87 research outputs found
An evaluation of the use of electronic monitoring as a condition of bail in Scotland
The aims of the evaluation were to assess the implementation of EM bail in replacing custodial remands, and to conduct a cost analysis of EM bail in contrast to those given custody. The study included the collection of qualitative and quantitative data, matched comparison data and cost analysis. Interviews were conducted with 10 Steering Group members and 45 professionals (comprising the police, social work, procurators fiscal, clerks of court, judges, sheriffs, defence agents, advocates, the electronic monitoring companies and victims' agencies). Interviews with 16 bailees and 15 household members were also undertaken. Quantitative data were collected from various sources, namely: court pro formas, Reliance/Serco databases, court files, social work files, police records, Scottish Criminal Record Office and data provided by the Scottish Executive Justice Statistics Branch, the Scottish Court Service and the Scottish Prison Service. Data from 3 comparison sheriff courts also provided a range of information on accused remanded in custody or bailed with or without conditions in areas outwith the pilot sites to ascertain whether EM bail is being used as a direct alternative to custodial remand and to explore differences in final sentences for the 2 groups
Activity-independent screening of secreted proteins using split GFP
The large-scale industrial production of proteins requires efficient secretion, as provided, for instance, by the Sec system of Gram-positive bacteria. Protein engineering approaches to optimize secretion often involve the screening of large libraries, e.g. comprising a target protein fused to many different signal peptides. Respective high-throughput screening methods are usually based on photometric or fluorimetric assays enabling fast and simple determination of enzymatic activities. Here, we report on an alternative method for quantification of secreted proteins based on the split GFP assay. We analyzed the secretion by Bacillus subtilis of a homologous lipase and a heterologous cutinase by determination of GFP fluorescence and enzyme activity assays. Furthermore, we identified from a signal peptide library a variant of the biotechnologically relevant B. subtilis protein swollenin EXLX1 with up to 5-fold increased secretion. Our results demonstrate that the split GFP assay can be used to monitor secretion of enzymatic and non-enzymatic proteins in B. subtilis in a high-throughput manner
Defining the Environmental Niche of the Two Main Clades of \u3ci\u3eTrichodesmium\u3c/i\u3e: A Study on the West Florida Shelf
Dinitrogen (N2) fixation is the process of taking widely abundant but mostly biologically inaccessible N2 gas and converting it into more biologically accessible forms of the essential macronutrient nitrogen. Only a small fraction of organisms known as diazotrophs can perform biological N2 fixation. Trichodesmium is one such genus of N2-fixing marine cyanobacteria that is commonly observed in waters along the West Florida Shelf (WFS). We hypothesize that the two main Trichodesmium clades (T. erythraeum and T. thiebautii) occupy distinct environmental niches, one being more coastal and one being more oceanic. To test this hypothesis, we quantified gene abundance of both clades and compared the results with hydrographic data to distinguish any trends in niche distribution in samples collected on the WFS from three separate cruises. T. thiebautii abundance was higher further from the coast (at stations with greater bottom depths) and the T. erythraeum abundance was higher closer to the coast (at stations with lower bottom depths). A lack of nearshore sampling in 2015 initially made it difficult to conclusively identify trends in niche distribution, however with the addition of 2018 and 2019 samples, we observed a consistent coastal vs. open ocean niche separation for the two clades. In addition, T.thiebautii abundance was also significantly positively correlated with salinity. While previous work has found T. thiebautii is more abundant than T. erythraeum in open ocean surface waters, this is the first study to examine Trichodesmium clade abundance in a near-shore environment.https://digitalcommons.odu.edu/gradposters2021_sciences/1010/thumbnail.jp
Defining the Realized Niche of the Two Major Clades of \u3ci\u3eTrichodesmium\u3c/i\u3e: A Study on the West Florida Shelf
The cyanobacterium Trichodesmium plays an essential role supporting ocean productivity by relieving nitrogen limitation via dinitrogen (N-2) fixation. The two common Trichodesmium clades, T. erythraeum and T. thiebautii, are both observed in waters along the West Florida Shelf (WFS). We hypothesized that these taxa occupy distinct realized niches, where T. thiebautii is the more oceanic clade. Samples for DNA and water chemistry analyses were collected on three separate WFS expeditions (2015, 2018, and 2019) spanning multiple seasons; abundances of the single copy housekeeping gene rnpB from both clades were enumerated via quantitative PCR. We conducted a suite of statistical analyses to assess Trichodesmium clade abundances in the context of the physicochemical data. We observed a consistent coastal vs. open ocean separation of the two clades: T. erythraeum was found in shallow waters where the concentrations of dissolved iron (dFe) and the groundwater tracer Ba were significantly higher, while T. thiebautii abundance was positively correlated with water column depth. The Loop Current intrusion in 2015 with entrained Missisippi River water brought higher dFe and elevated abundance of both clades offshore of the 50 m isobath, suggesting that both clades are subject to Fe limitation on the outer shelf. Whereas, previous work has observed that T. thiebautii is more abundant than T. erythraeum in open ocean surface waters, this is the first study to examine Trichodesmium niche differentiation in a coastal environment. Understanding the environmental niches of these two key taxa bears important implications for their contributions to global nitrogen and carbon cycling and their response to global climate change
The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples
Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women’s risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80–0.88) and 0.81 (95% CI: 0.76–0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.publishedVersio
A randomized study on the usefulness of an electronic outpatient hypoglycemia risk calculator for clinicians of patients with diabetes in a safety-net institution
Objective: Hypoglycemia (HG) occurs in up to 60% of patients with diabetes mellitus (DM) each year. We assessed a HG alert tool in an electronic health record system, and determined its effect on clinical practice and outcomes.
