Developing Crowdsourced Clinical Registry Studies.

ABSTRACT: Crowdsourced registries have been used to quickly gather information, especially during emerging public health concerns. Registries that began during the COVID-19 pandemic were used to rapidly answer key questions on coinfections, experimental treatments, and morbidity and mortality outcomes. Registries are also used more frequently to support clinical trials and track long-term outcomes in patient populations. This article reviews registry methodology, including the collection of data from crowdsourcing and real-world sources, that can be applied to nurse researcher and clinical research nurse skill sets. The authors illustrate a recently reported crowdsourced COVID-19 and cryptococcal disease registry that followed project management strategies and the Agency for Healthcare Research and Quality registry guidelines for planning, execution, and analysis of registries and other research methods.

Neuromodulation for the management of chronic pelvic pain syndromes: A systematic review.

BACKGROUND: Chronic pelvic pain is a burdensome condition that involves multiple medical sub-specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large-scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes. MATERIALS AND METHODS: A systematic review of the literature demonstrating the treatment of chronic pelvic pain syndromes with neuromodulation. Abstracts were reviewed and selected for inclusion, including case series, prospective studies, and randomized controlled trials (RCTs). Case studies and publications in abstract only were not included. The reporting for this systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed using MEDLINE, Embase, Cochrane Library, PubMed, CINAHL, and Scopus. RESULTS: A total of 50 studies were included in this review, three of which were randomized controlled trials, and the remaining were prospective and retrospective case series. The range of pelvic pain conditions treated included interstitial cystitis, peripheral neuralgia, pudendal neuralgia, gastrointestinal pain, urogenital pain, sacroiliac joint pain, and visceral chronic pelvic pain. We reported on outcomes involving pain, functionality, psychosocial improvement, and medication reduction. CONCLUSIONS: Neuromodulation is a growing treatment for various chronic pain syndromes. Peripheral nerve stimulation was the least studied form of stimulation. Posterior tibial nerve stimulation appears to offer short-term benefit, but long-term results are challenging. Sacral nerve stimulation is established for use in functional bladder syndromes and appears to offer pain improvement in these patients as well. Dorsal root ganglion stimulation and spinal cord stimulation have been used for a variety of conditions with promising results. Further studies of homogeneous patient populations are necessary before strong recommendations can be made at this time, although pooled analysis may also be impactful.

Sexing white 2D footprints using convolutional neural networks.

Footprints are left, or obtained, in a variety of scenarios from crime scenes to anthropological investigations. Determining the sex of a footprint can be useful in screening such impressions and attempts have been made to do so using single or multi landmark distances, shape analyses and via the density of friction ridges. Here we explore the relative importance of different components in sexing two-dimensional foot impressions namely, size, shape and texture. We use a machine learning approach and compare this to more traditional methods of discrimination. Two datasets are used, a pilot data set collected from students at Bournemouth University (N = 196) and a larger data set collected by podiatrists at Sheffield NHS Teaching Hospital (N = 2677). Our convolutional neural network can sex a footprint with accuracy of around 90% on a test set of N = 267 footprint images using all image components, which is better than an expert can achieve. However, the quality of the impressions impacts on this success rate, but the results are promising and in time it may be possible to create an automated screening algorithm in which practitioners of whatever sort (medical or forensic) can obtain a first order sexing of a two-dimensional footprint.

Application of non-contact scanning to forensic podiatry: A feasibility study.

Foot impression evidence recovered from crime scenes can be available in the form of barefoot prints, sock-clad footprints, or as impressions within footwear. In some cases, suspects leave their footwear at the scene of the crime, and the insoles from the footwear can be important in linking a person to the footwear. The application of 3D data-collecting technology is becoming more and more popular within forensic science and has been used to recover footwear impression evidence. The present study is a feasibility study to discover if 3D data capturing devices can be applied to insoles; to capture the footprint impression for measurement using the Gunn method (a method used in forensic podiatry casework). Three different methods of data capture were conducted; Adobe Photoshop, MeshLab, and calipers used directly on the insole. Paired t-tests and Intraclass Correlation Coefficient (ICC) were conducted for all three data capture methods. Seven measurements used in this study were significantly different across all three methods. ICC scores were moderate to excellent for the Photoshop method, poor to good for the 3D method, and moderate to excellent for the Direct method.

