Subset Of Population Research Articles

Identifying High-Need Primary Care Patients Using Nursing Knowledge and Machine Learning Methods.

Patient cohorts generated by machine learning can be enhanced with clinical knowledge to increase translational value and provide a practical approach to patient segmentation based on a mix of medical, behavioral, and social factors. This study aimed to generate a pragmatic example of how machine learning could be used to quickly and meaningfully cohort patients using unsupervised classification methods. Additionally, to demonstrate increased translational value of machine learning models through the integration of nursing knowledge. A primary care practice dataset (N = 3,438) of high-need patients defined by practice criteria was parsed to a subset population of patients with diabetes (n = 1233). Three expert nurses selected variables for k-means cluster analysis using knowledge of critical factors for care coordination. Nursing knowledge was again applied to describe the psychosocial phenotypes in four prominent clusters, aligned with social and medical care plans. Four distinct clusters interpreted and mapped to psychosocial need profiles, allowing for immediate translation to clinical practice through the creation of actionable social and medical care plans. (1) A large cluster of racially diverse female, non-English speakers with low medical complexity, and history of childhood illness; (2) a large cluster of English speakers with significant comorbidities (obesity and respiratory disease); (3) a small cluster of males with substance use disorder and significant comorbidities (mental health, liver and cardiovascular disease) who frequently visit the hospital; and (4) a moderate cluster of older, racially diverse patients with renal failure. This manuscript provides a practical method for analysis of primary care practice data using machine learning in tandem with expert clinical knowledge.

The STAT3-Regulated Autophagy Pathway in Glioblastoma.

Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.

Transmission of Behavioral Deficits in Rats Exposed to Folate Receptor Alpha Antibody In Utero. (S2.001)

<h3>Objective:</h3> We aim to investigate the behavioral deficits in rats exposed to folate receptor alpha antibodies (FRaAb) during fetal development. Furthermore, we aim to investigate the heritability of this autism spectrum disorder (ASD)-like phenotype by determining whether it is transmitted to a subsequent generation. <h3>Background:</h3> Folate deficiency is known to lead to disruptions in neurodevelopment including neural tube defects and developmental anomalies such as ASD. Folate receptor alpha (FRα) is the main transporter of folate from the mother to the fetus and into the brain. A major subset of the ASD population and their family members have auto antibodies against FRα that may cause neuroinflammation and block folate transport to the developing fetus. <h3>Design/Methods:</h3> Our laboratory has produced rat FRα specific antibody (FRαAb) that when injected intraperitoneally into a dam on gestation day 8, will produce a litter with ASD-like behavioral deficits. This phenotype can be prevented when the dam is given D, L-folinic acid, dexamethasone, or a combination of both at the time of FRαAb exposure. We tested both the litter directly exposed to FRαAb and the offspring of those with an affected phenotype using a battery of social and learning tests. <h3>Results:</h3> We observed deficits in social communication, social interaction, learning and memory in both the first and second generations which suggests transmission of the behavioral phenotype associated with FRαAb exposure. <h3>Conclusions:</h3> The intergenerational transmission of this phenotype to animals not directly exposed to FRαAb suggests that it may be mediated by epigenomic changes. We hypothesize that treatment of the directly exposed generation with folinic acid prior to mating may prevent transmission of behavioral deficits to a subsequent generation by altering the epigenome. This may be a strategy to decrease the risk in families with a history of ASD. <b>Disclosure:</b> Mr. Amaro-Barron has nothing to disclose. Ms. Bobrowski-Khoury has nothing to disclose. Edward Quadros has nothing to disclose.

Decrease in vancomycin MICs and prevalence of hGISA in MRSA and MSSA isolates from a German pediatric tertiary care center

PurposeResistance of Staphylococcus aureus to vancomycin includes a general increase of minimal inhibitory concentrations (MIC) within the susceptible range over time (Vancomycin MIC Creep) and the presence of a subset of the bacterial population that expresses resistance (heterogeneous glycopeptide-intermediate S. aureus; hGISA). Increased MICs have been associated with adverse clinical outcomes. However, the vancomycin MIC creep is not a uniform trend suggesting the importance of regional surveys.MethodsWe performed a retrospective analysis at a German pediatric tertiary care hospital. Isolates from 2002 to 2017 were selected which were newly identified methicillin-resistant S. aureus (MRSA) or samples from invasive methicillin-susceptible S. aureus (MSSA) or MRSA infections. Vancomycin and oxacillin MICs as well as GISA/hGISA were measured using MIC test strips and resistance was evaluated over time.ResultsA total of 540 samples were tested, 200 from the early (2002–2009) and 340 from the later period (2010–2017). All samples were vancomycin susceptible, but the MIC was higher for the earlier samples as compared to the later ones (1.11 vs 0.99; p < 0.001). 14% of the samples were hGISA, GISA strains were not detected. Again, vancomycin resistance decreased over time with 28 vs. 6% hGISA (p < 0.001). There was no significant difference between MRSA and MSSA samples with respect to vancomycin MIC and hGISA prevalence.ConclusionThis study shows a decreasing trend for both MIC values and presence of hGISA strains highlighting the importance of monitoring local susceptibilities. Vancomycin remains a first-line treatment option for suspected severe infection with Gram-positive cocci and proven infection with MRSA.

