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Background The typical method for multidisciplinary teams (MDT) to coordinate care in a rehabilitation setting is by holding weekly meetings. These MDT meetings are not always effective, with poor communication and vague plans of treatment leading to a lack of progress with rehabilitation and even delayed patient discharge. Methods The MDT of the older person’s rehabilitation unit aimed to improve their MDT meeting. A series of meetings, open to all members, identified the key issues. These were; variation in the level of contribution from attending disciplines, a lack of clarity on patients’ current status, a lack of SMART goals being set and Predicted Dates of Discharge (PDD) not being set. This was confirmed by clinical audit examining contribution levels of attending disciplines across four questions. The proposed solution was a structured document called the Collaborative Rehabilitation Plan (CRP) booklet for use at MDT meetings, which was designed by a subcommittee with feedback from the full group. The audit was repeated after a one-month trial of the booklet. Results The average contribution was highest on the current status of the patient (59%), and this was not changed post-booklet (59%). This was lower regarding the setting of goals (18%), and this improved post booklet (40%). The average contribution was lowest for the goals meeting SMART criteria (4%). This improved post booklet (28%). Improvement was also seen in the setting of PDDs (from 27% to 52%). While the level of contributions from all disciplines improved after the introduction of the booklet (from 27% to 42%) there was still a wide degree of variation. Conclusion The development of the CRP booklet was of value in increasing the contributions of the team in a number of key areas. Contributions were still low in some areas and further work is needed to improve this.

BackgroundThe cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions.MethodsWe quantified cerebellar lobule volumes using structural magnetic resonance imaging in 4,215 adults (PTSD n= 1640; Control n=2575) across 40 sites from the from the ENIGMA-PGC PTSD working group. Using a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation, we obtained volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum total and subregional volume in PTSD compared to healthy controls. The Benjamini-Hochberg procedure was used to control the false discovery rate (p-FDR< .05).ResultsPTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume. In addition, people with PTSD showed reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), but also the vermis (VI, VIII), flocculonodular lobe (lobule X), and cerebellar white matter (allp-FDR< 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status.ConclusionsThese findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in high-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Social hierarchies within groups define the distribution of resources and provide benefits that support the collective group or favor dominant members. The progression of individuals through social hierarchies is a valuable characteristic for quantifying population dynamics. On coral reefs, some clownfish maintain size-based hierarchical communities where individuals queue through social ranks. The cost of waiting in a lower-ranked position is outweighed by the reduced risk of eviction and mortality. The orange clownfish, Amphiprion percula, maintains stable social groups with subordinate individuals queuing to be part of the dominant breeding pair. Strong association with their host anemone, complex social interactions, and relatively low predation rates make them ideal model organisms to assess changes in group dynamics through time in their natural environment. Here, we investigate the rank changes and isometric growth rates of A. percula from 247 naturally occurring social groups in Kimbe Island, Papua New Guinea (5° 12′ 13.54″ S, 150° 22′ 32.69″ E). We used DNA profiling to assign and track individuals over eight years between 2011 and 2019. Over half of the individuals survived alongside two or three members of their original social group, with twelve breeding pairs persisting over the study period. Half of the surviving individuals increased in rank and experienced double the growth rate of those that maintained their rank. Examining rank change in a wild fish population provides new insights into the complex social hierarchies of reef fishes and their role in social evolution.

Fungal endophytes in perennial ryegrass are essential to New Zealand’s pastoral system due to anti-insect effects. However, endophytes also produce compounds which can be detrimental to animals. Furthermore, as these toxins have been detected in the milk and fat of animals grazing common-toxic (containing lolitrem B) or AR37 endophyte-infected herbage they could enter the human food chain. To assess the risk to human health mice were fed for 90 days with three dose rates of lolitrem B and of AR37. Parameters indicative of animal health were measured as well as chemical, hematological and histological analysis of samples collected on day 90. Since endophyte toxin residues have been detected in milk, they could be transferred from mother to offspring via breast milk. To evaluate possible effects on reproduction two complete generations of mice were fed lolitrem B or AR37. At the dose rates given no adverse effects were observed in either study. The 100-fold safety factor to allow the use of animal data in human health assessments was applied and by considering the concentrations of lolitrem B or AR37 metabolites which could be ingested by a consumer it is highly unlikely that they pose any risk to human health.