Library consultations and a global pandemic: An analysis of consultation difficulty during COVID-19 across multiple factors.

The purpose of this study is to examine the relationship between librarians' perception of the difficulty of patron consultations and a variety of factors that characterize these interactions in the context of an academic library at a large public university. The study also provides insight into how changes in library service operations due to the global COVID-19 pandemic have affected the perceived difficulty of library consultations. Data samples were drawn from a LibInsight dataset and limited to consultations from Fall 2019 and Spring 2020 (N = 3331). Statistical analysis was conducted using ordinal logistic regression to quantify the relationship between perceptions of difficulty and factors indicating pre/post-COVID-19 modifications, patron type, scheduling, question format, library department, consultation duration, semester, and campus. Most notably, results indicate a statistically significant (p < 0.001) increase in the perceived difficulty of consultations that followed the closure of the library's physical spaces due to COVID-19, even when controlling for other factors in multiple model formulations. These results, as well as insights pertaining to other factors associated with library consultations and perceptions of difficulty, have implications for how librarians frame, understand, and manage their workloads. Additionally, findings may provide library service managers with the evidence needed to better coordinate and evaluate library services.

Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention.

Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 and 2 diabetes. It is a leading cause of lower-limb amputation and disabling neuropathic pain. Amputations in patients with diabetes have a devastating effect on quality of life and are associated with an alarmingly low life expectancy (on average only 2 years from the amputation). Amputation also places a substantial financial burden on health-care systems and society in general. With the introduction of national diabetes eye screening programmes, the prevalence of blindness in working-age adults is falling. This is not the case, however, with diabetes related amputations. In this Review, we appraise innovative point-of-care devices that enable the early diagnosis of DPN and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN. We also propose a framework for screening and early multifactorial interventions as the best prospect for preventing or halting DPN and its devastating sequelae.

Intrapulmonary Autoantibodies to HSP72 Are Associated with Improved Outcomes in IPF.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease, with high mortality. Currently, the aetiology and the pathology of IPF are poorly understood, with both innate and adaptive responses previously being implicated in the disease pathogenesis. Heat shock proteins (Hsp) and antibodies to Hsp in patients with IPF have been suggested as therapeutic targets and prognostic biomarkers, respectively. We aimed to study the relationship between the expression of Hsp72 and anti-Hsp72 antibodies in the BAL fluid and serum Aw disease progression in patients with IPF. METHODS: A novel indirect ELISA to measure anti-Hsp72 IgG was developed and together with commercially available ELISAs used to detect Hsp72 IgG, Hsp72 IgGAM, and Hsp72 antigen, in the serum and BALf of a cohort of IPF (n = 107) and other interstitial lung disease (ILD) patients (n = 66). Immunohistochemistry was used to detect Hsp72 in lung tissue. The cytokine expression from monocyte-derived macrophages was measured by ELISA. RESULTS: Anti-Hsp72 IgG was detectable in the serum and BALf of IPF (n = 107) and other ILDs (n = 66). Total immunoglobulin concentrations in the BALf showed an excessive adaptive response in IPF compared to other ILDs and healthy controls (p = 0.026). Immunohistochemistry detection of C4d and Hsp72 showed that these antibodies may be targeting high expressing Hsp72 type II alveolar epithelial cells. However, detection of anti-Hsp72 antibodies in the BALf revealed that increasing concentrations were associated with improved patient survival (adjusted HR 0.62, 95% CI 0.45-0.85; p = 0.003). In vitro experiments demonstrate that anti-Hsp72 complexes stimulate macrophages to secrete CXCL8 and CCL18. CONCLUSION: Our results indicate that intrapulmonary anti-Hsp72 antibodies are associated with improved outcomes in IPF. These may represent natural autoantibodies, and anti-Hsp72 IgM and IgA may provide a beneficial role in disease pathogenesis, though the mechanism of action for this has yet to be determined.