Machine learning to predict myocardial injury and death after non-cardiac surgery.

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.

A Machine-Learning Approach to Target Clinical and Biological Features Associated with Sarcopenia: Findings from Northern and Southern Italian Aging Populations.

Epidemiological and public health resonance of sarcopenia in late life requires further research to identify better clinical markers useful for seeking proper care strategies in preventive medicine settings. Using a machine-learning approach, a search for clinical and fluid markers most associated with sarcopenia was carried out across older populations from northern and southern Italy. A dataset of adults >65 years of age (n = 1971) made up of clinical records and fluid markers from either a clinical-based subset from northern Italy (Pavia) and a population-based subset from southern Italy (Apulia) was employed (n = 1312 and n = 659, respectively). Body composition data obtained by dual-energy X-ray absorptiometry (DXA) were used for the diagnosis of sarcopenia, given by the presence of either low muscle mass (i.e., an SMI < 7.0 kg/m2 for males or <5.5 kg/m2 for females) and of low muscle strength (i.e., an HGS < 27 kg for males or <16 kg for females) or low physical performance (i.e., an SPPB ≤ 8), according to the EWGSOP2 panel guidelines. A machine-learning feature-selection approach, the random forest (RF), was used to identify the most predictive features of sarcopenia in the whole dataset, considering every possible interaction among variables and taking into account nonlinear relationships that classical models could not evaluate. Then, a logistic regression was performed for comparative purposes. Leading variables of association to sarcopenia overlapped in the two population subsets and included SMI, HGS, FFM of legs and arms, and sex. Using parametric and nonparametric whole-sample analysis to investigate the clinical variables and biological markers most associated with sarcopenia, we found that albumin, CRP, folate, and age ranked high according to RF selection, while sex, folate, and vitamin D were the most relevant according to logistics. Albumin, CRP, vitamin D, and serum folate should not be neglected in screening for sarcopenia in the aging population. Better preventive medicine settings in geriatrics are urgently needed to lessen the impact of sarcopenia on the general health, quality of life, and medical care delivery of the aging population.

Renal Tumours Of Non-Clear Cell Histology; 10 Years' Experience In A Specialized Centre.

Non-clear cell renal cell carcinomas are uncommon renal tumours with diverse histologically and genetically defined entities. Due to limited clinical outcomes data, no standardized management approach can be offered to these patients. This study aimed to analyse outcomes of non clear cell renal cell carcinoma after surgical resection of localized renal tumours in our population. Patients with renal tumours who underwent partial or radical nephrectomy at the Department of Urology, from January 2010 to December 2019 were identified and evaluated, in terms of prevalence, presentation, recurrence, and survival outcome. Non-clear cell tumours were found in one-fourth of the total number of nephrectomies performed during this period for renal cell carcinoma (RCC). The mean age was 50.48±14.76 years (range 18-89 years) with 57% being of the male gender. The predominant types were chromophobe RCC, papillary RCC, and sarcomatoid RCC, in all non-clear cell renal tumours. Mean Recurrence Free Survival (RFS) for all tumours was 75.26±2.7 months. The projected 5 years RFS of papillary RCC, chromophobe RCC and sarcomatoid RCC were 94.2%, 84.3% and 62.5% respectively. RCC of non-clear-cell histology depicts excellent survival in patients with localized renal tumours. Furthermore, sarcomatoid RCC has worse recurrence free survival followed by chromophobe RCC and papillary RCC, in our population subset.

Genetic population structure of the Xiongnu Empire at imperial and local scales.