Atomically thin semiconductors such as transition metal dichalcogenide (TMD) monolayers exhibit a very strong Coulomb interaction, giving rise to a rich exciton landscape. This makes these materials highly attractive for efficient and tunable optoelectronic devices. In this Research Update, we review the recent progress in the understanding of exciton optics, dynamics, and transport, which crucially govern the operation of TMD-based devices. We highlight the impact of hexagonal boron nitride-encapsulation, which reveals a plethora of many-particle states in optical spectra, and we outline the most novel breakthroughs in the field of exciton-polaritonics. Moreover, we underline the direct observation of exciton formation and thermalization in TMD monolayers and heterostructures in recent time-resolved, angle-resolved photoemission spectroscopy studies. We also show the impact of exciton density, strain, and dielectric environment on exciton diffusion and funneling. Finally, we put forward relevant research directions in the field of atomically thin semiconductors for the near future.

Metacognition reflects our capacity to monitor or evaluate other cognitive states as they unfold during task performance, for example, our level of confidence in the veracity of a memory. Impaired metacognition is seen in patients with traumatic brain injury (TBI) and substantially impacts their ability to manage functional difficulties during recovery. Recent evidence suggests that metacognitive representations reflect domain-specific processes (e.g., memory vs. perception) acting jointly with generic confidence signals mediated by widespread frontoparietal networks. The impact of neurological insult on metacognitive processes across different cognitive domains following TBI remains unknown.To assess metacognitive accuracy, we measured decision confidence across both a perceptual and memory task in patients with TBI (First, we observed a deficit in metacognitive efficiency across both tasks suggesting that patients show a loss of perceptual and memorial evidence available for confidence judgments despite equivalent accuracy levels to controls. Second, a late positive-going ERP waveform (500-700 ms) was greater in amplitude for high versus low-confidence judgements for controls across both task domains. By contrast, in patients with TBI, the same ERP waveform did not vary by confidence level suggesting a deficient or attenuated neural marker of decision confidence postinjury.These findings suggest that diffuse damage to putative frontoparietal regions in patients disrupts domain-general metacognitive accuracy and electrophysiological signals that accumulate evidence of decision confidence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011-2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.La prevención del VIH/VHC entre las personas que se inyectan drogas (PWID) es de vital importancia para la salud pública. Nuestro objetivo fue evaluar el impacto de COVID-19 y las medidas de respuesta asociadas en los servicios de prevención del VIH/VHC y el estado socioeconómico de las PWID en sitios de alto riesgo de VIH. Se contactó con sitios con brotes recientes (2011–2019) de VIH entre PWID en Europa, América del Norte e Israel, que habían sido previamente identificados, a principios de mayo de 2020. De los 17 sitios invitados a participar, 13 aceptaron. Se prepararon informes cualitativos semiestructurados del sitio que cubrían los datos de marzo a mayo de 2020, analizados/codificados y confirmados con un cuestionario estructurado, en el que todos los sitios respondieron explícitamente a los 103 asuntos reportados en los informes cualitativos. El tratamiento de mantenimiento con opiáceos, los programas de agujas/jeringas y el tratamiento antirretroviral/tratamiento de la hepatitis C continuaron, pero con importantes reducciones y cambios operativos. Se reportaron aumentos en las sobredosis, dificultades generalizadas con las necesidades alimentarias y de higiene, interrupciones en el suministro de medicamentos y aumento de personas sin hogar. Los programas de servicios reformaron rápidamente las políticas restrictivas de prestación de servicios, establecidas desde hace mucho tiempo y políticamente arraigadas. Las futuras medidas de control de epidemias deben incluir la mitigación de los efectos secundarios negativos en la prestación de servicios y los determinantes socioeconómicos en las PWID.

OBJECTIVES To evaluate risk factors for postdischarge sequelae in children and adolescents hospitalized for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C). METHODS Multicenter prospective cohort study conducted in 25 United States pediatric hospitals. Patients RESULTS Of 358 eligible patients, 2 to 4 month survey data were available for 119 of 155 (76.8%) with acute COVID-19 and 160 of 203 (78.8%) with MIS-C. Thirteen (11%) patients with acute COVID-19 and 12 (8%) with MIS-C had a readmission. Thirty-two (26.9%) patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) and 48 (30.0%) with MIS-C had persistent symptoms (20.0%) or activity impairment (21.3%). For patients with acute COVID-19, persistent symptoms (aRR, 1.29 [95% CI, 1.04–1.59]) and activity impairment (aRR, 1.37 [95% CI, 1.06–1.78]) were associated with more organ systems involved. Patients with MIS-C and pre-existing respiratory conditions more frequently had persistent symptoms (aRR, 3.09 [95% CI, 1.55–6.14]) and those with obesity more frequently had activity impairment (aRR, 2.52 [95% CI, 1.35–4.69]). New morbidities were infrequent (9% COVID-19, 1% MIS-C). CONCLUSIONS Over 1 in 4 children hospitalized with acute COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Patients with MIS-C and respiratory conditions or obesity are at higher risk of prolonged recovery.