Cardiovascular Disease, Cancer, and Mortality Among People With Type 2 Diabetes and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital Admission.

OBJECTIVE: To describe associations between alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study by using linked population-based routine data from diabetes registry, hospital, cancer, and death records for people aged 40-89 years diagnosed with T2DM in Scotland between 2004 and 2013 who had one or more hospital admission records. Liver disease and outcomes were identified by using ICD-9 and ICD-10 codes. We estimated hazard ratios (HRs) from Cox proportional hazards regression models, adjusting for key risk factors. RESULTS: A total of 134,368 people with T2DM (1,707 with ALD and 1,452 with NAFLD) were studied, with a mean follow-up of 4.3 years for CVD and 4.7 years for mortality. Among those with ALD, NAFLD, or without liver disease hospital records 378, 320, and 21,873 CVD events; 268, 176, and 15,101 cancers; and 724, 221, and 16,203 deaths were reported, respectively. For ALD and NAFLD, respectively, adjusted HRs (95% CIs) compared with the group with no record of liver disease were 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90) for CVD, 40.3 (28.8, 56.5) and 19.12 (11.71, 31.2) for hepatocellular carcinoma (HCC), 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer, and 4.86 (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality. CONCLUSIONS: Hospital records of ALD or NAFLD are associated to varying degrees with an increased risk of CVD, cancer, and mortality among people with T2DM.

Type 2 diabetes, socioeconomic status and life expectancy in Scotland (2012-2014): a population-based observational study.

AIMS/HYPOTHESIS: The aim of this study was to assess the role of socioeconomic status (SES) in the associations between type 2 diabetes and life expectancy in a complete national population. METHODS: An observational population-based cohort study was performed using the Scottish Care Information - Diabetes database. Age-specific life expectancy (stratified by SES) was calculated for all individuals with type 2 diabetes in the age range 40-89 during the period 2012-2014, and for the remaining population of Scotland aged 40-89 without type 2 diabetes. Differences in life expectancy between the two groups were calculated. RESULTS: Results were based on 272,597 individuals with type 2 diabetes and 2.75 million people without type 2 diabetes (total for 2013, the middle calendar year of the study period). With the exception of deprived men aged 80-89, life expectancy in people with type 2 diabetes was significantly reduced (relative to the type 2 diabetes-free population) at all ages and levels of SES. Differences in life expectancy ranged from -5.5 years (95% CI -6.2, -4.8) for women aged 40-44 in the second most-deprived quintile of SES, to 0.1 years (95% CI -0.2, 0.4) for men aged 85-89 in the most-deprived quintile of SES. Observed life-expectancy deficits in those with type 2 diabetes were generally greater in women than in men. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with reduced life expectancy at almost all ages and levels of SES. Elimination of life-expectancy deficits in individuals with type 2 diabetes will require prevention and management strategies targeted at all social strata (not just deprived groups).

Biocatalytic Stimuli-Responsive Asymmetric Triblock Terpolymer Membranes for Localized Permeability Gating.

The functionalization with phosphotriesterase of poly(isoprene-b-styrene-b-4-vinylpyridine)-based nanoporous membranes fabricated by self-assembly and nonsolvent induced phase separation (SNIPS) is shown to enable dynamically responsive membranes capable of substrate-specific and localized gating response. Integration of the SNIPS process with macroporous nylon support layers yields mechanically robust textile-type films with high moisture vapor transport rates that display rapid and local order-of-magnitude modulation of permeability. The simplicity of the fabrication process that is compatible with large-area fabrication along with the versatility and efficacy of enzyme reactivity offers intriguing opportunities for engineered biomimetic materials that are tailored to respond to a complex range of external parameters, providing sensing, protection, and remediation capabilities.

