Search

The National Technical Assistance Center on Transition's (NTACT) Competitive Integrated Employment (CIE) Toolkit was developed in accordance with the requirements of the Rehabilitation Act of 1973 (Rehabilitation Act), as amended by the Workforce Innovation and Opportunity Act (WIOA) and the Individuals with Disabilities Education Act (IDEA) as a resource for use by educational and vocational rehabilitation (VR) agencies to improve post school employment outcomes for students with disabilities. The toolkit was developed to facilitate the collaboration necessary to implement secondary transition services across agencies at the state, community and student levels and increase the use of evidence based practices (EBPs). It has been developed as a framework to assist state and local teams in collaboratively implementing transition services to improve post school employment outcomes for students with disabilities. The Framework is comprised of four areas: (1) Competitive Integrated Employment Overview; (2) Transition Services; (3) Interagency Collaboration; and (4) Professional Development. When combined, the four sections can assist education and VR agencies to collaboratively implement Pre-Educational Testing Services (ETS), and transition services. Each section of the Framework begins with "At a Glance" that provides a short introduction on how to best use that particular section of the Toolkit. Readers will then find content based on federal legislation and research followed by resources and tools relevant to that section as well as implications for practices that are areas to consider for teams or individuals using the Toolkit. The toolkit is dynamic in nature and as such, it continues to evolve as resources and tools that are useful in the implementation of Evidence Based Practices (EBPs) specific to Pre-ETS and transition services are implemented. [This toolkit was originally prepared in 2017.]

NECESSARY CONDITIONS: Understanding patterns and variations in math course-taking among high school seniors to increase completion of four years of math Abstract This mixed methods study explores high school seniors’ math course-taking decisions and what changes school leaders can take to increase the percentages of students taking four years of math in high school. Through an analysis of district-level administrative data and a survey completed by seniors at a high performing, diverse high school in Northern California, this study illuminates many reasons for why these patterns and inequalities occur. Findings reveal institutional, classroom and individual factors that impact students’ decision-making around taking math senior year. Keywords: secondary math course-taking, seniors, high school math pathways, equity in math

PurposeTo evaluate functional and structural assessments as endpoints for clinical trials for USH2A-related retinal degeneration.MethodsPeople with biallelic disease-causing variants in USH2A, visual acuity ≥ 20/80, and visual field ≥ 10° diameter were enrolled in a 4-year, natural history study. Participants underwent static perimetry, microperimetry, visual acuity, fullfield stimulus testing (FST), and optical coherence tomography annually. Rates of change estimated from mixed-effects linear models and percentages of eyes with changes exceeding the coefficient of repeatability (CoR) or thresholds conforming with U.S. Food and Drug Administration (FDA) guidelines were evaluated.ResultsRates of change were generally more sensitive to change than proportions of eyes exceeding a threshold such as the CoR. Baseline ellipsoid zone area ≥ 3 mm2 was necessary to detect change. Mean sensitivity and volumetric hill of vision measures on static perimetry had similar properties and were the most sensitive to changes of the continuous measures. The highest 4-year proportions of eyes exceeding the CoR were from FST testing (47%) and microperimetry (32%). Specification of loci as functional transition points (FTPs) resulted in 45% (static perimetry) and 46% (microperimetry) at 4 years, meeting FDA guidelines for progression.ConclusionsRate of change of mean sensitivity on static perimetry was a sensitive perimetric continuous measure. Percentages of within-eye change were largest with FST testing and microperimetry. FTPs appear to be particularly sensitive to change. These results affect clinical trial design for USH2A-related retinal degeneration.Translational relevanceAnalyses of natural history data from the Rate of Progression in USH2A-Related Retinal Degeneration (RUSH2A) study can inform eligibility criteria and endpoints for clinical trials.

Pollen, spores, and microscopic charcoal from the sediments of Grosssee (1,619 m a.s.l.), a small lake in the lower subalpine vegetation zone of the Glarus Alps, Switzerland, were analysed to reconstruct vegetation patterns and land use over the past ca. 12,300 calibrated C-14 years bp (cal bp). Pollen data revealed an open landscape covered with grasses and herbs such as Artemisia during the Late Glacial Period. The catchment was likely initially afforested with Betula and Pinus cembra or Pinus sylvestris during the Early Holocene. Thermophilous taxa such as Ulmus, Tilia, and Alnus glutinosa-type expanded from ca. 11,000-9,200 cal bp, and mesophyllic Picea abies and Fagus sylvatica followed, and expanded beginning from ca. 8,000-7,600 cal bp. Interestingly, Alnus viridis (synonym: A. alnobetula) expanded about 2,000 years earlier than at comparable sites in the northern Swiss Alps. Its expansion was profound and persistent, and percentages > 15% were already achieved by ca. 7,000 cal bp. Local erosion events that followed are well explained by vegetation changes and inferred human land use activities at Grosssee. In particular, this led to a more open landscape, and land uses (e.g. grazing) intensified from the Mid- to Late Holocene. Indicators of environmental disturbance including persistently high levels of A. viridis, monolete fern spores, and microscopic charcoal were pronounced after ca. 4,000 cal bp. At that time, high influxes of spores from coprophilous fungi and the consistent presence of cultural indicators (Cerealia-type, Plantago lanceolata) indicate increased grazing and high levels of human impact. Land use and grazing activities seemed to have been particularly pronounced and to have promoted diversity in the vegetation over the past 1,000 years.

