of hearing loss was mild hearing loss (58.85%) .Conductive hearing loss was the most common 310 (68.58%) type of hearing loss among children with hearing loss .Among children with hearing loss, 170 (51.83%) of children were females. The mean age of children with hearing loss was 13.31±3.39 years .7 An earlier study in the 1990s reported the prevalence of hearing impairment to be 4.52% among children aged 5-15 years in Nepal.4 The prevalence of hearing loss in school-aged children conducted at 509 government schools between 2015 to 2019 in Nepal covering all three regions  was 5.73%.5 The study from the early 1990s was a community-based study; the other was a school-based one from the past decade. The study settings of these two studies and our study are entirely different. The higher prevalence in our study can be related to the fact that our study was conducted in a tertiary-level referral otolaryngology hospital with dedicated audiology services, where suspected cases of children with hearing loss or at risk of hearing loss often visit. Nevertheless, the burden indicates that the prevalence of hearing loss among children is a public health problem that needs urgent attention in Nepal.The prevalence of hearing loss among children in our study was 10.75%. The previous study showed the prevalence to be 12.7%.5 The slight difference in sex in hearing loss implies that both sexes are equally prone to hearing loss. A study in Karnataka among school-going children showed that among 126 students with hearing loss, 50% were males and 50% were females.8 However, in a study among younger children aged 4-7 years with hearing loss in an underserved community in South Africa, 54.2% were females.9In our study, more than half (51.83%) of children with hearing loss were females. In a study among school-aged Nepalese Children, the prevalence of hearing loss was slightly higher in males (51.70%).10 However, the study in Karnataka showed that 78.45% of students with hearing loss had bilateral hearing loss.8 Studies from South Africa among younger children (4-7 years preschool children and children aged one months to six years old) with hearing loss also showed that bilateral hearing loss was more common.11 Among children with hearing loss, hearing loss was more common in children aged 10 years or older in our study. The study among school students in Nepal also showed hearing loss increased with age, and similar age groups had a higher prevalence of hearing loss.5In our study, among children with hearing loss, 62.20% had unilateral hearing loss. A similar finding was also observed in a school-based study in Nepal and Kyrgyzstan, where 68.18% and 65%, respectively had unilateral hearing loss among children with hearing loss.5 Mild hearing loss was also the most prevalent among preschool children (4-7 years old) with hearing loss in low-income South African communities.9 Among children with hearing loss, 68.58% had conductive hearing loss in our study. This was followed by sensorineural hearing loss (23.78%) and mixed hearing loss (7.74%). This finding is in agreement with another study in Nepal where conductive hearing loss was the most common type of hearing loss observed in a similar proportion (70.47%) of children with hearing loss as in our study, followed by sensorineural hearing loss in 25.68%, and mixed hearing loss in 3.84%.5 However, in a study in urban South Africa among 6-12-year-old school-going students with hearing loss, 57.1% had conductive hearing loss, 22.9% had mixed hearing loss, and 20.0% had sensorineural hearing loss.12 A study among primary school children aged 6-10 years with hearing loss in the North Arcot District of Tamil Nadu, India, also showed that conductive hearing loss was most common.13In our study, the commonest degree of hearing loss among children with hearing loss was mild hearing loss (58.85%), followed by moderate, moderately severe, severe, and profound hearing loss. A similar pattern was also reported in the study from Nepal.14 However, hearing aids and cochlear implants can be expensive and may not be affordable to every parent in Nepal. Hearing loss among children is a significant health concern, and early detection and intervention can significantly improve outcomes and enhance overall well-being in the immediate and future.Conductive hearing loss among these children can usually be managed by correcting the underlying aetiology, such as treating otitis media with antibiotics or surgically in cases of external ear atresia or ossicular malformations. Mild to moderate sensorineural hearing loss can be managed with hearing aids. Severe to profound bilateral SNHL can be managed by cochlear implantation  if picked up early, while mild to moderate bilateral SNHL is easier to manage with hearing aids.The major limitation of our study is that the study was conducted in a tertiary-level otolaryngology centre with regular audiology services, and the findings may not be generalizable to other community settings or institutional settings.The prevalence of hearing loss in our study was found to be lower than in other studies conducted in similar settings.


Single-sided deaf patients following cochlear implantation often compare the sound quality of their implanted ear with normal hearing. The interaural differences can result in dissatisfaction with speech comprehension and reduced time of usage of the speech processor; hence, prolonging auditory adaptation time. The proposed calibration method presented in this study demonstrates how the frequency distribution of the cochlear implant can be set to adequately approximate the pitch perception of the contralateral normal hearing ear towards improving speech intelligibility in a noisy environment.In 12 postlingual single-sided deaf patients, subjective interaural pitch-matching was carried out to determine new central frequencies for the reallocation of the frequency bands of their speech processor . The patients were asked to compare the pitch of the tones presented to their normal hearing ear to the pitch of individual channels of their cochlear implant . A third-degree polynomial curve was fit to the acquired matching frequencies to create the new frequency allocation table. Audiological measurements  in noise, together with a Speech, Spatial and Qualities of Hearing Scale (SSQ12) questionnaire  results were evaluated prior to the pitch-matching procedure, and again, 2 weeks later.t test comparison: p < 0.001). The results of the SSQ12 questionnaire also showed significant improvement in speech intelligibility, sound localization, and sound quality .The free-field aided thresholds of the patients showed no greater shift than ± 5 dB following the procedure; however, their monosyllabic word recognition score in noise improved significantly (mean − 9.58%, SD 4.98%, matched pairs Matching the pitch perception of the implanted cochlea with the sensation of the normal hearing contralateral ear, resulted in significant changes in the quality of hearing in patients with single-sided deafness. It is plausible the procedure can usher positive results in bimodal patients or following sequential bilateral cochlear implantation. The adequate means to rehabilitate single-sided deafness (SSD) has been a matter of debate addressed by comparative studies and systematic reviews in the recent past –3. Many The first standard recommendation for the treatment of SSD was to transfer the sound from the deaf ear’s side into the normal hearing cochlea via the Contralateral Routing of Signals (CROS) or with the application of a Bone Conduction Device (BCD), e.g., Bonebridge or BAHA , 18. CROCochlear implantation (CI) aims to rehabilitate the hearing of the impaired ear rather than transferring information to the contralateral side, restoring the patient’s access to binaural cues. CI has been demonstrated to improve sound localization and speech comprehension in noisy environments and significantly reduce tinnitus severity in adult SSD patients , 16, 19.As medical technology advances and newly published studies surface, the indication criteria for specific implantable hearing-aid devices often experience minor—or sometimes even significant—changes. In July 2019, the US Food and Drug Administration (FDA) first approved MED-EL cochlear implantation for single-sided deaf children 5 years or older [The perceived pitch of a tone is a function of not only the place of stimulation in the cochlea (tonotopy) but also the stimulation rate of the vibration. Moreover, the mismatch between the frequency and place encoding may negatively affect auditory processing. It has been demonstrated by Rader et al. that using place-dependent stimulation rates in CI improves tonotopic pitch perception in patients with SSD .Applying image-guided shifting or modification of the frequency allocation to match the individual tonotopy of cochlear implantees may also result in better pitch perception . GrasmedThe considerations and techniques referred to above are convenient if a High-Resolution Computed Tomography (HRCT) scan of the patient’s cochlea is available for image-guided mapping, such as MED-EL’s anatomy-based fitting provided by the connected application of the OTOPLAN and MAESTRO software –30. HoweInvolving the patients in optimizing their frequency maps and utilizing the guidance of their subjective pitch sensation may serve as a valuable tool in the hands of the audiologist. SSD patients and bimodally aided CI users can serve as ideal candidates for the pitch-matching procedure due to their motivation to minimize disturbing interaural frequency mismatch; hence, acquiring more natural bilateral sonority of hearing and achieving better speech