To describe the methods for the in-person assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors that promote bladder health and/or prevent lower urinary tract symptoms in adult women, conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS).A subset of RISE participants who express interest in the in-person assessment will be screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete 15 physical assessments in addition to height and weight, to assess pelvic floor muscle function, musculoskeletal (MSK) status, and pain, and to provide urogenital microbiome samples. Pelvic floor muscle assessments include presence of prolapse, strength, levator attachment integrity (tear) and myofascial pain. MSK tests evaluate core stability, lumbar spine, pelvic girdle and hip pain and function. Participants are asked to complete the Short Physical Performance Battery to measure balance, lower extremity strength, and functional capacity. All participants are asked to provide a voided urine sample and a vaginal swab for microbiome analyses; a subset of 100 are asked to contribute additional samples for feasibility and validation of a home collection of urinary, vaginal, and fecal biospecimens.Online and in-person training sessions were used to certify research staff at each clinical center before the start of RISE in-person assessments. Standardized protocols and data collection methods are employed uniformly across sites.The RISE in-person assessment is an integral portion of the overall population-based RISE study and represents an innovative approach to assessing factors hypothesized to promote bladder health and/or prevent lower urinary tract symptoms. Data collected from this assessment will be used to prioritize future research questions and prevention strategies and interventions. This description of the assessment methods is intended to provide methodologic transparency and inform other researchers who join efforts to understand and improve bladder health.

(s): Existing bladder-specific measures lack ability to assess a range of bladder health from poor to optimal health. We report evidence for validity of the self-administered, multidimensional Bladder Health Scales and Function Indices for research in adult women.A cross-sectional population-based validation study with random assignment to paper or electronic administration was conducted using national address-based probability sampling supplemented by purposive sampling of women with lower urinary tract symptoms surrounding 7 clinical research centers. Construct validity of the Bladder Health Scales and Function Indices was guided by Multitrait-Multimethod approach using health and condition-specific questionnaires, bladder diaries, expert ratings of bladder health, and noninvasive bladder function testing. Internal dimensional validity was evaluated using factor analysis; internal reliability was assessed using paired t-tests and 2-way mixed effects Intraclass Correlation Coefficient models. Mode comparisons used chi-square, Fisher Exact or t-tests. Convergent validity was evaluated using Pearson correlations with the external construct measures and known-group validity was established with comparison of women known and unknown to be symptomatic with urinary conditions.The sample included 1,072 participants. Factor analysis identified ten scales with Cronbach's alpha ranging 0.74-0.94. Intraclass correlation coefficients of scales ranged from 0.55-0.94. Convergent validity of ten scales and six indices ranged from 0.52- 0.83. Known-group validity was confirmed for all scales and indices. Item distribution was similar by mode of administration.The paper and electronic forms of the Bladder Health Scales and Function Indices are reliable and valid measures of bladder health for use in women's health research.

INTRODUCTION Pelvic girdle pain (PGP) is the most common musculoskeletal concern in pregnancy. The Active Straight Leg Raise (ASLR) test is diagnostic. Sacroiliac joint (SIJ) belts are included in multimodal therapy, but there is no established predictive measure to determine which pregnant women will benefit. OBJECTIVE To determine if the ASLR score is immediately reduced by SIJ belt application and whether PGP pain and function improves after 4 weeks of belt use. DESIGN Prospective observational cohort study. SETTING Academic medical center. PARTICIPANTS Pregnant women at least 18 years of age in the second or third trimester of pregnancy with posterior PGP and ASLR score of 2 to 10. INTERVENTIONS Four-week SIJ belt use. MAIN OUTCOME MEASURES ASLR, Numerical Rating Scale (NRS), Pelvic Girdle Questionnaire (PGQ), Perceived Global Impression of Improvement (PGII). RESULTS Sixty-three women enrolled. On multivariable analysis, immediate belted ASLR score was -2.70 points lower than the non-belted ASLR score (P