The Xiongnu established the first nomadic imperial power, controlling the Eastern Eurasian steppe from ca. 200 BCE to 100 CE. Recent archaeogenetic studies identified extreme levels of genetic diversity across the empire, corroborating historical records of the Xiongnu Empire being multiethnic. However, it has remained unknown how this diversity was structured at the local community level or by sociopolitical status. To address this, we investigated aristocratic and local elite cemeteries at the western frontier of the empire. Analyzing genome-wide data from 18 individuals, we show that genetic diversity within these communities was comparable to the empire as a whole, and that high diversity was also observed within extended families. Genetic heterogeneity was highest among the lowest-status individuals, implying diverse origins, while higher-status individuals harbored less genetic diversity, suggesting that elite status and power was concentrated within specific subsets of the broader Xiongnu population.

Characterization of western corn rootworm (Coleoptera: Chrysomelidae) susceptibility to foliar insecticides in northeast Nebraska.

Foliar-applied insecticides are commonly used for adult western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), control in Nebraska but little efficacy data is available. Anecdotal reports of reduced efficacy in areas of northeast Nebraska led to the conduct of this study. Objectives were to (i) evaluate the efficacy of commercial applications of commonly used formulated insecticides (bifenthrin, lambda-cyhalothrin, chlorpyrifos, or tank mixes) for WCR control in 7 northeast Nebraska counties during 2019 and 2020 and (ii) conduct adult WCR concentration-response vial bioassays with bifenthrin, chlorpyrifos, and dimethoate active ingredients on a subset of field populations. Whole plant counts (WPC) were used to measure WCR densities in insecticide-treated and untreated maize fields before and after insecticide application. Field control was excellent with organophosphate/pyrethroid tank mixes as proportional change in mean WPC of treated fields was significantly reduced (>0.90) versus untreated fields where little change in WPC occurred. The exception was one treated Boone County field where proportional reduction in WPC was ≤0.78. Bioassays revealed LC50s and resistance ratios of most populations exposed to bifenthrin and dimethoate were not significantly different than the susceptible control. Most populations exhibited a low level of chlorpyrifos resistance when compared to the susceptible control. Field and lab data suggest the local onset of practical WCR field-evolved resistance to bifenthrin in Boone County and chlorpyrifos in Boone and Colfax counties. Results of this study will increase our understanding of WCR resistance evolution, serve as a comprehensive baseline for future research, and inform WCR management programs.

Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets.

Osteoarthritis (OA), a multifaceted condition, poses a significant challenge for the successful clinical development of therapeutics due to heterogeneity. However, classifying molecular endotypes of OA pathogenesis could provide invaluable phenotype-directed routes for stratifying subgroups of patients for targeted therapeutics, leading to greater chances of success in trials. This study establishes endotypes in OA soft joint tissue driven by obesity in both load-bearing and non-load bearing joints. Hand, hip, knee and foot joint synovial tissue was obtained from OA patients (n=32) classified as obese (BMI>30) or normal weight (BMI 18.5-24.9). Isolated fibroblasts (OA SF) were assayed by Olink proteomic panel, seahorse metabolic flux assay, Illumina's NextSeq 500 bulk and Chromium 10X single cell RNA-sequencing, validated by Luminex and immunofluorescence. Targeted proteomic, metabolic and transcriptomic analysis found the inflammatory landscape of OA SFs are independently impacted by obesity, joint loading and anatomical site with significant heterogeneity between obese and normal weight patients, confirmed by bulk RNAseq. Further investigation by single cell RNAseq identified four functional molecular endotypes including obesity specific subsets defined by an inflammatory endotype related to immune cell regulation, fibroblast activation and inflammatory signaling, with up-regulated CXCL12, CFD and CHI3L1 expression. Luminex confirmed elevated chitase3-like-1(229.5vs. 49.5ng/ml, p<.05) and inhibin (20.6vs. 63.8 pg/ml, p<.05) in obese and normal weight OA SFs, respectively. Lastly, we find SF subsets in obese patients spatially localise in sublining and lining layers of OA synovium and can be distinguished by differential expression of the transcriptional regulators MYC and FOS. These findings demonstrate the significance of obesity in changing the inflammatory landscape of synovial fibroblasts in both load bearing and non-load bearing joints. Describing multiple heterogeneous OA SF populations characterised by specific molecular endotypes, which drive heterogeneity in OA disease pathogenesis. These molecular endotypes may provide a route for the stratification of patients in clinical trials, providing a rational for the therapeutic targeting of specific SF subsets in specific patient populations with arthritic conditions.

