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The Tol-Pal system spans the cell envelope of Gram-negative bacteria, transducing the potential energy of the proton motive force (PMF) into dissociation of the TolB-Pal complex at the outer membrane (OM), freeing the lipoprotein Pal to bind the cell wall. The primary physiological role of Tol-Pal is to maintain OM integrity during cell division through accumulation of Pal molecules at division septa. How the protein complex couples the PMF at the inner membrane into work at the OM is unknown. The effectiveness of this trans-envelope energy transduction system is underscored by the fact that bacteriocins and bacteriophages co-opt Tol-Pal as part of their import/infection mechanisms. Mechanistic understanding of this process has been hindered by a lack of structural data for the inner membrane TolQ-TolR stator, of its complexes with peptidoglycan (PG) and TolA, and of how these elements combined power events at the OM. Recent studies on the homologous stators of Ton and Mot provide a starting point for understanding how Tol-Pal works. Here, we combine ab initio protein modeling with previous structural data on sub-complexes of Tol-Pal as well as mutagenesis, crosslinking, co-conservation analysis and functional data. Through this composite pooling of in silico, in vitro, and in vivo data, we propose a mechanism for force generation in which PMF-driven rotary motion within the stator drives conformational transitions within a long TolA helical hairpin domain, enabling it to reach the TolB-Pal complex at the OM.

Quantifying the volume of erupted volcanic material, particularly lava flows and domes, provides critical insights into the dynamics of an eruption. This in turn aids in future hazard modeling, mitigation, and response. However, acquiring the necessary topographic datasets to calculate volumetric change is difficult, especially for active volcanoes in remote regions. The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument has acquired global photogrammetric data since 2000, from which individual scene digital elevation models (DEMs) are created. We present a new straight forward method using ASTER DEMs to measure the volume of emplaced lava flows, domes, and tephra cones. We focus on five case studies that represent different eruption styles and products. For each of these we compare the results to those from previous studies that used alternative topographic datasets, such as synthetic aperture radar (SAR), airborne photogrammetry, or Light Detection and Ranging (LiDAR) measurements. These datasets, however, are expensive to acquire or lack the needed temporal resolution. We show that in nearly all cases, our volume results are either within the reported range for the eruption or ≤0.05 km3 of the previously reported value derived from SAR or LiDAR. The simplicity of the ASTER DEM approach combined with the global coverage of the data products enables more timely production of accurate volumetric data during and following an eruption, which can then be used to assess past and future eruption dynamics.

The professional identity of scientists has historically been cultivated to value research over teaching, which can undermine initiatives that aim to reform science education. Course-Based Research Experiences (CRE) and the inclusive Research and Education Communities (iREC) are two successful and impactful reform efforts that integrate research and teaching. The aim of this study is to explicate the professional identity of instructors who implement a CRE within an established iREC and to explore how this identity contributes to the success of these programs. 97 CRE instructors from the Science Education Alliance (SEA) iREC participated in a 2-year, multi-stage, qualitative research project that involved weekly reflective journaling, autoethnographic description, small group evaluation and writing, and large-scale community checking. The resulting description of professional identity consisted of shared values (inclusivity, student success, community membership, ownership/agency, science, overcoming failure, and persistence), specified roles (mentor, advocate, scientist, educator, motivator, collaborator, community builder, learner, evaluator and project manager) and a stated sense of self (dedicated, resilient, pride in students, multiskilled, valued, community member, responsible and overworked). Analysis of individual reflective diary entries revealed how a professional identity underpinned and facilitated the ways in which faculty addressed challenges that arose and worked toward the success of every student. It is the self-concept of the professional identity of the instructor in the context of the CRE classroom that directed the extended commitment and effort that these instructors evidently put into their work with students, which facilitated student engagement, student persistence, and their collective scientific output. The study concludes that a professional identity of STEM faculty in the context of a CRE and iREC combines being a researcher and educator, and that this integrated identity is central for current initiatives aimed at transforming undergraduate STEM education.