For most of the scientific disciplines associated with coastal and estuarine research, workforce representation does not match the demographics of communities we serve, especially for Black, Hispanic or Latino, and Indigenous peoples. This essay provides an overview of this inequity and identifies how a scientific society can catalyze representational, structural, and interactional diversity to achieve greater inclusion. Needed changes go beyond representational diversity and require an intentional commitment to build capacity through inclusivity and community engagement by supporting anti-racist policies and actions. We want to realize a sense of belonging on the part of scientists in society at large and enable research pursuits through a lens of social justice in service of coastal communities. Minimally, this framework offers an avenue for increased recruitment of individuals from more diverse racial and ethnic identities. More broadly, the mechanisms described here aim to create a culture in scientific societies in which social justice, driven by anti-racist actions, produces systemic change in how members of scientific societies approach, discuss, and address issues of inequity. We have written this essay for members of the coastal and marine science community who are interested in change. We aim to call in new voices, allies, and champions to this work.

Individuals residing in more socioeconomically disadvantaged neighborhoods experience greater uncertainty through insecurity of basic needs such as food, employment, and housing, compared with more advantaged neighborhoods. Although the neurobiology of uncertainty has been less frequently examined in relation to neighborhood disadvantage, there is evidence that neighborhood disadvantage is associated with widespread neural alterations.Recently traumatically injured participants (There was a significant interaction during the anticipation period such that higher ADI rankings were related to greater activation of the right anterior cingulate cortex to predictable versus unpredictable neutral stimuli. Although no other robust interactions emerged related to ADI, we note several novel simple effects of ADI during anticipation and presentation periods in the hippocampus and prefrontal, cingulate, and occipital cortices.Together, these results may represent an adaptive response to predictable and/or negative stimuli, stemming from chronic exposure to socioeconomic-based uncertainties. Although effects were modest, future work should continue to examine pretrauma context on posttrauma outcomes. To better understand trauma outcomes, it is imperative that researchers consider the broader context in which trauma survivors reside.

INTRODUCTIONChest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs).METHODSWe performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens.RESULTSWe found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (supplemental oxygen or non-invasive ventilation [n=178]; invasive-mechanical ventilation [n=234], extracorporeal membrane oxygenation [n=13]) was significantly associated with RALE scores (median [interquartile range]: 20.0[14.1-26.7], 26.0[20.5-34.0] and 44.5[34.5-48.0], respectively, pCONCLUSIONReproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.

Growing evidence supports acupuncture for several pain conditions including chronic prostatitis. This study aimed to determine the safety, tolerability, and effectiveness of acupuncture in reducing pain in women with interstitial cystitis/bladder pain syndrome (IC/BPS).This prospective randomized single-blinded study compared electro-acupuncture (EA) to minimal acupuncture (MA) after 6 weekly treatments and again after 6 weeks of no treatment. Pain was assessed using the Brief Pain Inventory-Short Form (worst pain, average pain, pain severity, pain interference) and the Pain Catastrophizing Scale (PCS). Physical exams evaluated pelvic floor muscle tenderness. Mixed-effects models were used to estimate adjusted means over follow up.Patients were randomized to EA (n = 11) or MA (n = 10). There were no adverse events. Both groups' worst pain improved at 6 weeks, -2.91 ± 0.59 and -2.09 ± 0.68 for EA and MA respectively with no difference between groups (p = 0.37). Results were similar at 12 weeks. The EA group had greater improvement in pain interference at 6 weeks, -3.28 ± 0.51 versus -1.67 ± 0.58 (p = 0.049). The between group difference was not maintained at 12 weeks (p = 0.13). Average pain and pain severity showed no difference between groups (p0.05). The PCS improved overall at 6 weeks, -6.2 ± 2.5 (p = 0.03), with no difference between groups (p = 0.39). On physical exam, only the EA group showed a significant decrease in levator ani tenderness (p = 0.031) after treatment.Both EA and MA showed improvement in worst pain scores, however EA showed greater improvement in pain interference and pelvic floor muscle tenderness in women with IC/BPS.

