Machine learning for predicting cognitive deficits using auditory and demographic factors.

IMPORTANCE: Predicting neurocognitive deficits using complex auditory assessments could change how cognitive dysfunction is identified, and monitored over time. Detecting cognitive impairment in people living with HIV (PLWH) is important for early intervention, especially in low- to middle-income countries where most cases exist. Auditory tests relate to neurocognitive test results, but the incremental predictive capability beyond demographic factors is unknown. OBJECTIVE: Use machine learning to predict neurocognitive deficits, using auditory tests and demographic factors. SETTING: The Infectious Disease Center in Dar es Salaam, Tanzania. PARTICIPANTS: Participants were 939 Tanzanian individuals from Dar es Salaam living with and without HIV who were part of a longitudinal study. Patients who had only one visit, a positive history of ear drainage, concussion, significant noise or chemical exposure, neurological disease, mental illness, or exposure to ototoxic antibiotics (e.g., gentamycin), or chemotherapy were excluded. This provided 478 participants (349 PLWH, 129 HIV-negative). Participant data were randomized to training and test sets for machine learning. MAIN OUTCOME(S) AND MEASURE(S): The main outcome was whether auditory variables combined with relevant demographic variables could predict neurocognitive dysfunction (defined as a score of <26 on the Kiswahili Montreal Cognitive Assessment) better than demographic factors alone. The performance of predictive machine learning algorithms was primarily evaluated using the area under the receiver operational characteristic curve. Secondary metrics for evaluation included F1 scores, accuracies, and the Youden's indices for the algorithms. RESULTS: The percentage of individuals with cognitive deficits was 36.2% (139 PLWH and 34 HIV-negative). The Gaussian and kernel naïve Bayes classifiers were the most predictive algorithms for neurocognitive impairment. Algorithms trained with auditory variables had average area under the curve values of 0.91 and 0.87, F1 scores (metric for precision and recall) of 0.81 and 0.76, and average accuracies of 86.3% and 81.9% respectively. Algorithms trained without auditory variables as features were statistically worse (p < .001) in both the primary measure of area under the curve (0.82/0.78) and the secondary measure of accuracy (72.3%/74.5%) for the Gaussian and kernel algorithms respectively. CONCLUSIONS AND RELEVANCE: Auditory variables improved the prediction of cognitive function. Since auditory tests are easy-to-administer and often naturalistic tasks, they may offer objective measures or predictors of neurocognitive performance suitable for many global settings. Further research and development into using machine learning algorithms for predicting cognitive outcomes should be pursued.

Basophil-Derived IL-4 and IL-13 Protect Intestinal Barrier Integrity and Control Bacterial Translocation during Malaria.

Our previous work demonstrated that basophils regulate a suite of malaria phenotypes, including intestinal mastocytosis and permeability, the immune response to infection, gametocytemia, and parasite transmission to the malaria mosquito Anopheles stephensi. Given that activated basophils are primary sources of the regulatory cytokines IL-4 and IL-13, we sought to examine the contributions of these mediators to basophil-dependent phenotypes in malaria. We generated mice with basophils depleted for IL-4 and IL-13 (baso IL-4/IL-13 (-)) and genotype controls (baso IL-4/IL-13 (+)) by crossing mcpt8-Cre and Il4/Il13fl/fl mice and infected them with Plasmodium yoelii yoelii 17XNL. Conditional deletion was associated with ileal mastocytosis and mast cell (MC) activation, increased intestinal permeability, and increased bacterial 16S levels in blood, but it had no effect on neutrophil activation, parasitemia, or transmission to A. stephensi. Increased intestinal permeability in baso IL-4/IL-13 (-) mice was correlated with elevated plasma eotaxin (CCL11), a potent eosinophil chemoattractant, and increased ileal MCs, proinflammatory IL-17A, and the chemokines MIP-1α (CCL3) and MIP-1ß (CCL4). Blood bacterial 16S copies were positively but weakly correlated with plasma proinflammatory cytokines IFN-γ and IL-12p40, suggesting that baso IL-4/IL-13 (-) mice failed to control bacterial translocation into the blood during malaria infection. These observations suggest that basophil-derived IL-4 and IL-13 do not contribute to basophil-dependent regulation of parasite transmission, but these cytokines do orchestrate protection of intestinal barrier integrity after P. yoelii infection. Specifically, basophil-dependent IL-4/IL-13 control MC activation and prevent infection-induced intestinal barrier damage and bacteremia, perhaps via regulation of eosinophils, macrophages, and Th17-mediated inflammation.

