To assess the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for presumptive tuberculosis (TB) patients with intrathoracic enlarged lymph nodes in a country with low to moderate TB incidence.Thirty-one patients with clinical features of TB and intrathoracic lymphadenopathy, who had EBUS-TBNA sampling and final confirmation of intrathoracic TB lymphadenopathy, were retrospectively reviewed over an 8-year period. Routine clinical and laboratory evaluations including computerized tomography scans were performed before the EBUS-TBNA. Sociodemographic characteristics, clinical profile, pathological, and microbiological findings were collected.Mycobacterium tuberculosis. Pathological analysis had findings consistent with TB in 25 (80.6%) patients. Culture of the EBUS-TBNA sample was positive for Mycobacterium tuberculosis in 12 (38.7%) patients. Other supportive investigations like purified protein derivative (PPD) skin test was positive in 28 (90.3%) participants. Overall, the sensitivity of the EBUS-TBNA alone was 83.9%. No complications were recorded during the procedure. The EBUS-TBNA aspirate culture positivity was significantly related to having a larger size lymph node (p=0.048) only, while PPD positivity was significantly related to baseline and clinical features of the participants.The EBUS-TBNA confirmed TB diagnosis in 26 (83.9%) subjects with a consistent pathological finding or positive culture of The EBUS-TBNA demonstrated effective utility and safety in the evaluation and diagnosis of intrathoracic TB lymphadenopathy among individuals with compatible symptoms in a country with low-moderate TB-incidence. In 2020, the World Health Organization (WHO) estimated that tuberculosis (TB) is the most frequent cause of mortality from one infectious organism. Of approximately 10 million individuals worldwide who contracted TB in 2020, only approximately 50% (5.8 million cases) were notified, and approximately 1.3 million individuals who did not have human immunodeficiency virus (HIV) co-infection died from the disease (higher than the 1.2 million deaths reported in 2019); with another 214,000 deaths among persons co-infected with HIV. Adults accounted for 88% and children for 12% of people with TB. Successful TB treatment requires the combination of 4 anti-TB medications for at least 6 months, but the number of medications may increase in patients with resistance to first-line anti-TB agents. Tuberculosis treatment guidelines in recent times have highlighted the need for a confirmatory diagnosis of infection with Mycobacterium tuberculosis as well as their antimicrobial susceptibilities before treatment. In Australia, EPTB represented 34.2% of all notified TB cases, while in Morocco EPTB accounts for 43.5% of all cases of reported TB. A recent analysis carried out in Saudi Arabia estimates that a substantial fraction of notified TB cases are EPTB. In many of these cases TB involving the intrathoracic and extrathoracic lymph nodes are the most common presentation of EPTB. Obtaining the correct diagnosis in individuals with intrathoracic tuberculous lymphadenopathy (INTBLA) is crucial in order to rule out other differential diagnoses like sarcoidosis, lymphoma and intrathoracic metastasis, and before commencing anti TB drugs. Although mediastinoscopy is the gold standard technique for obtaining tissues samples from the mediastinum, it is limited by the fact that some lymph node stations are not accessible via mediastinoscopy, and the procedure requires surgical expertise and anesthesia. In addition, the procedure is associated with complications like bleeding, damage to contiguous structures, and pneumothorax.The burden of extrapulmonary TB (EPTB) varies according to region and countries. In European countries, an average of 21.7% of people with TB had EPTB, with the burden ranging from 21.1% to 45.2% among Member States, and some workers reporting a prevalence as high as 48%. Among individuals having lung cancer or sarcoidosis, EBUS-TBNA has demonstrated higher yield and sensitivity when compared to conventional TBNA or mediastinoscopy. Some studies have assessed the importance of EBUS-TBNA during the evaluation of individuals having suspected INTBLA and reported sensitivity rates of 59.3 to 94.0%. There is no data on the usefulness of EBUS-TBNA in the assessment of suspected INTBLA in Saudi Arabia whereas TB burden is relatively low. Therefore, the aim of this study was to describe the diagnostic utility of EBUS-TBNA in the assessment of suspected cases of INTBLA in a setting with a lower-moderate burden of TB.Transbronchial needle aspiration (TBNA), which involves the use of convex probe endobronchial ultrasound that permits real time sampling of the intrathoracic lymph nodes under direct visualization, has now emerged. This diagnostic modality is now a crucial procedure for the sampling of intrathoracic lymphadenopathy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is meritorious for being able to reach most of the intrathorcic lymph nodes under the guidance of ultrasonography – even nodes below 10 mm in diameter, and the procedure-related complications are very small compared to conventional TBNA or mediastinoscopy.A retrospective observational study was conducted between 2013 and 2020 at King Abdulaziz University Hospital, Jeddah, Western Region, Saudi Arabia.All patients with symptoms and signs suggestive of TB  who had intrathoracic lymphadenopathy, had undergone EBUS-TBNA, and had a final confirmation of INTBLA met the inclusion criteria. The exclusion criteria included adult patients with positive acid-fast bacilli in the sputum or bronchial washings, and those with a final diagnosis other than INTBLA like sarcoidosis and bronchogenic carcinoma. The final diagnosis of intrathoracic TBLA was made based on a combination of cytopathological assessment, microbiological evaluation and purified protein derivative (PPD) skin test. All patients participating in the EBUS-TBNA provided written informed consent, and the study approval was granted by the Research and Ethics Committee of the hospital. This report conforms to the Standards for Reporting Diagnostic accuracy studies (STARD) statement and the Helsinki Declaration principles.All study patients had a prior contrast chest computerized tomography (CT) scan to estimate the size and position of the enlarged lymph nodes before the EBUS-TBNA was performed. The process was carried out under conscious sedation using fentanyl and midazolam. The Olympus (BF UC260FW) EBUS scope was passed through the oral route and allowed for simultaneous endoscopic evaluation and linear ultrasound of mediastinal and hilar structures. The EBUS assessment of the large airways was carried out to identify the lymph nodal station with respect to the major vessels. Afterwards, the suction syringe was applied as previously described to obtain samples of the lymph node. Finally, the lymph node aspirates were smeared on glass slides. In most patients, multiple lymph node needle passes were carried out during TBNA sampling.During the EBUS-TBNA for each individual, the biggest and most hypoechogenic lymph node was chosen. The special EBUS (21-gauge) needle (NA-201SX-4021) was then passed through the working channel and inserted into the target lymph node guided by the endobronchial ultrasound to perform the TBNA. Once the needle tip was visualized within the lymph nodes, the stylet was pulled out after performing a repeated to and fro motion to remove any bronchial tissues or fibrocartilage. The unused samples were stored using appropriate fluid  for subsequent evaluation in the laboratory. 95% formalin was used to fix tissue fragments and cores, and hematoxylin and eosin  was used for staining.Once the TBNA was completed, the smears were quickly processed using Shandon Kwik-Diff stain for immediate cytopathologic assessment.Mycobacterium tuberculosis were considered confirmatory for TB. All subjects with a suspected TB diagnosis also had a PPD skin test, which was considered positive if the induration measurement was ≥5 or ≥10 in HIV-infected or non-HIV patients, respectively. The patients were given 6 months of anti-TB treatment, and they were monitored for 6 more months after completing anti-TB therapy in order to confirm they remained clinically stable and to exclude any false-negative diagnosis of an intrathoracic malignancy.Clinical and radiological properties, as well as pathological findings of caseating granulomas were used to confirm the diagnosis of TB. In addition, aspirates having a positive culture for Mycobacterium tuberculosis.Pathological features were grouped according to 5 grades as follows: Grade I-necrotizing granuloma, Grade II-non necrotizing granuloma, Grade III-necrosis with non-granulomatous reaction, Grade IV-lymphocytes only, and Grade V-inadequate sample. Provided the background clinical and radiological features, as well as the positive PPD skin test, patients with findings of pathological grades I to III were considered to have a diagnosis of intrathoracic TBLA. Microbiological assessment was considered consistent with a diagnosis of TB if the culture of the aspirates isolated The following data was collected from each patient: the patients’ age, gender, nationality, smoking status, HIV status, lymph node stations, lymph node size, number of needle passes during sampling, pathological grades, TBNA culture, PPD skin test, clinical symptoms at presentation, serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), red cell distribution width (RDW) and chest CT-scan findingsp<0.05 was the cut-off for statistical significance.Statistical analyses was carried out with IBM SPSS Statistics for Windows, version 24.0 . Considering the standard definition of sensitivity which is the proportion of the participants with confirmed TB using EBUS-TBNA, and the fact that in the study the prevalence of TB was 100%  we were able to estimate the sensitivity of the procedure but were unable to calculate its specificity and predictive values. Categorical variables were reported as proportion, while continuous variables were reported as median (range) or mean±standard deviation. Predictors of a positive culture or a positive PPD skin test were modelled using unadjusted logistic regression analysis. Multivariable regression analysis was not carried out due to inadequate sample size. All tests were 2 sided, and a During the time indicated, 31 consecutive presenting individuals who were eventually diagnosed as having INTBLA had EBUS-TBNA at our hospital. Overall, 17 (54.8%) of the patients were over 40 years old, their median age was 44 (range 15-81) years and 25 (80.6%) of them were males. Based on their clinical presentation and examination findings all the patients underwent EBUS-TBNA. We performed 115 needle passes for 37 lymph nodes. Seven (22.6%) patients had EBUS-guided sampling carried out on 2 or more nodal stations. The overall median number of needle passes per lymph node was 4 (3.8±1.8) . The medMycobacterium tuberculosis, one (3.2%) refused further testing and 4 (12.9%) underwent mediastinoscopy to confirm TB diagnosis. In addition, an assessment of the necrosis grade of the samples revealed that 14 (45.2%) patients had focal necrosis, 10 (32.3%) had extensive necrosis and 7 (22.6%) had none.The EBUS-TBNA confirmed TB disease in 26 patients (83.9%) consisting of patients with a consistent pathological finding or positive culture of Mycobacterium tuberculosis . PatholoMycobacterium tuberculosis in 12 (38.7%) patients. Other supportive investigations like PPD skin test was positive in 28 patients (90.3%). Culture of the EBUS-TBNA was positive for p=0.048). Furthermore, PPD positivity was significantly associated with older age (p=0.001), male gender (p=0.001), being a Saudi national (p=0.004), having a higher CRP (p=0.012), higher ESR (p=0.003), higher RDW (p<0.001), higher pathological grade (p=0.003) and higher number of needle passes (p=0.002).This study assesses the effectiveness and safety of diagnosing intrathoracic TBLA by reporting on 31 patients with suspected TB who underwent EBUS-TBNA. Using EBUS-TBNA, we were able to diagnose TB in 83.9% of the cases without any complications or the need for general anesthesia. Further, EBUS-TBNA samples were positive for mycobacterium culture in 38.7% of cases., 100 participants had EBUS TBNA for the assessment of intrathoracic lymphadenopathy with a mean age of 48.5±16.65 years. In a report by Erer et al, 28 individuals with mediastinal TB lymphadenopathy had EBUS-TBNA and their mean age was 53.4±15.9 years. In an Indian study, 100 individuals having mediastinal lymphadenopathy had EBUS-TBNA with a median age of 47.1 years (range 18-83 years).These findings indicate that most patients being investigated for mediastinal lymphadenopathy due to TB or other conditions like sarcoidosis or carcinoma of the lungs are middle-aged, yet the wide age range suggests the need for early diagnosis and treatment.The median age of the 31 (80.6%) patients consisting of mainly males was 44 years (range 15-81 years). The sample size, and the sociodemographic characteristics of participants in past studies on EBUS-TBNA, differed according to the indications for the procedure. In the study by Dar et al Similarly, studies carried out in India, France, Turkey and South Africa also revealed that mediastinal lymph nodes  constituted the largest percentage of the sampled nodes during EBUS-TBNA, while hilar nodes had the smallest proportion.Subcarinal lymph nodes (Station No. 7), accounting for approximately 51% of the EBUS-guided sampling, and paratracheal (2R and 4R), accounting for 35% of the lymph nodes sampled, constituted the majority of the nodes targeted in this study. These findings corroborate those of other studies assessing individuals with intrathoracic lymphadenopathy. A narrative review among patients with intrathoracic TBLA revealed that the subcarinal and paratracheal lymph nodes were the most frequently sampled nodes during EBUS-TBNA. The EBUS-TBNA sampling carried out among the study patients was adequate in 96.8% of the procedures. Previous studies among patients with intrathoracic lymphadenopathy who had clinical symptoms and signs suggestive of TB or sarcoidosis indicate that sample adequacy from EBUS-TBNA ranged from 89 to 98%. This indicates that EBUS-TBNA provides adequate sampling of the intrathoracic lymph nodes to ensure appropriate diagnosis of hilar and mediastinal lesions. In addition, adequacy of samples obtained by EBUS-TBNA prevented the need for mediastinoscopy. An earlier study of individuals with isolated mediastinal lymphadenopathy indicated that EBUS-TBNA averted 87% of mediastinoscopies. Moreover, in individuals with suspected TB along with compatible clinical or radiological features as in the present study, the use of additional investigative modalities like Ziehl-Neelsen staining for acid-fast bacilli, culture for Mycobacterium tuberculosis, PPD skin test, or polymerase chain reaction of the sample for Mycobacterium tuberculosisusing Xpert MTB/RIF or Cartridge Based Nucleic Acid Amplification test (CB-NAAT) may help extend the utility of EBUS-TBNA during the evaluation of individuals with INTBLA and thereby prevent unnecessary mediastinoscopies.The role of EBUS-TBNA has shown sustained growth over the past 2 decades, from its earlier use in lung cancer staging and evaluation of lesions in the mediastinum to a more extensive utility in the diagnosis of intrathoracic lymphadenopathy.Mycobacterium tuberculosis was cultured in 38.7% of the EBUS-TBNA samples and 90.2% of the patients had positive PPD skin tests in the present study. Our finding however, varies with those studies assessing the role of EBUS-TBNA during the evaluation of granulomatous pathology (such as TB and sarcoidosis) of the chest. Gahlot et al diagnosed 71/100 patients who had EBUS-TBNA as having granulomatous lymphadenitis (namely TB in 41 cases and sarcoidosis in 30 cases), with microbiologically verification of TB in 30% of the patients. In another study conducted by Nair et al, TB constituted the most frequent etiological factor (16/78) in individuals having non-malignant lymphadenopathy; followed by sarcoidosis (11/78). Furthermore, 25% of individuals who were diagnosed with TB had a positive microbiological result. Put together, this indicates that EBUS-TBNA is an important tool in the evaluation of individuals suspected with INTBLA.The diagnostic yield involving both histological and microbiological tests based on EBUS-TBNA samples in the present study was 83.9%. This was lower than the overall diagnostic accuracy which was 97.3% among patients suspected with TBLA in South Africa. In the present study, EBUS-TBNA had a sensitivity of 83.9% for the detection of INTBLA. Lucey et al who explored the utility of EBUS-TBNA among a cohort of individuals with intrathoracic lymphadenopathy of unclear etiology revealed that amongst the subgroup of subjects having TB, EBUS-TBNA had a sensitivity of 59.3% and a specificity of 100%. In a study of 527 individuals with pulmonary conditions and mediastinal lymphadenopathy in Turkey, the sensitivity and specificity of EBUS-TBNA for detecting INTBLA was 87.5% and 98.5%, respectively. Also, several studies have demonstrated the safety and efficacy of EBUS-TBNA for INTBLA and other mediastinal masses diagnosis. The differences in the diagnostic accuracy reported for EBUS-TBNA during the evaluation of individuals with INTBLA may be due to differences in the burden of TB in the setting where the study was carried out. For example, in Saudi Arabia, there is a lower-moderate burden of TB with TB incidence rate of 20.2/100,000 population in Makkah region, while the setting of the present study (Jeddah) had a rate of 25.4/100,000 population.The sensitivity and specificity findings of EBUS-TBNA in the evaluation of suspected patients with INTBLA are variable, but has been found to be very high in some settings.Mycobacterium tuberculosis of 38.7% observed using the EBUS-TBNA samples in this study is consistent with the culture positivity rates from lymph node sampling reported by similar studies and observed using other diagnostic methods. In a study of 315 suspected TB patients who underwent EBUS-TBNA in the United Kingdom, the culture rate was 35%; and a study by Erer et al of 28 individuals who had EBUS-TBNA due to suspected INTBLA in Turkey revealed a culture rate of 46.4%. A study in India revealed a culture rate of 12.5% among individuals with suspected INTBLA who underwent EBUS-TBNA. The low culture rates for Mycobacterium tuberculosis observed may likely be due to variation in the bacillary load of persons with INTBLA; however, the culture rate reported using EBUS-TBNA samples are consistent with the rates gotten with other diagnostic modalities. Further research are needed to evaluate the benefits, if any, of immediate inoculation of the TBNA samples in the TB culture medium. The potential benefits of carrying out rapid molecular techniques, like Xpert MTB/RIF or CB-NAAT system using TBNA samples in order to improve their diagnostic sensitivity deserves further investigation.The culture positivity rate for Mycobacterium tuberculosis of EBUS TBNA samples. This suggests that a larger lymph node size may have high bacillary load and may allow better tissue sampling during EBUS-TBNA. A previous study has reported that the presence of necrotic tissue in an EBUS-TBNA rinse fluid increases the diagnostic yield of the samples. It could be argued that the lymph nodes with necrotic tissue may have higher bacillary load in order to manifest with necrosis and thereby increase the likelihood for the Mycobacterium tuberculosis to be cultured. Furthermore, factors like older age, male grnder, being a Saudi national, having a high ESR, high RDW and high CRP as well as pathological grade and number of needle passes during the EBUS-TBNA significantly predicted PPD positivity in patients undergoing EBUS-TBNA. Some of these factors have been previously documented to be associated with PPD positivity. In this study, no major complications, whether procedure-related or anesthetic care-related, were recorded. This further emphasizes the safety profile of EBUS-TBNA.The factors that predict positive culture for Mycobacterium tuberculosis of EBUS TBNA samples were evaluated, and only having a bigger lymph node size was significantly related to culture positivity for  Nevertheless, our findings of the yield and diagnostic accuracy were comparable to other studies. Third, the study was carried out in one tertiary health facility and may not reflect the performance of EBUS-TBNA in a multicenter study involving multiple pulmonologists and cytopathologists.First, the study utilized a restrospective design, thus we were unable to collect any additional data beyond those documented at the time of the procedure. Second, the sample size was small compared to some previous studies. However, we included all cases of suspected intrathoracic TBLA during the 8-year study period and the sample size could not be increased despite the long study duration. This may be due to the relatively low TB burden in our area. In addition, studies with significantly larger sample sizes compared to this study were multicenter studies involving 4 or more center.In conclusion, EBUS-TBNA demonstrated effective utility and safety in the evaluation and the diagnosis of intrathoracic TB lymphadenopathy among individuals with compatible symptoms. The procedure proves its utility across regions with different levels of TB prevalence including relatively low-burden settings. Combined microbiological and cytopathological assessment of the EBUS-TBNA samples need to be carried out, which, combined with other investigative techniques, increases the accuracy of the EBUS-TBNA for the diagnosis of INTBLA. Future research to further address predictors of culture positivity in the EBUS-TBNA samples is recommended.