In this data paper, we describe environmental DNA (eDNA) cytochrome c oxidase (COI) amplicon sequence data from New York City’s Bronx River Estuary. As urban systems continue to expand, describing and monitoring their biodiversity is increasingly important for sustainability. Once polluted and overexploited, New York City’s Bronx River Estuary is undergoing revitalization and restoration. To investigate and characterize the area’s diversity, we collected and sequenced river sediment and surface water samples from Hunts Point Riverside and Soundview Parks (ntotal = 48; nsediment = 25; nwater = 23). COI analysis using universal primers mlCOIintF and jgHCO2198 detected 27,328 Amplicon Sequence Variants (ASVs) from 7,653,541 sequences, and rarefaction curves reached asymptotes indicating sufficient sampling depth. Of these, eukaryotes represented 9,841ASVs from 3,562,254 sequences. At the study sites over the sampling period, community composition varied by substrate (river sediment versus surface water) and with water temperature, but not pH. The three most common phyla were Bacillariophyta (diatoms), Annelida (segmented worms), and Ochrophyta (e.g. brown and golden algae). Of the eukaryotic ASVs, we identified 614 (6.2%) to species level, including several dinoflagellates linked to Harmful Algal Blooms such as Heterocapsa spp., as well as the invasive amphipod Grandidierella japonica. The analysis detected common bivalves including blue (Mytilus edulis) and ribbed (Geukensia demissa) mussels, as well as soft-shell clams (Mya arenaria), in addition to Eastern oysters (Crassostrea virginica) that are being reintroduced to the area. Fish species undergoing restoration such as river herring (Alosa pseudoharengus, A. aestivalis) failed to be identified, although relatively common fish including Atlantic silversides (Menidia menidia), menhaden (Brevoortia tyrannus), striped bass (Morone saxatilis), and mummichogs (Fundulus heteroclitus) were found. The data highlight the utility of eDNA metabarcoding for analyzing urban estuarine biodiversity and provide a baseline for future work in the area.

The relationship between external lumbar, hip, and/or pelvic girdle pain and internal vaginal pelvic floor myofascial pain is not well described. We assessed this relationship in a cohort of adult women.The cohort included women ≥ 18 years old who received care for external lumbar, hip, and/or pelvic girdle pain (reported or elicited on physical examination) who then underwent internal vaginal myofascial levator ani pain assessments, in a tertiary care Female Pelvic Medicine and Reconstructive Surgery pelvic pain clinic over a 2-year period (2013 and 2014).The cohort of 177 women had an average age of 44.9±16.0 years, an average body mass index of 27.2±7.0 kg/mAlthough participants did not describe "vaginal pelvic floor myofascial pain," the high detection rate for internal vaginal pelvic floor myofascial pain on clinical examination highlights an opportunity to improve treatment planning. These findings suggest that the vaginal pelvic floor muscle examination should be part of the assessment of all women with lumbar, hip, and/or pelvic girdle pain. The relationship between this finding and clinical outcomes following directed treatment warrants additional study.

BACKGROUND: Drug-loaded meshes offer a promising delivery strategy for the prevention of local recurrence. Patient-derived xenograft (PDX) models are representative of individual patient tumors and predictive of clinical outcomes. METHODS: A patient-derived xenograft model was established in NSG mice using tumor tissue from a patient with aggressive lung adenocarcinoma. Paclitaxel-loaded meshes (PGA+PTX) were electrospun. Tumor-bearing mice were randomized into four groups after macroscopic complete resection: 1) no treatment (n = 10); 2) intraperitoneal paclitaxel (IP PTX) at 20 mg/kg (n = 10); 3) PGA mesh without drug (n = 14); and 4) PGA+PTX mesh at 12 mg/kg (n = 14). A 1 cm(2) mesh was placed onto the tumor resection beds. Groups were observed for local recurrence for 120 post-operative days. RESULTS: PDX mice treated with PGA+PTX meshes post-resection exhibit a greater than 5-fold increase in recurrence-free survival (p

Physiological condition can affect survival and reproductive success in seabirds. However, seabirds rarely show outward signs of poor physiological condition, making it difficult to identify and address issues before they result in population level impacts. We investigate physiological condition of breeding northern gannets (Morus bassanus) between years and nesting stages. Blood smears were used to quantify blood cell profiles indicative of chronic stress, infection, disease, and immunocompetence. No blood parasites were observed, but elevated Heterophil to Lymphocyte (H:L) ratios, eosinophils, and monocytes suggest higher prevalence of infection in some years. Chronic stress levels, indicated by high H:L ratio, were elevated in incubation and early chick-rearing compared to late chick-rearing, which coincided with poorer body condition in breeding birds. This study highlights the value of haematology as a tool for identifying changing patterns of health that may serve as an early indicator of breeding failure, overwintering mortality, and population declines.