Characterization of Low-mass Companions to Kepler Objects of Interest Observed with APOGEE-N

We report the characterization of 28 low-mass (0.02 M ⊙ ≤ M 2 ≤ 0.25 M ⊙) companions to Kepler objects of interest (KOIs), eight of which were previously designated confirmed planets. These objects were detected as transiting companions to Sunlike stars (G and F dwarfs) by the Kepler mission and are confirmed as single-lined spectroscopic binaries in the current work using the northern multiplexed Apache Point Observatory Galactic Evolution Experiment near-infrared spectrograph (APOGEE-N) as part of the third and fourth Sloan Digital Sky Surveys. We have observed hundreds of KOIs using APOGEE-N and collected a total of 43,175 spectra with a median of 19 visits and a median baseline of ∼1.9 yr per target. We jointly model the Kepler photometry and APOGEE-N radial velocities to derive fundamental parameters for this subset of 28 transiting companions. The radii for most of these low-mass companions are overinflated (by ∼10%) when compared to theoretical models. Tidally locked M dwarfs on short-period orbits show the largest amount of inflation, but inflation is also evident for companions that are well separated from the host star. We demonstrate that APOGEE-N data provide reliable radial velocities when compared to precise high-resolution spectrographs that enable detailed characterization of individual systems and the inference of orbital elements for faint (H > 12) KOIs. The data from the entire APOGEE-KOI program are public and present an opportunity to characterize an extensive subset of the binary population observed by Kepler.

Young adults' beliefs about modern oral nicotine products: Implications for uptake in nonvapers, dual use with e-cigarettes, and use to reduce/quit vaping.

Modern oral nicotine products (ONPs; nontherapeutic nicotine pouches, gums, lozenges, and gummies) may be perceived in ways that could promote uptake in nonvapers, dual use with e-cigarettes, or use to quit vaping. In this cross-sectional digital remote survey of 1,460 respondents aged 21-24 from Southern California, we examined beliefs about ONPs among past-30-day e-cigarette nonusers, users unmotivated to quit vaping, and users motivated to quit vaping. Positive beliefs about ONPs were reported by 31.8% of the overall sample and higher in past-30-day e-cigarette users (with or without quit motivation) than nonusers. Perceiving ONPs to be easy to conceal, convenient, and able to be used where vaping/smoking is not allowed were the most common types of beliefs reported. Among e-cigarette users with quit motivation (n = 142), interest in using ONPs to quit/reduce vaping (44.4%) was higher than interest in using medicinal nicotine gum/lozenges (23.4%), nicotine patch (17.6%), or prescription medications (16.6%). Interest in using ONPs to reduce/quit vaping (vs. no interest) was greater among participants who reported vaping ≥ 20 (vs. < 10) days in the past month, vaping ≥ 10 (vs. < 10) times per day, low/moderate (vs. high) quit vaping self-efficacy, and low/moderate (vs. high) desire to quit vaping. These findings suggest that: (a) appreciable subsets of the young adult population may hold positive beliefs about ONPs that could promote ONP uptake, particularly e-cigarette users and (b) some young adult e-cigarette users may be interested in using ONPs to reduce/quit vaping, particularly frequent vapers with relatively lower self-efficacy and desire to quit vaping. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PASTE, Don't Cut: Genome Editing Tool Looks Beyond CRISPR and Prime

PASTE, Don't Cut: Genome Editing Tool Looks Beyond CRISPR and Prime

Rab11A Depletion in Microglia-Derived Extracellular Vesicle Proteome upon Beta-Amyloid Treatment

Microglia, the macrophage-like glial cells, behave as sentinels against exogenous pathogens invading the neural tissue. Their commitment is not only confined to the defensive function, but they also perform balancing trophic activities such as neuronal postnatal development, remodeling and pruning of synapses. Likewise, microglia-derived extracellular vesicles (EVs) can play strategic roles in maintaining a healthy brain by modulating neuronal activity and by controlling neurite outgrowth as well as innate immune response. Nevertheless, strong evidence also points to their role in the development of neurodegenerative pathologies such as Alzheimer’s disease (AD). Here, we explored EV protein content released by BV2 microglial cells in a resting state and after stimulation with beta-amyloid peptides (Aβ), mimicking conditions occurring in AD. In the resting BV2 cells, we extended the list of proteins present in mouse microglia EV cargo with respect to those reported in the Vesiclepedia exosome database while, in amyloid-triggered microglia, we highlighted a pronounced drop in EV protein content. Focusing on Rab11A, a key factor in the recycling routes of amyloid species, we observed a dramatic decrease of this protein in Aβ-treated microglia EV cargo with respect to the EVs from the untreated sample. This decrease might affect the delivery of Rab11A to neurons thus increasing the harmful amyloid burden in neuronal cells that eventually may lead to their death. We tentatively proposed that alterations observed in EVs derived from Aβ-treated microglia may represent molecular features that, among others, shape the disease-associated microglial phenotype, a recently proposed subset of microglial population, present in neurodegenerative pathologies.