comprehension, especially in noisy environments.Twelve patients  with acquired postlingual single-sided deafness (pure-tone air conduction thresholds ≤ 25 dB HL in the non-implanted ear) were included in the current study Table . The pat4) was performed, averaging the four main speech frequencies . Frequency-specific narrow band 60 dB SPL noise was presented by the secondary loudspeaker towards the normal hearing ear. Speech Reception Threshold (SRT50%) using sets of two-digit numbers, and monosyllabic Word Recognition Score (WRS65dB) were both tested using the official Hungarian tests [All audiological measurements were carried out in a free sound field using a clinical audiometer . The signal source loudspeaker was placed one meter lateral to the implanted ear of the patient, while a secondary loudspeaker produced a noise pattern (specified below for each measurement) one meter lateral to the contralateral ear, to simulate a noisy environment with the noise originating from the direction of the normal hearing ear. Free-field aided Pure-Tone Audiometry  questionnaire was carried out in parallel to the audiological measurements in support of the evaluation of changes in patients’ speech intelligibility in complex listening situations and their sound localization abilities. SSQ12 is a short, validated version of the original Speech, Spatial and Qualities of Hearing Scale suitable for clinical use . The tweAn Apple iPad Air3 with a tone generator application  was used to produce the waveforms, and the acoustic stimuli were presented to the normal hearing side of the patient by an active loudspeaker (JBL One Series 104). Adel et al. demonstrated the choice of acoustic stimulus type can have a significant effect on electric–acoustic pitch-matching results ; therefoThe tested CI channel was activated in Custom Sound Pro 6.3  in 2 Hz intermittent presentation of pulse trains  at a relatively loud intensity level (the patient’s everyday threshold level (T-level) + 75% of the dynamic range of that individual channel). The volume of the acoustic tone produced by the loudspeaker on the contralateral side was adjusted to the perceived level of the electric stimuli of the CI based on the subjective discernment of the patient. Afterwards, the pitch of the continuous acoustic tone was adjusted by the audiologist to approximate the perceived pitch of the electric stimulus relying on the patient’s feedback. We ensured all patients understood their task during the pitch-matching procedure which specifically, was comparing pitches and not volume levels. Seamless ascending and descending approximations were carried out randomly between 0.1 and 20 kHz  at least 4–5 times to determine the channel’s average Central Frequency (CF). All patients were asked to keep their eyes closed during the procedure to lower the bias of their subjectivity. Channels number 11, 17, 5, 22 and 1 were tested consecutively in the above-mentioned manner , C-levels (comfort levels), gains, repetition rate, number of maxima, loudness growth factor or coding strategy (ACE) were adjusted during the pitch-matching session. In consideration of the statistical analysis, a matched pairs The interactive portion of the procedure spanned an average of 20–30 min depending on how quickly the patient could accurately determine the acoustic tones matched with the five tested channels of the cochlear implant. The calculations and programming  required approximately an extra 5 min—except in the first case, where an additional 15–20 min were required to create the template  used to calculate the average CF values for each tested channels, to fit the third-degree polynomial curve to the acquired datapoints, and to calculate the lowest and highest frequency of each frequency bands for the new FAT.Following a switch to the new map, nearly all the patients reported an immediate positive effect regarding their hearing quality and experienced a “more natural sounding” or described “more similar hearing to normal”. All patients were instructed to use only the new map for 2 weeks of testing. Changing the volume levels and the sensitivity of the microphones (if enabled) were allowed during the test period; however, both levels were set to default during the follow-up audiological measurements.4 measurements showed no difference . This result substantiates, changing the FAT does not affect the hearing thresholds of the patients if the T-levels were correctly set prior to the procedure. The SRT50% measurements demonstrated a similar outcome: the FAT rearrangement resulted in an average of 0.21 dB difference (SD 3.71 dB). However, the WRS65dB demonstrated a significant improvement with the experimental map . The purpose of the SRT50% test is to measure the minimal loudness level the patient requires for gaining sufficient vocal information to decide which phrase was presented from a pool. Therefore, this method might be less sensitive to interaural frequency mismatch and distortions than WRS65dB in which the patient needs to clearly understand monosyllabic words without further clues. This may serve as an explanation to why WRS65dB still improved despite potential ceiling effects while SRT50% did not.The summary of the audiological measurements and average scores of the SSQ12 questionnaire are presented in Table t test comparison: p < 0.001). Figures 65dB and SSQ12 results of the 12 patients, respectively.The results of the SSQ12 questionnaire also showed significant improvement regarding speech intelligibility, sound localization, and sound quality . Following the reallocations of the frequency bands, the patients reported an improved hearing experience, and their audiological scores also increased. Patient 8 did not have hearing loss prior to the surgery (average of PTA4 < 25 dB HL in quiet), nevertheless, she was suffering from severe vertigo, therefore, underwent simultaneous labyrinthectomy with cochlear implantation. She quickly regained a satisfying speech comprehension after the surgery; however, she could not adapt to the different tone of the device for 2 years. With the new experimental FAT, as she described, “the sound of the speech processor was more comfortable and much more acceptable”. The results of Patients 7 and 12 showed less improvement, and they reported nearly no subjective change in their quality of hearing following the procedure. The explanation may likely be both patients were deaf for an extremely long period prior to the cochlear implantation , and as a result, they could only achieve very poor speech intelligibility with the CI. It is worth mentioning prior to surgery both patients had been informed, after a prolonged unaided period they could only expect the ability of detecting sounds and noises with the cochlear implant; however, it is unlikely they will be able to understand speech. Nevertheless, both patients insisted on undergoing the surgery. After the follow-up measurement, Patient 12 needed an additional fitting session to adjust the shifted T and C levels. Following the switch to the new FAT the WRS65% scores of Patient 10  did not increase at all, yet he reported a “more natural color” of hearing. With the experimental FAT, some of the participants reported, they did not hear two different voices with their two ears anymore when someone was talking.Patients 4 and 11 already had high WRSIt is important to consider all the participants had been selected specifically for this experiment due to their unsatisfactory speech comprehension and their subjective general opinion regarding their quality of hearing . This may likely be the reason for the significant differences between the hearing intelligibility prior to and following the frequency matching session. Canfarotta compared postoperative CT scans of 111 cochlear implanted ears and found significant variability in frequency-to-place mismatch among CI-alone and Electric Acoustic Stimulation (EAS) users with default FAT parameters . MertensTan concluded despite years of CI experience some electrode channels remain perceived as higher pitched than the acoustic frequencies with which they are associated . In thosIt bears highlighting, although all participants had full-length insertion of the CI electrodes, none of the patients had postoperative CT scans or X-ray measurements to verify or disprove migration of the electrode in the cochlea prior to the pitch-matching session; therefore, it cannot be rejected as a possible explanation for the experienced frequency mismatch. Nevertheless, the telemetry showed no signs of incomplete insertion , and all participants could differentiate between the pitches of all 22 stimulating channels.It is important to state, there was no control group set to measure a potential Hawthorne Effect (HE), since all participants were informed about the idea of the experimental method.The results demonstrate the proposed pitch-matching method may increase the quality of hearing and speech comprehension in CI patients with SSD. This method can also usher in positive results in bimodal patients , or in pitch-matching the two CIs in bilateral patients. The disadvantages of the method include its time-consuming, and the patient needs to fully cooperate with the clinician and at a more demanding level. Understanding and performing the task of comparing pitches and not loudness levels is crucial to achieving beneficial results. The procedure, as an optional tool, can be implemented in any cochlear implant fitting software together with the automatization of the computations necessary to reallocate the frequency bands.It will also be illustrative in a future study to compare the FATs generated with the two methods  in consideration of patient satisfaction.