Winter/spring runoff has changed in streams worldwide due to climate change, particularly in temperate areas where winter/spring streamflow depends on snowmelt. Such changes potentially affect receiving waters through altered nutrient loading and mixing patterns. The Laurentian Great Lakes are an important freshwater resource and have experienced a myriad of impacts due to climate change. We analyzed 70 years of stream gauge data in the Great Lakes Basin to test for changes in timing, duration, and amount of winter/spring runoff during the period 1950–2019. We found strong evidence for earlier runoff in each of the Great Lakes except Lake Erie, protracted winter/spring runoff throughout the Great Lakes Basin, and a higher runoff depth during the winter-spring period over time for all watersheds except Lake Superior. Lake Ontario had the greatest change in the date by which 50% of the Jan–May runoff had been discharged (6 days earlier from 1950 to 2019). For winter/spring runoff duration, the most extreme change was observed in Lake Erie (increase of 19 days), and for runoff depth, the greatest change was in the Lake Huron Basin (increase of 3.3 cm). Results were similar for natural and impacted streams. Our results demonstrate dramatic changes in runoff patterns over the last seven decades in the Great Lakes Basin concomitant with previously published changes in precipitation and snowpack. Shifts toward earlier, more protracted, and more voluminous runoff likely change nutrient loading and mixing patterns that influence primary producers, particularly in the nearshore areas of the Great Lakes.

Objective: The EUSCREEN project concerns the study of European vision and hearing screening programmes. Part of the project was the development of a cost-effectiveness model to analyse such programmes. We describe the development and usability of an online tool to enable stakeholders to design, analyse or modify a newborn hearing screening (NHS) programme. Design: Data from literature, from existing NHS programmes, and observations by users were used to develop and refine the tool. Required inputs include prevalence of the hearing impairment, test sequence and its timing, attendance, sensitivity, and specificity of each screening step. Outputs include the number of cases detected and the costs of screening and diagnostics. Study sample: Eleven NHS programmes with reliable data. Results: Three analyses are presented, exploring the effect of low attendance, number of screening steps, testing in the maternity ward, or screening at a later age, on the benefits and costs of the programme. Knowledge of the epidemiology of a staged screening programme is crucial when using the tool. Conclusions: This study presents a tool intended to aid stakeholders to design a new or analyse an existing hearing screening programme in terms of benefits and costs.

Communication reinforces vital social bonds across the animal kingdom. Some of the most rare and specialized social systems require similarly specialized communication. One of the rarest social organizations in the animal kingdom, especially amongst mammals, is monogamy. Monogamous mates rely on a variety of communication modalities to find and initiate a bond, maintain their bond, coordinate daily activity, raise offspring, avoid predation, and defend shared resources, among other behaviors . Understanding these communication signals, both their structure and function, is of utmost importance in order to fully understand closely bonded social species. Coppery titi monkeys (Plecturocebus cupreus) are monogamous, South American monkeys who form selective, enduring psychosocial emotion attachments, referred to as pair bonds. Titi monkeys must form and maintain long term relationships, coordinate biparental care, and maintain control over a shared territory. These pair-bonded monkeys provide the perfect model system in which to investigate a variety of communication modalities in relationship to the unique pair bond. At the California National Primate Research Center, I investigated three aspects of titi monkey communication. First, I assessed patterns of individual identity in the morning adult duet contributions and infant trill vocalizations of this species. Strong patterns of individuality exist in adult duets, such that individuals are identifiable based on vocalizations alone. Second, I assessed female titi monkey responses to a variety of vocal stimuli in a playback experiment. Female titi monkey responses depended more on their own pairing status and reproductive status than the content of the social vocalization, suggesting titi monkeys respond generally to any unfamiliar acoustic signal. Finally, I presented titi monkeys with paired faces of their mate and a stranger in order to test for a partner preference in looking behavior. I found little evidence of vis

Primates live in a variety of social groupings and vary in the expression of species-typical behaviors depending upon social conditions. Coppery titi monkeys (Plecturocebus cupreus) are pair-bonding, territorial primates often used to study neurobiology and social behavior in captivity at the California National Primate Research Center (CNPRC). At the center, titi monkeys are housed in cages of standardized size. However, the number of cages--and thus families--per room varies based upon the room size (small or large). Anecdotal evidence suggests titi monkeys behave differently in the two different room sizes. To empirically test this, we measured rates of pair-bonding related affiliation in 23 pairs of titi monkeys. We predicted that monkeys in small rooms would show higher rates of affiliation compared to large rooms. We used a between- and within- subjects design in which all subjects moved from either small to large or large to small rooms. Affiliative behavior was recorded via bihourly instantaneous scan samples. We found that titi monkey pairs affiliated significantly more in small rooms compared to large rooms (partial R2 = 0.1468, t(33) = -3.729, p-value < .0005). We also confirmed that the presence of offspring negatively impacts pair affiliation rates (partial R2 = 0.2240, t(33) = -0.181, p-value = 0.0011). The results of this study suggest that titi monkey pair behavior is influenced by room size, and thus the number of neighboring groups. Management decisions should consider the implications that housing may have on the results of social behavior research.

