Emergency Department Super-utilizer Program Involvement: Pilot Data and Methods Challenges

Super-utilizers are patients who use extreme amounts of medical services, often due to comorbid medical, social, and mental health issues. The MyLink Evaluation Project (MEP) studies MyLink, a program that connects super-utilizers with community support workers (CSWs) to improve the patient experience and reduce costs. The MEP-eligible population is ≥18 years old with at least 5 Emergency Department (ED) visits within 12 months and no other exclusions (e.g., language barriers, living out-of-region). During MEP’s pilot, among 58 eligible patients, 28 consented to being referred to MyLink and followed up. Of these, 7 could not be located for follow-up, 8 refused enrollment, and the remaining 13 enrolled and “engaged” (had at least 3 face-to-face contacts and developed an initial plan). All 13 enrollees were followed at 6 months vs. 4 of the 8 not enrolled. Consequently, we expect about 50% of eligible patients to consent to the main randomized study, with the vast majority of the MyLink-assigned group becoming engaged and completing follow-up. Achieving this requires identifying patients in real-time at the ED, frequent communications between researchers and CSWs, cultivating rapport during patient referral, enrollment, and follow-up, coordinating with other care management programs serving our patients, and adhering to MEP protocols that are rapidly evolving to address and overcome barriers. Challenges include: increasingly heavy CSW case-loads that decrease “warm” handoffs during the ED visit; problematic patient contact information; and incomplete program and follow-up assessments due to patient withdrawal, relocation, or death. These challenges lead to missing quality-of-life and healthcare utilization data needed for program evaluation. To reduce incomplete assessments, we lengthened time windows and expanded outreach methods (e.g., in-person upon ED revisit, web and medical record searches for updated contact information). We hypothesize that MyLink will improve patient quality-of-life and reduce ED utilization and total costs of care for super-utilizers

Dynamical Tide in Solar-Type Binaries

Circularization of late-type main-sequence binaries is usually attributed to turbulent convection, while that of early-type binaries is explained by resonant excitation of g modes. We show that the latter mechanism operates in solar-type stars also and is at least as effective as convection, despite inefficient damping of g modes in the radiative core. The maximum period at which this mechanism can circularize a binary composed of solar-type stars in 10 Gyr is as low as 3 days, if the modes are damped by radiative diffusion only and g-mode resonances are fixed; or as high as 6 days, if one allows for evolution of the resonances and for nonlinear damping near inner turning points. Even the larger theoretical period falls short of the observed transition period by a factor two.Comment: 17 pages, 2 postscript figures, uses aaspp4.sty. Submitted to Ap

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Live Tissue Imaging Shows Reef Corals Elevate pH under Their Calcifying Tissue Relative to Seawater

The threat posed to coral reefs by changes in seawater pH and carbonate chemistry (ocean acidification) raises the need for a better mechanistic understanding of physiological processes linked to coral calcification. Current models of coral calcification argue that corals elevate extracellular pH under their calcifying tissue relative to seawater to promote skeleton formation, but pH measurements taken from the calcifying tissue of living, intact corals have not been achieved to date. We performed live tissue imaging of the reef coral Stylophora pistillata to determine extracellular pH under the calcifying tissue and intracellular pH in calicoblastic cells. We worked with actively calcifying corals under flowing seawater and show that extracellular pH (pHe) under the calicoblastic epithelium is elevated by ∼0.5 and ∼0.2 pH units relative to the surrounding seawater in light and dark conditions respectively. By contrast, the intracellular pH (pHi) of the calicoblastic epithelium remains stable in the light and dark. Estimates of aragonite saturation states derived from our data indicate the elevation in subcalicoblastic pHe favour calcification and may thus be a critical step in the calcification process. However, the observed close association of the calicoblastic epithelium with the underlying crystals suggests that the calicoblastic cells influence the growth of the coral skeleton by other processes in addition to pHe modification. The procedure used in the current study provides a novel, tangible approach for future investigations into these processes and the impact of environmental change on the cellular mechanisms underpinning coral calcification

Mechanisms for a nutrient-conserving carbon pump in a seasonally stratified, temperate continental shelf sea