Access to ear and hearing health services are limited or non-existent in low-income countries, with less than 10% of the global production of hearing aids distributed to this population. The aim of this feasibility study was to compare the outcomes of an ultra-low-cost hearing aid (LoCHAid) to programmable, refurbished hearing aids for adults with high-frequency hearing loss, in Blantyre, Malawi.Sixteen adults with high frequency hearing loss, and no prior experience of hearing aids, took part in this study, nine were fitted with the LoCHAid and seven were fitted with refurbished, programmable hearing aids, for a one-month trial. Five standardized hearing qualities questionnaires were used to compare outcomes pre and post device fitting and between devices. Questionnaire scales were analysed using general linear models and inductive thematic analysis was used to evaluate qualitative data.Overall, there was no significant difference found between LoCHAid and refurbished hearing aids, and the two device types each showed a similar degree of improvement after fitting. Qualitative data analysis identified two key themes: Sound Quality and User experience.The results from this feasibility study are encouraging, but a comprehensive, larger clinical study is needed to draw firm conclusions about the LoCHAid's performance. This study has identified key improvement indicators required to enhance sound quality and user experience of the LoCHAid. Access to ear and hearing health services are limited or non-existent in low-income countries , with leOne of the factors contributing to variable hearing aid uptake is cost. Hearing aids can cost between $500–$3,000 in the US. The WHO guideline states that a hearing aid should be no more than 3% of the gross national product, per capita, per hearing aid . TherefoMalawi is a landlocked country located in southeastern Africa, sharing borders with Tanzania, Mozambique, and Zambia. It has a population of around 20 million people. Audiology and hearing healthcare services are extremely limited in Malawi . There aHearing aids are not routinely provided by the Malawian Ministry of Health. Instead, the country relies on donated hearing aids provided by charitable organisations . DespitePreliminary data from both electroacoustic testing and simulated gain measurements demonstrates that a low-cost device, LoCHAid, provides amplification in the high frequency region that is needed for individuals with mild- to moderate ARHL . It is aThis feasibility study involved the following phases: protocol development, participant recruitment, outcome measure translation, staff training and the clinical validation of the LoCHAid. The study was carried out at Queen Elizabeth Central Hospital Audiology department (QECH), Blantyre, Malawi.Ethical approval was obtained from the Malawian College of Medicine Research and Ethics Committee (COMREC) (P.07/20/3091). Informed consent was obtained from all participants before the intervention was received. An information sheet was given to the participants, which outlined the purposes of the study. This was also summarized verbally before written consent was obtained.A purposive sampling strategy was implemented to select people over the age of 18 years with bilateral mild to moderate high frequency sensorineural hearing loss, and no experience of hearing aid use, and no reported cognitive or neurological conditions. Recruitment took place during outreach clinical activities or clinical activities within QECH Audiology. Audiology clinicians carried out diagnostic otoscopy, pure tone audiometry and tympanometry on all patients. All participants were reimbursed their travel costs and given a financial incentive to attend each research session.The QECH audiology team were given remote and in-person training by a practicing audiologist (first author BP). Training included how to use the LoCHAid device, hearing aid fitting, hearing aid testing, counselling, study procedures, clinical testing, follow up and data management. Staff were in regular contact with the UK audiology team throughout the project. All QECH audiology technicians involved were also trained in basic research methods to aid the data collection process. All QECH staff assisted in creating the English and Chichewa hearing aid instruction manuals for the LoCHAid and the refurbished hearing aids.The five standardized hearing qualities or hearing aid benefit measures used in this project were chosen after a joint discussion within the research team. All outcome measures captured self-reported listening experiences (rather than measuring aided speech perception performance). The outcome measures were: Glasgow Hearing aid Benefit Questionnaire part one (GHABP) , Speech,As all questionnaires were originally written and validated in English and because of the lack of hearing related outcome measures available in the Malawian national language of Chichewa, the questionnaires were translated to Chichewa by a qualified Malawian translator with had previously translated for research studies , 21. ForTwo types of hearing device were used in this feasibility study see : a fixedInitially, 18 participants consented to take part in the study where nine were randomized to the LoCHAid group, and nine to the refurbished hearing aid group. After hearing device fitting, 2 people from the refurbished hearing aid group withdrew from the study due to unforeseen circumstances. Therefore, sixteen participants with bilateral mild to moderate sensorineural hearing loss participated in this study. Demographics are described in Each participant completed three in-person visits to the QECH Audiology department for this study.-Demographics Questionnaire-Glasgow Hearing aid Benefit Questionnaire part one (GHABP) -Speech, Spatial and Qualities of Hearing Scale (SSQ-12) -Listening Effort Assessment Scale (EAS) Participants were then randomly assigned to one of two groups: LoCHAid or refurbished hearing aids. The audiology clinicians carried out the hearing aid fittings using the allocated devices. Both groups were given detailed instruction booklets, specifically created for this study (written in Chichewa and English), to show them how to use the hearing aids and how to contact the audiology department. They were asked to use the hearing device as much as possible, in a variety of situations over the one-month trial. They were counseled on good communication tactics, realistic expectations, and acclimatization to the new sense of amplification, in line with typical clinical hearing aid fittings.During visit 1 participants completed a diagnostic audiological assessment, including the following 4 questionnaires:-Glasgow hearing aid benefit questionnaire (GHABP) part two -Speech, Spatial and Qualities of Hearing Scale (SSQ-12) -Listening Effort Assessment Scale (EAS) -Satisfaction with Amplification in Daily Life Questionnaire (SADL) -International Outcome Inventory: Hearing Aids (IOI-HA) During the questionnaires, participants were asked to base their answers on their experience of hearing aid use within the one-month trial. After the follow up, participants were able to keep their trial hearing device if they wanted to. Additional open questions were asked in an interview style to explore the users' general usage and experience of the allocated hearing devices.The follow up visit took place 4 weeks after the initial hearing aid fitting. The Chichewa versions of the following questionnaires were completed during the session:A second follow up was carried out 3 months after fitting to check for medium term hearing aid use. During the session, open questions were asked, and notes were transcribed by the QECH team.As recommended in the literature, the SSQ12 subscales  were calculated by averaging the scores of the four items in each category together. The GHABP disability subscale was calculated by averaging across the four disability scenarios. Improvement in hearing was evaluated by comparing the extent of initial disability (recorded upon inclusion before device implementation) and the extent of residual disability (recorded at follow-up after device implementation). The SADL was analysed by using individual items and its established subscales. The listening effort assessment scale and the IOI-HA were evaluated by global score differences and with individual item comparisons, between hearing aid types.lme4. Satisfaction with amplification in daily life and IOI-HA items were each addressed individually, using a general linear model, with each item tested for differences between devices. Estimated marginal means were calculated using the R package lsmeans , between devices (LoCHAid vs. refurbished), and for an interaction between the two to indicate whether one device changed more than another over time. We additionally included a random grouping factor for participant to control for repeated measures. Repeated measures modeling was completed using the R package  lsmeans . For allInductive thematic analysis  was carrHearing aid fitting and follow ups were conducted in Chichewa by trained audiology technicians . BP (first author) was present in the clinic to assist the clinicians during the hearing device fitting appointments but did not make their presence known in case this influenced the flow of