On December 16, 2019, the U.S. Court of Appeals for the Fifth Circuit held in Doe v. Mckesson that a court could hold DeRay Mckesson liable for damages to a police officer whom an unidentified assailant injured at a 2016 Black Lives Matter protest that Mckesson helped organize. Mckesson did not cause the officer’s injuries, and he did not order, encourage, or incite the protestors at the demonstration to act violently. The Fifth Circuit held that Mckesson could be liable only because he played a role in organizing the demonstration. In 1982, the U.S. Supreme Court set forth an important principle in NAACP v. Claiborne Hardware Co. that limited the extent to which a court could hold protest organizers engaged in protected First Amendment activity liable for the violent acts of third parties. Many First Amendment scholars considered the Fifth Circuit’s decision in Doe v. Mckesson a direct affront to the principle set out in Claiborne Hardware. Indeed, Mckesson engaged in core protected speech activity when he protested police misconduct and thus should have fallen under the protection of the stringent standard. In November of 2020, in Doe v. Mckesson, the Supreme Court reversed and remanded the Fifth Circuit’s decision, but it did so in a per curiam opinion based only on issues concerning Louisiana tort law theories, leaving the First Amendment implications unanswered. This Note argues that the limited liability principle set forth in Claiborne Hardware is an essential protection for organizers and for democracy, such that the Supreme Court should look for opportunities to reaffirm it in the wake of the Fifth Circuit’s latest attack.

Pseudo-nitzschia species are one of the leading causes of harmful algal blooms (HABs) along the western coast of the United States. Approximately half of known Pseudo-nitzschia strains can produce domoic acid (DA), a neurotoxin that can negatively impact wildlife and fisheries and put human life at risk through amnesic shellfish poisoning. Production and accumulation of DA, a secondary metabolite synthesized during periods of low primary metabolism, is triggered by environmental stressors such as nutrient limitation. To quantify and estimate the feedbacks between DA production and environmental conditions, we designed a simple mechanistic model of Pseudo-nitzschia and domoic acid dynamics, which we validate against batch and chemostat experiments. Our results suggest that, as nutrients other than nitrogen (i.e., silicon, phosphorus, and potentially iron) become limiting, DA production increases. Under Si limitation, we found an approximate doubling in DA production relative to N limitation. Additionally, our model indicates a positive relationship between light and DA production. These results support the idea that the relationship with nutrient limitation and light is based on direct impacts on Pseudo-nitzschia biosynthesis and biomass accumulation. Because it can easily be embedded within existing coupled physical-ecosystem models, our model represents a step forward toward modeling the occurrence of Pseudo-nitzschia HABs and DA across the U.S. West Coast.

The landscape of deprescribing has been rapidly evolving and expanding globally with the formation of regional and national deprescribing networks. The work of these networks is primarily focused on older adults and high-risk medications. The purpose of the current qualitative study is to describe successes and challenges of deprescribing from thought-leaders across the world. Fourteen key informant interviews were conducted from various disciplines, levels of experiences, and regions around the globe. From the interviews, six major themes across two domains were identified: (a) network structure, (b) public perception, (c) policy implications, (d) implementation, (e) challenges, and (f) recommendations. These domains, themes, and insight provided by deprescribing leaders contribute to the advancement of deprescribing networks as global efforts continue to focus on optimizing medication management. Collaboration among interprofessional team members will be critical to the expansion as well as sustainability of this important work. [Journal of Gerontological Nursing, 48(1), 7-14.].

Pseudo-nitzschia species with the ability to produce the neurotoxin domoic acid (DA) are the main cause of harmful algal blooms (HABs) along the U.S. West Coast, with major impacts on ecosystems, fisheries, and human health. While most Pseudo-nitzschia (PN) HAB studies to date have focused on their characteristics at specific sites, few cross-regional comparisons exist, and mechanistic understanding of large-scale HAB drivers remains incomplete. To close these gaps, we compiled a nearly 20-year time series of in situ particulate DA and environmental observations to characterize similarities and differences in PN HAB drivers along the California coast. We focus on three DA hotspots with the greatest data density: Monterey Bay, the Santa Barbara Channel, and the San Pedro Channel. Coastwise, DA outbreaks are strongly correlated with upwelling, chlorophyll-a, and silicic acid limitation relative to other nutrients. Clear differences also exist across the three regions, with contrasting responses to climate regimes across a north to south gradient. In Monterey Bay, PN HAB frequency and intensity increase under relatively nutrient-poor conditions during anomalously low upwelling intensities. In contrast, in the Santa Barbara and San Pedro Channels, PN HABs are favored under cold, nitrogen-rich conditions during more intense upwelling. These emerging patterns provide insights on ecological drivers of PN HABs that are consistent across regions and support the development of predictive capabilities for DA outbreaks along the California coast and beyond.

BackgroundThe composition of the skin microbiome varies from infancy to adulthood and becomes most stable in adulthood. Adult acne patients harbour an 'acne microbiome' dominated by specific strains of Cutibacterium acnes. However, the precise timing of skin microbiome evolution, the development of the acne microbiome, and the shift to virulent C. acnes strain composition during puberty is unknown.ObjectivesWe performed a cross-sectional pilot study in a paediatric population to understand how and when the skin microbiome composition transitions during puberty and whether a distinct 'acne microbiome' emerges in paediatric subjects.MethodsForty-eight volunteers including males and females, ages 7-17 years, with and without acne were enrolled and evaluated for pubertal development using the Tanner staging criteria. Sebum levels were measured, and skin microbiota were collected by sterile swab on the subject's forehead. DNA was sequenced by whole genome shotgun sequencing.ResultsA significant shift in microbial diversity emerged between early (T1-T2) and late (T3-T5) stages of puberty, coinciding with increased sebum production on the face. The overall relative abundance of C. acnes in both normal and acne skin increased during puberty and individual C. acnes strains were uniquely affected by pubertal stage and the presence of acne. Further, an acne microbiome signature associated with unique C. acnes strain composition and metabolic activity emerges in late puberty in those with acne. This unique C. acnes strain composition is predicted to have increased porphyrin production, which may contribute to skin inflammation.ConclusionsOur data suggest that the stage of pubertal development influences skin microbiome composition. As children mature, a distinct acne microbiome composition emerges in those with acne. Understanding how both puberty and acne influence the microbiome may support novel therapeutic strategies to combat acne in the paediatric

