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An important transport process for particles and gases from the atmosphere to aquatic and terrestrial environments is through dry and wet deposition. An open-source, modular, off-grid, and affordable instrument that can automatically collect wet-deposition samples allows for more extensive deployment of deposition samplers in fieldwork and would enable more comprehensive monitoring of remote locations. Precipitation events selectively sampled using a conductivity sensor powered by a battery-based supply are central to off-grid capabilities. The prevalence of conductive precipitation – that which initially contains high solute levels and progresses through trace-level concentrations to ultrapure water in full atmospheric washout – depends on the sampling location but is ubiquitous. This property is exploited here to trigger an electric motor (via limit switches) to open and close a lid resting over a funnel opening. The motors are operated via a custom-built and modular digital logic control board, which has a low energy demand. All components, their design and rationale, and their assembly are provided for community use. The modularity of the control board allows the operation of up to six independent wet-deposition units, such that replicate measurements (e.g., canopy throughfall) or different collection materials for various targeted pollutants can be implemented as necessary. We demonstrate that these platforms are capable of continuous operation off-grid for integrated monthly and bimonthly collections performed across the Newfoundland and Labrador Boreal Ecosystem Latitudinal Transect (47 to 53° N) during the growing seasons of 2015 and 2016. System performance was assessed through the measured power consumption from 115 V of alternating current (VAC; grid power) or 12 V of direct current from battery supplies during operation under both standby (40 or 230 mA, respectively) and in-use (78 or 300 mA, respectively) conditions. In the field, one set of triplicate samplers was deployed in the open to collect incident precipitation (open fall), while another set was deployed under the experimental forest canopy (throughfall). The proof-of-concept systems were validated with basic measurements of rainwater chemistry, which found (i) pH values ranging from 4.14 to 5.71 in incident open fall rainwater, (ii) conductivities ranging from 21 to 166 µS cm−1, and (iii) dissolved organic carbon concentrations in open fall and canopy throughfall of 16±10 and 22±12 mg L−1, respectively, with incident fluxes spanning 600 to 4200 mg C m−2 a−1 across the transect. Ultimately, this demonstrates that the customized precipitation sampling design of this new platform enables more universal accessibility of deposition samples for the atmospheric observation community – for example, those who have made community calls for targeting biogeochemical budgets and/or contaminants of emerging concern in sensitive and remote regions.

Abstract Advances in gene sequencing technologies have accelerated the identification of genetic variants, but better tools are needed to understand which are causal of disease. This would be particularly useful in fields where gene therapy is a potential therapeutic modality for a disease-causing variant such as inherited retinal disease (IRD). Here, we apply structure-based network analysis (SBNA), which has been successfully utilized to identify variant-constrained amino acid residues in viral proteins, to identify residues that may cause IRD if subject to missense mutation. SBNA is based entirely on structural first principles and is not fit to specific outcome data, which makes it distinct from other contemporary missense prediction tools. In 4 well-studied human disease-associated proteins (BRCA1, HRAS, PTEN, and ERK2) with high-quality structural data, we find that SBNA scores correlate strongly with deep mutagenesis data. When applied to 47 IRD genes with available high-quality crystal structure data, SBNA scores reliably identified disease-causing variants according to phenotype definitions from the ClinVar database. Finally, we applied this approach to 63 patients at Massachusetts Eye and Ear (MEE) with IRD but for whom no genetic cause had been identified. Untrained models built using SBNA scores and BLOSUM62 scores for IRD-associated genes successfully predicted the pathogenicity of novel variants (AUC = 0.851), allowing us to identify likely causative disease variants in 40 IRD patients. Model performance was further augmented by incorporating orthogonal data from EVE scores (AUC = 0.927), which are based on evolutionary multiple sequence alignments. In conclusion, SBNA can used to successfully identify variants as causal of disease in human proteins and may help predict variants causative of IRD in an unbiased fashion.