Objectives: To evaluate the feasibility of implementation of an extremity exercise program and to examine its preliminary effects in breast cancer survivors suffering from chemotherapy-induced peripheral neuropathy (CIPN). Sample & Setting: Thirteen breast cancer survivors from one hospital in northern Taiwan. Methods and Variables: A single group with repeated measures, and a quasi-experimental design. The intervention program was a four week, home-based extremity exercise program that was comprised of 10 skilled hand exercises and Buerger-Allen exercises. The Total Neuropathy Scale , Functional Assessment of Cancer Therapy/Gynecologic Oncology Group, Neurotoxicity (13-Item Version), Identification Pain Questionnaire, and pain Visual Analogue Scale were used to measure CIPN before exercise (T1), during (T2~T4), and after exercise (T5). Qualitative data were also collected at each time point. Data were analyzed by using descriptive statistics, generalized estimating equations, and directed content analysis. Results: None of the participants reported adverse events during the study period. The extremity exercise program significantly improved patient-reported CIPN after intervention at T4 or T5 but was insignificant on clinician-assessed CIPN. The qualitative data of participant experience indicated that this program is feasible and easy to follow. Conclusion: The extremity exercise program is feasible but needs to increase the sample size and prolong the intervention period for confirmation. Breast cancer is the most common cancer in women worldwide, with an estimated 2.3 million new cases in 2021 ,5. CIPN To manage CIPN, researchers have identified various underlying causal mechanisms of CIPN, such as mitochondrial and vascular dysfunction, oxidative stress, DNA damage, and neuroinflammation , which hAccording to the American Society of Clinical Oncology’s CIPN guidelines, after reviewing a total of four randomized controlled trials (RCTs), the strength of the evidence regarding exercise interventions and the benefits of exercise interventions in treating and managing CIPN is weak . In contOur extremity exercise program comprises the “Ten Skilled Hand Exercise” (TSHE) and the Buerger-Allen Exercise (BAE). The TSHE is part of traditional Chinese medicine and focuses on clapping or hitting acupoints over the upper extremities to dilate peripheral blood vessels and stimulate overall blood circulation . An expeThis was a single group, repeated measures, quasi-experimental study. The outcome measure was conducted five times, at the baseline  and at the end of each week (T2~T5). Purposive sampling was employed. The inclusion criteria included (1) aged 18 years or order; (2) being diagnosed with breast cancer; (3) having completed chemotherapy; and (4) complaining of CIPN symptoms with an assessment result of Total Neuropathy Scale–clinical version (TNSc) score above 0. We excluded those who were (1) diagnosed with brain, spine, or spinal cord metastasis, (2) spinal cord diseases, (3) a second type of cancer, or (4) psychiatric illness. The institutional review board of Taipei Veterans General Hospital (2016-05-009B) approved this study. The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.Patients were referred by the cooperating attending physician in a medical center located in northern Taiwan between September 2016 and March 2018. After a potential eligible patient was referred, a research assistant (RA) called the patient to explain the study and provide sufficient time for the patient to consider participating. Once the patient agreed to participate, the RA scheduled a time with the patient to meet in person to sign the written informed consent before undertaking any study activity. After obtaining the informed consent, the RA assessed the TNSc to confirm the survivor’s eligibility. Those had a TNSc > 0 filled in the questionnaire and watched an extremity exercise program video on YouTube. After watching the video, sufficient time was provided for participants to ask any questions related to the intervention. A weekly log for recording exercise adherence and adverse events was distributed to participants. Lastly, participants’ contact information was obtained and a time for a follow-up meeting was arranged. The research team’s contact information was given to participants in case they had questions. Before each follow-up meeting, the RA called participants to confirm the meeting’s time and place.The qualitative inquiry method seeks to understand the feasibility of the extremity exercise program of patients utilizing face-to-face interviews along with filed notes to collect data. The semi-structured questions in one-on-one interviews lasted 20–30 min. Interviews were conducted with patients at home, in restaurants, or at the hospital. Guidelines for the interview included the following: (1) How do you feel about the program? (2) Did you encounter obstacles when performing the exercises? (3) Do you think the exercise program is acceptable or practical? (4) Did you gain benefits or experience setbacks during the program? (5) Is there anything else you would like to share with us or with other patients regarding the program?This is a four-week extremity exercise program comprising the video-taped procedure of TSHE and BAE in Mandarin. The TSHE is a 10-action hand exercise program lasting 2.5 to 5 min. Actions 1 through 9 involve clapping or hitting the hands 36 times in each acupoint to stimulate the various meridians. The steps are as follows: (1) flat clapping two purlicues, (2) clapping two lateral palms, (3) hitting two wrists, (4) clapping two purlicues (one against the other at a 90-degree angle), (5) hitting opened fingers (one against the other), (6) the left fist hitting right palm, (7) the right fist hitting the left palm, (8) clapping the two backs of the hands, and (9) using thumbs and index fingers to rub the earlobes from top to bottom. The tenth action involves rubbing the two palms six times until they are warm, placing the palms on the eyelids, and moving the eyeballs from left to right for six cycles; this must be done six times.Participants had to perform the TSHE four times per day  and to finish one cycle of the above 10 actions in under five minutes. The BAE includes three steps: (1) lie down on the bed, raise the legs between 45 and 60 degrees for one minute supported by a pillow, and maintain that position for 3 min once balance has been achieved; (2) sit up at the bedside, move the foot from extension to flexion, and then change position from the posterior varus to valgus for 3 min; and (3) lie down and warm the legs using a blanket for 3 min. Participants had to repeat the above three steps for three cycles twice a day immediately after waking up and before retiring.Sim found that a sample size of 12 in a Tai Chi feasibility study for breast cancer survivors was able to detect a minimum important difference within-group over time but would not allow for a robust causal inference with a single group analysis . TherefoOutcomes included safety, feasibility, clinician-assessed CIPN , and patient-reported CIPN .Safety was examined via the occurrence of patient-reported adverse effects. The feasibility was examined via participants’ retention rate, adherence rate to the exercise program, and experience. The retention rate was defined as the percentage of participants who completed the four-week extremity program. The adherence rate was defined as the percentage of upper and lower extremity exercise sections completed by participants each week. These data were collected using the weekly log and the semi-structured interviews. Specifically, the weekly log was given to the participants to record any adverse events, sections of the TSHE and BAE that were completed daily, and participants’ feelings during the program.The TNSc was utilized to assess the objective severity of CIPN. The TNSc consists of seven items including sensory symptoms, motor symptoms, autonomic symptoms, pin sensitivity, vibration sensitivity, strength, and deep tendon reflex (DTR). Each item scores from 0 to 4. The total score ranges from 0–28. The higher score indicates worse CIPN . The scaThe NTX-13 is a 13-item measure used to assess subjective neurotoxicity which included sensory CIPN, motor CIPN, as well as auditory and cold sensitivity. Each item scores from 0 to 4. The total score ranges between 0 and 52; 0~4 for each item. A higher the NTX-13 score indicates less CIPN symptoms. The internal consistency, content validity, and concurrent validity have been tested with sensitivity to change over time in breast cancer survivors ,23.The ID-pan has six items. It was used to measure subjective neuropathic pain. The total score of ID pain is between −1 and 5. A score of 2 or higher indicates neuropathic pain. “Yes” is scored as 1 and −1 for item 1~5 and item 6, respectively. “No” is scored as 0 for all items. The ID pain has been tested for its intra-class correlation (0.72–0.74) and k statistic (0.74–0.69) ,25.The pain VAS is a one-item measure which scores from 0 to 100. A higher pain VAS score indicates more severe pain. It is known to be valid and to be sensitive to measures of pain intensity and was used to measure subjective peripheral pain in this study . The relSPSS 22 software was used to analyze the quantitative data. Mean, standard deviation, frequency, and percentage were used to describe the distribution of sample characteristics, clinician-assessed CIPN, patient-reported CIPN, retention rate, and adherence rate. The generalized estimating equation was used to test the preliminary effectiveness of the exercise program on CIPN over time. Qualitative data were saved as a Word document and analyzed by the primary investigator utilizing directed content analysis. Analysis of participant experience was guided by a framework focus on acceptability, demand, implementation, and practicality, the necessary focus of any feasibility study . The resA total of 138 breast cancer survivors were referred, and 89 verbally agreed to participate and were screened for eligibility. The enrollment rate was 64.5%. After screening with the TNSc, 13 survivors (14.8%) were deemed eligible, finished the baseline measure and began the intervention. Two participants, one with severe pain in the lower extremities and a second with a busy schedule or exhaustion were discontinued at T2 and T3, respectively. Finally, 10 participants completed the program and all follow-up measures .The enrollment rate, retention rate and prevalence rate of CIPN were 64.5%, 76.9%, and 14.8% in this study, respectively. The small sample size in this study may be due to the two inclusion criteria: (1) after completion of chemotherapy and (2) TNSc > 0. Eighty-nine participants subjectively reported CIPN symptoms but only 14.8% of survivors met inclusion criteria of TNSc > 0. The majority (84.3%) were not eligible. The discrepancy between subjective and objective CIPN measures were also found in the literature . MoreoveNone of our participants reported adverse events. The mean adherence rates of this program were 61.5% for the TSHE and 66.3% for the BAE. Patient-reported CIPN significantly improved after the intervention. However, clinician-assessed CIPN was insignificant after the intervention. Participants reported that the program was effective and feasible. Moreover, they were willing to continue the program following study completion because it is easy to follow and convenient to do.The enrollment rate of our study was 64.5%, which was higher than the results of an integrative review of the effects of exercise on CIPN, which indicated an overall enrollment rate of 53.16% . Still, The average adherence rate to our program was 61.5% for the TSHE and 66.3% for the BAE, which is similar to the home-based part (66.7%) of a comprehensive exercise rehabilitation program  . AlthougOur outcome measure was insignificant for clinician-assessed CIPN but significant for patient-reported CIPN after the intervention. Our significant result of subjective CIPN (NTX-13) after the intervention was consistent with the yoga