Policy implementation strategies to address rural disparities in access to care for stroke patients

ContextStroke systems of care (SSOC) promote access to stroke prevention, treatment, and rehabilitation and ensure patients receive evidence-based treatment. Stroke patients living in rural areas have disproportionately less access to emergency medical services (EMS). In the United States, rural counties have a 30% higher stroke mortality rate compared to urban counties. Many states have SSOC laws supported by evidence; however, there are knowledge gaps in how states implement these state laws to strengthen SSOC.ObjectiveThis study identifies strategies and potential challenges to implementing state policy interventions that require or encourage evidence-supported pre-hospital interventions for stroke pre-notification, triage and transport, and inter-facility transfer of patients to the most appropriate stroke facility.DesignResearchers interviewed representatives engaged in implementing SSOC across six states. Informants (n = 34) included state public health agency staff and other public health and clinical practitioners.OutcomesThis study examined implementation of pre-hospital SSOCs policies in terms of (1) development roles, processes, facilitators, and barriers; (2) implementation partners, challenges, and solutions; (3) EMS system structure, protocols, communication, and supervision; and (4) program improvement, outcomes, and sustainability.ResultsChallenges included unequal resource allocation and EMS and hospital services coverage, particularly in rural settings, lack of stroke registry usage, insufficient technologies, inconsistent use of standardized tools and protocols, collaboration gaps across SSOC, and lack of EMS stroke training. Strategies included addressing scarce resources, services, and facilities; disseminating, training on, and implementing standardized statewide SSOC protocols and tools; and utilizing SSOC quality and performance improvement systems and approaches.ConclusionsThis paper identifies several strategies that can be incorporated to enhance the implementation of evidence-based stroke policies to improve access to timely stroke care for all patient populations, particularly those experiencing disparities in rural communities

Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features

Background: The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc domain and cognate receptors may afford protection are poorly understood, however, in the context of HIV/SHIV infections. Many different in vitro assays have been developed and utilized to measure effector functions, but the extent to which these assays capture distinct antibody activities has not been fully elucidated. Results: In this study, six Fc-mediated effector function assays and two biophysical antibody profiling assays were performed on a common set of samples from HIV-1 infected and vaccinated subjects. Biophysical antibody profiles supported robust prediction of diverse IgG effector functions across distinct Fc-mediated effector function assays. While a number of assays showed correlated activities, supervised machine learning models indicated unique antibody features as primary contributing factors to the associated effector functions. Additional experiments established the mechanistic relevance of relationships discovered using this unbiased approach. Conclusions: In sum, this study provides better resolution on the diversity and complexity of effector function assays, offering a clearer perspective into this family of antibody mechanisms of action to inform future HIV-1 treatment and vaccination strategies

Regional Invasive Species & Climate Change Management Challenge: Gardening with climate-smart native plants in the Northeast

An estimated 80% of ornamental plants for sale are non-native. This means that the average yard does a poor job of supporting native flora and fauna. By shifting our plantings towards natives, we can dramatically increase the diversity of bees, butterflies, birds and other animals. In contrast, non-native plants do not support local food webs and can become invasive. Native plants increase biodiversity and reduce risks associated with invasive species, which supports resilient ecosystems in the face of climate change

Neuronal sensitivity to TDP-43 overexpression is dependent on timing of induction

Ubiquitin-immunoreactive neuronal inclusions composed of TAR DNA binding protein of 43 kDa (TDP-43) are a major pathological feature of frontotemporal lobar degeneration (FTLD-TDP). In vivo studies with TDP-43 knockout mice have suggested that TDP-43 plays a critical, although undefined role in development. In the current report, we generated transgenic mice that conditionally express wild-type human TDP-43 (hTDP-43) in the forebrain and established a paradigm to examine the sensitivity of neurons to TDP-43 overexpression at different developmental stages. Continuous TDP-43 expression during early neuronal development produced a complex phenotype, including aggregation of phospho-TDP-43, increased ubiquitin immunoreactivity, mitochondrial abnormalities, neurodegeneration and early lethality. In contrast, later induction of hTDP-43 in the forebrain of weaned mice prevented early death and mitochondrial abnormalities while yielding salient features of FTLD-TDP, including progressive neurodegeneration and ubiquitinated, phospho-TDP-43 neuronal cytoplasmic inclusions. These results suggest that neurons in the developing forebrain are extremely sensitive to TDP-43 overexpression and that timing of TDP-43 overexpression in transgenic mice must be considered when distinguishing normal roles of TDP-43, particularly as they relate to development, from its pathogenic role in FTLD-TDP and other TDP-43 proteinopathies. Finally, our adult induction of hTDP-43 strategy provides a mouse model that develops critical pathological features that are directly relevant for human TDP-43 proteinopathies

Effects of Increased Pork Hot Carcass Weights. II: Loin Quality Characteristics and Palatability Ratings

The objective of this study was to evaluate the effects of increased pork hot carcass weight on loin quality and palatability of top loin chops. Pork loins (N = 200) were collected from 4 different hot carcass weight groups: A light weight (LT; less than 111.8 kg), medium-light weight (MLT; 111.8 to 119.1 kg), medium-heavy weight (MHVY; 119.1 to 124.4), and a heavyweight group (HVY; 124.4 and greater). Following fabrication, chops were assigned to fat and moisture analysis, Warner-Bratzler shear force (WBSF), consumer sensory panels, or trained sensory panels. Chops from the HVY group were rated as more (P 0.05) consumer flavor liking ratings. Hot carcass weight treatment did not contribute (P > 0.05) to the percentage of chops rated acceptable for flavor and overall liking. The greatest (P 0.05), with greater (P < 0.05) overall tenderness ratings compared to chops from LT carcasses. These results indicate chops from heavier weight carcasses may have improved tenderness and juiciness compared to chops from lighter carcasses

Effects of Increased Pork Hot Carcass Weights. I: Chop Thickness Impact on Consumer Visual Ratings

The objective of this study was to evaluate the effect of increased pork hot carcass weights on consumer visual acceptability and purchase intent ratings of top loin chops cut to various thicknesses in a price labeled versus unlabeled retail display scenario. Pork loins (N = 200) were collected from 4 different hot carcass weight groups: light weight (LT; less than 111.8 kg), medium-light weight (MLT; 111.8 to 119. kg), medium-heavy weight (MHVY; 119.1 to 124.4 kg), and a heavy weight group (HVY; 124.4 kg and greater). Loins were fabricated into 4 pairs of chops of specified thicknesses (1.27, 1.91, 2.54, and 3.18 cm). One chop from each pair was assigned to be packaged with or without a label. Consumers assessed chops for appearance, desirability, and purchase intent. For both appearance and purchase intent ratings, chops from HVY carcasses were given more desirable (P < 0.05) ratings compared to LT chops. Consumers gave greater (P < 0.05) appearance ratings to thicker cut chops. There was a hot carcass weight × chop thickness interaction (P < 0.05) for the percentage of consumers that indicated the chop was desirable overall. Regardless of hot carcass weight group, chops with a thickness of 1.27 cm had the lowest (P < 0.05) percentage of consumers indicate they were desirable overall. A greater (P < 0.05) percentage of consumers indicated “yes” they would purchase chops cut to a thickness of 2.54 cm compared to all other thicknesses. Additionally, there was a greater (P < 0.05) percentage of consumers who indicated they would purchase unlabeled chops compared to labeled chops. These results, within the population sampled, indicate that carcass weight and chop thickness can affect consumer preference and thus should be considered by retailers when marketing fresh pork loin chops

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data