Mast cell-derived IL-10 protects intestinal barrier integrity during malaria in mice and regulates parasite transmission to Anopheles stephensi with a female-biased immune response.

Malaria is strongly predisposed to bacteremia, which is associated with increased gastrointestinal permeability and a poor clinical prognosis. We previously identified mast cells (MCs) as mediators of intestinal permeability in malaria and described multiple cytokines that rise with parasitemia, including interleukin (IL)-10, which could protect the host from an inflammatory response and alter parasite transmission to Anopheles mosquitoes. Here, we used the Cre-loxP system and non-lethal Plasmodium yoelii yoelii 17XNL to study the roles of MC-derived IL-10 in malaria immunity and transmission. Our data suggest a sex-biased and local inflammatory response mediated by MC-derived IL-10, supported by early increased number and activation of MCs in females relative to males. Increased parasitemia in female MC IL-10 (-) mice was associated with increased ileal levels of chemokines and plasma myeloperoxidase (MPO). We also observed increased intestinal permeability in female and male MC IL-10 (-) mice relative to MC IL-10 (+) mice but no differences in blood bacterial 16S DNA levels. Transmission success of P. yoelii to A. stephensi was higher in female relative to male mice and from female and male MC IL-10 (-) mice relative to MC IL-10 (+) mice. These patterns were associated with increased plasma levels of pro-inflammatory cytokines in female MC IL-10 (-) mice and increased plasma levels of chemokines and markers of neutrophil activation in male MC IL-10 (-) mice. Overall, these data suggest that MC-derived IL-10 protects intestinal barrier integrity, regulates parasite transmission, and controls local and systemic host immune responses during malaria, with a female bias.

A Central Auditory Test reveals differences between drug treatment regimens in adults living with HIV.

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.

Ingested histamine and serotonin interact to alter Anopheles stephensi feeding and flight behavior and infection with Plasmodium parasites.

Blood levels of histamine and serotonin (5-HT) are altered in human malaria, and, at these levels, we have shown they have broad, independent effects on Anopheles stephensi following ingestion by this invasive mosquito. Given that histamine and 5-HT are ingested together under natural conditions and that histaminergic and serotonergic signaling are networked in other organisms, we examined effects of combinations of these biogenic amines provisioned to A. stephensi at healthy human levels (high 5-HT, low histamine) or levels associated with severe malaria (low 5-HT, high histamine). Treatments were delivered in water (priming) before feeding A. stephensi on Plasmodium yoelii-infected mice or via artificial blood meal. Relative to effects of histamine and 5-HT alone, effects of biogenic amine combinations were complex. Biogenic amine treatments had the greatest impact on the first oviposition cycle, with high histamine moderating low 5-HT effects in combination. In contrast, clutch sizes were similar across combination and individual treatments. While high histamine alone increased uninfected A. stephensi weekly lifetime blood feeding, neither combination altered this tendency relative to controls. The tendency to re-feed 2 weeks after the first blood meal was altered by combination treatments, but this depended on mode of delivery. For blood delivery, malaria-associated treatments yielded higher percentages of fed females relative to healthy-associated treatments, but the converse was true for priming. Female mosquitoes treated with the malaria-associated combination exhibited enhanced flight behavior and object inspection relative to controls and healthy combination treatment. Mosquitoes primed with the malaria-associated combination exhibited higher mean oocysts and sporozoite infection prevalence relative to the healthy combination, with high histamine having a dominant effect on these patterns. Compared with uninfected A. stephensi, the tendency of infected mosquitoes to take a second blood meal revealed an interaction of biogenic amines with infection. We used a mathematical model to project the impacts of different levels of biogenic amines and associated changes on outbreaks in human populations. While not all outbreak parameters were impacted the same, the sum of effects suggests that histamine and 5-HT alter the likelihood of transmission by mosquitoes that feed on hosts with symptomatic malaria versus a healthy host.

Web-Based, Interactive, Interest-Based Negotiation Training for Managing Conflict in Isolated Environments: Opportunistic Study With an e-Survey.