The declining trend in vehicle emissions has underscored the growing significance of volatile organic compound (VOC) emissions from volatile chemical products (VCPs). However, accurately representing VOC chemistry in simplified chemical mechanisms remains challenging due to its chemical complexity including speciation and reactivity. Previous studies have predominantly focused on VOCs from fossil fuel sources, leading to an underrepresentation of VOC chemistry from VCP sources. We developed an integrated chemical mechanism, RACM2B-VCP, that is compatible with WRF-Chem and is aimed at enhancing the representation of VOC chemistry, particularly from VCP sources, within the present urban environment. Evaluation against the Air Quality System (AQS) network data demonstrates that our model configured with RACM2B-VCP reproduces both the magnitude and spatial variability of O3 and PM2.5 in Los Angeles. Furthermore, evaluation against comprehensive measurements of O3 and PM2.5 precursors from the Reevaluating the Chemistry of Air Pollutants in California (RECAP-CA) airborne campaign and the Southwest Urban NOx and VOC Experiment (SUNVEx) ground site and mobile laboratory campaign confirm the model's accuracy in representing NOx and many VOCs and highlight remaining biases. Although there exists an underprediction in the total VOC reactivity of observed VOC species, our model with RACM2B-VCP exhibits good agreement for VOC markers emitted from different sectors, including biogenic, fossil fuel, and VCP sources. Through sensitivity analyses, we probe the contributions of VCP and fossil fuel emissions to total VOC reactivity and O3. Our results reveal that 52 % of the VOC reactivity and 35 % of the local enhancement of MDA8 O3 arise from anthropogenic VOC emissions in Los Angeles. Significantly, over 50 % of this anthropogenic fraction of either VOC reactivity or O3 is attributed to VCP emissions. The RACM2B-VCP mechanism created, described, and evaluated in this work is ideally suited for accurately representing ozone for the right reasons in the present urban environment where mobile, biogenic, and VCP VOCs are all important contributors to ozone formation.

Climate change is a complex problem involving nonlinearities and feedback that operate across scales. No single discipline or way of thinking can effectively address the climate crisis. Teams of natural scientists, social scientists, engineers, economists, and policymakers must work together to understand, predict, and mitigate the rapidly accelerating impacts of climate change. Transdisciplinary approaches are urgently needed to address the role that microorganisms play in climate change. Here, we demonstrate with case studies how diverse teams and perspectives provide climate-change insight related to the range expansion of emerging fungal pathogens, technological solutions for harmful cyanobacterial blooms, and the prediction of disease-causing microorganisms and their vector populations using massive networks of monitoring stations. To serve as valuable members of a transdisciplinary climate research team, microbiologists must reach beyond the boundaries of their immediate areas of scientific expertise and engage in efforts to build open-minded teams aimed at scalable technologies and adoptable policies.

Sustainability of livestock systems encompasses social, economic, and environmental concerns. Environmental sustainability issues surrounding livestock production include greenhouse gas emissions, land use, water use, and water quality. Mitigating negative environmental contributions and enhancing positive contributions from livestock production is critical for the long-term viability of the industry. While livestock production can impact the environment, livestock can in turn be affected by environmental conditions. Climate change poses unique challenges for livestock production in the future via impacts on feed availability, quality, and potential for increased thermal stress on livestock themselves. In aggregate, livestock production must adapt to both societal expectations and climatic conditions in the future, which will require both technical solutions and viable socioeconomic drivers to encourage implementation of solutions.

Abstract Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age‐related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine‐Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age‐related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients.

This qualitative follow up study sought the impressions of students after a two year program. The analysis of this data involved grounded theory qualitative methods. The primary means of data collection for the qualitative portion of this study was through digitally-recording and transcribing of participants' voices in response to individual interview prompts. Seven themes emerged from the first interviews which included: Perceptions of leadership; changing perceptions of the Jesuit ideas of Magis/cura personalis; changing perceptions of social justice; perceptions of motivation or desire to lead; Catholic identification; theory to practice; and suggested changes to the program. These themes were reinforced and refined in the second interviews, but a few new themes emerged from the additional data. Specifically, the value of the cohort was strongly expanded in the data from the second interviews. Other new themes included special education, the action research project, and some systems issues.