PurposeLimited research exists on the time course of long-term retinal and cerebral deficits in diabetic rodents. Previously, we examined short term (4-8 weeks) deficits in the Goto-Kakizaki (GK) rat model of Type II diabetes. Here, we investigated the long-term (1-8 months) temporal appearance of functional deficits (retinal, cognitive, and motor), retinal vascular pathology, and retinal dopamine levels in the GK rat.MethodsIn GK rats and Wistar controls, retinal neuronal function (electroretinogram), cognitive function (Y-maze), and motor function (rotarod) were measured at 1, 2, 4, 6, and 8 months of age. In addition, we evaluated retinal vascular function (functional hyperemia) and glucose and insulin tolerance. Retinas from rats euthanized at ≥8 months were assessed for vascular pathology. Dopamine and DOPAC levels were measured via HPLC in retinas from rats euthanized at 1, 2, 8, and 12 months.ResultsGoto-Kakizaki rats exhibited significant glucose intolerance beginning at 4 weeks and worsening over time (p < 0.001). GK rats also showed significant delays in flicker and oscillatory potential implicit times (p < 0.05 to p < 0.001) beginning at 1 month. Cognitive deficits were observed beginning at 6 months (p < 0.05), but no motor deficits. GK rats showed no deficits in functional hyperemia and no increase in acellular retinal capillaries. Dopamine levels were twice as high in GK vs. Wistar retinas at 1, 2, 8, and 12 months (p < 0.001).ConclusionAs shown previously, retinal deficits were detectable prior to cognitive deficits in GK rats. While retinal neuronal function was compromised, retinal vascular pathology was not observed, even at 12+ months. High endogenous levels of dopamine in the GK rat may be acting as an anti-angiogenic and providing protection against vascular pathology.

Kirsha S Gordon,1,2 Eugenia Buta,3 Mandi L Pratt-Chapman,4 Cynthia A Brandt,1,3,5 Ralitza Gueorguieva,3 Allison R Warren,6,7 T Elizabeth Workman,8,9 Qing Zeng-Treitler,8,9 Joseph L Goulet1,5 1Research, VA Connecticut Healthcare System, West Haven, CT, USA; 2General Internal Medicine, Yale School of Medicine, New Haven, CT, USA; 3Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA; 4Department of Medicine and The George Washington Cancer Center, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA; 5Department of Emergency Medicine, Yale School of Medicine, New Haven, CT, USA; 6Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 7Pain Research, Informatics, Multi-Morbidities, and Education Center, VA Connecticut Healthcare System, West Haven, CT, USA; 8Biomedical Informatics Center, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA; 9Research, Washington VA Medical Center, Washington, DC, USACorrespondence: Kirsha S Gordon, VA Connecticut Healthcare System, Bldg. 35A, 950 Campbell Avenue, West Haven, CT, 06516, USA, Tel +1 203-932-5711, Email kirsha.gordon2@va.govBackground: Pain assessment is performed in many healthcare systems, such as the Veterans Health Administration, but prior studies have not assessed whether pain screening varies in sexual and gender minority populations that include individuals who identify as lesbian, gay, bisexual, and/or transgender (LGBT).Objective: The purpose of this study was to evaluate pain screening and reported pain of LGBT Veterans compared to non-LGBT Veterans.Methods: Using a retrospective cross-sectional cohort, data from the Corporate Data Warehouse, a national repository with clinical/administrative data, were analyzed. Veterans were classified as LGBT using natural language processing. We used a robust Poisson model to examine the association between LGBT status and binary outcomes of pain scree

Newborn hearing screening (NHS) was implemented in Albania in four maternity hospitals in 2018 and 2019. Implementation outcome, screening outcome, and screening quality measures were evaluated. Infants were first screened by midwives and nurses before discharge from the maternity hospital and returned for follow-up screening. Acceptability, appropriateness, feasibility, adoption, fidelity, coverage, attendance, and stepwise and final-referral rates were assessed by onsite observations, interviews, questionnaires, and a screening database. A post hoc analysis was performed to identify reasons for loss to follow up (LTFU) in a multivariate logistic regression. In total, 22,818 infants were born, of which 96.6% were screened. For the second screening step, 33.6% of infants were LTFU, 40.4% for the third, and 35.8% for diagnostic assessment. Twenty-two (0.1%) were diagnosed with hearing loss of ≥40 dB, six unilateral. NHS was appropriate and feasible: most infants are born in maternity hospitals, hence nurses and midwives could perform screening, and screening rooms and logistic support were supplied. Adoption among screeners was good. Referral rates decreased steadily, reflecting increasing skill. Occasionally, screening was repeated during a screening step, contrary to the protocol. NHS in Albania was implemented successfully, though LTFU was high. It is important to have effective data tracking and supervision throughout the screening.