Background: Posterior cervical fusion (PCF) with lateral mass screws is a favorable treatment option to revise a symptomatic pseudarthrosis due to reliable rates of arthrodesis; however, this technique introduces elevated risk for wound infection and hospital readmission. A tissue-sparing PCF approach involving facet fixation instrumentation reduces the rates of postoperative complications while stabilizing the symptomatic level to achieve arthrodesis; however, these outcomes have been limited to small study cohorts from individual surgeons commonly with mixed indications for treatment. Materials and Methods: One hundred and fifty cases were identified from a retrospective chart review performed by seven surgeons across six sites in the United States. All cases involved PCF revision for a pseudarthrosis at one or more levels from C3 to C7 following anterior cervical discectomy and fusion (ACDF). PCF was performed using a tissue-sparing technique with facet instrumentation. Cases involving additional supplemental fixation such as lateral mass screws, rods, wires, or other hardware were excluded. Demographics, operative notes, postoperative complications, hospital readmission, and subsequent surgical interventions were summarized as an entire cohort and according to the following risk factors: age, sex, number of levels revised, body mass index (BMI), and history of nicotine use. Results: The average age of patients at the time of PCF revision was 55 ± 11 years and 63% were female. The average BMI was 29 ± 6 kg/m2 and 19% reported a history of nicotine use. Postoperative follow-up visits were available with a median of 68 days (interquartile range = 41–209 days) from revision PCF. There were 91 1-level, 49 2-level, 8 3-level, and 2 4±-level PCF revision cases. The mean operative duration was 52 ± 3 min with an estimated blood loss of 14 ± 1.5cc. Participants were discharged an average of 1 ± 0.05 days following surgery. Multilevel treatment resulted in longer procedure times (single = 45 min, multi = 59 min, P = 0.01) but did not impact estimated blood loss (P = 0.94). Total nights in the hospital increased by 0.2 nights with multilevel treatment (P = 0.01). Sex, age, nicotine history, and BMI had no effect on recorded perioperative outcomes. There was one instance of rehospitalization due to deep-vein thrombosis, one instance of persistent pseudarthrosis at the revised level treated with ACDF, and four instances of adjacent segment disease. In patients initially treated with multilevel ACDF, revisions occurred most commonly on the caudal level (48% of revised levels), followed by the cranial (43%), and least often in the middle level (9%). Conclusions: This chart review of perioperative and safety outcomes provides evidence in support of tissue-sparing PCF with facet instrumentation as a treatment for symptomatic pseudarthrosis after ACDF. The most common locations requiring revision were the caudal and cranial levels. Operative duration and estimated blood loss were favorable when compared to open alternatives. There were no instances of postoperative wound infection, and the majority of patients were discharged the day following surgery.

NLRP3 is an inflammasome seeding pattern recognition receptor activated in response to multiple danger signals which perturb intracellular homeostasis. Electrostatic interactions between the NLRP3 polybasic (PB) region and negatively charged lipids on the trans-Golgi network (TGN) have been proposed to recruit NLRP3 to the TGN. In this study, we demonstrate that membrane association of NLRP3 is critically dependant on S-acylation of a highly conserved cysteine residue (Cys-130), which traps NLRP3 in a dynamic S-acylation cycle at the Golgi, and a series of hydrophobic residues preceding Cys-130 which act in conjunction with the PB region to facilitate Cys-130 dependent Golgi enrichment. Due to segregation from Golgi localised thioesterase enzymes caused by a nigericin induced breakdown in Golgi organisation and function, NLRP3 becomes immobilised on the Golgi through reduced de-acylation of its Cys-130 lipid anchor, suggesting that disruptions in Golgi homeostasis are conveyed to NLRP3 through its acylation state. Thus, our work defines a nigericin sensitive S-acylation cycle that gates access of NLRP3 to the Golgi.

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15–49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each surveyʼs complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Wastewater-based epidemiology (WBE) has become a valuable tool for monitoring the prevalence of SARS-CoV-2 on university campuses. However, concerns about effectiveness of raw sewage as a COVID-19 early warning system still exist, and it’s not clear how useful normalization by simultaneous comparison of Pepper Mild Mottle Virus (PMMoV) is in addressing variations resulting from fecal discharge dilution. This study aims to contribute insights into these aspects by conducting an academic-year field trial at the student residences on the University of Tennessee, Knoxville campus, raw sewage. This was done to investigate the correlations between SARS-CoV-2 RNA load, both with and without PMMoV normalization, and various parameters, including active COVID-19 cases, self-isolations, and their combination among all student residents. Significant positive correlations between SARS-CoV-2 RNA load a week prior, during the monitoring week, and the subsequent week with active cases. Despite these correlations, normalization by PMMoV does not enhance these associations. These findings suggest the potential utility of SARS-CoV-2 RNA load as an early warning indicator and provide valuable insights into the application and limitations of WBE for COVID-19 surveillance specifically within the context of raw sewage on university campuses.