arm of an RCT study at week 4 that proposed that yoga may increase blood flow and oxygen supply to protect peripheral nerves, which is similar to our extremity exercise program aimed at increasing blood flow . HoweverResults of our study indicated that CIPN symptoms measured by TNSc and NTX−13 worsened at one week after the intervention. Berthelot et al. identified the negative Hawthorne effect, which is defined as research participants reporting increased symptoms or overexpressing symptom severity during or after an intervention . Our parParticipants reported that they found the extremity exercise program to be feasible, effective, and easy to follow. However, survivors still reported two weaknesses of the program: A lack of time to perform the extremity exercises and the inconvenience and complexity of the BAE. Based on the recommendation of Bowen et al. to design a pilot intervention, our extremity exercise program was acceptable, requested by survivors, and practical, although there was some debate on its implementation in terms of the inconvenience of utilizing information technology and the complexity of the program’s prescription .To our knowledge, this is the first study to introduce an extremity exercise program to manage CIPN symptoms in breast cancer survivors suffering from CIPN after cancer treatment completion. Moreover, the study adds information regarding the management of PN symptoms through exercise intervention with subjective CIPN improvement after intervention. Although the clinician-assessed CIPN was insignificant, results of our participants’ experience confirmed the feasibility and effectiveness of our program. Our extremity exercise program also met the Oncology Nursing Society’s research priorities for 2019 to 2022, which emphasize developing interventions to manage symptoms and improve survivors’ outcomes .The weaknesses of this feasibility study were the following. Firstly, the prevalence rate of CIPN was relatively low because we recruited survivors who had completed cancer treatment and who were suffering from CIPN. Secondly, our adherence rate of exercise prescription was also lower and the duration of the intervention was shorter than that of other exercise studies as well as of individual, home-based ones. This low adherence rate may have affected the negligible results of the clinician-assessed CIPN. Lastly, as only 10 participants completed this study, our results will require validation through further interventional studies using a larger sample size.Our study was limited by a small sample size, the brevity of the intervention, and the lack of a control group. Moreover, the adherence rate of 61.5% for the TSHE and 66.3% for the BAE must be taken into account as a possible cause of the negligible clinician-assessed CIPN after the intervention. Additionally, twelve of the study participants were regular exercisers, and this may be a confounding factor of the study results. Therefore, the feasibility reported by participants has to be modest, due to the small sample size and a shortened exercise period. The efficacy of this study might be lost in the long run or many patients might quit earlier and thus mean it is less feasible. Moreover, the CPIN might correlate inversely with exercise, and patients are more motivated to maintain the habit.The extremity exercise program may improve patient-reported CIPN in breast cancer survivors suffering from CIPN after cancer treatment completion. Furthermore, according to participants’ experience, the program is feasible, effective, and practical. However, as only 10 participants completed our study, it is necessary to increase the sample size and prolong the intervention period to confirm the results of this study. We recommend that future studies increase their sample size, add a control group, extend their intervention time, and formulate strategies to strengthen participant adherence to the exercise prescription.


To increase access to evidence-based supportive cancer care, building on our prior work we have developed a toolkit which provides guidance for the implementation of a culturally appropriate and resource adaptable, peer-to-peer support program.The global burden of cancer falls heavily on low-and middle-income countries (LMICs), where there are critical gaps in the provision of supportive care. Initiatives to translate effective, resource-appropriate preventions and clinical treatments in LMICs have been gathering pace, yet few examples exist to guide the translation of interventions that address the high unmet psychosocial needs among cancer patients. To address this gap, we have recently published a theory-based cultural adaptation of this peer mentoring program to the context of Viet Nam  is an open-source, self-guided peer support program that allows for the provision of cultural and resource adaptation. STT includes six modules which use resources such as videos, slides, and worksheets, to define the intervention, engage and communicate with stakeholders, assess for readiness and plan for implementation, train program coordinators and peer mentors, evaluate training and implementation, create policies and procedures for different contexts, and identify opportunities for sustainable funding.STT can be used to increase access to supportive cancer care in a way that ensures that the program and activities are acceptable and appropriate to the culture, health system, and resources of the local community and setting. In addition, the STT can be adapted to introduce peer to peer support across additional disease platforms.


Linear models accounting for earthquake strength and proximity revealed significant relationships between change in calling activity surrounding earthquakes and prior calling activity ; however, these same relationships were true for ‘null’ periods without earthquakes , indicating that the pattern is driven by blue whale calling context regardless of earthquake presence. Our findings that blue whales do not respond to episodic natural noise provide context for interpreting documented acoustic responses to anthropogenic noise sources, including shipping traffic and petroleum development, indicating that they potentially evolved tolerance for natural noise sources but not novel noise from anthropogenic origins.Quantifying how animals respond to disturbance events bears relevance for understanding consequences to population health. We investigate whether blue whales respond acoustically to naturally occurring episodic noise by examining calling before and after earthquakes . Two vocalization types were evaluated: New Zealand blue whale song and downswept vocalizations . Blue whales did not alter the number of D calls, D call received level or song intensity following earthquakes (paired  Examiniorldwide –13. Impoorldwide –16, seisorldwide , underwaorldwide , increasorldwide , changesorldwide .Aotearoa New Zealand and the surrounding waters lie at the intersection of the Australian and Pacific tectonic plates, creating a seismically active region with frequent earthquakes ,20 that Blue whales produce two main vocalization types: song is produced by males and probably serves a reproductive function, whereas downswept vocalizations known as D calls are social calls produced by both sexes and are associated with foraging behaviour ,26 figu. Both ar. 2. 2.1Acoustic recordings were collected in the STB as part of a broader effort to understand spatio-temporal occurrence patterns of blue whale vocalizations in the region  figure . Five ma. 2.2https://www.GeoNet.org.nz/), which collates data on known earthquakes identified from a network of seismic sensors around Aotearoa New Zealand. Earthquakes were identified for magnitudes greater than 3.0 that occurred within the study area (between 38–43° S and 172–176° E) during the study period. The magnitude, depth, origin time and epicentre location were extracted for each earthquake. Earthquakes were subset to include only instances where one earthquake was identified in an 8 h period to isolate singular events rather than earthquake swarms or drums. Finally, a subset of 32 individual earthquakes was selected using a stratified-random approach that ensured at least one earthquake was selected for each week to achieve temporal coverage over the recording period.Earthquakes were identified from the GeoNet database , and comparisons were visualized using violin plots. Linear models were used to examine whether change in calling  was related to any earthquake metrics . Linear models also included day of year to account for seasonal patterns in blue whale calling, number of calls prior to the event to account for ecological context in blue whale calls and hydrophone unit as a factor , and duration of acoustic earthquake events was typically 1 min or less. D calls were detected in all temporal windows surrounding earthquakes, yielding 27 040 calls included in the analysis at the 4 h window. Statistical results and observed patterns were consistent across the four temporal windows ; therefore, results from the 2 h window before and after each earthquake are presented here.a). Furthermore, paired t-tests revealed no significant difference in mean calling before versus after earthquakes for any call metric . While the time-series visualization of the calling metrics at the 15 min resolution revealed fluctuations around earthquake events, the standard error ranges overlapped. Furthermore, fluctuations immediately surrounding earthquakes are not notably different from general fluctuations between 15 min intervals regardless of earthquake presence (b).There was no visually apparent difference in blue whale calling before and after earthquakes a. Furthepresence b.FigureLinear models revealed no significant relationships between change in calling and any of the predictor variables for D call RL . Howeverc).Further examination revealed that call metrics yielding significant linear model results  have a negative relationship with the amount of calling in the period prior to an earthquake or null event. Namely, if there was less calling in the period prior, an increase in calling was likely, whereas if there was more calling in the period prior, a decrease in calling was likely. Importantly, this pattern was true for both the earthquake and null periods c.. 4We demonstrate that blue whales show no acoustic response to earthquakes, a naturally reoccurring acute noise source, and this finding provides valuable context for how baleen whales respond to anthropogenic noise. The absence of any change in calling activity surrounding earthquakes could indicate acclimation, as blue whales in New Zealand may be accustomed to noise from earthquakes due to their frequent occurrence in the region and over evolutionary time ,21. AlthWhile we found that earthquakes had no impact on blue whale vocalizations, prior calling context did influence subsequent calling activity. Periods with elevated calling activity  were significantly related to decreased calling in the subsequent period. This finding may be an artefact of the constraint that calling cannot decrease if there was little calling to begin with. Additionally, in periods with high calling activity, a further increase in calling is unlikely as there may be some degree of call ‘saturation’ already. In other words, in periods with high calling activity, it is more likely for the subsequent period to have less calls irrespective of whether an earthquake occurred. Examination of other temporal properties of the calls  may yield additional insight into these findings on the importance of calling context.We did not have the ability to localize individual calling whales due to the configuration of the hydrophones in our study, which presents an interesting area for future research into questions we were unable to answer with our data. One way that baleen whales can respond to increasing noise levels is to increase the loudness of their calls, known as the Lombard effect. While this pattern has been described for humpback ,41, minkOur finding that blue whales do not acoustically respond to natural episodic noise is particularly important when considering that they do respond to a range of anthropogenic noise sources –17. The