the appointments. BP completed the data analysis in collaboration with the Malawian audiology team to ensure contextual details were not overlooked or misinterpreted.Data from sixteen participants are presented in this study. Nine had been fitted with the LoCHAid device and seven wore bilateral refurbished hearing aids.F = 5.15, p = 0.041]. However, there was no significant difference found between devices (LoCHAid vs. Refurbished), and the two device types each showed a similar degree of improvement after fitting.Part one of the GHABP was completed at the first session, and part two was completed at the follow up session. F = 13.24, p = 0.003], spatial  and qualities  subscales, as shown in There was a significant improvement after device fitting in each of the speech [How easily can you ignore other sounds when trying to listen to something”. Overall, there was no significant difference between LoCHAid vs. refurbished devices in any of the items, and the degree of improvement between time points was not significantly different between devices for any item. This same pattern was true for the global score, as shown in Of the six items addressed in the EAS, five showed significant improvements over time, as outlined in Of the fifteen items in the SADL questionnaire, four indicated a significant preference toward refurbished devices relative to LoCHAid devices. These items are shown in Of the seven items in the IOI-HA questionnaire, only one showed a significant difference between device types. Users of refurbished devices reported significantly less difficulty than they used to have in the situations that they considered most important for requiring a hearing aid, compared to the LoCHAid users see .Two key themes from analysing the qualitative data obtained in the first follow up appointment are described below, with some example quotes. Participants commented on the sound quality of the amplification and the internal noise of the hearing device. Overall, all participants reported positive experiences of the refurbished hearing aid's sound quality. However, those in the LoCHAid group reported that although the device improved their hearing ability, the internal noise from the device negatively impacted the listening experience.“Apart from amplifying sound, the sound it also produces is a noise like when you are tuning a radio” (LoCHAid)“Volume control would be very helpful because sometimes I needed it higher” (LoCHAid)“I liked everything about the sound” (Refurbished)“I can hear much better with the device and I can hear the things I couldn’t hear without it” (LoCHAid)“I think I hear perfectly but it took some time to get used to it” (Refurbished)“too noisy” (LoCHAid)Some participants liked the appearance of the LoCHAid as it did not look like a traditional hearing aid and therefore helped them avoid unnecessary attention. However, others felt the use of headphones made it look like they were using a music device, e.g., radio, and therefore not paying attention to their surroundings. The structure of the LoCHAid was reported to be quite delicate and there were some concerns raised about the number of visible open ports which may cause the device to malfunction in humid, dusty environment. Participants also commented on overall appearance and usability of each device.“The appearance is good, nobody knew it is hearing aid and that I have a hearing loss” (LoCHAid)“It makes me look older” (Refurbished)“Very easy to use” (Refurbished)“Since it has headphones, you might wear it in places, you are not supposed to put headphones, people get disappointed in you” (LoCHAid)“The machine has lots of open spaces where dust can get in, like where the headphones go and the on button switch” (LoCHAid)“Needs to be more powerful or have a volume control so I can control it, also sometimes headphones come out of my ear if I am eating/chewing” (LoCHAid)“At church people thought I was listening to my phone or the radio. People thought because I am old that I am wearing this device to listen to music and look younger. Maybe they thought I was being rude. It is a problem when it doesn’t look like something that is helping my medical condition” (LoCHAid)“less visible headphones needed” (LoCHAid)“The machine looks like it will break easily, what if I need a replacement or if the headphones stop working- can I use any headphones?” (LoCHAid)“it is easy to put on and off, the colour of the headset makes it get dirty quickly. It improves my hearing, but the headphones can fall out easily. I don’t like being able to see inside the machine as I am worried it will break easily” (LoCHAid)This feasibility study is the first to clinically evaluate the effectiveness of the LoCHAid in a low resource setting. The results, from this Malawian population, found that the LoCHAid and the refurbished programmed hearing aids were similarly beneficial for people with high frequency hearing loss but that some improvements are required to improve the LoCHAid sound quality and user experience.Low hearing aid uptake or hearing aid availability in Sub Saharan Africa has been noted in the literature , 27. FurThe present study found the LoCHAid had potential to serve people with hearing loss in Malawi and broadly performed similarly to digitally programmed refurbished, donated, behind-the-ear hearing aids. Three standardized measures, SSQ-12, GHABP and EAS, were carried out before and after hearing aid fitting to explore the effectiveness of hearing aid use on various listening situations. Results from each of these outcome measures found that both devices, the LoCHAid and refurbished hearing aid, improved hearing abilities and listening effort (compared to the unaided experiences) at a similar degree. Two outcome measures reviewed overall hearing aid use and experience and were completed at the follow up appointment. Results from the SADL found that the LoCHAid was less helpful compared to the refurbished hearing aid in helping to understand people during conversation, the LoCHAid was less natural sounding and less dependable overall. Results from the IOI-HA found that users of refurbished devices reported significantly less difficulty, compared to LoCHAid, than they used to have in the situations that they considered most important for requiring a hearing aid. The poorer satisfaction of LoCHAid users could be due to the device providing sound pseudo-binaurally (through headphones playing the same sound in each ear), and the position of the body-worn microphone, affecting sound localisation and overall sound quality.During the follow up visits, participants were asked open questions about their overall hearing aid use and experience and probing questions about how their device does or does not benefit them. This feedback was analysed to present key themes and summarized to identify some key improvement indicators required to improve the LoCHAid user experience. These improvement indicators included factors affecting the design, hearing aid output, features and accessories and are shown in The study had some limitations. Firstly, due to the nature of the device and its role in providing only high frequency amplification, finding the appropriate patient population for this trial was challenging. Despite running many outreach recruitment events, in neighboring villages and towns, the number with mild-moderate high frequency hearing loss, with no other otological symptoms was low. One of the reasons for this may have been because although recruitment activities were carried out in the community, the testing and hearing aid fitting was completed in a tertiary hospital setting (QECH). Other studies have found low-cost hearing aid provision to be similarly effective in community settings , therefoA key strength of this study was the involvement of the Malawian audiology clinicians as they were trained to recruit and consent participants, run the feasibility trial and had key involvement in the development of the outcome measures and the hearing aid instruction booklets. This experience and training would help future trials that take place at QECH.There are currently no validated hearing aid outcome measures (speech perception tests or questionnaires) in Malawi. However, during the development phase of this study five hearing qualities/hearing aid benefit questionnaires were translated to Chichewa and validated with a small normal hearing adult population. Backwards and forwards translation was implemented by a professional English-Chichewa translation service and the audiology team at QECH cross checked all translations. Additional validation of these Chichewa questionnaires using a larger population would further confirm the consistency of the measures. Speech perception and speech in noise perception measures are used to guide and evaluate hearing aid fittings in audiology settings , but ChiThe results from this feasibility study are encouraging, but a comprehensive, larger clinical study is needed to draw firm conclusions about the LoCHAid's performance. This study has identified key improvement indicators required to enhance sound quality and user experience of the LoCHAid. Once these improvements are made, further electroacoustic, speech perception and self-report testing should be completed on similar patient populations.