BackgroundThere is a gross shortage of sleep specialist providers within the military health system. Telehealth and mobile health represent promising approaches to increase access to high quality, cost-effective care in the U.S military.ObjectivesThis paper reports findings from a mixed-methods clinical implementation study of a novel sleep telehealth platform at two military treatment facilities in the National Capitol Region. The platform includes a mobile app and integrated wearable sensors (i.e., a commercial off-the-shelf sleep tracker [Fitbit]). The primary purpose was to evaluate the implementation of a 10-day remote monitoring assessment and provision of evidence-based sleep treatment recommendations to patients and providers. In addition, we sought to observe, in an exploratory manner, subsequent engagement with the app during 5 days of personalized sleep education and training.MethodsPatients with sleep problems completed an intensive 10-day remote monitoring assessment that included a baseline intake questionnaire, daily sleep diaries, twice daily symptom surveys, and Fitbit. Based on this assessment, patients received personalized assessment results. Concurrently, a provider report was generated that included provisional diagnoses and evidence-based treatment recommendations. Next, participants gained access to personalized sleep education and trainings within the mobile app. Within an established implementation science framework, outcomes were assessed via behavioral adherence (engagement with the app) and separate questionnaires for patients and providers. Last, we conducted four focus groups with patients and 12 key informant interviews with primary care managers (PCMs) and economic stakeholders to seek feedback and recommendations for future directions.ResultsTwo hundred and seventy patients participated in the study. Using validated research questionnaires, participants reported high-risk for obstructive sleep apnea (65.6%), moderate to severe insomnia (38.2%), and moderate to severe daytime sleepiness (38.5%), and moderate to severe anxiety (14.1%) and depressive (20.4%) symptoms. Total sleep time was 6.6 (SD = 1.8) h based on sleep diaries and 6.1 (SD = 1.8) h based on Fitbit. Regarding implementation, reach, effectiveness, adoption, implementation, and maintenance were all notably high, based on quantitative and qualitative data from participants and PCMs.ConclusionsSleep telehealth and mobile health represent promising approaches to increase access to cost-effective, evidence-based care for sleep disorders in the U.S. military.

First measurements of the emission of lava worlds with the James Webb Space Telescope (JWST) probe the conditions on worlds so hot that their surfaces are likely molten or partially molten. These observations provide a unique opportunity to explore rocky planets’ evolution. Surfaces of lava world exoplanets can give insights into their composition and their interior workings. However, data of spectral emissivity of a wide range of potential exoplanet surface compositions and temperatures is required to understand JWST data. Here, we chose eight synthetic, potential exoplanet surfaces that span a wide range of chemical compositions to provide observers with a tool for the interpretation of JWST data for the exploration of lava worlds. We present the measured infrared emissivity spectra (2.5–20 μ m) of these materials for temperatures between 800° C and 1350° C. Our data comprise the first spectral library of possible high-temperature exoplanet surfaces. From these measurements, we establish the link between composition and a strong spectral feature at around 9 μ m, the Christiansen frequency (CF) for different temperatures. Additionally, we report that the shift in the CF associated with the bulk composition of the material is significantly more important than its temperature. This provides a critical tool to aid in interpreting future spectra of lava worlds that will be collected by the JWST and future missions.

Understanding the composition, texture, and morphology of volcanic rocks that have erupted at the surface better constrains the eruption style and is vital to infer subsurface processes, the development of magma upon ascent, and the potential for future eruptions. The reflectance and emission spectroscopy of these rocks, collected from the near-infrared (NIR) through the thermal infrared (TIR) portion of the electromagnetic (EM) spectrum, provides the data necessary to retrieve composition, micron-scale surface roughness, and particle size. Remote imaging systems enable the analyses of active volcanoes in remote regions, where sample collection for laboratory analysis poses a significant challenge. Laboratory hyperspectral data of samples acquired at volcanic deposits are easily resampled to the spectral resolution of any infrared sensor and provide a means of estimating the composition of volcanoes and their products worldwide, as well as those on other planetary bodies such as the Moon and Mars. In this review paper, we provide an overview of the current use of infrared reflectance and emission spectroscopy as an analysis tool in volcanology, including ground-based imaging systems that acquire unprecedented detail and serve as testbeds for new orbital concepts. We also discuss the potential impact that future satellite missions will have on volcano science as spectral, spatial, and temporal resolutions improve.

Abstract This study describes the composition and potential metabolic adaptation of microbial communities in northeastern Siberia, a repository of the oldest permafrost in the Northern Hemisphere. Samples of contrasting depth (1.75 to 25.1 m below surface), age (from ~ 10 kyr to 1.1 Myr) and salinity (from low 0.1–0.2 ppt and brackish 0.3–1.3 ppt to saline 6.1 ppt) were collected from freshwater permafrost (FP) of borehole AL1_15 on the Alazeya River, and coastal brackish permafrost (BP) overlying marine permafrost (MP) of borehole CH1_17 on the East Siberian Sea coast. To avoid the limited view provided with culturing work, we used 16S rRNA gene sequencing to show that the biodiversity decreased dramatically with permafrost age. Nonmetric multidimensional scaling (NMDS) analysis placed the samples into three groups: FP and BP together (10–100 kyr old), MP (105–120 kyr old), and FP (> 900 kyr old). Younger FP/BP deposits were distinguished by the presence of Acidobacteriota, Bacteroidota, Chloroflexota_A, and Gemmatimonadota, older FP deposits had a higher proportion of Gammaproteobacteria, and older MP deposits had much more uncultured groups within Asgardarchaeota, Crenarchaeota, Chloroflexota, Patescibacteria, and unassigned archaea. The 60 recovered metagenome-assembled genomes and un-binned metagenomic assemblies suggested that despite the large taxonomic differences between samples, they all had a wide range of taxa capable of fermentation coupled to nitrate utilization, with the exception of sulfur reduction present only in old MP deposits.