BACKGROUND: Effective negotiation in relationships is critical for successful long-duration space missions; inadequate conflict resolution has shown serious consequences. Less desirable forms of negotiation, including positional bargaining (eg, negotiating prices), can exacerbate conflicts. Traditional positional bargaining may work for simple, low-stakes transactions but does not prioritize ongoing relationships. High-stakes situations warrant interest-based negotiation, where parties with competing interests or goals collaborate in a mutually beneficial agreement. This is learnable but must be practiced. Refresher training during conflicts is important to prevent out-of-practice crew members from using less effective negotiation techniques. Training should be self-directed and not involve others because, on a space mission, the only other people available may be part of the conflict. OBJECTIVE: We aimed to develop and test an interactive module teaching principles and skills of interest-based negotiation in a way that users find acceptable, valuable for learning, and enjoyable. METHODS: Using a web-based, interactive-media approach, we scripted, filmed, and programmed an interest-based negotiation interactive training module. In the module, the program mentor introduces users to "The Circle of Value" approach to negotiation and highlights its key concepts through interactive scenarios requiring users to make selections at specific decision points. Each selection prompts feedback designed to reinforce a teaching point or highlight a particular negotiation technique. To evaluate the module, we sought populations experiencing isolation and confinement (an opportunistic design). This included 9 participants in isolated, confined environments in the Australian Antarctic Program and the Hawai'i Space Exploration Analog and Simulation Mars simulation, as well as a subset of people who self-identified as being isolated and confined during the COVID-19 pandemic. Feedback was collected from participants (n=54) through free-response answers and questionnaires with numerical scaling (0=strongly disagree to 4=strongly agree) at the end of the module. RESULTS: In total, 51 of 54 (94%) participants found the activity valuable for learning about conflict management (identified by those who selected either "somewhat agree" or "strongly agree"), including 100% of participants in the isolated and confined environment subset (mode=3). In total, 79% (128/162) of participant responses indicated that the module was realistic (mode=3), including 85% (23/27) of responses from participants in isolated and confined environments (mode=3). Most participants felt that this would be particularly valuable for new team members in an isolated, confined environment (46/54, 85% of all participants, mode 4; 7/9, 78% of the isolated and confined environment subset, mode 3) as well as veterans. CONCLUSIONS: This module offers a self-directed, consistent approach to interest-based negotiation training, which is well received by users. Although the data are limited due to the opportunistic study design, the module could be useful for individuals in isolated and confined environments and for anyone involved in high-stakes negotiations where sustaining relationships is essential.

Gap detection responses modelled using the Hill equation in adults with well-controlled HIV.

OBJECTIVE: This study's objective was determining whether gap detection deficits are present in a longstanding cohort of people living with HIV (PLWH) compared to those living without HIV (PLWOH) using a new gap detection modelling technique (i.e. fitting gap responses using the Hill equation and analysing the individual gap detection resulting curves with non-linear statistics). This approach provides a measure of both gap threshold and the steepness of the gap length/correct detection relationship. DESIGN: The relationship between the correct identification rate at each gap length was modelled using the Hill equation. Results were analysed using a nonlinear mixed-effect regression model. STUDY SAMPLE: 45 PLWH (age range 41-78) and 39 PLWOH (age range 38-79) were enrolled and completed gap detection testing. RESULTS: The likelihood ratio statistic comparing the full regression model with the HIV effects to the null model, assuming one population curve for both groups, was highly significant (p < 0.001), suggesting a less precise relationship between gap length and correct detection in PLWH. CONCLUSIONS: PLWH showed degraded gap detection ability compared to PLWOH, likely due to central nervous system effects of HIV infection or treatment. The Hill equation provided a new approach for modelling gap detection ability.

Prospective measurements of hearing threshold during military rifle training with in-ear, protected, noise exposure monitoring.