Identifying suicidality including suicidal ideation, attempts, and risk factors in electronic health record data in clinical notes is difficult. A major difficulty is the lack of training samples given the small number of true positive instances among the increasingly large number of patients being screened. This paper describes a novel methodology that identifies suicidality in clinical notes by addressing this data sparsity issue through zero-shot learning. U.S. Veterans Affairs clinical notes served as data. The training dataset label was determined using diagnostic codes of suicide attempt and self-harm. A base string associated with the target label of suicidality was used to provide auxiliary information by narrowing the positive training cases to those containing the base string. A deep neural network was trained by mapping the training documents contents to a semantic space. For comparison, we trained another deep neural network using the identical training dataset labels and bag-of-words features. The zero shot learning model outperformed the baseline model in terms of AUC, sensitivity, specificity, and positive predictive value at multiple probability thresholds. In applying a 0.90 probability threshold, the methodology identified notes not associated with a relevant ICD 10 CM code that documented suicidality, with 94 percent accuracy. This new method can effectively identify suicidality without requiring manual annotation., Comment: 8 pages, 4 figures, 5 tables

One of the most challenging computational problems in the Run 3 of the Large Hadron Collider (LHC) and more so in the High-Luminosity LHC (HL-LHC) is expected to be finding and fitting charged-particle tracks during event reconstruction. The methods used so far at the LHC and in particular at the CMS experiment are based on the Kalman filter technique. Such methods have shown to be robust and to provide good physics performance, both in the trigger and offline. In order to improve computational performance, we explored Kalman-filter-based methods for track finding and fitting, adapted for many-core SIMD architectures. This adapted Kalman-filter-based software, called "mkFit", was shown to provide a significant speedup compared to the traditional algorithm, thanks to its parallelized and vectorized implementation. The mkFit software was recently integrated into the offline CMS software framework, in view of its exploitation during the Run 3 of the LHC. At the start of the LHC Run 3, mkFit will be used for track finding in a subset of the CMS offline track reconstruction iterations, allowing for significant improvements over the existing framework in terms of computational performance, while retaining comparable physics performance. The performance of the CMS track reconstruction using mkFit at the start of the LHC Run 3 is presented, together with prospects of further improvement in the upcoming years of data taking., Comment: Contribution to the ACAT 2022

Objective For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. Methods The EUSCREEN Questionnaire, conducted in 2017-2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow-up, were reappraised with an additional questionnaire. Results The practice of data collection in vision screening was reported in 36% (N = 42) of countries and in hearing screening in 81% (N = 43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. Conclusions Data collection is insufficient in hearing screening and even more so in vision screening: data essential for cost-effectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency.

The Snake Detection Theory implicates constricting snakes in the origin of primates, and venomous snakes for differences between catarrhine and platyrrhine primate visual systems. Although many studies using different methods have found very rapid snake detection in catarrhines, including humans, to date no studies have examined how quickly platyrrhine primates can detect snakes. We therefore tested in captive coppery titi monkeys (Plecturocebus cupreus) the latency to detect a small portion of visible snake skin. Because titi monkeys are neophobic, we designed a crossover experiment to compare their latency to look and their duration of looking at a snake skin and synthetic feather of two lengths (2.5 cm and uncovered). To test our predictions that the latency to look would be shorter and the duration of looking would be longer for the snake skin, we used survival/event time models for latency to look and negative binomial mixed models for duration of looking. While titi monkeys looked more quickly and for longer at both the snake skin and feather compared to a control, they also looked more quickly and for longer at larger compared to smaller stimuli. This suggests titi monkeys' neophobia may augment their visual abilities to help them avoid dangerous stimuli.

On July 8th, 2020, the United States Supreme Court held in Our Lady of Guadalupe School v. Morrissey-Berru that two parochial school teachers, Kristen Biel and Agnes-Morrissey-Berru, were ministers for purposes of the First Amendment’s ministerial exception. This meant that the First Amendment barred their respective employment discrimination actions notwithstanding the merit of their claims. When the Court first recognized the ministerial exception in 2012, in Hosanna-Tabor Evangelical Lutheran Church & School v. Equal Employment Opportunity Commission, it determined that an employee qualified as a minister through a multi-factor, totality of the circumstances analysis. Yet, in reaching its conclusion in Our Lady of Guadalupe School, the Court focused predominantly on one factor—whether the employees performed religious functions. This Comment argues that the Court’s sole focus on religious function has significantly expanded the scope of the ministerial exception, such that more employees of more religious institutions are likely to qualify as ministers and thus lose their federal antidiscrimination employment protections. Given the policy interests at stake, courts applying the ministerial exception after Our Lady of Guadalupe School should recognize that a broad reading invites exploitation and interpret the opinion in its narrowest form.

Introduction: To improve early identification and assessment of patients at risk of developing poststroke spasticity (PSS), Global Spasticity Experts collaborated to develop the PSS Risk Classification System. This tool provides clinicians with a framework and criteria for screening PSS patients to identify appropriate treatment referrals in a timely manner. This study aimed to validate the content of the initial version to ensure its relevance and appropriateness for clinicians in referring PSS patients to a specialist. Method(s): Cognitive interviews were conducted with clinicians who treat PSS to assess the PSS Risk Classification System and its domains: a) urgent referral, b) routine referral, and c) periodic monitoring. Verbatim transcripts were analysed using qualitative data analysis software (ATLAS.ti) to assess clinicians' understanding of the tool. Eligible clinicians did not inject onabotulinumtoxinA to treat spasticity, and did not participate in the development of the PSS Risk Classification System. Result(s): Thirteen clinicians (US n=5; Canada n=8) were interviewed and expressed favourable impressions and deemed the tool fit for purpose with some revisions. Recommended revisions were minor and focused on language to increase clarity and relevance through simple text revisions and addition of verbiage, as well as revisions to layout and presentation for print/digital versions. Conclusion(s): Clinician feedback supports the relevance and appropriateness of the PSS Risk Classification System. Clinicians requested that this tool be available in multiple formats, and available to occupational therapists, physiatrists, and primary care providers. Next steps include implementing revisions and confirming inter-rater reliability of the updated tool in the real world.

BackgroundUnderstanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.SettingCenters for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.MethodsWe identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores.ResultsOf 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm 3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm 3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm 3 , diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died.ConclusionsPWH with CD4 count <350 cells/mm 3 , and a history of CD4 count <200 cells/mm 3 , have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.

Dataset: GO-SHIP Line I07N POM Concentrations, This dataset includes particulate organic matter (POM) concentrations for carbon, nitrogen, and phosphorus. Data are from samples collected from NOAA Ship R/V Ronald H. Brown (cruise EXPOCODE: 33RO20180423), acting under the auspices of the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP), I07N GO-SHIP/CO2 Repeat Hydrography Cruise in 2018. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/879076, NSF Division of Ocean Sciences (NSF OCE) OCE-1848576

Objective: For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. Methods: The EUSCREEN Questionnaire, conducted in 2017–2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow- up, were reappraised with an additional questionnaire. Results: The practice of data collection in vision screening was reported in 36% (N =42) of countries and in hearing screening in 81% (N=43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. Conclusions: Data collection is insufficient in hearing screening and even more so in vision screening: data essential for costeffectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency.

Lassa fever is a severe viral hemorrhagic fever caused by a zoonotic virus that repeatedly spills over to humans from its rodent reservoirs. It is currently not known how climate and land use changes could affect the endemic area of this virus, currently limited to parts of West Africa. By exploring the environmental data associated with virus occurrence using ecological niche modelling, we show how temperature, precipitation and the presence of pastures determine ecological suitability for virus circulation. Based on projections of climate, land use, and population changes, we find that regions in Central and East Africa will likely become suitable for Lassa virus over the next decades and estimate that the total population living in ecological conditions that are suitable for Lassa virus circulation may drastically increase by 2070. By analysing geotagged viral genomes using spatially-explicit phylogeography and simulating virus dispersal, we find that in the event of Lassa virus being introduced into a new suitable region, its spread might remain spatially limited over the first decades.

Social monogamy is a reproductive strategy characterized by pair living and defense of a common territory. Pair bonding, sometimes displayed by monogamous species, is an affective construct that includes preference for a specific partner, distress upon separation, and the ability of the partner to buffer against stress. Many seahorse species show a monogamous social structure in the wild, but their pair bond has not been well studied. We examined the gene expression of lined seahorses (Hippocampus erectus) during and after the process of pairing in the laboratory as well as color change (luminance), a potential form of social communication and behavioral synchrony between pair mates. When a seahorse of either sex was interacting with its pair mate, their changes in luminance ("brightness") were correlated and larger than when interacting with an opposite-sex stranger. At the conclusion of testing, subjects were euthanized, RNA was extracted from whole brains and analyzed via RNA sequencing. Changes in gene expression in paired males versus those that were unpaired included processes governing metabolic activity, hormones and cilia. Perhaps most interesting is the overlap in gene expression change induced by pairing in both male seahorses and male prairie voles, including components of hormone systems regulating reproduction. Because of our limited sample size, we consider our results and interpretations to be preliminary, and prompts for further exploration. Future studies will expand upon these findings and investigate the neuroendocrine and genetic basis of these behaviors.

Little is known about how demographic, employment and meteorological factors impact physical activity. We conducted an analysis to explore these associations from participants (N = 447) from six cities in the United States and matched their activity data with abstracted local meteorological data from National Oceanic and Atmospheric Administration (NOAA) weather reports. Participants were purposively recruited in 3-month blocks, from December 2015 to October 2017, to reflect physical activity engagement across the seasons. We calculated total physical activity (minutes/week) based on 7-day physical activity recall. Mild correlations were observed between meteorological factors and correlated with lower physical activity. Participants were least active in autumn (Median = 220 min/week) and most active in spring (Median = 375 min/week). In addition to level of education and total hours of work, maximum temperature, relative humidity, heating degree day, precipitation and sunset time together explained 17.6% of variance in total physical activity. Programs assisting in employment for PLHIV and those that promote indoor physical activity during more strenuous seasons are needed. Additional research to better understand the selection, preferences, and impact of indoor environments on physical activity is warranted.

Acoustic signals are ubiquitous across mammalian taxa. They serve a myriad of functions related to the formation and maintenance of social bonds and can provide conspecifics information about caller condition, motivation and identity. Disentangling the relative importance of evolutionary mechanisms that shape vocal variation is difficult, and little is known about heritability of mammalian vocalizations. Duetting--coordinated vocalizations within male and female pairs--arose independently at least four times across the Primate Order. Primate duets contain individual- or pair-level signatures, but the mechanisms that shape this variation remain unclear. Here, we test for evidence of heritability in two call types (pulses and chirps) from the duets of captive coppery titi monkeys (Plecturocebus cupreus). We extracted four features--note rate, duration, minimum and maximum fundamental frequency--from spectrograms of pulses and chirps, and estimated heritability of the features. We also tested whether features varied with sex or body weight. We found evidence for moderate heritability in one of the features examined (chirp note rate), whereas inter-individual variance was the most important source of variance for the rest of the features. We did not find evidence for sex differences in any of the features, but we did find that body weight and fundamental frequency of chirp elements covaried. Kin recognition has been invoked as a possible explanation for heritability or kin signatures in mammalian vocalizations. Although the function of primate duets remains a topic of debate, the presence of moderate heritability in titi monkey chirp elements indicates duets may serve a kin recognition function.

We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose-dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue-specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.