Emotional prosody is known to play an important role in social communication. Research has shown that children with cochlear implants (CCIs) may face challenges in their ability to express prosody, as their expressions may have less distinct acoustic contrasts and therefore may be judged less accurately. The prosody of children with milder degrees of hearing loss, wearing hearing aids, has sparsely been investigated. More understanding of the prosodic expression by children with hearing loss, hearing aid users in particular, could create more awareness among healthcare professionals and parents on limitations in social communication, which awareness may lead to more targeted rehabilitation. This study aimed to compare the prosodic expression potential of children wearing hearing aids (CHA) with that of CCIs and children with normal hearing (CNH).In this prospective experimental study, utterances of pediatric hearing aid users, cochlear implant users, and CNH containing emotional expressions  were recorded during a reading task. Of the utterances, three acoustic properties were calculated: fundamental frequency (F0), variance in fundamental frequency (SD of F0), and intensity. Acoustic properties of the utterances were compared within subjects and between groups.A total of 75 children were included . Participants were between 7 and 13 years of age. The 15 CCI with congenital hearing loss had received the cochlear implant at median age of 8 months. The acoustic patterns of emotions uttered by CHA were similar to those of CCI and CNH. Only in CCI, we found no difference in F0 variation between happiness and anger, although an intensity difference was present. In addition, CCI and CHA produced poorer happy–sad contrasts than did CNH.The findings of this study suggest that on a fundamental, acoustic level, both CHA and CCI have a prosodic expression potential that is almost on par with normal hearing peers. However, there were some minor limitations observed in the prosodic expression of these children, it is important to determine whether these differences are perceptible to listeners and could affect social communication. This study sets the groundwork for more research that will help us fully understand the implications of these findings and how they may affect the communication abilities of these children. With a clearer understanding of these factors, we can develop effective ways to help improve their communication skills. In spoken language, both linguistic and paralinguistic information are essential to convey the content and the emotional context of a message . ParalinAs young listeners map distinct acoustical features of the voice onto speakers’ emotional states, they learn to decode emotional information conveyed by a speaker . TypicalHearing loss can negatively impact the ability to detect prosodic cues, even with auditory rehabilitation . StudiesPrevious studies have analyzed children’s prosodic expression potential through assessment of various acoustic properties, including fundamental frequency, variations in fundamental frequency, and intensity. These properties represent crucial aspects of prosody and are relatively easy to measure and examine. As most pediatric studies investigating emotional prosodic conveyance focused on children with severe to profound hearing loss using cochlear implants, very little is known about the prosodic expression by children with mild to severe hearing loss wearing hearing aids. These children with milder hearing losses may also experience significant speech recognition challenges because of reduced audibility and decreased temporal and spectral processing sensitivity and selectivity . HoweverIn the present study, we compared the prosodic expression potential of children with mild to severe hearing loss wearing hearing aids bilaterally or unilaterally to that of age-equivalent CCI and CNH. The following acoustic properties were established: fundamental frequency, variance in fundamental frequency, and mean intensity of the children’s utterances. We aimed to investigate (1) the difference in acoustic properties of emotional utterances of CHA compared with CCI and CNH, (2) the individual acoustic differences between the three emotions within the three groups, and (3) acoustic contrasts between emotions uttered by CHA or CCI compared with CNH, as these contrasts can provide insight into how emotions can be distinguished from each other. Acoustic contrasts have been used in previous studies and are an essential component in investigating the potential for prosodic expression.Given the cochlear implants’ limitations in sound representation and the previous findings on their users’ prosodic conveyance, we hypothesized fewer acoustic differences and lower acoustic contrasts between emotions in this group than in the CNH. Although the impact of lower degrees of hearing loss on prosodic expression is not yet known, we expect this group to also experience limitations in prosodic expression compared with those with normal hearing.Three groups of participants were included in the study: CHA, CCI, and CNH. To ensure that all participants could complete the reading task without age-related reading difficulties, we set the inclusion age to begin at 7 years. For this study, we included children up to the age of 13, because it is commonly believed that prosodic expression would have leveled off beyond this age. Because we wanted to include children with milder losses, hearing thresholds had to be at least 35 dB HL on 0.5, 1, 2, and 4 kHz on average in the best hearing ear. To ascertain the inclusion of adequately fitted participants, intervention with hearing aid or cochlear implant had to be at least 6 months before inclusion. To ensure the inclusion of participants with an appropriate reading level. Parents were asked to provide information regarding their child’s reading performance and confirm that their child had reached or surpassed a third-grade reading level. Of the children who were included, all were able to complete the task sufficiently. All participants with hearing loss were being treated in the Audiology Department of the Erasmus University Medical Center for hearing aid fitting, cochlear implant programming, and regular annual appointments with audiologists and/or speech therapists who worked closely with the children and their families. The focus of these appointments was to optimize the performance of their hearing devices through proper adjustments, and providing support by a speech therapist. In addition, the rehabilitation process involved other assistance, such as providing assistive listening devices, to support effective communication in various settings. These interventions were tailored to individual needs, aiming to enhance participants’ hearing experience, optimize communication, and mitigate challenges associated with hearing loss.p = 0.26). A total of 75 children participated in this study; the sample comprised 26 CHA, 23 CCIs, and 26 with CNHs  or an Advanced Bionics (Naida Q70 or Naida Q90) device. CNH, between the ages of 6 and 13 years and without any history of hearing loss or current complaints of such, were recruited for the study through employees of the Erasmus University Medical Center and their personal networks. Ages did not differ between the groups with hearing loss (10.3 yr) and normal hearing . The same test protocol and set-up were used throughout the study, both in the hospital and at home. No differences in mean fundamental frequency (F0), variance in F0, and intensity, for all three emotions were observed between home and hospital recordings. All testing was performed in one session, taking between 2 and 5 minutes. Tests were performed in a quiet room, under the supervision of an investigator who was aware of the purpose of the study. Tasks were explained in live voice.The prosodic expression of the children was tested subsequent to the children’s scheduled outpatient visit. Testing took place between January 2021 and June 2021. Due to the COVID-19 pandemic, not all CNH group were able to visit the hospital; therefore, children were tested either at the hospital (n = 13) or at home (n = 13). No differences in ambient noise intensity were found between recordings made at home (average 31.6 dB SPL) or at the hospital  were made of the averages in mean F0, F0 variation, and mean intensity per emotion . These comparisons were performed using Kruskal-Wallis tests for independent samples.In the second analysis, the averages in mean F0, F0 variation, and mean intensity were compared between emotions  within the three different groups, with a Wilcoxon Signed-Ranks test.x–dBy| as emotion contrast for intensity. This approach was similar to that of In the third analysis, emotion contrasts were investigated. The contrasts were calculated as the ratio between the acoustics of two emotions per utterance, per child. For instance, mean F0 of sentence 11 expressed with happy intent by one participant, was divided by the mean F0 of sentence 11 expressed with sad intent by the same participant. Because decibels, the unit for intensity, expresses a ratio itself, we used the absolute difference in dB |dBp values are corrected for family-wise error, for which the Benjamini–Hochberg procedure was followed in all analyses . For CHA, pure-tone thresholds were mostly moderate , 5 children (19%) had mild, and 9 (35%) had severe-profound hearing losses. Children in this group had an average device experience at moment of testing of 6.6 years, and 23 children (88%) wore hearing aids bilaterally. In the CCI group, children had a mean device experience of 7.4 years, used cochlear implants bilaterally in 15 of the cases (65%), and 7 (30%) were bimodal users .Within each group, the differences between emotions were compared  and anger , whereas happiness only had a higher F0 variation than anger in CNH (p < 0.01). In CHA and CCI, no difference in F0 variation could be found between happiness and anger.F0 variation was significantly lower in sadness versus happiness in all groups (CHA: Intensity differences between happiness and sadness (and sadness and anger) were significant for all groups. Group angry utterances were louder than happy, which in turn were louder than sad utterances. On average, mean intensity differed significantly between all three emotions in CCI. This was the only group that exhibited significant intensity differences between happiness and anger, in contrast with both CNH and CHA.H(2) = −14, p = 0.02 for CCI versus CNH, H(2) = −13, p = 0.04 for CHA versus CNH). Test statistics for all emotion contrasts are provided in Supplemental Appendix 2, Supplement Digital Content, http://links.lww.com/EANDH/B183.We compared the distribution of emotion contrasts between the three groups. Between CCI, CHA, and CNH, there was no difference in emotion contrasts, except for the emotion contrast between happy and sad utterances. For mean F0, the happy–sad contrasts in CCI and CHA were significantly poorer than those in CNH (p = 0.04) and variance in F0 (ρ(47) = −0.42, p = 0.04) correlated significantly with device experience, in terms that children with lower device experience had greater acoustic contrasts between sadness and anger. Device experience was significantly higher in children with a congenital onset of hearing loss .Post hoc analysis showed no correlation between the size of emotion contrasts and age at testing and speech perception performance in quiet. Sad–angry contrasts in both mean F0 (ρ(47) = −0.39, In this prospective study, we included 26 children with mild to severe hearing loss wearing hearing aids (CHA), and compared their prosodic