A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms

The assessment of left ventricular diastolic function: guidance and recommendations from the British Society of Echocardiography

Impairment of left ventricular (LV) diastolic function is common amongst those with left heart disease and is associated with significant morbidity. Given that, in simple terms, the ventricle can only eject the volume with which it fills and that approximately one half of hospitalisations for heart failure (HF) are in those with normal/’preserved’ left ventricular ejection fraction (HFpEF) (Bianco et al. in JACC Cardiovasc Imaging. 13:258–271, 2020. 10.1016/j.jcmg.2018.12.035), where abnormalities of ventricular filling are the cause of symptoms, it is clear that the assessment of left ventricular diastolic function (LVDF) is crucial for understanding global cardiac function and for identifying the wider effects of disease processes. Invasive methods of measuring LV relaxation and filling pressures are considered the gold-standard for investigating diastolic function. However, the high temporal resolution of trans-thoracic echocardiography (TTE) with widely validated and reproducible measures available at the patient’s bedside and without the need for invasive procedures involving ionising radiation have established echocardiography as the primary imaging modality. The comprehensive assessment of LVDF is therefore a fundamental element of the standard TTE (Robinson et al. in Echo Res Pract7:G59–G93, 2020. 10.1530/ERP-20-0026). However, the echocardiographic assessment of diastolic function is complex. In the broadest and most basic terms, ventricular diastole comprises an early filling phase when blood is drawn, by suction, into the ventricle as it rapidly recoils and lengthens following the preceding systolic contraction and shortening. This is followed in late diastole by distension of the compliant LV when atrial contraction actively contributes to ventricular filling. When LVDF is normal, ventricular filling is achieved at low pressure both at rest and during exertion. However, this basic description merely summarises the complex physiology that enables the diastolic process and defines it according to the mechanical method by which the ventricles fill, overlooking the myocardial function, properties of chamber compliance and pressure differentials that determine the capacity for LV filling. Unlike ventricular systolic function where single parameters are utilised to define myocardial performance (LV ejection fraction (LVEF) and Global Longitudinal Strain (GLS)), the assessment of diastolic function relies on the interpretation of multiple myocardial and blood-flow velocity parameters, along with left atrial (LA) size and function, in order to diagnose the presence and degree of impairment. The echocardiographic assessment of diastolic function is therefore multifaceted and complex, requiring an algorithmic approach that incorporates parameters of myocardial relaxation/recoil, chamber compliance and function under variable loading conditions and the intra-cavity pressures under which these processes occur. This guideline outlines a structured approach to the assessment of diastolic function and includes recommendations for the assessment of LV relaxation and filling pressures. Non-routine echocardiographic measures are described alongside guidance for application in specific circumstances. Provocative methods for revealing increased filling pressure on exertion are described and novel and emerging modalities considered. For rapid access to the core recommendations of the diastolic guideline, a quick-reference guide (additional file 1) accompanies the main guideline document. This describes in very brief detail the diastolic investigation in each patient group and includes all algorithms and core reference tables

Cryptic Eimeria genotypes are common across the southern but not northern hemisphere

The phylum Apicomplexa includes parasites of medical, zoonotic and veterinary significance. Understanding the global distribution and genetic diversity of these protozoa is of fundamental importance for efficient, robust and long-lasting methods of control. Eimeria spp. cause intestinal coccidiosis in all major livestock animals and are the most important parasites of domestic chickens in terms of both economic impact and animal welfare. Despite having significant negative impacts on the efficiency of food production, many fundamental questions relating to the global distribution and genetic variation of Eimeria spp. remain largely unanswered. Here, we provide the broadest map yet of Eimeria occurrence for domestic chickens, confirming that all the known species (Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria mitis, Eimeria necatrix, Eimeria praecox, Eimeria tenella) are present in all six continents where chickens are found (including 21 countries). Analysis of 248 internal transcribed spacer sequences derived from 17 countries provided evidence of possible allopatric diversity for species such as E. tenella (FST values ⩽0.34) but not E. acervulina and E. mitis, and highlighted a trend towards widespread genetic variance. We found that three genetic variants described previously only in Australia and southern Africa (operational taxonomic units x, y and z) have a wide distribution across the southern, but not the northern hemisphere. While the drivers for such a polarised distribution of these operational taxonomic unit genotypes remains unclear, the occurrence of genetically variant Eimeria may pose a risk to food security and animal welfare in Europe and North America should these parasites spread to the northern hemisphere

Long-term ecological research on Colorado Shortgrass Steppe

The SGS-LTER research site was established in 1980 by researchers at Colorado State University as part of a network of long-term research sites within the US LTER Network, supported by the National Science Foundation. Scientists within the Natural Resource Ecology Lab, Department of Forest and Rangeland Stewardship, Department of Soil and Crop Sciences, and Biology Department at CSU, California State Fullerton, USDA Agricultural Research Service, University of Northern Colorado, and the University of Wyoming, among others, have contributed to our understanding of the structure and functions of the shortgrass steppe and other diverse ecosystems across the network while maintaining a common mission and sharing expertise, data and infrastructure.Poster presented at the LTER All Scientists Meeting held in Estes Park, CO on September 10-13, 2012

Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Clinical: Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Clinical: Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57