Although a causal relationship exists between military occupational noise exposure and hearing loss, researchers have struggled to identify and/or characterize specific operational noise exposures that produce measurable changes in hearing function shortly following an exposure. Growing evidence suggests that current standards for noise-exposure limits are not good predictors of true hearing damage. In this study, the aim was to capture the dose-response relationship during military rifle training exercises for noise exposure and hearing threshold. To capture exposure, a wearable system capable of measuring impulse noise simultaneously on-body and in-ear, behind hearing protection was used. To characterize hearing threshold changes, portable audiometry was employed within 2 h before and after exposure. The median 8-h time-weighted, protected, free-field equivalent in-ear exposure was 87.5 dBA at one site and 80.7 dBA at a second site. A significant dose-response correlation between in-ear noise exposure and postexposure hearing threshold changes across our population ( R = 0.40 , p = 0.0281) was observed. The results demonstrate an approach for establishing damage risk criteria (DRC) for in-ear, protected measurements based on hearing threshold changes. While an in-ear DRC does not currently exist, it may be critical for predicting the risk of injury for noise environments where protection is mandatory and fit status can vary.

International Multicenter Registry for Hyperbaric Oxygen Therapy: Results through June 2021.

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

The Resting State Central Auditory Network: a Potential Marker of HIV-Related Central Nervous System Alterations.

OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.

Distortion product otoacoustic mapping measured pre- and post-loud sound exposures.

OBJECTIVE: Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. DESIGN: A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. STUDY SAMPLE: The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. RESULTS: After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. CONCLUSIONS: Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.

The Relationship Between Central Auditory Tests and Neurocognitive Domains in Adults Living With HIV.

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV- controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models. Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests. Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders.

Unexplained multi-sensory neuropathy syndrome in young Tanzanian adults.

BACKGROUND: A unique syndrome affecting young adults of unexplained hearing loss often associated with uncorrectable poor visual acuity and lower extremity numbness is endemic in Dar es Salaam. This study characterized the hearing loss, associated it with other symptoms, and gathered information on potential causes. METHODS: Forty-seven patients (23 men, 24 women) <40 years old with a symptom consistent with the syndrome, negative syphilis test, and no head injury history were recruited from Muhimbili National Hospital. 18 controls (10 men, 8 women) were recruited from the same neighborhoods as patients. Hearing ability and cochlear outer hair cell function (distortion-product otoacoustic emissions (DPOAEs)) were assessed, as were visual acuity and color vision. Peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument (MNSI), and physical examination. Blood C-reactive protein levels and toenail trace metal concentrations were measured. Environmental exposures were elicited using a questionnaire. Patients with at least two of the following signs were defined as having the syndrome: poor hearing with normal DPOAEs, vision not correctable to better than 20/30, or a MNSI score greater than 4. RESULTS: 29 participants met the case definition. CRP levels did not differ between groups but manganese, cobalt and tin levels were each greater in the cases than controls. No other environmental exposure differences were noted. CONCLUSIONS: Toenail manganese, cobalt, and tin levels were higher in those with the syndrome. These metals are potential neurotoxins suggesting a possible environmental origin for this unique and debilitating syndrome.

Corrigendum: Increased Right Frontal Brain Activity During the Mandarin Hearing-in-Noise Test.

[This corrects the article DOI: 10.3389/fnins.2020.614012.].

Proposed mechanism for reduced jugular vein flow in microgravity.

Internal jugular flow is reduced in space compared with supine values, which can be associated with internal jugular vein (IJV) thrombosis. The mechanism is unknown but important to understand to prevent potentially serious vein thromboses on long duration flights. We used a novel, microgravity-focused numerical model of the cranial vascular circulation to develop hypotheses for the reduced flow. This model includes the effects of removing hydrostatic gradients and tissue compressive forces - unique effects of weightlessness. The IJV in the model incorporates sensitivity to transmural pressure across the vein, which can dramatically affect resistance and flow in the vein. The model predicts reduced IJV flow in space. Although tissue weight in the neck is reduced in weightlessness, increasing transmural pressure, this is more than offset by the reduction in venous pressure produced by the loss of hydrostatic gradients and tissue pressures throughout the body. This results in a negative transmural pressure and increased IJV resistance. Unlike the IJV, the walls of the vertebral plexus are rigid; transmural pressure does not affect its resistance and so its flow increases in microgravity. This overall result is supported by spaceflight measurements, showing reduced IJV area inflight compared with supine values preflight. Significantly, this hypothesis suggests that interventions that further decrease internal IJV pressure (such as lower body negative pressure), which are not assisted by other drainage mechanisms (e.g. gravity), might lead to stagnant flow or IJV collapse with reduced flow, which could increase rather than decrease the risk of venous thrombosis.