Abstract Background A physically active lifestyle is beneficial during pregnancy. However, little is known about physical activity (PA) behaviour and psychosocial factors in women during and after pregnancy. This study examined exercise behavioural regulation, exercise self-efficacy, health-related quality of life, sickness absence and musculoskeletal pain in pregnant women offered either structured supervised exercise training, motivational counselling on PA, or standard prenatal care in the FitMum randomised controlled trial. Methods Two hundred and eighteen healthy inactive pregnant women were randomised to structured supervised exercise training (n = 87), motivational counselling on PA (n = 86) or standard prenatal care (n = 45). The women answered the Behavioural Regulation in Exercise Questionnaire-2 (BREQ-2), the Pregnancy Exercise Self-Efficacy Scale (P-ESES-DK) and the Short Form 36 Health Survey Questionnaire (SF-36) at baseline (gestational age (GA) of max 15 weeks), GA 28 and 34 weeks, and one year after delivery. Sickness absence and low back and/or pelvic girdle pain were likewise reported in questionnaires at baseline and GA 28 weeks. Results Participants offered structured supervised exercise training or motivational counselling on PA had higher autonomous motivation for exercise during pregnancy compared with participants receiving standard prenatal care (e.g., difference in intrinsic regulation at GA 28 weeks, structured supervised exercise training vs. standard prenatal care: mean difference in score 0.39 [0.16; 0.64], p

Postpartum depression affects nearly a quarter of women up to a year after childbirth. Although it is treatable, significant barriers to help-seeking prevent women from being treated. This paper assesses key literature on the barriers for help-seeking among women with postpartum depression. The barriers identified have been mapped onto the socio-ecological model in addition to potential recommendations that professionals can use to address barriers on individual, interpersonal, organizational, community and societal levels. The recommendations provided are meant to serve as leverage points for professionals in efforts to create appropriate support and interventions. As such, this paper serves as a mapping tool for healthcare and public health professionals to assess obstacles to women's help-seeking and to guide multi-pronged interventions on various levels of the socio-ecological model that may increase help-seeking among women with postpartum depression. Holistically and comprehensively providing support to women will require significant effort throughout all sectors of society as opposed to isolated, siloed interventions.

Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O2 levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O2 levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.

Summary: Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene. Here, we show that SMC3 behaves as an archetypal haploinsufficient gene: it is highly constrained against pLoF variants, strongly depleted for missense variants, and pLoF variants are associated with a range of developmental phenotypes. Among 14 individuals with SMC3 pLoF variants, phenotypes were variable but coalesced on low growth parameters, developmental delay/intellectual disability, and dysmorphism, reminiscent of atypical CdLS. Comparisons to individuals with SMC3 missense/in-frame indel variants demonstrated an overall milder presentation in pLoF carriers. Furthermore, several individuals harboring pLoF variants in SMC3 were nonpenetrant for growth, developmental, and/or dysmorphic features, and some had alternative symptomatologies with rational biological links to SMC3. Analyses of tumor and model system transcriptomic data and epigenetic data in a subset of cases suggest that SMC3 pLoF variants reduce SMC3 expression but do not strongly support clustering with functional genomic signatures of typical CdLS. Our finding of substantial population-scale LoF intolerance in concert with variable growth and developmental features in subjects with SMC3 pLoF variants expands the scope of cohesinopathies, informs on their allelic architecture, and suggests the existence of additional clearly LoF-constrained genes whose disease links will be confirmed only by multilayered genomic data paired with careful phenotyping.

Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475]. Thirty-seven patients enrolled with a median age at enrollment of 8.4 (range, 1-20) years. There were no dose limiting toxicities among the enrolled patients, including two patients with Down syndrome. The recommended phase 2 dose of decitabine in combination with vorinostat and FLAG was 10 mg/m2 . The expanded cohort design allowed for an efficacy evaluation and the overall response rate among 35 evaluable patients was 54% (16 complete response (CR) and 3 complete response with incomplete hematologic recovery (CRi)). Ninety percent of responders achieved minimal residual disease (MRD) negativity (

Daylighting plays a crucial role in building science, impacting both occupants’ well-being and energy consumption in buildings. Balancing the size of openings with energy efficiency has long been a challenge. To address this, various daylight metrics have been developed to assess interior spaces’ daylight quality. Additionally, architects have been using simulation algorithms to predict postconstruction light conditions. In recent years, machine learning (ML) has revolutionized daylight simulations, offering a way to predict daylight conditions without cumbersome 3D modeling or heavy computational resources. However, accommodating architects’ creativity remains a challenge for current machine learning-based models. Specifically, the diversity of window shapes and their locations on facades poses difficulties for prediction accuracy. To overcome this limitation, this paper proposes a novel method that transforms wall information into matrices and uses them as input to train an artificial neural network-based model; this model can well predict the annual daylight simulation result generated by the Climate-Based Daylight Modeling tools. This method allows the model to adapt to various real-world design scenarios in real time, and its robust reliability has been demonstrated through evaluations of prediction accuracy concerning different annual daylight metrics. This approach caters to specific cases and opens possibilities for application in other machine learning and deep learning-based methods.

Abstract Background Decreased ryanodine receptor type 1 (RyR1) protein levels are a well‐described feature of recessive RYR1‐related myopathies. The aim of the present study was twofold: (1) to determine whether RyR1 content is also decreased in other myopathies and (2) to investigate the mechanisms by which decreased RyR1 protein triggers muscular disorders. Methods We used publicly available datasets, muscles from human inflammatory and mitochondrial myopathies, an inducible muscle‐specific RYR1 recessive mouse model and RyR1 knockdown in C2C12 muscle cells to measure RyR1 content and endoplasmic reticulum (ER) stress markers. Proteomics, lipidomics, molecular biology and transmission electron microscopy approaches were used to decipher the alterations associated with the reduction of RyR1 protein levels. Results RYR1 transcripts were reduced in muscle samples of patients suffering from necrotizing myopathy (P = 0.026), inclusion body myopathy (P = 0.003), polymyositis (P

Objective: To compare the consistency of endometrial receptivity array (ERA) and histologic dating among 3 spatially distinct endometrial samples obtained during a cycle of exogenous estrogen and progesterone. Design: Prospective blinded study. Setting: University practice. Patients: Twelve patients undergoing a mock frozen embryo transfer cycle. Intervention: Endometrial biopsy was performed in a manner that provided a spatially organized endometrial specimen, corresponding to the fundus, middle, and lower segment. Each of these 3 sections was further divided into immediately adjacent specimens for ERA and histology. Main Outcome Measure: Consistency of the ERA and histology results among fundal, mid, and lower endometrial biopsy specimens. Results: The ERA showed variability in outcome among different patients but dated all specimens originating from the same patient identically. Histologic dating showed variability between patients as well as between different locations within the uterus. When comparing average dating results for each patient, we saw a positive correlation between histologic and ERA dating (Spearman Rho = 0.45); however, this did not reach statistical significance. The ERA results from upper, mid, and lower uterine biopsy specimens were identical for each autologous biopsy, whereas histologic dating showed variability with an average standard deviation of 0.71 days. Conclusions: The increased heterogeneity of histologic dating is likely to be attributed to the subjectivity of the test. Furthermore, we did not observe a consistent lag or advancement in histologic or ERA dating between the fundal or lower uterine biopsies. Overall, clinicians should be reassured that endometrial tissue will return consistent ERA results independent of the location within the uterus in which it was obtained.