Strong-motion records of earthquakes are used not only to evaluate the source rupture process, seismic wave propagation and strong ground motion characteristics, but also to provide valuable data for earthquake disaster mitigation. The Kathmandu Valley, Nepal, which is characterised by having soft sediments that have been deposited in an earthquake-prone zone, has experienced numerous earthquakes. We have operated four strong-motion stations in the Kathmandu Valley since 2011. These stations recorded the 2015 magnitude 7.8 Gorkha Nepal earthquake that occurred in the Himalayan continental collision zone. For several months after the mainshock, we deployed four additional temporary stations. Here, we describe the seismic data for 18 earthquakes over magnitude 5.0 collected by this array, including the 2015 magnitude 7.3 Dolakha earthquake of maximum aftershock and three large aftershocks of magnitude 6-class. These data are essential for validating the sedimentary structure of the basin and for evaluating the hazard and risk of future earthquakes in the Kathmandu Valley.  The 1934 Nepal-Bihar earthquake, which had a magnitude (M) of approximately 8.1, occurred in the Eastern Himalaya region and damaged 19% of buildings in the Kathmandu Valley, more than 100 km away from the epicentre5. It is considered that great earthquakes could potentially occur in the Central Seismic Gap of the Main Frontal Thrust in the near future7.The Nepal Himalaya, which formed as a result of the Indian Plate colliding with the Eurasian Plate, underthrusts at a low angle from the Main Frontal Thrust. The Himalayan continental collision zone is one of the most earthquake-prone regions and has experienced several devastating earthquakes in the last millennium 8, which are more than 650 m thick in the central part of the valley10. Consequently, the valley is highly susceptible to the risks associated with site amplification11. In addition, the explosive population growth that has occurred in recent years has markedly increased the risk of earthquake damage in the valley12.The capital city of Nepal, Kathmandu, is located in the Kathmandu Valley. The oval intermontane valley is approximately 30 km long in the east-west direction and approximately 25 km wide in the north-south direction. The valley floor is overlain by soft, thick fluvial, fluvio-lacustrine, and fluvio-deltaic sediments of Plio-Pleistocene originMw) 7.8 Gorkha earthquake struck Nepal 19, and the station operated by the Department of Mines and Geology, Ministry of Industry20. These data are valuable for evaluating strong ground motion characteristics and clarifying the relationship between strong ground motions and damage. For example, the relationship between the building damage ratios based on the visual damage assessments and fragility curves was discussed21.Our array in the valley successfully captured strong ground motion records22. Ten days after the mainshock, four additional stations were installed temporarily along a north-south profile of the valley to investigate the distribution of site amplification in the valley using strong-motion records from the aftershocks. Our array captured the aftershocks23, including the largest aftershock (Mw 7.3) on 12 May 2015 occurred in the Dolakha region24 , TVU , PTN , and THM . Ten days after the 25 April 2015 Gorkha earthquake, three stations were added along an approximately 8-km north-south axis in the valley: stations RNB , PPR , KPN , and one station was added at Bhaktapur (BKT), a city that suffered heavy damage during the earthquake. A total of eight stations distributed within a radius of approximately 7 km were operated from 5 May 2015 to August 2015. Figure −2. The data loggers at the permanent stations were powered by a DC supply and fitted with a 12 V rechargeable car battery along with a voltage stabiliser. The data loggers at the temporary stations were powered by a 12 V car battery. Due to safety considerations and the high population density in the study area, these instruments were installed on the foundation-level floor of reinforced concrete buildings that were one to four stories high, and outside buildings for a few temporary stations. The GPS antennas were either positioned outside of the buildings or at windows so that they could receive satellite signals. The permanent accelerometers were affixed to the floor with bolts, while temporary accelerometers were affixed using two-part epoxy adhesives. Accelerometers were levelled and oriented along the building or to the magnetic north. Recorded data were stored on 16 GB SD cards and data were collected on-site. Maintenance of the permanent stations was performed at six-month intervals. Permanent stations were maintained two weeks before the 2015 Gorkha earthquake.The observation equipment was selected to obtain stable records, even under conditions of unstable power supply in Kathmandu. The installed instruments consisted of a highly damped moving coil-type three-component accelerometer  which does not require a power supply, and a 24 Analog-to-Digital bit low-power data logger  with an external GPS antenna for time calibration. The sampling rate was 100 Hz and data were recorded continuously at all stations. The accelerometer had a flat response (−3 dB) for ground acceleration from 0.1 Hz to an aliasing frequency with a sensitivity of 0.22 V/m sM < 7.3) with the strong-motion data of signal-to-noise ratios > 2 located within the epicentral area. Source parameters were from the USGS National Earthquake Information Center (NEIC: https://www.usgs.gov/programs/earthquake-hazards/earthquakes). As examples, Fig. Mw 6.7 earthquake , east-west (EW), up-down (UD) data in ASCII text format. A recording length is set to 180 s before and after the P- and S-waves. Table The data files as shown in Table h is a damping constant of 26, and the natural frequency f0 is 3 Hz. The frequency response function Λ(ω) has an amplitude of 1 and can be estimated as follows:ω is the angular frequency and ω0 is the resonance angular frequency of the pendulum. Therefore, the accelerometer had a flat response for ground acceleration over 0.1 Hz.Since the JEP-6A3 accelerometer is an over-damped moving coil mechanical seismograph, it is possible to derive accurate long-period ground motions at <0.1 Hz by correcting for the sensor response. The pendulum motion is proportional to the ground velocity, 21. In addition, continuous recordings without any missing data were obtained throughout the event. However, since Kathmandu is a populous city with numerous buildings and heavy traffic, these sources of artificial ambient noise may have contaminated the observed seismic records.After the 25 April 2015 Gorkha earthquake, we checked the permanent strong-motion stations. The instruments were undamaged and the buildings in which the equipment were installed were visually assessed as being either undamaged or only slightly damaged−6 m/s2 with no weighting of the vibration sensation. The vibration levels exhibited daily cycles in the high-frequency range; specifically, the difference in the noise level between day and night differed by approximately 20 dB. The microtremors attributed to human activity affect this frequency range, and the vibration levels measured at the sedimentary stations in the central urban areas were larger than those at KTP station on the hilly rock. Conversely, although the amplitudes of the microseisms were small, predominant low-frequency peaks were observed at sedimentary sites.In populated metropolitan areas, noise levels attributed to microtremors generated by human activities such as traffic can be very high. Therefore, we estimated the vibration level from the power spectral density (PSD) of acceleration at each site. As an example, the horizontal vibration levels for one week, from 15 to 21 May 2015, are shown in Fig. 31, which uses the average value of the high background noise power obtained from broadband seismometers, the PSDs recorded by our array were slightly higher than those estimated by this model. Although the noise levels were relatively high, the PSDs for the recorded earthquake data far exceed those estimated using the model. However, the observed data may contain records from multiple earthquakes because recordings were performed immediately after large earthquakes.Figure Mw 7.3 Dolakha earthquake are shown in Fig. et al.18 who compared the displacement waveforms of the 2015 Gorkha earthquake to the high-rate GNSS waveforms and obtained similar waveforms with static deformation.The 0.05–0.2 Hz bandpass-filtered velocity waveforms for the UD component from the


Background: Families of refugee background have complex, multigenerational mental health and developmental needs that are not accounted for in current programming frameworks in Canada. Providing appropriate support services and educational resources that address the unique concerns of families of refugee background will allow for improved family cohesion and developmental outcomes for children. Parenting programs have been shown to be successful in improving parental stress, parental efficacy, and children’s mental health and well-being. This study gathers data about the experiences of caregivers of refugee background in order to develop a novel, multi-dimensional parenting program model using Community-Based Participatory Research (CBPR) principles. Methodology: This was a qualitative, CBPR study using a formative research framework. In-depth interviews (IDIs) were conducted with caregivers of refugee background and service providers that work closely with this population. Data were recorded, transcribed, and coded using deductive and inductive coding methods by two independent coders. Results: A total of 20 IDIs were conducted (7 caregivers and 13 service providers). The main topics that were identified to be incorporated into the program include: features of child development, how to address resettlement issues, child advocacy, and parenting after resettlement. Participants felt that tackling language barriers, addressing the overlapping responsibilities of caregivers attending the sessions, providing incentives, increasing awareness of the program, and using an anti-racist and anti-oppressive approach was key to the program’s success. Participants emphasized the need for trauma-informed mental health supports within the program model. Conclusion: This study describes the key considerations for a novel parenting program for families of refugee background, by engaging them as key stakeholders in the program design process. Future iterations of this project would involve a pilot and evaluation of the program. As of date, the world is witnessing the highest levels of human displacement. In 2022, 100 million people globally were forced to flee their homes due to conflict or persecution. Among these, nearly 27 million are refugees, 41% of whom are children under the age of 18 ,4. Thus,However, caregivers of refugee backgrounds face unique barriers in supporting their children’s development. Families potentially may encounter a range of mental health concerns associated with traumatic pre-migration events. As a result, caregivers may feel overwhelmed, disorientated, depressed, non-responsive, and have overwhelming grief that may make coping with daily tasks especially difficult . ParentsMoreover, caregivers may face language difficulties upon resettlement. Lack of proficiency in the primary language of the country of resettlement affects all stages of healthcare access, from booking an appointment to filling a prescription, thus emphasizing the importance of supporting the language education of families of refugee background . Yet, inThe re-establishment of identity may also present a challenge to caregivers in supporting their children’s development because refugees in Canada may face many barriers in finding skilled employment, forcing many individuals to take several steps back in their careers, impacting not only their