Complex Coacervate Core Micelles for the Dispersion and Stabilization of Organophosphate Hydrolase in Organic Solvents.

Organophosphate (OP) nerve agents are a class of chemical warfare agents (CWAs) that exist as bulk stocks in current and past war zones. Thus, a technology that can perform on-site decontamination in a safe and timely fashion is desirable. Here, complex coacervate core micelles (C3Ms) were used to encapsulate organophosphate hydrolase (OPH) and chemostabilize it to maintain activity after exposure to organophosphate simulants ethanol and dimethyl methylphosphonate (DMMP). C3Ms were formed by two polymers-poly(acrylic acid) (PAA) and poly(oligo(ethylene glycol) methacrylate)-b-poly(4-vinyl N-methylpyridyl iodide), (POEGMA-b-qP4VP). Complexes of the coacervate micelles with the enzyme OPH were investigated by small angle neutron scattering (SANS), dynamic light scattering (DLS), and transmission electron microscopy (TEM), demonstrating the formation of micellar structures in solution. The activity of OPH against methyl paraoxon in these C3Ms under aqueous conditions was assayed after heat treatment for 3 days at 37 °C. The OPH in C3Ms retained 88 ± 7% of its initial activity, as compared to the 48 ± 3% activity retained by OPH alone, indicating that the C3Ms were able to stabilize the enzyme to heat treatment. C3Ms transferred into the two organic solvents formed larger structures than inverse micelles formed by the block copolymer alone. The addition of OPH to the C3Ms in organic solvents did not significantly change their structure. The activity of OPH (again, against methyl paraoxon) after 24 h of incubation at 4 °C was measured and compared to that of OPH in C3Ms. While OPH alone retained less than 5% of its activity after this incubation in both solvents, OPH in C3Ms retained 35 ± 3% of its activity in DMMP and 26 ± 1% of its activity in ethanol.

Optimal Design of Low-Density SNP Arrays for Genomic Prediction: Algorithm and Applications.

Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for the optimal design of LD SNP chips. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optimal LD SNP chips that can be imputed accurately to medium-density (MD) or high-density (HD) SNP genotypes for genomic prediction. The objective function facilitates maximization of non-gap map length and system information for the SNP chip, and the latter is computed either as locus-averaged (LASE) or haplotype-averaged Shannon entropy (HASE) and adjusted for uniformity of the SNP distribution. HASE performed better than LASE with ≤1,000 SNPs, but required considerably more computing time. Nevertheless, the differences diminished when >5,000 SNPs were selected. Optimization was accomplished conditionally on the presence of SNPs that were obligated to each chromosome. The frame location of SNPs on a chip can be either uniform (evenly spaced) or non-uniform. For the latter design, a tunable empirical Beta distribution was used to guide location distribution of frame SNPs such that both ends of each chromosome were enriched with SNPs. The SNP distribution on each chromosome was finalized through the objective function that was locally and empirically maximized. This MOLO algorithm was capable of selecting a set of approximately evenly-spaced and highly-informative SNPs, which in turn led to increased imputation accuracy compared with selection solely of evenly-spaced SNPs. Imputation accuracy increased with LD chip size, and imputation error rate was extremely low for chips with ≥3,000 SNPs. Assuming that genotyping or imputation error occurs at random, imputation error rate can be viewed as the upper limit for genomic prediction error. Our results show that about 25% of imputation error rate was propagated to genomic prediction in an Angus population. The utility of this MOLO algorithm was also demonstrated in a real application, in which a 6K SNP panel was optimized conditional on 5,260 obligatory SNP selected based on SNP-trait association in U.S. Holstein animals. With this MOLO algorithm, both imputation error rate and genomic prediction error rate were minimal.

Metformin and survival of people with type 2 diabetes and pleural mesothelioma: A population-based retrospective cohort study.