expression with that of 23 CCI, and 26 CNH. On average, the distributions of mean F0, F0 variation, and mean intensity per emotion in CHA were similar to those in the CCI and CNH groups. CCI may well experience more difficulties with the perception of subtle variations in voice pitch due to a lack of resolved harmonics in cochlear implants and a lack of temporal fine structure coding—most current implants convey only temporal envelope information and discard the temporal fine structure. This could be a reason for the more monotonous expression of emotion in these children compared to that of CNH, a finding also reported by We used the ratio of acoustic values between emotions to investigate the emotion contrasts between groups. We found a poorer mean F0 contrast between happiness and sadness in CHA and CCI compared with that of CNH. Despite diminished perception of sound of even the CHAs and CCIs, these children were capable of expressing emotions distinguishable by acoustic patterns. This may be due to the auditory and linguistic rehabilitation that the children with hearing loss received, in accordance with Dutch national guidelines , and earThe present study has several strengths: (1) it is the first to investigate emotional prosodic expression in children with mild to moderate hearing loss, contributing new information to the general understanding of prosodic conveyance in children with hearing loss, (2) it has a sample size exceeding that of previous investigations , resultiThe findings of this study suggest that on a fundamental, acoustic level, both CHA and CCI have a prosodic expression potential that is almost on par with normal hearing peers. However, there were some minor limitations observed in the prosodic expression of these children, it is important to determine whether these differences are perceptible to listeners and could affect social communication. This study sets the groundwork for more research that will help us fully understand the implications of these findings and how they may affect the communication abilities of these children. With a clearer understanding of these factors, we can develop effective ways to help improve their communication skills.M.M.H. and J.L.V. were involved in conceptualization; T.J.d.J. was involved in data curation; T.J.d.J. was involved in formal analysis; M.P.S. and J.L.V. were involved in funding acquisition; T.J.d.J., M.M.H., M.P.S., and J.L.V. were involved in investigation; T.J.d.J., M.M.H., M.P.S., and J.L.V. were involved in methodology; T.J.d.J., M.M.H., M.P.S., and J.L.V. were involved in project administration; T.J.d.J., M.M.H., M.P.S., and J.L.V. were involved in resources; M.P.S. and J.L.V. were involved in software and supervision; M.M.H. and J.L.V. were involved in validation; T.J.d.J. was involved in visualization; T.J.d.J., M.M.H., M.P.S., and J.L.V. were involved in roles/writing—original draft; T.J.d.J., M.M.H., M.P.S., and J.L.V were involved in writing—review and editing.


Horizontal gene transfer (HGT) is an important driver in genome evolution, gain-of-function, and metabolic adaptation to environmental niches. Genome-wide identification of putative HGT events has become increasingly practical, given the rapid growth of genomic data. However, existing HGT analysis toolboxes are not widely used, limited by their inability to perform phylogenetic reconstruction to explore potential donors, and the detection of HGT from both evolutionarily distant and closely related species.Saccharomyces cerevisiae and Candida versatilis demonstrate the ability of HGTphyloDetect to identify horizontally acquired genes with high accuracy. In addition, HGTphyloDetect enables phylogenetic analysis to illustrate a likely path of gene transmission among the evolutionarily distant or closely related species.In this study, we have developed HGTphyloDetect, which is a versatile computational toolbox that combines high-throughput analysis with phylogenetic inference, to facilitate comprehensive investigation of HGT events. Two case studies with https://github.com/SysBioChalmers/HGTphyloDetect.The HGTphyloDetect computational toolbox is designed for ease of use and can accurately find HGT events with a very low false discovery rate in a high-throughput manner. The HGTphyloDetect toolbox and its related user tutorial are freely available at  Horizontal gene transfer (HGT), also known as lateral gene transfer, refers to the exchange of genetic material between disparate groups of organisms other than from parent to offspring . This haAlthough the mechanism of HGT is very complex and often occurs at different rates across prokaryotes and eukaryotes, there are still a few computational approaches available to predict HGT events. For example, HGT-Finder is a phyletic distribution-based tool that calculates a horizontal transfer index and probability value for each query gene, but, unfortunately, this software is no longer available for download . HGTectoSaccharomyces cerevisiae and Candida versatilis). It can be found that HGTphyloDetect presents its great performance by comparing the predicted horizontally acquired genes with those published in previous studies. More importantly, the HGTphyloDetect toolbox enables the generation of high-quality phylogenetic trees to further facilitate the navigation of potential donors and detailed elucidation of a feasible path of gene transmission.To this end, we therefore developed HGTphyloDetect, an open-source computational toolbox to investigate HGT events by combining with phylogenetic inference. In this work, we adopted high-throughput algorithms for the identification of HGT events no matter whether the target horizontally acquired genes are from evolutionarily distant species or from closely related species, showcasing its versatility. Furthermore, we applied this new bioinformatics software to the whole genomes of two species , we defined a robust and phylogeny-based approach as shown in Here, bbhG and bbhO represent the E-values of the best BLAST hit in ingroup and outgroup lineages, respectively. The ingroup lineage is defined as the species inside of the kingdom, but outside of the subphylum. The outgroup lineage is defined as all species outside of the kingdom. The Alien Index mathematical formula used here has previously been defined in an impactful study by Gladyshev et al., who found that AI ≥ 45 is a good indicator of foreign origin . In addiFinally, those genes with AI ≥ 45 and out_pct ≥ 90% are assumed as likely HGT candidates from evolutionarily distant species , 13. TheAlthough the above workflow is powerful to detect HGT events from evolutionarily distant organisms, we have also constructed a complementing workflow for automated detection of HGT events from more closely related organisms  [To corroborate the accurate identification of HGT genes by their AI values, as described above, we extended HGTphyloDetect with a phylogenetic analysis pipeline. First, the top 300 homologs with different taxonomic species names are selected from the BLASTP hits for each query sequence. HGTphyloDetect then aligns these homologs with MAFFT v7.310  using dembl.de/)  to asseshttps://github.com/SysBioChalmers/HGTphyloDetect). is relatively easy to use, as users only need to prepare a FASTA file containing both protein identifier and protein sequence as input. The large NCBI nr protein and taxonomy databases that are used in the pipeline are accessed remotely on demand, precluding the need to download these large databases. The installation with only few dependencies and a detailed user tutorial is all well documented .HGTphyloDetect  approaches to reveal the main driving force behind metabolic innovation for expanding substrate usage across more than 300 yeast species , 22. In S. cerevisiae and C. versatilis) that have manually curated HGT events described in previously published works, allowing benchmarking of our approach [S. cerevisiae, 10 horizontally acquired genes from bacteria have been reported by previous work [S. cerevisiae with the default parameters, we were able to identify 23 HGT gene candidates from bacteria  have been reported, rendering it suitable to further benchmark HGTphyloDetect. Here, by applying the high-throughput pipeline into the whole (more than 5000) genes of C. versatilis with the default parameters, we were able to identify 148 out of 169 genes as horizontally acquired genes , including more than 15 000 unique genes in total. HGT detection workflows were run for all those genes with HGTphyloDetect and HGTector, and various evaluation metrics were used for comparison, e.g. accuracy, sensitivity, specificity, etc. HGTphyloDetect had somewhat higher accuracy and specificity than HGTector (We further evaluated HGT detection performance by comparing HGTphyloDetect with other existing computational tools, e.g. the HGTector toolbox that can also be used to detect HGT events in a high-throughput manner . For thiHGTector , but morHGTector .S. cerevisiae enabling alkyl sulfatase activity and arylsulfatase activity that is assumed to be acquired through HGT [The most accurate and golden-standard approach for the identification of horizontally acquired genes is gene-by-gene phylogenetic analysis , which cough HGT . To probGiven the rapid increase in newly sequenced genome data, we observe a great demand for a software solution capable of identifying HGT events for the further investigation of gene variation and evolution. The high-quality performance of HGTphyloDetect that we demonstrated here render it able to meet wide biological application demands from various fields, e.g. interpreting the pathogen phenotype in fungi , analyziAs an alternative approach, it is conceivable that machine learning could be utilized to predict horizontally acquired genes. Machine learning has been applied and shown its great power in solving various gene- or protein-related problems such as in prediction of gene essentiality , gene exHGTphyloDetect will continue to be developed and maintained on GitHub together with its users and researchers in the HGT ecosystem. We hope that HGTphyloDetect can become a standardized toolbox for identifying HGT and its underlying mechanisms in the large scientific community.In summary, we created HGTphyloDetect, a versatile toolbox to automatically identify potential HGT events via a high-throughput approach combined with phylogenetic analysis. It is applicable to detect the probable mechanisms underlying gain-of-function that are highly relevant to evolutionary biology, systems biology, synthetic biology and many other domains.L.Y., H.Z.L. and E.J.K. designed the research. L.Y. performed the research. L.Y., H.Z.L., F.R.L., J.N. and E.J.K. analyzed the data. H.Z.L. and E.J.K. supervised the work. All authors interpreted the results, discussed, drafted and approved the final manuscript.https://github.com/SysBioChalmers/HGTphyloDetect.HGTphyloDetect is freely available, open source and distributed on GitHub. The computational software, installation, examples and documentation file for user tutorial are available in the repository: HGTphyloDetect is a comprehensive toolbox to facilitate the identification of horizontal gene transfer events, no matter whether the horizontally acquired genes are from evolutionarily distant species or from close species.S. cerevisiae and C. versatilis demonstrate the ability of HGTphyloDetect to identify horizontally acquired genes with high accuracy.Two case studies with In-depth phylogenetic analysis facilitates the navigation of potential donors and detailed elucidation of a feasible path of gene transmission.supplementaryFile_bbad035Click here for additional data file.