Metrics of student dissatisfaction and disagreement: longitudinal explorations of a national survey instrument.

This study explores dissatisfaction and neutrality metrics from 12years of a national-level undergraduate student survey. The notion of dissatisfaction is much less prevalent in the narratives surrounding student survey outcomes, and the underpinning metrics are seldom considered. This is despite an increasingly vociferous debate about 'value for money' of higher education and the positioning of students as consumers in a marketised sector. We used machine learning methods to explore over 2.7 million national survey outcomes from 154 institutions to describe year-on-year stability in the survey items that best predicted dissatisfaction and neutrality, together with their similarity to known metric predictors of satisfaction. The widely publicised annual increases in student 'satisfaction' are shown to be the result of complex reductions in the proportions of disagreement and neutrality across different survey dimensions. Due to the widespread use of survey metrics in university league tables, we create an anonymised, illustrative table to demonstrate how UK institutional rankings would have differed if dissatisfaction metrics had been the preferred focus for reporting. We conclude by debating the tensions of balancing the provision of valuable information about dissatisfaction, with perpetuating negative impacts that derive from this important subset of the survey population.

GENERATOR HEART FAILURE DataMart: An integrated framework for heart failure research.

Heart failure (HF) is a multifaceted clinical syndrome characterized by different etiologies, risk factors, comorbidities, and a heterogeneous clinical course. The current model, based on data from clinical trials, is limited by the biases related to a highly-selected sample in a protected environment, constraining the applicability of evidence in the real-world scenario. If properly leveraged, the enormous amount of data from real-world may have a groundbreaking impact on clinical care pathways. We present, here, the development of an HF DataMart framework for the management of clinical and research processes. Within our institution, Fondazione Policlinico Universitario A. Gemelli in Rome (Italy), a digital platform dedicated to HF patients has been envisioned (GENERATOR HF DataMart), based on two building blocks: 1. All retrospective information has been integrated into a multimodal, longitudinal data repository, providing in one single place the description of individual patients with drill-down functionalities in multiple dimensions. This functionality might allow investigators to dynamically filter subsets of patient populations characterized by demographic characteristics, biomarkers, comorbidities, and clinical events (e.g., re-hospitalization), enabling agile analyses of the outcomes by subsets of patients. 2. With respect to expected long-term health status and response to treatments, the use of the disease trajectory toolset and predictive models for the evolution of HF has been implemented. The methodological scaffolding has been constructed in respect of a set of the preferred standards recommended by the CODE-EHR framework. Several examples of GENERATOR HF DataMart utilization are presented as follows: to select a specific retrospective cohort of HF patients within a particular period, along with their clinical and laboratory data, to explore multiple associations between clinical and laboratory data, as well as to identify a potential cohort for enrollment in future studies; to create a multi-parametric predictive models of early re-hospitalization after discharge; to cluster patients according to their ejection fraction (EF) variation, investigating its potential impact on hospital admissions. The GENERATOR HF DataMart has been developed to exploit a large amount of data from patients with HF from our institution and generate evidence from real-world data. The two components of the HF platform might provide the infrastructural basis for a combined patient support program dedicated to continuous monitoring and remote care, assisting patients, caregivers, and healthcare professionals.

The Relationship Between Periodontal Disease (PD) and Recurrent Vascular Events in Ischemic Stroke/Transient Ischemic Attack (TIA) Patients: A Hospital-Based Cohort Study