Abstract Background Image and performance enhancing drugs (IPEDs) are commonly used in resistance trained (RT) individuals and negatively impact left ventricular (LV) structure and function. Few studies have investigated the impact of IPEDs on atrial structure and function with no previous studies investigating bi-atrial strain. Additionally, the impact of current use vs. past use of IPEDs is unclear. Methods Utilising a cross-sectional design, male (n = 81) and female (n = 15) RT individuals were grouped based on IPED user status: current (n = 57), past (n = 19) and non-users (n = 20). Participants completed IPED questionnaires, anthropometrical measurements, electrocardiography, and transthoracic echocardiography with strain imaging. Structural cardiac data was allometrically scaled to body surface area (BSA) according to laws of geometric similarity. Results Body mass and BSA were greater in current users than past and non-users of IPEDs (p 0.05). Left atrial reservoir (p = 0.008, p

Abstract Objective To examine family medicine (FM) and obstetrician-gynecologist (OB/GYN) residents’ experiences with CenteringPregnancy (CP) group prenatal care (GPNC) as a correlate to perceived likelihood of implementing CP in future practice, as well as knowledge, level of support, and perceived barriers to implementation. Methods We conducted a repeated cross-sectional study annually from 2017 to 2019 with FM and OB/GYN residents from residency programs in the United States licensed to operate CP. We applied adjusted logistic regression models to identify predictors of intentions to engage with CP in future practice. Results Of 212 FM and 176 OB/GYN residents included in analysis, 67.01% of respondents intended to participate as a facilitator in CP in future practice and 51.80% of respondents were willing to talk to decision makers about establishing CP. Both FM and OB/GYN residents who spent more than 15 h engaged with CP and who expressed support towards CP were more likely to participate as a facilitator. FM residents who received residency-based training on CP and who were more familiar with CP reported higher intention to participate as a facilitator, while OB/GYN residents who had higher levels of engagement with CP were more likely to report an intention to participate as a facilitator. Conclusion Engagement with and support towards CP during residency are key factors in residents’ intention to practice CP in the future. To encourage future adoption of CP among residents, consider maximizing resident engagement with the model in hours of exposure and level of engagement, including hosting residency-based trainings on CP for FM residents.

Nitrogen oxides (NOx≡NO+NO2) are involved in most atmospheric photochemistry, including the formation of tropospheric ozone (O3). While various methods exist to accurately measure NOx concentrations, it is still a challenge to quantify the source and flux of NOx emissions. We present airborne measurements of NOx and winds used to infer the emission of NOx across Los Angeles. The measurements were obtained during the research aircraft campaign RECAP-CA (Re-Evaluating the Chemistry of Air Pollutants in CAlifornia) in June 2021. Geographic allocations of the fluxes are compared to the NOx emission inventory from the California Air Resources Board (CARB). We find that the NOx fluxes have a pronounced weekend effect and are highest in the eastern part of the San Bernardino Valley. The comparison of the RECAP-CA and the modeled CARB NOx fluxes suggests that the modeled emissions are higher than expected near the coast and in Downtown Los Angeles and lower than expected further inland in the eastern part of the San Bernardino Valley.

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Dinoflagellates are one of the largest groups of marine microalgae and exhibit diverse trophic strategies. Some dinoflagellates can produce secondary metabolites that are known to be toxic, which can lead to ecologically harmful blooms. Amphidinium carterae is one species of dinoflagellate that produces toxic compounds and is used as a model for dinoflagellate studies. The impact of the microbiome on A. carterae growth and metabolite synthesis is not yet fully understood, nor is the impact of bacterial data on sequencing and assembly. An antibiotic cocktail was previously shown to eliminate 16S amplification from the dinoflagellate culture. Even with drastically reduced bacterial numbers during antibiotic treatment, bacterial sequences were still present. In this experiment, we used novel Nanopore long-read sequencing techniques on A. carterae cultures to assemble 15 full bacterial genomes ranging from 2.9 to 6.0 Mb and found that the use of antibiotics decreased the percentage of reads mapping back to bacteria. We also identified shifts in the microbiome composition and identified a potentially deleterious bacterial species arising in the absence of the antibiotic treatment. Multiple antibiotic resistance genes were identified, as well as evidence that the bacterial population does not contribute to toxic secondary metabolite synthesis.