Recent investigations have shown a robust signature of poleward migration of the tropical cyclone latitudes using observations and climate model simulations. Most of these studies invoked the role of the Hadley circulation (HC) expansion in the poleward shifting of tropical cyclones. However, none of these studies focused on the dissection of the zonally asymmetric HC into ascending and descending regions at regional scales, which holds the key in establishing the association between these two phenomena. Here, we are reporting the poleward migration of tropical cyclones and their association with ascending region boundaries of the HC at regional scales for the first time. The results emphatically show that the tropical cyclone latitudes as well as latitudes of maximum lifetime intensity vary in tandem with boundaries of the ascending region of the HC as compared to its descending region thus providing a vital clue on processes governing poleward migration of tropical cyclones. The current reports show warming of more than 1 °C on average as compared to the pre-industrial era2. One of the important consequences of this warming is an increase in the intensity of extreme weather events. For example, it was shown that the impacts of typhoon Haiyan, which is the strongest storm ever recorded, were extreme because of climate change3. Recent investigations report an increase in intensity7 and a decline in the frequency of tropical cyclones (TC)10 along with their poleward migration14, which is attributed to anthropogenic-induced warming16. Another important consequence of the warming affecting the formation of TCs is the expansion of the Hadley circulation (HC)19. The HC expansion reported in the recent decades has a plethora of imprints20 such as poleward shifting of subtropical dry zones22, changing precipitation patterns25and poleward migration of TCs27.Earth's temperature has been rising rapidly since the mid-twentieth century and the warming has increased from 0.08 to 0.18 °C per decade (more than double) since 198014. Initial reports showed that the latitude of lifetime maximum intensity (LMI) of TC migrated approximately 53 and 62 km per decade in the Northern and Southern hemisphere, respectively with a global migration rate of 115 km per decade according to global 'best-track' datasets28. A few studies showed that the inter-basin differences in the frequency of occurrence of TC affect the estimated trends in LMI latitudes29. It is noted that the trends in the northern hemisphere (NH) are contributed mostly by the differences in the frequency of TC rather than the migration of LMI. However, in the southern hemisphere (SH) observed trends are immensely contributed by the actual migration of TC29. Despite these disparities, a robust poleward shift of TCs over the majority of oceanic basins is noted in observations as well as climate model simulations. There has been a handful of investigations to identify the driving mechanisms for this phenomenon and the majority of them are associated with the HC expansion30. As both poleward migrations of TC and HC expansion share similar magnitudes (~ 0.5° to 0.8° latitude/decade), it was proposed that there might be an association between them. In a seminal study30 using multiple reanalysis datasets, it was reported that the HC edges and meridional distribution of TC vary concurrently. Further, it was reported that the weakening of HC, especially in the upper troposphere, plays a key role in the poleward migration of TCs26.In the beginning of the last decade, the phenomenon 'poleward migration of TC' was coined33. However, the mechanism behind how HC expansion drives the poleward migration of TCs is yet to be ascertained. It is known that the ascending region of the HC plays a key role in triggering the tropical deep convection, which forms the basis for the formation of TCs. Any changes to the ascending region of the HC will have a profound impact on the TC formation as well as their propagation. Almost all the investigations on poleward migration of TCs focused on the total width of the HC rather than bisecting it into ascending and descending regions. There are no studies conducted so far on TC latitude distribution with respect to HC ascending region boundaries at regional scales. In this study, we provide new insights into the poleward migration of TC activity with respect to the ascending region of the HC at regional scales using 41 years of TC track observations and reanalysis datasets.Recent studies on poleward migration of TCs linked this phenomenon to the HC expansion at regional as well as hemispheric scales28  and HC boundaries retrieved from ERA-5 reanalysis datasets41 are employed for the present investigation  and Interdecadal Pacific Oscillation (IPO) influencing the TCs formation in the West North Pacific (WNP) basin35 and North Atlantic Oscillation (NAO) in the North Atlantic (NA) Ocean. We will discuss the role of these oscillations in modulating the LFO and LMI in respective oceanic basins in the later part of this section. The time series over the North Indian Ocean is not included due to the inhomogeneities in the observations of TC tracks. From Fig. The TC track observations provided by the IBTrACS35. It becomes essential to remove their effect while estimating the migration rates of TCs in the WNP. We have estimated the time series of residuals of LFO and LMI after removing the PDO/IPO signals from the original time series shown in Fig. 35. The analysis emphasizes the role of natural variability in the observed migration rates of TCs. A similar analysis is carried out to remove the NAO signal from the LFO/LMI over the NA basin. However, an insignificant correlation is found between NAO index and LFO/LMI and there were no notable changes in estimated migration rates before and after removal of NAO signal as shown in the Supplementary Figure As mentioned earlier, it is reported that PDO/IPO influences the TCs in the WNP basin. We have noted a significant negative correlation between PDO/IPO and LFO/LMI in line with the earlier reports36 abbreviated as WTC and ITC, respectively. This classification is made to verify the relative contributions of WTC and ITC to the observed migration rates in the WNP basin. The analysis is carried out using both original time series as well as residuals of LFO/LMI. Figure 36. The potential reasons for the observed differences in the poleward migration of weak TC and intense TC in the WNP are discussed in an earlier study36.Based on the maximum sustained winds, the TCs are classified as weak (< 65 knots) and intense tropical cyclones (≥ 65 knots)30. There were no attempts in the past to examine the co-variability of ascending region boundaries with the TCs, which can be partly attributed to the lack of a zonally resolved metric for identifying the ascending region boundaries over the various oceanic basins. A similar depiction is made for the LFO of TCs and is shown in Figure To provide further insights into the association between the poleward migration of TC and HC, we have used the zonally resolved HC boundaries at regional scales using Helmholtz's decomposition of winds (refer to “The peak TC seasons are identified over each oceanic basin as mentioned earlier and the co-variability between HC boundaries and TCs (LFO and LMI) are examined. Figure It is evident from Table 26, which is one of the important factors in the formation of TCs. The regions with low VWS favour the formation of TCs as higher magnitude of VWS inhibits the vertical development of convective systems before cyclogenesis. To further investigate the VWS distribution with respect to the HC boundaries, its climatology for the WNP cyclonic season JASO is constructed and its long-term trends are estimated as shown in Fig. The sea surface temperature, low-level vorticity, low-level convergence and vertical shear of horizontal winds are some of the most prominent parameters influencing the formation of TCs. Especially, changes in the HC dynamics can result in the redistribution of vertical shear of horizontal winds (VWS)36. Recent studies have reported a robust increasing trend in SST across the tropical as well as sub-tropical latitudes and attributed it to anthropogenic global warming. On the other hand, it is noted that the changes in meridional gradient in SST influence the HC dynamics37. Figure 38. The shifting of the descending region of the HC result in shifting of dry zones, which