In socially monogamous titi monkeys, involuntary separation from a pair mate can produce behavioral distress and increased cortisol production. The neuropeptide oxytocin (OXT) is thought to play an important role in the separation response of pair-bonded species. Previous studies from our lab have shown that chronic intranasal oxytocin (IN OXT) during development can have long-term effects on adult social behavior. In the current study, we examined the chronic and acute effects of IN OXT or Saline (SAL) on the subjects' response to a brief separation from their pair mates. Subjects with a history of chronic IN OXT or SAL treatment during development received a single dose of OXT or SAL as adults 30 min before being separated from their pair mate. Chronic treatment consisted of a daily dose of IN OXT (0.8 IU/kg) or SAL (control) from 12 to 18 months of age. Subjects (N = 29) were introduced to a pair mate at 30 months of age. After the pairs had cohabitated for 5 months, pairs underwent two "Brief Separation" (OXT and SAL) and two "Non-Separation" (OXT and SAL) test sessions. Vocalizations and locomotion were measured as behavioral indices of agitation or distress during the Brief Separation and Non-Separation periods (30 min each). We collected blood samples after the Brief Separation and Non-Separation periods to measure cortisol levels. Our results showed subjects treated with chronic OXT had a reduction in long call and peep vocalizations compared to subjects treated with chronic SAL. Subjects treated with chronic SAL and acute OXT produced more peeps and long calls compared to animals treated with acute SAL; however, patterns in this response depended on sex. Cortisol and locomotion were significantly higher during the Brief Separation period compared to the Non-Separation period; however, we did not find any treatment or sex effects. We conclude that chronic IN OXT given during development blunts the separation response, while acute OXT in chronic SAL subjects

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown. Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury. In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury. Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway. Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1-3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.

Concentrations and elemental stoichiometry of suspended particulate organic carbon, nitrogen, phosphorus, and oxygen demand for respiration (C:N:P:-O2) play a vital role in characterizing and quantifying marine elemental cycles. Here, we present Version 2 of the Global Ocean Particulate Organic Phosphorus, Carbon, Oxygen for Respiration, and Nitrogen (GO-POPCORN) dataset. Version 1 is a previously published dataset of particulate organic matter from 70 different studies between 1971 and 2010, while Version 2 is comprised of data collected from recent cruises between 2011 and 2020. The combined GO-POPCORN dataset contains 2673 paired surface POC/N/P measurements from 70°S to 73°N across all major ocean basins at high spatial resolution. Version 2 also includes 965 measurements of oxygen demand for organic carbon respiration. This new dataset can help validate and calibrate the next generation of global ocean biogeochemical models with flexible elemental stoichiometry. We expect that incorporating variable C:N:P:-O2 into models will help improve our estimates of key ocean biogeochemical fluxes such as carbon export, nitrogen fixation, and organic matter remineralization.

BACKGROUND: An effective newborn hearing screening programme has low referral rate and low loss to follow-up (LTFU) rate after referral from initial screening. This systematic review identified studies evaluating the effect of protocol and programme factors on these two outcomes, including the screening method used and the infant group. METHODS: Five databases were searched (latest: April 2021). Included studies reported original data from newborn hearing screening and described the target outcomes against a protocol or programme level factor. Studies were excluded if results were only available for one risk condition, for each ear, or for < 100 infants, or if methodological bias was observed. Included studies were evaluated for quality across three domains: sample, screening and outcome, using modified criteria from the Ottawa-Newcastle and QUADAS-2 scales. Findings from the included studies were synthesised in tables, figures and text. RESULTS: Fifty-eight studies reported on referral rate, 8 on LTFU rate, and 35 on both. Only 15 studies defined LTFU. Substantial diversity in referral and LTFU rate was observed across studies. Twelve of fourteen studies that evaluated screening method showed lower referral rates with aABR compared to TEOAE for well babies (WB). Rescreening before hospital discharge and screening after 3 days of age reduced referral rates. Studies investigating LTFU reported lower rates for programmes that had audiologist involvement, did not require fees for step 2, were embedded in a larger regional or national programme, and scheduled follow-up in a location accessible to the families. In programmes with low overall LTFU, higher LTFU was observed for infants from the NICU compared to WB. CONCLUSION: Although poor reporting and exclusion of non-English articles may limit the generalisability from this review, key influential factors for referral and LTFU rates were identified. Including aABR in WB screening can effectively reduce referral rate

BACKGROUND: An effective newborn hearing screening programme has low referral rate and low loss to follow-up (LTFU) rate after referral from initial screening. This systematic review identified studies evaluating the effect of protocol and programme factors on these two outcomes, including the screening method used and the infant group. METHODS: Five databases were searched (latest: April 2021). Included studies reported original data from newborn hearing screening and described the target outcomes against a protocol or programme level factor. Studies were excluded if results were only available for one risk condition, for each ear, or for < 100 infants, or if methodological bias was observed. Included studies were evaluated for quality across three domains: sample, screening and outcome, using modified criteria from the Ottawa-Newcastle and QUADAS-2 scales. Findings from the included studies were synthesised in tables, figures and text. RESULTS: Fifty-eight studies reported on referral rate, 8 on LTFU rate, and 35 on both. Only 15 studies defined LTFU. Substantial diversity in referral and LTFU rate was observed across studies. Twelve of fourteen studies that evaluated screening method showed lower referral rates with aABR compared to TEOAE for well babies (WB). Rescreening before hospital discharge and screening after 3 days of age reduced referral rates. Studies investigating LTFU reported lower rates for programmes that had audiologist involvement, did not require fees for step 2, were embedded in a larger regional or national programme, and scheduled follow-up in a location accessible to the families. In programmes with low overall LTFU, higher LTFU was observed for infants from the NICU compared to WB. CONCLUSION: Although poor reporting and exclusion of non-English articles may limit the generalisability from this review, key influential factors for referral and LTFU rates were identified. Including aABR in WB screening can effectively reduce referral r