OBJECTIVES: This study aimed to investigate the effect of metformin on survival of people with type 2 diabetes and pleural mesothelioma. MATERIALS AND METHODS: We conducted a retrospective cohort study of people with type 2 diabetes diagnosed with pleural or unspecified mesothelioma between 1993 and 2014 using linked Scottish population-based diabetes and cancer datasets. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards regression models were used to describe the association between use of metformin and all-cause mortality following diagnosis of pleural mesothelioma. RESULTS: There were 300 people with type 2 diabetes and pleural or unspecified mesothelioma of whom 148 had ever used metformin and 290 died during follow up. The median survival time was 8.8 months and 6.5 months for metformin users and non-users respectively (p=0.37, log-rank test). After adjusting for age, sex, diabetes duration, socio-economic status, and other anti-diabetic medications the hazard ratio for mortality associated with metformin was 0.99 (95% confidence intervals: 0.76-1.28; p=0.92). Similar non-statistically significant associations were obtained in sensitivity analyses based on metformin use in year prior to diagnosis of mesothelioma, use of metformin for more than one year, in people below the mean age at diagnosis of mesothelioma (74 years) and 74 years of age or older, limitation to pleural mesothelioma and following further adjustment for body mass index and smoking. CONCLUSION: There was no evidence that metformin improved survival among people with type 2 diabetes and pleural mesothelioma or to support trials of metformin in people with mesothelioma.

Light Scattering Analysis of Mono- and Multi-PEGylated Bovine Serum Albumin in Solution: Role of Composition on Structure and Interactions.

The effect of polymer conjugation on the interactions between proteins in solution is evaluated by systematic analysis of the second virial coefficient (A2) for the particular example of single- and double-PEGylated bovine serum albumin (PEG-BSA) in dilute PBS solution. The effect of PEGylation on A2 is found to sensitively depend on both the composition and the distribution of PEG segments within the conjugate. Most importantly, at a given PEG volume fraction, A2 significantly increases with the degree of polymerization of tethered chains. Hence, a lesser number of long chains is more effective in solubilizing BSA than a correspondingly larger number of short chains. Analysis of the hydrodynamic radii of protein-PEG conjugates suggests that the increased solubility is concurrent with a structural transition in the case of high molecular PEG grafts that results in compact core-shell-type structures. The results reveal a link between the composition, structure, and solubility of polymer conjugates that might benefit the understanding of their biochemical characteristics and their design for functional material applications.

Socioeconomic status, comorbidity and mortality in patients with type 2 diabetes mellitus in Scotland 2004-2011: a cohort study.

BACKGROUND: Mortality in people with and without diabetes often exhibits marked social patterning, risk of death being greater in deprived groups. This may reflect deprivation-related differences in comorbid disease (conditions additional to diabetes itself). This study sought to determine whether the social patterning of mortality in a population with type 2 diabetes mellitus (T2DM) is explained by differential comorbidity. METHODS: Hospital records for 70 197 men and 56 451 women diagnosed with T2DM at 25 years of age and above in Scotland during the period 2004-2011 were used to construct comorbidity histories. Sex-specific logistic models were fitted to predict mortality at 1 year after diagnosis with T2DM, predicted initially by age and socioeconomic status (SES) then extended to incorporate in turn 5 representations of comorbidity (including the Charlson Index). The capacity of comorbidity to explain social mortality gradients was assessed by observing the change in regression coefficients for SES following the addition of comorbidity. RESULTS: After adjustment for age and Charlson Index, the OR for the contrast between the least deprived and most deprived quintiles of SES for men was 0.79 (95% CI 0.67 to 0.94). For women, the OR was 0.81 (0.67 to 0.97). Similar results were obtained for the 4 other comorbidity measures used. CONCLUSIONS: The social patterning of mortality in people with T2DM is not fully explained by differing levels of comorbid disease additional to T2DM itself. Other dimensions of deprivation are implicated in the elevated death rates observed in deprived groups of people with T2DM.

A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions.

Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product.