are void of clouds, towards north and thus resulting in relatively large warming rates over the subtropics as shown in Fig. 40. The changes in latitudinal distribution of SST in turn alter the HC and associated dynamics including the large-scale dynamical conditions affecting the TC formation and intensification. The vertical air motions over the equatorial and low-latitudes, which form the ascending limb of the HC, depend on the SST and its meridional gradient. The SST play a key role in altering the ascending limb and hence the HC as discussed in a seminal study37. Thus, though the warmer SST associated with global warming in all the ocean basins in NH peak TC season is favorable for increasing the frequency of TC genesis, a decreasing trend is found as shown in Fig. 36. The spatial pattern of SST changes is attributed to HC expansion14. However, it is to be noted that the seasonal variation of MPI in the WNP is also contributed by upper-level outflow temperature apart from the SST. The SST analysis thus shows an overall warming of the sea surface consistent with global warming and meridional gradient in the warming rates having a potential to modulate the large-scale circulation.The sea surface temperature (SST) and its variability in the tropical oceans play a key role in controlling the TCs formation as well as their propagation during their life-cycleThe time series of the number of TCs forming in the various ocean basins show a robust decreasing trend in almost all the basins except in the NA, where it shows an increasing trend. The large decline in the number of TCs in a year is noted in the SP (~ 6.8 in 4 decades.) followed by WNP (~ 2.62 in 4 decades). It is also noted that both LFO and LMI show poleward migration in the majority of the oceanic basins except in the NA, where it shows an equatorward migration. The PDO/IPO, which has known influence on the TCs forming in the WNP basin, has shown a significant negative correlation with LFO/LMI. It is noted that the observed poleward migration rates of LFO and LMI are reduced by 38.5 and 51.2%, respectively. However, no significant changes are observed in the migration rates of LFO and LMI after and before removing the NAO index signal in the NA basin. Further, the analysis carried out separately for weak and intense TCs has revealed that the WTC contributes relatively more to the poleward migration rates of TCs. Though a few earlier works studied the poleward migration of TCs with HC expansion, none of them focused on the dissection of HC further into ascending and descending region boundaries. The present analysis focused on the zonally resolved ascending and descending region boundaries using Helmholtz decomposition of horizontal winds and investigated the poleward migration of TCs with respect to these boundaries. The LMI distribution showed that most of the TCs occur around the boundaries of ascending region of the HC in the respective hemisphere in most of the oceanic basins. This observation provided a clue that the ascending region boundaries of the HC may be holding the key in the observed poleward migration of the TCs. Further investigations showed that the ascending and descending region boundaries of the HC are moving poleward at different rates over most of the oceanic basins and the TCs show significantly higher co-variability with the ascending region boundaries. Both residuals as well as original time series of LFO and LMI have shown significant co-variability with HC boundaries in the WNP. This perspective is emerged for the first time, which provides new insights into this phenomenon.The changes in HC dynamics in the recent past may have a potential impact on the VWS distribution, which is one of the important parameters associated with TC formation. The climatology of VWS has shown a low wind shear regime around the poleward edges of ascending region, which is a conducive condition for tropical cyclogenesis. The long-term trends in VWS show enhanced magnitude mostly within the ascending region and reduced magnitude around its poleward edges over most of the ocean basins, in general. This is one of the important aspects of both poleward migrations as well as the reduced number of cyclones in a given ocean basin except in the NA. It is known that the conditions within the ascending region of the HC are relatively more conducive for cyclogenesis in terms of higher SST compared to its poleward latitudes. The high SST triggers the mesoscale convection over the oceanic regions and depending on the VWS, low-level vorticity and Coriolis parameter, these convective systems organise themselves to initiate the cyclogenesis. As noted in the present study, the TCs are shifting poleward, which can be attributed to the strengthening of VWS within the ascending region of the HC and weakening at its edges associated with the changes in the intensity of the HC during recent times. However, as favourable VWS conditions are shifting poleward where SST is relatively low as compared to its equatorward latitudes, the number of TCs is showing a decreasing trend in most of the oceanic basins. The number of TCs seems to be a trade-off between reduced VWS (favourable condition) and reduced SST (unfavourable condition). The long-term trends in SST have shown an overall warming of the oceans with relatively large warming rates at the subtropical zones over the WNP basin leading to meridional gradients in the SST, which in turn can affect the HC dynamics. The SST is a key factor for the TC genesis and the latitudinal gradient in SST is key for the HC dynamics.33 and this phenomenon in turn affects the regional climate by modulating the various geophysical processes in and around the ascending and descending region boundaries of the HC. The present results can serve as key inputs for climate modellers as they shed light on the pathways through which HC expansion is affecting TCs. Most of the climate models are forecasting that the HC expansion will continue till the end of this century33, which may result in further poleward migration of TCs. This may further alter the established precipitation patterns associated with TCs and expose the biota living in the subtropical regions to the wrath of these extreme weather events.The observations over the NA show an equatorward migration of TCs and an increase in the number of TCs. Interestingly, over this oceanic basin, the VWS is decreasing around the equatorward edges of the ascending region of the HC whereas it is increasing over other ocean basins, especially over the Pacific during the JASO season as shown in Fig. 28  dataset for the analysis of TC climatology and trends and the state-of-the-art ERA-5 reanalysis dataset41 for characterising the HC at regional scales. The parameters of TCs viz., the latitude of first occurrence(LFO) and latitude of maximum intensity (LMI) are extracted from the IBTrACS whereas the monthly mean zonal and meridional winds of ERA-5 reanalysis are used for the computation of Meridional Mass Stream function and thereby, the HC boundaries during 1980–2020.The present study used the IBTrACS28. The parameters of TC considered for analysis are annual averaged LFO, LMI and frequency of occurrence. All TCs with maximum sustained wind speeds greater than 33 knots are considered for the analysis. The trend analysis including a significant test is carried out using Mann–Kendall Test using the Pymann–Kendall module in Python.IBTrACS provides the 'best track' measurements of a TC, which includes the best estimate of the TC position, maximum sustained wind speed, and central pressure on a 6-h basis42 to describe the HC as these estimations require mass conservation. The present study retrieved zonally resolved HC boundaries from ERA-5 reanalysis41 by employing Helmholtz decomposition of horizontal winds into divergent and non-divergent components using windspharm module43. Subsequently, the meridional component of divergent winds is used to compute the mass stream function using the following equation,Most of the earlier studies have employed zonal mean meridional mass stream function (MSF)The mean mass stream function between 400 and 800 hPa levels is used for retrieving the boundaries of HC (both ascending and descending regions) as demonstrated in Supplementary Figure Vertical wind shear (VWS) of horizontal winds is estimated from zonal and meridional winds at 200 and 850 hPa using the following equation,Supplementary Information.