Inadequate sampling approaches to wastewater analyses can introduce biases, leading to inaccurate results such as false negatives and significant over- or underestimation of average daily viral concentrations, due to the sporadic nature of viral input. To address this challenge, we conducted a field trial within the University of Tennessee residence halls, employing different composite sampling modes that encompassed different time intervals (1 h, 2 h, 4 h, 6 h, and 24 h) across various time windows (morning, afternoon, evening, and late-night). Our primary objective was to identify the optimal approach for generating representative composite samples of SARS-CoV-2 from raw wastewater. Utilizing reverse transcription-quantitative polymerase chain reaction, we quantified the levels of SARS-CoV-2 RNA and pepper mild mottle virus (PMMoV) RNA in raw sewage. Our findings consistently demonstrated that PMMoV RNA, an indicator virus of human fecal contamination in water environment, exhibited higher abundance and lower variability compared to pathogenic SARS-CoV-2 RNA. Significantly, both SARS-CoV-2 and PMMoV RNA exhibited greater variability in 1 h individual composite samples throughout the entire sampling period, contrasting with the stability observed in other time-based composite samples. Through a comprehensive analysis of various composite sampling modes using the Quade Nonparametric ANCOVA test with date, PMMoV concentration and site as covariates, we concluded that employing a composite sampler during a focused 6 h morning window for pathogenic SARS-CoV-2 RNA is a pragmatic and cost-effective strategy for achieving representative composite samples within a single day in wastewater-based epidemiology applications. This method has the potential to significantly enhance the accuracy and reliability of data collected at the community level, thereby contributing to more informed public health decision-making during a pandemic.

Summary: The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity. Sensitivity for SARS-CoV-2 seroprevalence was enhanced when N and M IgG detection was combined. These findings indicate that screening for M seroconversion may be a good approach for detecting additional vaccine breakthrough infections and highlight the potential to use HCM as a rapidly deployable method to identify the most immunogenic targets of newly emergent pathogens.

Using an idealized climate model incorporating seasonal forcing, we investigate the impact of rotation rate on the abundance of clouds on an Earth-like aquaplanet, and the resulting impacts upon albedo and seasonality. We show that the cloud distribution varies significantly with season, depending strongly on the rotation rate, and is well explained by the large-scale circulation and atmospheric state. Planetary albedo displays nonmonotonic behavior with rotation rate, peaking at around 1/2Ω _E . Clouds reduce the surface temperature and total precipitation relative to simulations without clouds at all rotation rates, and reduce the dependence of total precipitation on rotation rate, causing nonmonotonic behavior and a local maximum around 1/8Ω _E ; these effects are related to the impacts of clouds on the net atmospheric and surface radiative energy budgets. Clouds also affect the seasonality. The influence of clouds on the extent of the winter Hadley cell and the intertropical convergence zone is relatively minor at slow rotation rates (

Abstract The Surface Biology and Geology (SBG) mission is part of the National Aeronautics and Space Administration's planned Earth System Observatory. The mid/thermal infrared (MIR/TIR) portion of SBG will deliver high spatial and temporal resolution data designed (in part) to answer fundamental volcano science questions, as outlined in the 2018 Decadal Survey (DS). The planned 60 m spatial resolution, high TIR saturation temperature (∼500 K), and addition of two high temperature MIR bands (∼800–1200 K) will improve thermal feature and spatial variability detection across all volcanic surfaces, as well as limit data saturation over high temperature targets such as lava flows. However, the MIR/TIR part of the mission also has design aspects that will hinder volcanic science. The ability to derive accurate spectral information of volcanic, and indeed other geologic surfaces, is a function of the number and placement of the TIR bands. The originally proposed five TIR bands do not advance these diagnostic investigations beyond what is currently available. In fact, it may hinder them. Six or more TIR bands are vital for accurate assessment of mineral and glass abundances in volcanic deposits. The SBG MIR/TIR mission temporal resolution (3–5 days) will improve repeat coverage of volcanic systems, aiding in longer‐term monitoring, but observations of highly dynamic processes will not be possible, despite their importance in the 2018 DS. Most problematic is the proposed local overpass time of 12:30, which will result in cloudier scenes (especially in tropical/lower latitude regions) and complicate atmospheric corrections compared to the traditional morning overpass times of earlier TIR missions.