Recent calls for engaging communities in biotechnology development do not draw enough attention to the hurdles that must be overcome for engagement strategies to effectively feed back into research design and conduct. These hurdles call into question many standard ways of operating and assessing in traditional scientific disciplines. The first steps in addressing these hurdles can be the most difficult. In reflecting on our own experiences in the early-stage development of environmental biotechnologies, we provide a set of techniques to help scientists and their collaborators learn to become more responsive to the needs and attitudes of communities with which they are engaging. Graphical Abstract

When longshore transport systems encounter tidal inlets, complex mechanisms are involved in bypassing sand to downdrift barriers. Here, this process is examined at Plum Island Sound and Essex Inlets, Massachusetts, USA. One major finding from this study is that sand is transferred along the coast—especially at tidal inlets—by parcels, in discrete steps, and over decadal-scale periods. The southerly orientation of the main-ebb channel at Plum Island Sound, coupled with the landward migration of bars from the ebb delta to the central portion of the downdrift Castle Neck barrier island, have formed a beach protuberance. During the constructional phase, sand is sequestered at the protuberance and the spit-end of the barrier becomes sediment starved, leading to shoreline retreat and a broadening of the spit platform at the mouth to Essex Bay (downdrift side of Castle Neck). Storm-induced sand transport from erosion of the spit and across the spit platform is washed into Essex Bay, filling channels and enlarging flood deltas. This study illustrates the pathways and processes of sand transfer along the shoreline of a barrier-island/tidal-inlet system and provides an important example of the processes that future hydrodynamic and sediment-transport modeling should strive to replicate.

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5 ). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target.

OBJECTIVE The aim of this study was to describe patient-reported longitudinal outcomes in a multidisciplinary female chronic pelvic pain (CPP) program. METHODS We conducted a retrospective cohort study for women cared for in a tertiary, multidisciplinary, female (CPP) program between 2012 and 2017. Patient demographics were collected from electronic medical records. Patients completed the numerical rating scale for pain, Pain Disability Index (PDI), and Patient Global Impression of Improvement scale at each visit. Mixed-effects models were used to assess change in patient responses over time. RESULTS Patients (N = 317) with a mean age of 44.3 years (SD, 14.6) and median duration of symptoms of 3 years (interquartile range, 1.0-7.0) were assessed in this analysis. The primary diagnosis was pelvic floor myofascial pain (67%). On multivariable analysis, numerical rating scale scores decreased by -0.11 point [95% confidence interval (CI), -0.20 to -0.01] every 3 months (P = 0.03). On multivariable analysis, total PDI score decreased by -0.88 point (95% CI, -1.43 to -0.33) (P = 0.003), and PDI sexual subscores decreased by -0.29 point (95% CI, -0.44 to -0.14) (P < 0.001) every 3 months. A higher (worse) Patient Global Impression of Improvement score was associated with a higher (worse) PDI score at follow-up (odds ratio, 1.04; 95% CI, 1.01-1.07; P = 0.01). CONCLUSIONS Patients in a multidisciplinary CPP program demonstrated improvement over time in pain disability that was associated with an overall global impression of improvement.

Background Family history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease. Objective To detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa. Design, setting, and participants A two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls. Outcome measurements and statistical analysis Frequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls. Results and limitations Eleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa. Conclusions Our approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease. Patient summary Multiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa.

There is significant heterogeneity in pain outcomes following motor vehicle crashes (MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain months after injury while others recover. Despite variable outcomes, the pathogenesis of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting state functional magnetic resonance imaging studies find increased functional connectivity (FC) between the dACC and regions involved in pain processing in those with chronic pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore relate to pain severity. The present study completed rsfMRI scans on N = 22 survivors of MVCs collected within 2 weeks of the incident to test whole-brain dACC-FC as a predictor of pain severity 6 months later. At 2 weeks, pain symptoms were predicted by positive connectivity between the dACC and the premotor cortex. Controlling for pain symptoms at 2 weeks, pain symptoms at 6 months were predicted by negative connectivity between the dACC and the precuneus. Previous research implicates the precuneus in the individual subjective awareness of pain. Given a relatively small sample size, approximately half of which did not experience chronic pain at 6 months, findings warrant replication. Nevertheless, this study provides preliminary evidence of enhanced dACC connectivity with motor regions and decreased connectivity with pain processing regions as immediate and prospective predictors of pain following MVC. Perspective This article presents evidence of distinct neural vulnerabilities that predict chronic pain in MVC survivors based on whole-brain connectivity with the dorsal anterior cingulate cortex.