Continental shelf seas may have a significant role in oceanic uptake and storage of carbon dioxide (CO2) from the atmosphere, through a ‘continental shelf pump’ mechanism. The northwest European continental shelf, in particular the Celtic Sea (50°N 8°W), was the target of extensive biogeochemical sampling from March 2014 to September 2015, as part of the UK Shelf Sea Biogeochemistry research programme (UK-SSB). Here, we use the UK-SSB carbonate chemistry and macronutrient measurements to investigate the biogeochemical seasonality in this temperate, seasonally stratified system. Following the onset of stratification, near-surface biological primary production during spring and summer removed dissolved inorganic carbon and nutrients, and a fraction of the sinking particulate organic matter was subsequently remineralised beneath the thermocline. Water column inventories of these variables throughout 1.5 seasonal cycles, corrected for air-sea CO2 exchange and sedimentary denitrification and anammox, isolated the combined effect of net community production (NCP) and remineralisation on the inorganic macronutrient inventories. Overall inorganic inventory changes suggested that a significant fraction (>50%) of the annual NCP of around 3 mol-C m–2 yr–1 appeared to be stored within a long-lived organic matter (OM) pool with a lifetime of several months or more. Moreover, transfers into and out of this pool appeared not to be in steady state over the one full seasonal cycle sampled. Accumulation of such a long-lived and potentially C-rich OM pool is suggested to be at least partially responsible for the estimated net air-to-sea CO2 flux of ∼1.3 mol-C m–2 yr–1 at our study site, while providing a mechanism through which a nutrient-conserving continental shelf pump for CO2 could potentially operate in this and other similar regions

Environmental heterogeneity modulates the effect of plant diversity on the spatial variability of grassland biomass

Plant productivity varies due to environmental heterogeneity, and theory suggests that plant diversity can reduce this variation. While there is strong evidence of diversity effects on temporal variability of productivity, whether this mechanism extends to variability across space remains elusive. Here we determine the relationship between plant diversity and spatial variability of productivity in 83 grasslands, and quantify the effect of experimentally increased spatial heterogeneity in environmental conditions on this relationship. We found that communities with higher plant species richness (alpha and gamma diversity) have lower spatial variability of productivity as reduced abundance of some species can be compensated for by increased abundance of other species. In contrast, high species dissimilarity among local communities (beta diversity) is positively associated with spatial variability of productivity, suggesting that changes in species composition can scale up to affect productivity. Experimentally increased spatial environmental heterogeneity weakens the effect of plant alpha and gamma diversity, and reveals that beta diversity can simultaneously decrease and increase spatial variability of productivity. Our findings unveil the generality of the diversity-stability theory across space, and suggest that reduced local diversity and biotic homogenization can affect the spatial reliability of key ecosystem functions.Fil: Daleo, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Alberti, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Chaneton, Enrique Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Iribarne, Oscar Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Tognetti, Pedro Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Bakker, Jonathan. University of Washington; Estados UnidosFil: Borer, Elizabeth. University of Minnesota; Estados UnidosFil: Bruschetti, Carlos Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: MacDougall, Andrew S.. University Of Guelph. Department Of Integrative Biology.; CanadáFil: Pascual, Jesus Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Sankaran, Mahesh. University of Leeds; Reino Unido. Tata Institute of Fundamental Research; IndiaFil: Seabloom, Eric. University of Minnesota; Estados UnidosFil: Wang, Shaopeng. Peking University; ChinaFil: Bagchi, Sumanta. Indian Institute of Science; IndiaFil: Brudvig, Lars A.. Michigan State University; Estados UnidosFil: Catford, Jane A.. University of Melbourne; Australia. Kings College London (kcl);Fil: Dickman, Chris R.. The University Of Sydney; AustraliaFil: Dickson, Tymothy L.. University of Nebraska; Estados UnidosFil: Donohue, Ian. Trinity College Dublin; Reino UnidoFil: Eisenhauer, Nico. Universitat Leipzig; Alemania. German Centre for Integrative Biodiversity Research; AlemaniaFil: Gruner, Daniel S.. University of Maryland; Estados UnidosFil: Haider, Sylvia. German Centre for Integrative Biodiversity Research; Alemania. Martin Luther University Halle-Wittenberg; Alemania. Leuphana University of Lüneburg; AlemaniaFil: Jentsch, Anke. University of Bayreuth; AlemaniaFil: Knops, Johannes M. H.. Xi’an Jiaotong-Liverpool University; ChinaFil: Lekberg, Ylva. University of Montana; Estados UnidosFil: McCulley, Rebecca L.. University of Kentucky; Estados UnidosFil: Moore, Joslin L.. University of Melbourne; Australia. Monash University; Australia. Arthur Rylah Institute for Environmental Research; AustraliaFil: Mortensen, Brent. Benedictine College; Estados UnidosFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria; Argentina. Universidad Nacional de la Patagonia Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocca, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.