IntroductionAlthough severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA has been frequently detected in sewage from many university dormitories to inform public health decisions during the COVID-19 pandemic, a clear understanding of SARS-CoV-2 RNA persistence in site-specific raw sewage is still lacking. To investigate the SARS-CoV-2 RNA persistence, a field trial was conducted in the University of Tennessee dormitories raw sewage, similar to municipal wastewater.MethodsThe decay of enveloped SARS-CoV-2 RNA and non-enveloped Pepper mild mottle virus (PMMoV) RNA was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in raw sewage at 4°C and 20°C.ResultsTemperature, followed by the concentration level of SARS-CoV-2 RNA, was the most significant factors that influenced the first-order decay rate constants (k) of SARS-CoV-2 RNA. The mean k values of SARS-CoV-2 RNA were 0.094 day−1 at 4°C and 0.261 day−1 at 20°C. At high-, medium-, and low-concentration levels of SARS-CoV-2 RNA, the mean k values were 0.367, 0.169, and 0.091 day−1, respectively. Furthermore, there was a statistical difference between the decay of enveloped SARS-CoV-2 and non-enveloped PMMoV RNA at different temperature conditions.DiscussionThe first decay rates for both temperatures were statistically comparable for SARS-CoV-2 RNA, which showed sensitivity to elevated temperatures but not for PMMoV RNA. This study provides evidence for the persistence of viral RNA in site-specific raw sewage at different temperature conditions and concentration levels.

Background We examined the epidemiology and transmission potential of HIV population viral load (VL) in 12 sub-Saharan African countries. Methods We analyzed data from Population-based HIV Impact Assessments (PHIAs), large national household-based surveys conducted between 2015 and 2019 in Cameroon, Cote d’Ivoire, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. Blood-based biomarkers included HIV serology, recency of HIV infection, and VL. We estimated the number of people living with HIV (PLHIV) with suppressed viral load (Results The proportion of female PLHIV with viral suppression was higher than that among males in all countries, however, the number of unsuppressed females outnumbered that of unsuppressed males in all countries due to higher overall female HIV prevalence, with ratios ranging from 1.08 to 2.10 (median: 1.43). The spatial distribution of HIV seroprevalence, viremia prevalence, and number of unsuppressed adults often differed substantially within the same countries. The 1% and 5% of PLHIV with the highest VL on average accounted for 34% and 66%, respectively, of countries’ total VL. HIV transmission ratios varied widely across countries and were higher for male-to-female (range: 2.3–28.3/100 PY) than for female-to-male transmission (range: 1.5–10.6/100 PY). In all countries mean log10 VL among unsuppressed males was higher than that among females. Correlations between VL measures and incident HIV varied, were weaker for VL metrics among females compared to males and were strongest for the number of unsuppressed PLHIV per 100 HIV-negative adults (R2 = 0.92). Conclusions Despite higher proportions of viral suppression, female unsuppressed PLHIV outnumbered males in all countries examined. Unsuppressed male PLHIV have consistently higher VL and a higher risk of transmitting HIV than females. Just 5% of PLHIV account for almost two-thirds of countries’ total VL. Population-level VL metrics help monitor the epidemic and highlight key programmatic gaps in these African countries.

IntroductionLate diagnosis of HIV (LD) increases the risk of morbidity, mortality, and HIV transmission. We used nationally representative data from population-based HIV impact assessment (PHIA) surveys in Malawi, Zambia, and Zimbabwe (2015-2016) to characterize adults at risk of LD and to examine associations between LD and presumed HIV transmission to cohabiting sexual partners.MethodsWe estimated the prevalence of LD, defined as CD4 count ResultsOf 1,804 adults who were newly diagnosed with HIV in the surveys, 49% (882) were diagnosed late. LD was associated with male sex, older age, and almost five times the odds of having an HIV-positive household sexual partner (adjusted odds ratio [aOR], 4.65 [95% confidence interval: 2.56-8.45]). Longer duration of HIV exposure in a relationship and higher viral load of the index case were both independently associated with higher odds of having HIV-positive household sexual partners. Individuals with HIV exposure of more than 5 years had more than three times (aOR 3.42 [95% CI: 1.63-7.18]) higher odds of being HIV positive than those with less than 2 years HIV exposure. The odds of being HIV positive were increased in individuals who were in a relationship with an index case with a viral load of 400-3499 copies/mL (aOR 4.06 [95% CI 0.45-36.46]), 3,500-9,999 copies/mL (aOR 11.32 [95% CI: 4.08-31.39]), 10,000-49,999 copies/mL (aOR 17.07 [95% CI: 9.18-31.72]), and ≥50,000 copies/mL (aOR 28.41 [95% CI: 12.18-66.28]) compared to individuals who were in a relationship with an index case with a viral load of ConclusionsLD remains a challenge in Southern Africa and is strongly associated with presumed HIV transmission to household sexual partners. Our study underscores the need for earlier HIV diagnosis, particularly among men and older adults, and the importance of index testing.