Methods: The tool applied a statistical model, yielding patient-specific information about HG risk. We randomized outpatient primary-care providers (PCPs) to see or not see the alerts. Patients were assigned to study group according to the first PCP seen during four months. We assessed prescriptions, testing, and HG. Variables were compared by multinomial, logistic, or linear model. ClinicalTrials.gov ID: NCT04177147 (registered on 22 November 2019).
Results: Patients (N = 3350) visited 123 intervention PCPs; 3395 patients visited 220 control PCPs. Intervention PCPs were shown 18,645 alerts (mean of 152 per PCP). Patients’ mean age was 55 years, with 61% female, 49% black, and 49% Medicaid recipients. Mean baseline A1c and body mass index were similar between groups. During follow-up, the number of A1c and glucose tests, and number of new, refilled, changed, or discontinued insulin prescriptions, were highest for patients with highest risk. Per 100 patients on average, the intervention group had fewer sulfonylurea refills (6 vs. 8; p < .05) and outpatient encounters (470 vs. 502; p < .05), though the change in encounters was not significant. Frequency of HG events was unchanged.
Conclusions: Informing PCPs about risk of HG led to fewer sulfonylurea refills and visits. Longer-term studies are needed to assess potential for long-term benefits
allodb: An R package for biomass estimation at globally distributed extratropical forest plots
Allometric equations for calculation of tree above-ground biomass (AGB) form the basis for estimates of forest carbon storage and exchange with the atmosphere. While standard models exist to calculate forest biomass across the tropics, we lack a standardized tool for computing AGB across boreal and temperate regions that comprise the global extratropics. Here we present an integrated R package, allodb, containing systematically selected published allometric equations and proposed functions to compute AGB. The data component of the package is based on 701 woody species identified at 24 large Forest Global Earth Observatory (ForestGEO) forest dynamics plots representing a wide diversity of extratropical forests. A total of 570 parsed allometric equations to estimate individual tree biomass were retrieved, checked and combined using a weighting function designed to ensure optimal equation selection over the full tree size range with smooth transitions across equations. The equation dataset can be customized with built-in functions that subset the original dataset and add new equations. Although equations were curated based on a limited set of forest communities and number of species, this resource is appropriate for large portions of the global extratropics and can easily be expanded to cover novel forest types
Hsp90 inhibition disrupts JAK-STAT signaling and leads to reductions in splenomegaly in patients with myeloproliferative neoplasms
Target 2035-update on the quest for a probe for every protein
Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. The challenge of translating the wealth of new knowledge from genomics into new medicines is that proteins, and not genes, are the primary executers of biological function. Therefore, much of how biology works in health and disease must be understood through the lens of protein function. Accordingly, a subset of human proteins has been at the heart of research interests of scientists over the centuries, and we have accumulated varying degrees of knowledge about approximately 65% of the human proteome. Nevertheless, a large proportion of proteins in the human proteome (∼35%) remains uncharacterized, and less than 5% of the human proteome has been successfully targeted for drug discovery. This highlights the profound disconnect between our abilities to obtain genetic information and subsequent development of effective medicines. Target 2035 is an international federation of biomedical scientists from the public and private sectors, which aims to address this gap by developing and applying new technologies to create by year 2035 chemogenomic libraries, chemical probes, and/or biological probes for the entire human proteome
Communities organizing to promote equity: engaging local communities in public health responses to health inequities exacerbated by COVID-19–protocol paper
BackgroundThe COVID-19 pandemic has disproportionately impacted rural and under-resourced urban communities in Kansas. The state’s response to COVID-19 has relied on a highly decentralized and underfunded public health system, with 100 local health departments in the state, few of which had prior experience engaging local community coalitions in a coordinated response to a public health crisis.MethodsTo improve the capacity for local community-driven responses to COVID-19 and other public health needs, the University of Kansas Medical Center, in partnership with the Kansas Department of Health and Environment, will launch Communities Organizing to Promote Equity (COPE) in 20 counties across Kansas. COPE will establish Local Health Equity Action Teams (LHEATs), coalitions comprised of community members and service providers, who work with COPE-hired community health workers (CHWs) recruited to represent the diversity of the communities they serve. CHWs in each county are tasked with addressing unmet social needs of residents and supporting their county’s LHEAT. LHEATs are charged with implementing strategies to improve social determinants of health in their county. Monthly, LHEATs and CHWs from all 20 counties will come together as part of a learning collaborative to share strategies, foster innovation, and engage in peer problem-solving. These efforts will be supported by a multilevel communications strategy that will increase awareness of COPE activities and resources at the local level and successes across the state. Our mixed methods evaluation design will assess the processes and impact of COPE activities as well as barriers and facilitators to implementation using aspects of both the Consolidated Framework for Implementation Research (CFIR) and Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) models.DiscussionThis protocol is designed to expand community capacity to strategically partner with local public health and social service partners to prioritize and implement health equity efforts. COPE intentionally engages historically resilient communities and those living in underserved rural areas to inform pragmatic strategies to improve health equity
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