Data curation is the process of making a dataset fit-for-use and archiveable. It is critical to data-intensive science because it makes complex data pipelines possible, makes studies reproducible, and makes data (re)usable. Yet the complexities of the hands-on, technical and intellectual work of data curation is frequently overlooked or downplayed. Obscuring the work of data curation not only renders the labor and contributions of the data curators invisible; it also makes it harder to tease out the impact curators' work has on the later usability, reliability, and reproducibility of data. To better understand the specific work of data curation -- and thereby, explore ways of showing curators' impact -- we conducted a close examination of data curation at a large social science data repository, the Inter-university Consortium of Political and Social Research (ICPSR). We asked, What does curatorial work entail at ICPSR, and what work is more or less visible to different stakeholders and in different contexts? And, how is that curatorial work coordinated across the organization? We triangulate accounts of data curation from interviews and records of curation in Jira tickets to develop a rich and detailed account of curatorial work. We find that curators describe a number of craft practices needed to perform their work, which defies the rote sequence of events implied by many lifecycle or workflow models. Further, we show how best practices and craft practices are deeply intertwined., Comment: submitted to CSCW 2022 (Feb revision cycle)

ADARs catalyze adenosine-to-inosine (A-to-I) editing of double-stranded RNA and regulate global gene expression output through interactions with RNA and other proteins. ADARs play important roles in development and disease, and previous work has shown that ADAR1 is oncogenic in a growing list of cancer types. Here we show that ADAR1 is a critical gene for triple-negative breast cancer cells, as ADAR1 loss results in reduced growth (viability and cell cycle progression), invasion, and mammosphere formation. Whole transcriptome sequencing analyses demonstrate that ADAR1 regulates both coding and noncoding targets by altering gene expression level, A-to-I editing, and splicing. We determine that a recoding edit in filamin B (FLNB chr3:58156064) reduces the tumor suppressive activities of the protein to promote growth and invasion. We also show that several tumor suppressor miRNAs are upregulated upon ADAR1 loss and suppress cell-cycle progression and invasion. This work describes several novel mechanisms of ADAR1-mediated oncogenesis in triple-negative breast cancer, providing support to strategies targeting ADAR1 in this aggressive cancer type that has few treatment options.

As social animals, many primates use acoustic communication to maintain relationships. Vocal individuality has been documented in a diverse range of primate species and call types, many of which have presumably different functions. Auditory recognition of one's neighbors may confer a selective advantage if identifying conspecifics decreases the need to participate in costly territorial behaviors. Alternatively, vocal individuality may be nonadaptive and the result of a unique combination of genetics and environment. Pair-bonded primates, in particular, often participate in coordinated vocal duets that can be heard over long distances by neighboring conspecifics. In contrast to adult calls, infant vocalizations are short-range and used for intragroup communication. Here, we provide two separate but complementary analyses of vocal individuality in distinct call types of coppery titi monkeys (Plecturocebus cupreus) to test whether individuality occurs in call types from animals of different age classes with presumably different functions. We analyzed 600 trill vocalizations from 30 infants and 169 pulse-chirp duet vocalizations from 30 adult titi monkeys. We predicted that duet contributions would exhibit a higher degree of individuality than infant trills, given their assumed function for long-distance, intergroup communication. We estimated 7 features from infant trills and 16 features from spectrograms of adult pulse-chirps, then used discriminant function analysis with leave-one-out cross-validation to classify individuals. We correctly classified infants with 48% accuracy and adults with 83% accuracy. To further investigate variance in call features, we used a multivariate variance components model to estimate variance partitioning in features across two levels: within- and between-individuals. Between-individual variance was the most important source of variance for all features in adults, and three of four features in infants. We show that pulse-chirps of adult

RationaleIndividuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD.ObjectivesTo determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks.MethodsWe used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD.ResultsTolcapone significantly reduced self-reported alcohol consumption (t (54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r (45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo.ConclusionsThese data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.Trial registrationClinicalTrials.gov Identifier: NCT02740582.

Climate-driven depletion of ocean oxygen strongly impacts the global cycles of carbon and nutrients as well as the survival of many animal species. One of the main uncertainties in predicting changes to marine oxygen levels is the regulation of the biological respiration demand associated with the biological pump. Derived from the Redfield ratio, the molar ratio of oxygen to organic carbon consumed during respiration (i.e., the respiration quotient, [Formula: see text]) is consistently assumed constant but rarely, if ever, measured. Using a prognostic Earth system model, we show that a 0.1 increase in the respiration quotient from 1.0 leads to a 2.3% decline in global oxygen, a large expansion of low-oxygen zones, additional water column denitrification of 38 Tg N/y, and the loss of fixed nitrogen and carbon production in the ocean. We then present direct chemical measurements of [Formula: see text] using a Pacific Ocean meridional transect crossing all major surface biome types. The observed [Formula: see text] has a positive correlation with temperature, and regional mean values differ significantly from Redfield proportions. Finally, an independent global inverse model analysis constrained with nutrients, oxygen, and carbon concentrations supports a positive temperature dependence of [Formula: see text] in exported organic matter. We provide evidence against the common assumption of a static biological link between the respiration of organic carbon and the consumption of oxygen. Furthermore, the model simulations suggest that a changing respiration quotient will impact multiple biogeochemical cycles and that future warming can lead to more intense deoxygenation than previously anticipated.