Penelitian ini bertujuan mengetahui unjuk kerja komposit hibrida dalam proses adsorpsi air permukaan. Komposit hibrida merupakan bahan yang terdiri dari morninga olifera (MO) dan activated carbon (AC) sebagai fillers, dan tepung lengket sebagai polimer yang diproduksi menggunakan cetakan penekanan panas (hot-press mold) pada temperatur 200°C. Komposisi filler dan polimer didasarkan pada rasio fraksi berat yaitu 40% filler dan 60% polimer. Kualitas absorpsi komposit hibrida dilakukan melalui proses perendaman dan turbidity test. Hasil pengujian perendaman benda kerja selama dua minggu adalah waktu paling optimal dari kenaikan massa komposit hibrida yang direndam pada air permukaan untuk masing-masing variasi hibrida. Peningkatan jumlah prosentase AC pada benda uji meningkatkan kekeruhan air karena adanya pelepasan unsur C pada air sesuai dengan test turbiditasnya. Kemudian, kandungan coliform dan E-coli pada air permukaan menurun disebabkan oleh meningkatnya prosentase MO pada benda uji. Dari hasil tersebut, disimpulkan bahwa hibridisasi filler MO dan AC memberikan dampak positif terhadap kualitas air permukaan.

Wildfire is a complex problem because of the diverse mix of actors and landowners involved, uncertainty about outcomes and future conditions, and unavoidable trade-offs that require ongoing negotiation. In this perspective, we argue that addressing the complex challenge of wildfire requires governance approaches designed to fit the nature of the wildfire problem. For instance, while wildfire is often described as a cross-boundary problem, understanding wildfire risk as transboundary highlights important political and institutional challenges that complicate collaboration across jurisdictions and shared stewardship. Transboundary risk requires collaborative governance that attends to the distribution of power, authority, and capacity across the range of actors relevant to particular fire-prone landscapes. Wildfire is also changing in unprecedented ways and multiple, interacting uncertainties make predicting future wildfires difficult. Anticipatory governance can build our capacity to integrate uncertainty into wildfire decision-making and manage risk in proactive ways. Finally, competing interests and values mean that trade-offs are inherent to the wildfire problem. Risk governance links science and society through deliberative, participatory processes that explicitly navigate tradeoffs and build legitimacy for actions to address wildfire risk. Governance approaches that better target the nature of the wildfire problem will improve our ability to coexist with fire today and in the future.

Dormancy is a physiological state that plants enter for winter hardiness. Environmental-induced dormancy onset and release in temperate perennials coordinate growth cessation and resumption, but how the entire process, especially chilling-dependent dormancy release and flowering, is regulated remains largely unclear. We utilized the transcriptome profiles of floral buds from fall to spring in apricot (Prunus armeniaca) genotypes with contrasting bloom dates and peach (Prunus persica) genotypes with contrasting chilling requirements (CR) to explore the genetic regulation of bud dormancy. We identified distinct gene expression programming patterns in endodormancy and ecodormancy that reproducibly occur between different genotypes and species. During the transition from endo- to eco-dormancy, 1,367 and 2,102 genes changed in expression in apricot and peach, respectively. Over 600 differentially expressed genes were shared in peach and apricot, including three DORMANCY ASSOCIATED MADS-box (DAM) genes (DAM4, DAM5, and DAM6). Of the shared genes, 99 are located within peach CR quantitative trait loci, suggesting these genes as candidates for dormancy regulation. Co-expression and functional analyses revealed that distinctive metabolic processes distinguish dormancy stages, with genes expressed during endodormancy involved in chromatin remodeling and reproduction, while the genes induced at ecodormancy were mainly related to pollen development and cell wall biosynthesis. Gene expression analyses between two Prunus species highlighted the conserved transcriptional control of physiological activities in endodormancy and ecodormancy and revealed genes that may be involved in the transition between the two stages.

Sorghum (Sorghum bicolor L. Moench) offers substantial potential as a feedstock for the production of sugar-derived biofuels and biochemical products from cell wall polysaccharides (i. e., cellulose and hemicelluloses) and water-extractable sugars (i.e., glucose, fructose, sucrose, and starch). A number of preprocessing schemes can be envisioned that involve processes such as sugar extraction, pretreatment, and densification that could be employed in decentralized, regional-scale biomass processing depots. In this work, an energy sorghum exhibiting a combination of high biomass productivity and high sugar accumulation was evaluated for its potential for integration into several potential biomass preprocessing schemes. This included counter-current extraction of water-soluble sugars followed by mild NaOH or liquid hot water pretreatment of the extracted bagasse. A novel processing scheme was investigated that could integrate with current diffuser-type extraction systems for sugar extraction. In this approach, mild NaOH pretreatment (i.e., 8%) at high metabolic yields without detoxification using a Saccharomyces cerevisiae strain metabolically engineered and evolved to ferment xylose.

This article examines the breadth of the current forecast literature as it relates to public budget making. It serves to provide summary information to decision-makers who otherwise do not have the resources to learn more than a small amount focused on much more narrowly defined areas of forecasting (such as the politics of forecast bias). Next, it serves those who perform forecasting related to budgeting by reviewing the current methods and practices commonly used in this domain. It also provides a ground level for future public budget forecasting research. Finally, this article identifies several areas in which the public forecasting literature needs additional development. Several of these areas, such as the effectiveness of nonregression-based forecasting techniques, are quite important to the majority of governments in the United States and other subnational jurisdictions, where budget offices are limited and resource investments in technology are scarce.