financial stability but also their self-concept and identity .The unique challenge of unstable housing and frequent relocations of refugees due to national policies and regulations, have been associated with the disruption of the continuity of care for children. Finally, caregivers may have different cultural understandings of what comprises healthy child development. Since parenting practices are entrenched in cultural values, programs must include culturally sensitive adaptations in order to increase responsiveness .Children with multiple and complex medical problems are especially vulnerable and can face their own unique set of challenges including transitioning back to school after a period of inconsistent education, learning a new language, coping with recent trauma, and adapting to the host community.Parents who have generally demonstrated resilience in these emerging adversities may protect their child’s overall development ,14. One However, the literature surrounding supporting families of refugee background in their parenting practices as well as navigating health and education systems in their new country, remains relatively unexplored. El-Khani and colleagues reports the parenting support needs of Syrian caregivers who have resettled in shelters in Syria and Turkey . Their fThis study aims to identify the salient features that should be incorporated into the design of a novel parenting program that is tailored to address the unique needs of families of refugee background in the Greater Toronto Area (GTA), particularly when caring for a child with developmental or behavioural concerns.This qualitative study used a descriptive phenomenological approach. A semi-structured interview guide was developed for in-depth, individual interviews. Interviews were conducted by one of three members of the research team who have been trained in qualitative methodologies. Interviews were held at a pediatrics clinic, community centres, or over the phone. An interpreter was made available for all participants, however, only one participant requested an interpreter, and the remaining interviews were conducted in English.Two groups of participants were enlisted for this research study. The first group of participants were key stakeholder groups that were identified using purposive sampling via community mapping exercises to ensure major categories of participants are represented in the study. The second group of participants represented a convenience sample from the pediatrics department of an urban academic health sciences centre and its partnering agencies and included families of refugee backgrounds and service providers that work closely with the population. Informed consent was received from all participants. Caregivers were offered grocery gift cards to honour their time in participating in their study.Data was collected by the research team through telephone and in-person interviews between August 2019 to July 2020. The interviews lasted between 45 to 60 min and were audio-recorded and transcribed verbatim by a transcription application and then checked by members of the research team. The semi-structured interview guide was designed and utilized during the interviews to gather experiences about parenting practices from families of refugee background and key stakeholders that work closely with this population. Interviews were conducted until saturation was achieved.Data analysis took place alongside data collection to monitor the saturation of data. Transcriptions were hand-coded first inductively, for any patterns in participants’ experiences, and then deductively to identify categories of themes by three researchers . The interview transcript was imported into Dedoose for initial coding and organization of the data . The traUsing these themes, a description of the experiences of families of refugee background and key stakeholders who work with this population was written. The analysis focused on identifying major themes and subthemes and grounded in the interviewee’s statements. Interpretation of the data focused on both the thematic and content analysis. Thematic analysis involved an interpretation of the underlying meaning of text, and content analysis involved gathering answers to questions that were directly queried in the interviews rather than inferred in the analysis. To add to the rigour of the analysis, the authors maintained discussion notes logging the process.Due to the nature of qualitative studies, the background, experiences, assumptions, beliefs, and biases of the research team could influence the research process. To minimize this, the research team debriefed after every interview and adjusted their approach as needed. This included reframing questions or changing the location of where the interview was held to ensure inclusivity, accessibility, and comfort for participants. The interviewers all identified as people of colour who had close family members who experienced resettlement .Research ethics approval was obtained from the Unity Health Toronto Research Ethics Board. The participants were offered full information of the study’s purpose, conduct, privacy, and confidentiality. The participants had the right to withdraw from the project at any time.A total of 20 individual in-depth interviewers (IDIs) were conducted. 13 of which were service providers who work closely with this population and 7 were caregivers of refugee background. 6 caregivers and 12 service providers self-identified as female A,B. ResuSUBTHEME 1: Child Development KnowledgeThe caregivers expressed that they would value knowledge about the different developmental stages of children, what physical, mental, and emotional characteristics are considered normal or abnormal in each stage, how to care for a child with special needs, and what specific topics should be addressed at a given life stage.“I would like to understand different stages of her life, different ages.”“As a parent with a child with cerebral palsy, from the beginning, we don’t know anything or we have to face everything without knowing it, but I think if we know information about my son’s case or what we have to face from the beginning, it will be more different.”This includes when and how to speak to their child about sexual health and reproduction.“My daughter asks me questions sometimes that I don’t know the answers to… or don’t know how to answer, she asked me where does a baby come from and I would like help to learn how to explain stuff that is hard for me to her.”Stakeholders expressed that an understanding of child development is essential, especially in the event that there is a neurodevelopmental diagnosis. Understanding typical and atypical child development and diagnoses would facilitate timely access of services.“I think probably for me, the biggest challenge is families not understanding the diagnosis. They are perhaps worried about being ostracized by their community...not sure how to get the services that their child needs because they really don’t understand what the disorder is.”SUBTHEME 2: Navigating the Healthcare SystemIn order to fully support the needs of their children, the caregivers believe it is necessary that they learn how to navigate the Canadian infrastructure. This includes how to secure employment, and navigating the healthcare system, especially for caregivers who need to care for their children with special needs.“Also, for children with? special needs. They want to know the information about how to get through the system to have their children covered.”SUBTHEME 3: Self-AdvocacyThe caregivers expressed a deep desire to learn how to advocate for their own and their children’s rights given the inherent unfamiliarity that comes with adjusting to a foreign environment. Specifically, they would like to know what they are eligible or ineligible for, and how to obtain such services and resources.“There is a certain language, kind of language when you stand for your kids (...) I need to know how to get my rights and my kids rights. I don’t know how.”Stakeholders stated that families should be provided with the tools to advocate within schools and the health care system.“Learning how to advocate within the school system or within the healthcare system...as simple as learning how to go into your doctor’s appointment with your list of questions ready and feeling the confidence to get those questions asked and answered.”SUBTHEME 4: Caregiving Practices in the Country of ResettlementThe caregivers indicated various topics on raising a child they hope will be taught in the parenting program. The caregivers suggested that the parenting program cover how to integrate their child into a healthy lifestyle including good eating habits and engagement in physical activity.“They change their way of eating by style of food. Now they usually eat carbs and pizza to follow their kids, for me it’s a challenge, because it will affect their health.”As well, the caregivers would like to learn how to address their children when they are upset.“I would like to learn how I can deal with my daughter when she gets angry.”Finally, the caregivers would like to know how to raise good-mannered children.“This is the main topic for me… respectful with personality kids, it’s so important for me.”Stakeholders indicated that it would be important to discuss the role of child protective services because there can be misconceptions within families of refugee background as to the agencies’ role and caregivers’ rights.“I think when programs really explain some of the rules...what’s considered acceptable parenting and what’s not, there’s a lot of conflicts like caregivers are having with the schools and with Children’s Aid that just comes out of like cultural misunderstandings. So I think it’d be very helpful for caregivers to have this explained in their first language.”SUBTHEME 5: Balancing Self-Identity and AcculturationCaregivers asserted that, while it is important for the children to integrate with the culture of their resettled environment, it is important for the children to keep their cultural roots. Thus, caregivers expressed a desire to learn how to teach their children about cultural adaptation, while also learning how to pass on their own culture and language.“So it’s important to learn English but it’s important to also to learn our language and our culture. So I think it’s important to the caregivers who… to know how to, to do this.”SUBTHEME 6: Caregivers’ Mental Health NeedsStakeholders emphasized the need for trauma-informed mental health care because addressing these concerns will allow caregivers to engage in parenting programs.“If you’re a refugee, and by definition, you may have experienced some significant trauma and so working from like the mental health perspective, a lot of times when you achieve stability and safety, which is what it would be in Canada because the threat is no longer there, then you can have like a flooding of emotional experiences.”SUBTHEME 1: LanguageUnderstanding that families come from various countries where the primary language is not English, caregivers indicated that language is the first barrier to address to ensure the program’s success. Specifically, the caregivers expressed the desire to learn English for benefits beyond understanding the program modules, including the ability to seek their basic needs.“But until they practice English, until they mastered English, the language would be a very huge barrier between them and even seek for the facilities and seek for the things they need. So the biggest challenge for me is language”Stakeholders echoed the concerns of language and the availability of interpretation services. This becomes difficult when trying to navigate Canadian systems.“Many of these families do not have English as a first language. The vast majority and depending on where you are, it can be difficult to access services particularly medical translation services, which are very different from just cultural and language translation services.”SUBTHEME 2: Inability to AdvocateThe caregivers believe that the inability to advocate for their rights may hinder them from accessing the parenting program.