Background In this cohort study, the association between periodontal disease (PD) andrecurrent vascular events was determined among the subjectswithischemic stroke/transient ischemic attack (TIA), and the extent and severity of periodontal disease were estimated among these subjects. Methods This prospective, longitudinal, hospital-based cohort study included 153 individuals who had a stroke or TIA. They were divided into two groups: high periodontal disease (HPD) (N=55, mean age: 59.40±12.21) and low periodontal disease (LPD) (N=98, mean age: 53.03±12.82). Clinical attachment loss (CAL) and probing pocket depth (PPD) were used to measure the severity of the periodontal disease. TOAST criteria were used to determine the ischemic stroke etiology, and the NIH Stroke Scale (NIHSS) was used to determine theischemic stroke severity. A follow-up survey found that vascular incidents recurred. Results HPD individualsexhibited a higher median NIHSS (eight) than LPD patients (seven) in a subset of stroke population (N=23). Thirty-eight cardiovascular events occurred in the first three months after enrollment, including 23 strokes and seven TIAs, and five myocardial infarctions(MIs). There were three deaths from vascular causes. There was a non-significant association between PD and composite vascular events (HR 1.06, 95% CI, 1.03 to 1.09, p=0.71). Compound vascular events were not related to severe HPD (HR 1.31, 95 % CI 0.54 to 3.16, p=0.07). Conclusion In stroke/TIA patients, there is no link between high periodontal disease and recurrent vascular episodes. The proportions of stroke subtypes were not substantially differentbetween HPDand LPD.

Elephants Not in the Room: Systematic Review Shows Major Geographic Publication Bias in African Elephant Ecological Research

African savanna elephants (Loxodonta africana) are a keystone species in African ecosystems. As a result of increasing anthropogenic pressure, elephant populations have declined significantly in the last two centuries. Research on a broad sample of these populations is necessary to inform management strategies over a range of environmental and socio-political conditions. In order to evaluate the current state of literature that is informing evidence-based management and conservation of elephants, we systematically reviewed all research published on the ecology of African elephants from the last 20 years (492 publications). We contrasted the geographic distribution of published research against the 2016 IUCN elephant census. We found several statistically significant biases in the geographic distribution of elephant research. South Africa has 4.54% of the total elephant population and accounted for 28.28% of all research publications. Kenya has 5.49% the total elephant population but accounts for 20.6% of the research. Conversely, Botswana has 31.68% of the total elephant population but accounts for only 9.29% of the research and Zimbabwe has 19.89% of the total elephant population with only 10.50% of research. We also found that 41.85% of areas with ~60,100 elephants have not had any research published on their populations in the last 20 years. This publication imbalance may encourage management strategies that are overly dependent on misrepresentative information from a small subset of the elephant population. We recommend that (1) marginalised areas with large elephant populations (e.g., Botswana and Zimbabwe) should receive higher priority for future research, (2) new research and proposals should design theoretical frameworks to account for and overcome the present biases, and (3) local community-based management approaches should be prioritised and amplified in order to overcome the barriers to conducting research in priority areas.

Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials.

Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It is caused by mutations in the DMD gene and is characterized by progressive muscle degeneration that results in loss of function and early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets of the patient population, DMD remains a disease with large unmet medical needs. The adeno-associated virus (AAV) vector is the leading gene delivery system for addressing genetic neuromuscular diseases. Since the gene encoding the full-length dystrophin protein exceeds the packaging capacity of a single AAV vector, gene replacement therapy based on AAV-delivery of shortened, yet, functional microdystrophin genes has emerged as a promising treatment. This article seeks to explain the rationale for use of the accelerated approval pathway to advance AAV microdystrophin gene therapy for DMD. Specifically, we provide support for the use of microdystrophin expression as a surrogate endpoint that could be used in clinical trials to support accelerated approval.

Incidence of primary anatomic and reverse total shoulder arthroplasty in patients less than 50 years of age and high early revision risk

Compared to the overall incidence of shoulder arthroplasty (SA), the relative risk and burden of revision may vary amongst patients specifically 40-50 years of age, and less than 40 years of age. Our aim was to investigate the incidence of primary anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA), rate of revision within one year, and determine the associated economic burden in patients <50 years. 509 patients <50 years old who underwent SA were included, using a national private insurance database. Costs were based on the grossed covered payment. Multivariate analyses were performed to identify risk factors associated with revisions within one year of index procedure. SA incidence in patients <50 years old increased from 2.21 to 2.5 per 100,000 patients from 2017-2018. The overall revision rate was 3.9% with a mean time to revision of 96.3 days. Diabetes was a significant risk factor for revision (p=0.043). Surgeries performed in patients <40 years cost more than those performed in patients aged 40-50 years for both primary ($41,943 ± 23,842 versus $39,477 ± 20,874) and revision cases ($40,370 ± 21,385 versus $31,669 ± 10,430). This study demonstrates that the incidence of SA in patients <50 years is higher than previously reported in the literature, and most commonly reported for primary osteoarthritis. Given the high incidence of SA and subsequent high early revision rate in this subset population, our data portends a large associated socioeconomic burden. Policymakers and surgeons should use this data for implementing training programs focused on joint sparing techniques.