This article employs a historical analysis of the religious composition of the pro-life movement to explain why the partisan identity of the movement shifted from the left to the right between the late 1960s and the 1980s. Many of the Catholics who formed the first anti-abortion organizations in the late 1960s were liberal Democrats who viewed their campaign to save the unborn as a rights-based movement that was fully in keeping with the principles of New Deal and Great Society liberalism, but when evangelical Protestants joined the movement in the late 1970s, they reframed the pro-life cause as a politically conservative campaign linked not to the ideology of human rights but to the politics of moral order and “family values.” This article explains why the Catholic effort to build a pro-life coalition of liberal Democrats failed after Roe v. Wade, why evangelicals became interested in the antiabortion movement, and why the evangelicals succeeded in their effort to rebrand the pro-life campaign as a conservative cause.

Inactivation of selected neurons in vivo can define their contribution to specific developmental outcomes, circuit functions, and behaviors. Here, we show that the optogenetic tool KillerRed selectively, rapidly, and permanently inactivates different classes of neurons in C. elegans in response to a single light stimulus, through the generation of reactive oxygen species (ROS). Ablation scales from individual neurons in single animals to multiple neurons in populations and can be applied to freely behaving animals. Using spatially restricted illumination, we demonstrate that localized KillerRed activation in either the cell body or the axon triggers neuronal degeneration and death of the targeted cell. Finally, targeting KillerRed to mitochondria results in organelle fragmentation without killing the cell, in contrast to the cell death observed when KillerRed is targeted to the plasma membrane. We expect this genetic tool to have wide-ranging applications in studies of circuit function and subcellular responses to ROS.

Background Ankylosing spondylitis (AS) is a chronic inflammatory condition characterised by spinal arthritis and exercise is often recommended to reduce the symptoms and improve mobility. However, very little evidence exists for the value of exercise in AS. Objectives Firstly, this pilot study aimed to evaluate an eHealth tool, the AS Observer, specifically designed to monitor symptoms, quality of life and physical activity in AS, in terms of patient experience and suitability in generating data for epidemiological studies. Secondly, it also investigated the collected data to determine if physical activity benefited individuals with AS. Methods The AS Observer was designed to enable weekly monitoring of AS symptoms and exercise using a web based platform. Participants with AS (n = 223) were recruited to use the AS observer. They provided baseline data and completed online weekly data entry for 12 weeks (e.g. Bath Ankylosing Spondylitis Activity Index (BASDAI), howRu, International Physical Activity Questionnaire (IPAQ)). Panel data analysis with fixed effects models investigated associations between variables. Activity type data and exit questionnaires were subjected to qualitative thematic analysis. Results In general, the AS Observer was well received and considered useful by participants, with 66% providing a positive response. The collected data suggested that IPAQ is inversely associated with total BASDAI, stiffness, tenderness and pain, but not fatigue. Stratified analysis demonstrated differential associations between BASDAI, IPAQ and howRU based on sex, HLA-B27 status and disease duration. Approximately half of the participants frequently did therapy and three-quarters undertook at least some vigorous activity ranging from formal exercise to recreation and (house) work. Despite some technical challenges, tool evaluation suggested that the AS Observer was a useful self-monitoring tool for participants. Conclusions This pilot study demonstrated that increased exercise intensity and duration were associated with an improved BASDAI symptom score in a cohort of participants with AS. Furthermore, it provided further evidence of the value of using eHealth tools for clinical purposes and data collection for research, inclusive of the development of treatment pathways and disease management strategies.

Assisted reproductive technology with intracytoplasmic sperm injection (ICSI) is becoming an international panacea for couples struggling with infertility. The increasing popularity of these techniques and the data generated has given us a better understanding of the efficacy, consequences and costs of these procedures. There still remain many unanswered questions and controversies surrounding the use of IVF and ICSI. Increased experience, better refinement of these techniques and clearer indications for IVF and ICSI will inevitably minimize the risks associated with this procedure.

This article explores the uses made of comparison in transcending the alleged invisibility of minorities. Beginning with the suggestive fact that African-American Ralph Ellison began conceiving of his seminal novel Invisible Man while a merchant marine stationed in wartime Swansea, South Wales, the article proceeds to explore the ways in which Welsh nationalist authors and thinkers have compared their plight to that of others. Emrys ap Iwan was one of the first to describe the Welsh experience in broadly colonial terms, and to lampoon English monolingualism in the mirror of European multilingualism. Saunders Lewis developed ap Iwans thinking by emphasising the ways in which Wales had been cut off form its natural home in Europe by the development of the imperial British state. If some writers turned to Europe, others turned to the United Staes for comparative sources. Jon Dressels problematic comparison of Wales with the Southern States is discussed as an example of the dangerous implications of some comparisons. The article seeks to demonstrate that national visibility and invisibility can only emerge in relation to one another. Recognition - that is recognising the Other and being recognised by an other - is where nationalism finds its cultural embodiment and expression.