Use of a Self-guided Computerized Cognitive Behavioral Tool During COVID-19: Evaluation Study.

BACKGROUND: Internet-based programs can help provide accessible and inexpensive behavioral health care to those in need; however, the evaluation of these interventions has been mostly limited to controlled trials. Data regarding patterns of use and effectiveness of self-referred, open-access online interventions are lacking. We evaluated an online-based treatment designed to address stress, depression, and conflict management, the Dartmouth PATH Program, in a freely available and self-guided format during the COVID-19 pandemic. OBJECTIVE: The primary aim is to determine users' levels of stress and depression, and the nature of problems and triggers they reported during the COVID-19 pandemic. A secondary objective is to assess the acceptability and usability of the PATH content and determine whether such a program would be useful as a stand-alone open-access resource. The final objective is understanding the high dropout rates associated with online behavioral programs by contrasting the use pattern and program efficacy of individuals who completed session one and did not return to the program with those who came back to complete more sessions. METHODS: Cumulative anonymous data from 562 individuals were analyzed. Stress triggers, stress responses, and reported problems were analyzed using qualitative analysis techniques. Scores on usability and acceptability questionnaires were evaluated using the sign test and Wilcoxon signed rank test. Mixed-effects linear modeling was used to evaluate changes in stress and depression over time. RESULTS: A total of 2484 users registered from April through October 2020, most of whom created an account without initiating a module. A total of 562 individuals started the program and were considered in the data analysis. The most common stress triggers individuals reported involved either conflicts with family or spouses and work or workload. The most common problems addressed in the mood module were worry, anxiousness, or stress and difficulty concentrating or procrastination. The attrition rate was high with 13% (21/156) completing the conflict module, 17% (50/289) completing session one of the mood module, and 14% (16/117) completing session one of the stress module. Usability and acceptability scores for the mood and stress modules were significantly better than average. In those who returned to complete sessions, symptoms of stress showed a significant improvement over time (P=.03), and there was a significant decrease in depressive symptoms over all time points (P=.01). Depression severity decreased on average by 20% (SD 35.2%; P=.60) between sessions one and two. CONCLUSIONS: Conflicts with others, worry, and difficulty concentrating were some of the most common problems people used the programs to address. Individuals who completed the modules indicated improvements in self-reported stress and depression symptoms. Users also found the modules to be effective and rated the program highly for usability and acceptability. Nevertheless, the attrition rate was very high, as has been found with other freely available online-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02726061; https://clinicaltrials.gov/ct2/show/NCT02726061.

Use of custom-moulded earmoulds to improve repeatability of DPOAE map measurements.

OBJECTIVE: Distortion product otoacoustic emission (DPOAE) mapping characterises cochlear function, can include both the 2f1-2f2 and 2f2-2f1 DPOAEs, and shows promise for tracking cochlear changes. DPOAE amplitude measurements are not as repeatable longitudinally as pure-tone audiometry, likely due in part to probe placement sensitivity. We hypothesised that DPOAE level map variation over multiple testing sessions could be minimised by replacing traditional rubber tips with custom-moulded probe tips. DESIGN: Traditional rubber tips (TRT) and custom-moulded probes tips (CMPT) were used to measure DPOAE level maps repeatedly over five sessions. Probe placement was assessed using a frequency sweep in the ear canal. Repeatability of the DPOAE level maps was assessed using a Bland-Altman analysis. Overall map repeatability was assessed by measuring differences in distortion product amplitude over sessions. STUDY SAMPLE: Crossover study with a convenience sample size of six adults. RESULTS: The CMPT frequency sweeps showed reduced variability in probe placement. The repeatability coefficient for individual DPOAEs measurements improved from 6.9 dB SPL with the TRT to 5.1 dB SPL with the CMPT. Map repeatability improved for most subjects with the CMPT.

Optic Nerve Length before and after Spaceflight.

PURPOSE: The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS. DESIGN: Cohort study. PARTICIPANTS: Twenty-two astronauts (age 48 ± 4 years). METHODS: The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path. MAIN OUTCOME MEASURES: Optic nerve length, ONH movement, and OC movement after time in microgravity. RESULTS: Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS. CONCLUSIONS: The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.