“Here are a lot of beautiful things they [newcomers] can make use of it, but they are afraid to ask.Some caregivers believe that their willingness to ask for help and necessary services may be bolstered by a supportive environment fostered by stakeholders they directly engage with.“So also the welcoming environment for the newcomer is very important. Yeah, it will encourage him to ask about things he need to know.”SUBTHEME 3: Overlapping ResponsibilitiesThe caregivers that were less likely to attend the parenting program attested to the fact that they may be occupied with time-competing responsibilities, including English classes, working, and taking care of their children.“You know, I would like to but right now I don’t have time because I go to school, and I have my kids.”Stakeholders expressed that overlapping responsibilities may deter families from attending parenting programs. They mentioned that providing childcare may encourage families to attend.“A lot of the families that I work with, I have dads that are working two jobs and mom has got all the kids. And so the time that might be convenient for me to run the program might not be convenient for her to attend. So ensuring there is adequate child care is important.”SUBTHEME 4: Awareness of ProgramMany caregivers believe that a families are not aware of the various facilities that exist in Canada  and this pattern of unawareness may also apply to the parenting program. Therefore, caregivers can be better informed about the program through dissemination within culture-specific community offices, flyers, letters, and phone calls.“So most of the newcomer would even know that there is something like YMCA, like libraries, like anything. I read about it, because I know a little bit of English. And I read about it, I knew about it but for a newcomer you will not be able to discover all these facilities and all these opportunities for him and for his children.”The attendance to the parenting program may be further increased if when disseminating information about the program, there was an emphasis on the program’s benefits to the children.“To motivate people to go to the program… I think if they know for sure that they will benefit from this program and their children will benefit from this program.”SUBTHEME 5: Anti-Racist, Anti-Oppressive (ARAO) FrameworksStakeholders emphasized the need for cultural competency and anti-racist, anti-oppressive approaches within programming. Parenting frameworks in North America differ from other parts of the world and it needs to be taken into consideration.“There’s some cultural competence that needs to happen...what is considered culturally appropriate? We have different expectations about play, tummy time or swaddling. So I think there needs to be definitely cultural competence when thinking about parenting because we have lots of things that we do that don’t happen in other parts of the world.”SUBTHEME 6: Encouraging Families to Attend with IncentivesStakeholders expressed that a facilitator to program attendance may be providing families with incentives to minimize barriers such as transportation costs and provide them with food or gift cards.“It’s always great to have some food and maybe offer subway or bus tokens... maybe even at first, some kind of material incentive. A gift card for their children or something else that they may need.”SUBTHEME 1: LocationIn terms of where the program should be offered, the caregivers expressed a preference for a variety of locations they are already familiar with for easier access, and thus greater likelihood of attendance. This includes their local community centre, the clinic, and schools. If it’s a successful program. one participant voiced for the expansion of the program more than one location.“In my opinion, if it’s that good of a program, then it should be conducted everywhere.”SUBTHEME 2: TimingThe caregivers provided mixed responses to their preferred frequency of the program. The suggestions ranged from twice a week to once a month to ensure that the sessions are not interfering with the caregivers’ other responsibilities, and also occurring in relatively close frequency for caregivers to retain what they were taught in the previous session. In general, the sessions should be scheduled based on the group’s needs and should be a short duration program.“Once a week or twice a week because they will not feel like they have to change their schedule according to this one hour in a week.”In terms of the length of the individual sessions, most caregivers suggested one hour.“45 min to one hour.”Finally, in terms of the time of day, the caregivers preferred if the sessions occurred during the day, as their children would be in school, so their responsibilities as a parent would not compete with the attendance of the program. This timing may not be ideal for caregivers who have to work during the day.“For me, I think when the kids at school and it’s the perfect time for me, but for other people, maybe the timing of work or other things.”SUBTHEME 3: ParticipantsThe caregivers indicated a desire for the sessions to be held in a mixed-group setting as it allows for interactions between participants, relatability and support from other caregivers on how to raise their children given their unique lived experiences as refugees, efficiency, and in general will make the program more enjoyable.“If you do it individually, it will take hours if you do it in a group you can do it in less time, you will be able to make people laugh and you will get answers from different caregivers from different places.”It will mainly be mothers that are attending the program given their husbands are the breadwinners. Ideally, the husband can attend too.“Yes, I would like to speak to other caregivers. My husband doesn’t have time go for work though.”This study describes the key features of a parenting program tailored to the unique needs of refugee families by engaging caregivers of refugee background and services providers that work with this population as key stakeholders in the program design process.Refugee caregivers may have difficulty supporting their children’s development due to multiple factors including experiences of distressing pre-migration events, racism and xenophobia upon arrival to their country or resettlement, language difficulties, economic instability, unstable housing and frequent relocations, lack of centralized medical and developmental services, challenges in self-advocacy, and compromised parental mental health and well-being. Having the structure, resources, and health systems to support them and their children is of critical importance as they will ultimately contribute to the national fabric via various systems .The main priorities that were identified for incorporation into the program include: features of child development, how to address resettlement issues, child advocacy, and parenting after resettlement. Participants felt that tackling language barriers, addressing the overlapping responsibilities of the caregivers attending the sessions, providing incentives, increasing awareness of the program, and using an anti-racist and anti-oppressive approach is key to the program’s success. Participants emphasized the need for trauma-informed mental health support within the program model. In order to ensure success in parenting it is essential to address the basic concerns of families. Addressing resettlement concerns such as housing, employment, legal aid, allows families to engage with programming designed to foster their child’s development. Based on the recommendations provided a program curriculum was developed , and their pre- and post-migration experiences may vary. Furthermore, since this study was conducted in an urban setting, the experiences of refugees in rural or other remote regions may not be consistent with the findings presented. Moreover, families were connected to an academic practice and results may differ for families that may be having challenges acquiring consistent care. Additionally, given that there were only 7 caregivers who participated, the results may not be generalizable based on these small numbers. However, these methods can be adapted and replicated with a larger sample size to further delineate the needs of this population group. Lastly, refugee groups are not homogenous. Even within similar refugee classes, their experiences may vary drastically due to different cultural, ethnic, and linguistic backgrounds and their associated socio-political contexts from their country of origin.Future iterations of this project would involve piloting a program model based on the results of this study and undergo an iterative review process with stakeholders. Methods to leverage expertise within refugee communities will be explored. Due to the COVID-19 pandemic, virtual delivery methods of this program are being explored in order to disseminate the information in a manner that is consistent with COVID-19 guidelines around social distancing and gatherings. Once a consensus on the acceptability of the program model has been achieved, a pilot and evaluation of the program can occur.


Lactate is a universal metabolite produced and released by all cells in the body. Traditionally it was viewed as energy currency that is generated from pyruvate at the end of the glycolytic pathway and sent into the extracellular space for other cells to take up and consume. In the brain, such a mechanism was postulated to operate between astrocytes and neurons many years ago. Later, the discovery of lactate receptors opened yet another chapter in the quest to understand lactate actions. Other ideas, such as modulation of NMDA receptors were also proposed. Up to this day, we still do not have a consensus view on the relevance of any of these mechanisms to brain functions or their contribution to human or animal physiology. While the field develops new ideas, in this brief review we analyze some recently published studies in order to focus on some unresolved controversies and highlight the limitations that need to be addressed in future work. Clearly, only by using similar and overlapping methods, cross-referencing experiments, and perhaps collaborative efforts, we can finally understand what the role of lactate in the brain is and why this ubiquitous molecule is so important. Our appreciation of the diversity of the actions and interactions of L-lactate (Lac) in the brain continues to expand, and with it, our understanding of the potential mechanisms by which Lac fulfils its diverse roles. While several recent reviews have discussed specific aspects of central Lac effects ,2,3,4, tFollowing glycolysis, Lac is generated from pyruvate by lactate dehydrogenase (LDH), an enzyme that operates in both directions, using NADH to reduce pyruvate into Lac . Even thAll Lac release mechanisms identified so far are gradient-dependent. These involve monocarboxylate transporters (MCT) of which isoforms 1 and 4 are predominantly expressed by astrocytes and MCT2 is mainly found in neurons . In addi13C-labelled glucose and other compounds have indicated that in the brain, in contrast to peripheral tissues, glucose rather than Lac is the primary source of TCA metabolites [The concept of Lac being passed on between different cell types is well established for peripheral tissues . For theabolites . Other sabolites ,16,20. H+/NADH ratio changes (see next section) or of intracellular acidification.The hypothesis that astrocytic Lac is the preferred substrate for ATP generation in neurons goes back to the initial Lac shuttle concept as mentioned above ,21,22. I+/NADH ratio (see section below) since LDH will use NADH to re-establish the Lac-pyruvate equilibrium.Studies from two laboratories as examples of Lac-dependent processes that are attributed to Lac’s caloric value for neurons are discussed in this section. In 2011, the group of C. Alberini published a paper implicating Lac shuttle in memory at the level of the hippocampus . More reIn order to selectively inhibit Lac export from astrocytes, AS-ODN was used to suppress the expression of MCT1 and MCT4 . AS-ODN +/NADH ratio or pH. A further complication is that 4-CIN, while an effective inhibitor of cellular Lac ex- and import, may also effectively deprive neurons (and astrocytes) of ATP generated by the mitochondria , increased memory when performed during acquisition [Another study confirmed that activation of astrocytes, in this case using a Guisition  but thesuisition , such ac+/NADH ratio was found in carotid body glomus cells [+/NADH ratio may cause activation of non-selective cation channels that are sensitive to the non-selective cation channel blocker 2-APB and belong to the transient receptor potential (TRP) channel family. As a result, neurons depolarize and start firing action potentials, leading to Ca2+ entry and elevation of intracellular Ca2+ concentration. Entry of Lac is mediated by a co-transport with protons and therefore decreases intracellular pH. The authors argue that acidification increases mitochondrial reactive oxygen species production, which further activates glomus cells [An interesting mechanism related to the NADus cells . Althougus cells . This isIn order to prove the involvement of the Lac shuttle, any effect of Lac needs to be primarily sensitive to the blockade of Lac entry into neurons. Inhibition of Lac-pyruvate interconversion by LDH enzymes is also used as an argument to support the notion of Lac shuttle. However, block of the transporters by 4-CIN is bound to inhibit Lac release from astrocytes, while block of LDH should also block the generation of Lac in astrocytes. Drugs which are currently used are not selective to a specific location of any of these processes.