Aims To identify the incidence of allergic conjunctivitis in patients with allergic rhinitis.Methods One hundred and eighty seven consecutive patients with allergic rhinitis (AR) were directly questioned if they have allergic conjunctivitis (AC) and this was clarified using standard screening questions relating to red, itchy and watery eyes recorded through a total ocular symptom score (TOSS). Patients were also asked about further symptoms that may be attributable to AC: eyelid dermatitis, frequent blinking; eye sensitivity and frontal headache from squinting or. blinking. All patients were given a drop of olopatadine hydrochloride 0.1% in each eye to help identify “silent” disease. 20 healthy non-atopic controls were also treated with olopatadine drops and questioned on ocular symptoms.Results Fifty five percent of patients with AR were identified as having AC by direct questioning and the use of the TOSS questionaire. A further 41% were identifiable by asking additional questions and performing therapeutic challenge with olopadatine.Conclusions AC is a frequent comorbid condition occurring in 95% of our patients with AR. Only 55% of patients were able to identify that they had AC based on standard screening questions. Additional specific questioning and a therapeutic challenge in suspected patients can help identify patients who may benefit from treatment of AC.

Paroxysmal hypnogenic dyskinesia is a rare clinical entity characterized by intermittent dystonia and choreoathetoid movements that begin exclusively during sleep, often with consciousness preserved once the patient is awakened during the episodes. They occur almost every night and are often misdiagnosed as sleeping disorders. Paroxysmal hypnogenic dyskinesia is currently known to be a form of frontal lobe epilepsy, but not in all cases. We present a 19-year-old male patient with paroxysmal hypnogenic dyskinesia who responded to antihistamines. This supports an alternative theory from 1977 (before the cases had been adequately described) that the disorder lies in dysregulation in the basal ganglia. This description now appears similar to acute dystonic reactions such as extrapyramidal symptoms from antipsychotic medications, which also respond to antihistamines.

Circadian changes in cardiovascular function during the progression of diabetes mellitus in the diabetes prone rat (BBDP) (n=8) were studied. Age-matched diabetes-resistant rats (BBDR) served as controls. BP was recorded via telemetry in contiguous 4 hr time periods over 24 hours starting with 12 midnight to 4 am as period zero (P0). Prior to onset of diabetes BP was high at P0, peaked at P2, and then fell again at P3; BP and heart rate (HR) then increased gradually at P4 and leveled off at P5, thereby exhibiting a bipodal rhythm. These patterns changed during long-term diabetes. The cross-correlation coefficient of BP and HR was not significantly different across groups at onset, but it fell significantly at 9 months of duration of diabetes (BBDP: 0.39 ± 0.06; BBDR: 0.65 ± 0.03; P

The current concepts, recommendations, and principles of sperm banking as it pertains to the comprehensive care of young men of reproductive age with cancer are reviewed. Obstacles to sperm banking are addressed as well as future directions for fertility-preserving technologies. All cancer therapies—chemotherapy, radiation, and surgery—are potential threats to a man’s reproductive potential. In addition, cancer itself can impair spermatogenesis. Thus, sperm cryopreservation prior to initiating life-saving cancer treatment offers men and their families the best chance to father biologically related children and should be offered to all men with cancer before treatment. Better patient and provider education, as well as deliberate, coordinated strategies at comprehensive cancer care centers are necessary to make fertility preservation for male cancer patients a priority during pretreatment planning.

BACKGROUND:Growth and division of Saccharomyces cerevisiae is dependent on the action of SNARE proteins that are required for membrane fusion. SNAREs are regulated, through a poorly understood mechanism, to ensure membrane fusion at the correct time and place within a cell. Although fusion of secretory vesicles with the plasma membrane is important for yeast cell growth, the relationship between exocytic SNAREs and cell physiology has not been established. METHODOLOGY/PRINCIPAL FINDINGS:Using genetic analysis, we identified several influences on the function of exocytic SNAREs. Genetic disruption of the V-ATPase, but not vacuolar proteolysis, can suppress two different temperature-sensitive mutations in SEC9. Suppression is unlikely due to increased SNARE complex formation because increasing SNARE complex formation, through overexpression of SRO7, does not result in suppression. We also observed suppression of sec9 mutations by growth on alkaline media or on a non-fermentable carbon source, conditions associated with a reduced growth rate of wild-type cells and decreased SNARE complex formation. CONCLUSIONS/SIGNIFICANCE:Three main conclusions arise from our results. First, there is a genetic interaction between SEC9 and the V-ATPase, although it is unlikely that this interaction has functional significance with respect to membrane fusion or SNAREs. Second, Sro7p acts to promote SNARE complex formation. Finally, Sec9p function and SNARE complex formation are tightly coupled to the physiological state of the cell.