Migratory species are particularly vulnerable to climate change because habitat throughout their entire migration cycle must be suitable for the species to persist. For migratory species in rivers, predicting climate change impacts is especially difficult because there is a lack of spatially continuous and seasonally varying stream temperature data, habitat conditions can vary for an individual throughout its life cycle, and vulnerability can vary by life stage and season. To predict thermal impacts on migratory riverine populations, we first expanded a spatial stream network model to predict mean monthly temperature for 465,775 river km in the western U.S., and then applied simple yet plausible future stream temperature change scenarios. We then joined stream temperature predictions to 44,396 spatial observations and life-stage-specific phenology (timing) for 26 ecotypes (i.e., geographically distinct population groups expressing one of the four distinct seasonal migration patterns) of Chinook salmon (Oncorhynchus tshawytscha), a phenotypically diverse anadromous salmonid that is ecologically and economically important but declining throughout its range. Thermal stress, assessed for each life stage and ecotype based on federal criteria, was influenced by migration timing rather than latitude, elevation, or migration distance such that sympatric ecotypes often showed differential thermal exposure. Early-migration phenotypes were especially vulnerable due to prolonged residency in inland streams during the summer. We evaluated the thermal suitability of 31,699 stream km which are currently blocked by dams to explore reintroduction above dams as an option to mitigate the negative effects of our warmer stream temperature scenarios. Our results showed that negative impacts of stream temperature warming can be offset for almost all ecotypes if formerly occupied habitat above dams is made available. Our approach of combining spatial distribution and phenology data with spatially explicit and temporally explicit temperature predictions enables researchers to examine thermal exposure of migrating populations that use seasonally varying habitats.

Sensitive and specific detection of low frequency mutations in acute myeloid leukemia (AML) is critical in research of minimal residual disease (MRD). At variant allele frequencies (VAF) below approximately 1%, PCR and sequencing errors result in prohibitive signal-to-noise ratios with next generation sequencing (NGS). Duplex Sequencing (DS) relates the original top and bottom DNA strands to make double stranded consensus sequences to greatly reduce errors. In two experiments we show further improvement of DS of AML-related genes by the use of enzymatic fragmentation (EF) and an updated gene panel that incorporates 2022 European LeukemiaNet (ELN) recommendations. In the first DS study, 29 AML-related genes (59 kb) were targeted in hybrid capture. Mutant cell line DNA was mixed into DNA from a healthy young donor to simulate MRD. Expected VAFs in mixtures were 1.0-0.003%. Samples comprised a mix of 4 insertions and deletions (indel), a mix of 15 single nucleotide variants (SNV), and 4 serial dilutions of a FLT3 ITD plus an NPM1 insertion. Pure diluent DNA was used as a negative control. Each sample was prepared in quadruplicate with mechanical fragmentation (MF) vs EF. DNA input mass was 1,500 ng per replicate, except for 50-250 ng for the FLT3/NPM1 mixes with expected VAF of 1% and 0.1%, respectively. Input masses were set to ensure >95% probability of detection of all mutations in the combined data. All targeted variants down to 0.003% VAF were detected in spike-in mixtures, with expected vs observed VAF highly correlated whether using MF or EF (R2 >0.98 for all mixtures). Duplex molecular depth was 1.2-2.0x higher with EF vs MF across input masses. Panel-wide mean duplex depth per 1,500 ng replicate was 30,376x for MF and 48,036x for EF, for combined mean depths of 121,508x for MF and 192,144x for EF. In the negative control, background mutational calls at spike-in positions were 4/2,993,429 duplex bases using MF and 0/4,780,491 duplex bases with EF, reflecting increased specificity with EF. Next, a revised panel targeting 36 AML-related genes (80 kb) was used for DS with EF. Here differing mutant cell line DNA was mixed into the same diluent from above (the negative control). This mixture harbors 27 variants with expected VAFs of 0.125-0.006% (4 indels, 21 SNVs, a FLT3 ITD and an NPM1 insertion), 17 of which (2 indels, 14 SNVs and the NPM1 insertion) span VAFs of 0.011-0.009% to establish a limit of detection of 0.01%. With 2,000 ng (+/- 10%) input, for 14 samples, panel-wide mean duplex depth was 56,528x. For variants with expected VAF ≥ 0.009%, the assay had >98% sensitivity, >96% specificity, and >98% accuracy at genomic positions of known true positive variants. In summary, DS with EF yields more data per nanogram of DNA than MF, maximizing the use of precious samples. This method exhibits extremely low background mutation signal and a low limit of detection across targets that are valuable in AML MRD research. Citation Format: Elizabeth Schmidt, Devon M. Fitzgerald, Camila Zanette, Gavin D. Meredith, Mark A. McElwain, Raul Burciaga, Kevin C. Vavra, Thomas H. Smith, Jesse J. Salk, Jake Higgins. Accurate detection of low frequency AML-associated mutations in vitro using Duplex Sequencing with enzymatic fragmentation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB254.

Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1,879 were depressed at baseline. Participants were given 100mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression (CES-D-10) scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; Chi-square (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (−0.7; 95% CI −1.4 to −0.1; Chi-square (1) =4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms., One Sentence Summary: Contrary to hypotheses, this study demonstrates for the first time that aspirin might have an adverse effect on the mood of older adults with pre-existing depression.

This chapter summarizes Micro‐Electromechanical Systems (MEMS) inertial sensors and their application to navigation solutions, with the goal of providing a practical introduction for those readers unfamiliar with MEMS. A MEMS accelerometer (“accel”) converts an applied force into an electrical output proportional to acceleration, just as a traditional electromechanical sensor would. As with MEMS accelerometers, the type of MEMS gyro is determined by its transduction principle, each with specific advantages and disadvantages. The chapter provides an overview of common gyroscope types. The typical MEMS inertial measurement units contains, at minimum, a 3‐axis accelerometer and a 3‐axis gyroscope. Some considerations specific to selecting and applying MEMS sensors are described. MEMS inertial sensors offer a new source of position, orientation, and motion data to navigation solutions. MEMS sensors provide an enticing option for the navigation engineer, particularly for applications in the GNSS‐denied environment.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

BackgroundKnowledge of rare, inherited variants in DNA damage repair (DDR) genes is informing clinical management in common cancers. However, defining the rare disease- associated variants in prostate cancer (PrCa) is challenging due to their low frequency.MethodHere, whole-genome and -exome sequencing data from two independent, high- risk Australian and North American familial PrCa datasets were interrogated for novel, rare DDR variants. Segregating, high-risk, likely pathogenic DDR gene variants were identified and subsequently genotyped in 1,963 individuals (700 familial and 459 sporadic PrCa cases, 482 unaffected relatives, and 322 screened controls) and association analyses performed accounting for relatedness (MQLS).ResultsRare variants significantly associated with PrCa risk were identified inERCC3(rs145201970, p=2.57×10−4) andBRIP1(rs4988345, p=0.025) in the combined datasets. APARP2(rs200603922, p=0.028) variant in the Australian dataset and aMUTYH(rs36053993, p=0.031) variant in the North American dataset were also associated with PrCa risk. No evidence for a younger age or higher-grade disease at diagnosis was evident in variant carriers.ConclusionsHere, we provide new evidence for four novel germline DDR PrCa risk variants. Defining the full spectrum of PrCa associated DDR genes is important for effective clinical screening and disease management.

The aim of this study was to compare patients' preferred role in medical decision-making before the initial urogynecology visit to their perceived role after the visit.This prospective cohort study enrolled women presenting for their initial urogynecology visit. Before and after the visit, patients completed the Control Preference Scale (CPS), which categorizes the role that patients want to have in medical decision-making: active, collaborative, or passive. Patients also completed the Pelvic Floor Distress Inventory, CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, and Short Test of Functional Health Literacy in Adults questionnaires. Univariable and multivariable generalized estimating equations were used.Women (n = 100) with a mean age of 59.1 years (SD = 15.5) participated in the study. Based on CPS before the visit, 50% of the women preferred active involvement, whereas 45% preferred collaborative and 5% preferred passive involvement. After the visit, these rates change to 40%, 48%, and 11%, respectively. On univariable analysis, women were 1.56 times more likely to report a collaborative or passive CPS response after the visit (P = 0.02). This remained true on multivariable analysis (odds ratio, 1.57; P = 0.04). Patients' CPS responses were not associated with their responses on CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, or Short Test of Functional Health Literacy in Adults. Eighty-eight percent of women reported a fully collaborative visit based on CollaboRATE, and 87% reported being "completely satisfied" with the visit.Despite a change in women's reported involvement in decision-making after their first urogynecology visit compared with their preferences before the visit, most women perceived collaboration during their visit and were completely satisfied.