+/K+ exchanger, astrocytes depolarize and this can cause the release of various signaling molecules, such as purines or possibly glutamate, which would result in the activation of adjacent neurons [The MCT blocker 4-CIN (α-cyano-4hydroxycinnamate or CHC) is used in many studies on this topic and will block astrocytic release as well as neuronal uptake of Lac. However, it was established long ago that 4-CIN is two orders of magnitude more potent at inhibiting pyruvate transport into mitochondria than at inhibiting Lac transport across the plasma membrane (reviewed in ). Theref neurons . It follFinally, as mentioned earlier, we should not disregard the fact that entry of Lac into the cells through MCT must necessarily lead to acidification of the cytoplasm by the co-imported protons. These effects may become particularly prominent when concentrations of Lac are used that exceed the physiological range, which is thought to be below 2 mM (reviewed in ). Indeedhttps://www.guidetopharmacology.org/ (accessed on 1 December 2022)) as HCA1 . It is encoded by the gene HCAR1. The physiological role of HCA1 is best established in adipocytes where it inhibits lipolysis via the Gi-protein signaling cascade [i signaling is characteristically associated with the inhibition of action potential activity and transmitter release. Lac has very low potency on HCA1. In the original publication, EC50 for Lac for HCA from different species are listed between 3.7–6.9 mM ([It is well established that Lac can affect cell function via cell surface G-protein coupled receptors (GPCR) without the need to access the cytoplasm . Lac has cascade . In neur–6.9 mM , and depolarization, although the paper does not appear to contain direct evidence in support of this suggestion [A study by Ordenes and colleagues offers a completely different view of the potential mechanism by which HCA1 can modulate neurons . They st studies ,56,57. Tggestion .Locus coeruleus . We coneus , it shares little homology with other GPCRs and its coupling to G-proteins has not been confirmed (IUPHAR guidetopharmacology.org). Nevertheless, its expression is verified by multiple databases, and it has been preferentially localized to the lysosomal compartment . The potential physiological roles of GPR137 are still little understood. According to in situ hybridization data in the Allen Brain Atlas, there is a widespread expression of the GPR137 transcript in mouse brain (http://mouse.brain-map.org/experiment/show/75651149 (accessed on 1 December 2022). While apparently present in human and mouse, in rat it may not even exist as a full-length protein (https://www.guidetopharmacology.org/ (accessed on 1 December 2022). We believe that the effect of Lac via this receptor should be investigated further.We undertook a screening effort, analyzed a range of orphan GPCRs that are expressed by LC neurons and found one receptor that could be a viable candidate for further experimentation . In a luSimilarly, we also found that in cells transfected to express GPR180, Lac could reduce cAMP . While rAn interesting and entirely unexpected avenue might have been opened by a recent discovery of biological activity of the Lac metabolite N-lactoyl-phenylalanine (Lac-Phe). This product of conjugation of Lac with phenylalanine is formed in the periphery when Lac levels are increased by exercise in mice, humans and racehorses, and can suppress food consumption . This efTo summarize this section, in order to eventually gain a better understanding of the full scale of Lac actions in the brain, there is scope in searching for additional receptors which can be either specifically activated by Lac or modulated by it in a biologically relevant manner.For the sake of completion, we draw the reader’s attention to yet another possible mode of Lac action, i.e., via lactylation of histone lysines ,68. Via As of today, there is no generally accepted theory which explains how astrocytes “know” that the neighboring neurons are active and require metabolic support, or modulation via Lac release is indicated. Moreover, it may be that such a general mechanism does not exist or there is more than one acting together, as it is so often in nature. So, what are the main listed coupling mechanisms between neurons and astrocytes?+, NO, glutamate and possibly NH4+ [+ is a result of neuronal activity and the subsequent opening of voltage-gated K+ channels required to restore and maintain the neuronal resting membrane potential. An increase in extracellular K+ concentration has a depolarizing effect on the membrane potential of astrocytes, and this could be the signal to activate glycolysis, resulting in Lac output. One concept proposes Na+ as a link between extracellular signals, astrocytic energy metabolism and Lac production [+ gradient-dependent manner, raising intra-astrocytic Na+ that then needs to be extruded by the Na+/K+-ATPase. The resulting drop in ATP/ADP ratio is proposed as one of the triggers of glucose uptake and anaerobic glycolysis. Hence, according to this view, Na+ is the “energy currency” and a “mediator of metabolic signals in the context of neuron-glia interaction” [The group of L.F. Barros focused on this topic for several years and explains such coupling by the action of elevated extracellular Kbly NH4+ ,70. Elevoduction . Large qraction” , see alsraction” . Depolarraction” .2+ as a link between neuronal activation and astrocytic signaling [2+ channels results in rapid Ca2+ influx into the neurons and thus a drop in its local extracellular concentration. This opens astrocytic connexin Cx43 channels which may release ATP. While that paper does not touch upon the Lac shuttle concept, the release of ATP by an astrocyte can be postulated to feedback to the astrocyte via an autocrine loop, since astrocytes express numerous P2Y receptors and are extremely sensitive to ATP and vigorously respond to it in vivo and in vitro [2+ waves in astrocytes are a well-known phenomenon [2+ with the resultant release of ATP could link neuronal activity, astrocytic metabolism, and the release of gliotransmitters together.An earlier study by M. Nedergaard’s group emphasizes the role of Caignaling . It was in vitro , see revin vitro . ATP-trienomenon . In addienomenon . Hence, 2+ and cAMP responses that are implicated in gliotransmitter release in general, and Lac release in particular [Finally, regarding the communication between noradrenergic neurons and glia, the expression of adrenoceptors on astrocytes is well described and confirmed by RNA sequencing . Astrocyrticular ,78. The rticular ).To summarize, currently, we do not have a unifying concept which could explain how the activity of neuronal networks engages astrocytes to release Lac. Development of such is an important goal that requires further evidence linking various mechanisms that have been established to date.What are the most obvious controversies surrounding the role of astrocyte-generated Lac, where should we move next? The analysis presented here shows that the experimental conditions, concentrations of Lac which are seen as acceptable, tools and interpretation of the results are so different between individual groups that in many cases it is hard to compare them or come to any consensus. We believe that the following questions require a concerted effort of various laboratories, possibly via directly coordinated efforts and sharing of the same tools between them.+/NADH ratio physiologically relevant?Under which conditions are the effects of Lac at concentrations exceeding 3–5 mM physiologically relevant, especially if the impacts of intracellular acidification were not monitored? In that context, when are the changes in the NADWhat is the role of the HCA1 receptor in the brain—is Lac actually inhibitory to many neurons in the cortex and hippocampus and how could this tie together with the proposed role of Lac in the process of memory formation?What are the local dynamics of Lac in the extracellular space? Can local Lac concentrations significantly exceed the “average” extracellular concentrations reported in the literature? This would require measurements with a new type of genetically encoded biosensor.Are there any other receptors that are responsive to Lac in the brain, with sensitivity better suited to the reported Lac physiological concentrations (<2 mM)? By what mechanism does Lac excite LC and RVLM catecholaminergic neurons?What is the trigger for the production of Lac by astrocytes in response to the activation of the neuronal networks? Are there several mechanisms, are they brain area-specific?This list may be continued. We hope that this review will stimulate and facilitate further collaborative efforts to resolve some of the long-standing mysteries surrounding the roles of Lac in the brain.


As Americans live longer, many are finding they need or want to remain longer in the workforce. When the COVID-19 pandemic transitioned much of the U.S. workforce into temporary or permanent remote employment, many older job seekers were left behind, wanting to compete in the ever-more technology-based job market but often without the requisite skills to do so. The present study evaluated a workforce training program (funded by a Department of Labor demonstration grant) that trained low-income workers over the age of 55 for remote employment. Approximately 60 older adults were trained across three 20-week cohorts. Our data sources included biweekly participant surveys, typing speed and Microsoft Office skill assessments, exit interviews with program “drop-outs,” focus groups, training observations, data from participant applications, and instructor assessments of each participant’s level of “job readiness” at the end of the program. Results revealed that participants had acute financial need for employment, a keen interest in working remotely, and a wide range of employment experiences and past job stability. Many of their career trajectories and workplace needs were affected by COVID-19. Results also showed promising improvements in participants’ technology skills and confidence in their ability to conduct a job search over the course of the program. The need for greater connectivity between participants and employers was identified as an area for improvement for the program. The results of this study contribute to the literature on workforce development by exploring how training programs might better prepare older adults for an increasingly remote job market.