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Objective: To assess the real-world use of home health services (HHS) among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD).Methods: Adults (18–6...

RATIONALE: Chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype is a clinical concept describing the broad group of ILDs characterized by progressive pulmonary fibrosis. The prevalence of progressive fibrotic ILDs other than idiopathic pulmonary fibrosis (IPF) is not well understood. OBJECTIVES: We used a novel algorithm to estimate the prevalence range of disease progression among patients with non-IPF fibrotic ILD in a U.S. claims database. METHODS: This was a retrospective study including adults with commercial or Medicare Advantage with Part D (MAPD) insurance using administrative claims data from October 2015 to September 2019. Patients likely to have non-IPF fibrosing ILD with a progressive phenotype were identified via an algorithm that incorporated ILD-related diagnosis codes (excluding IPF) and claims-based proxies for fibrotic ILD progression, including pulmonary function tests, chest imaging, oral corticosteroid (OCS) medications, immunosuppressive medications, lung transplant, oxygen therapy, palliative care, and respiratory hospitalization. The prevalence range of non-IPF fibrotic ILD with progressive disease behavior was calculated using strict and lenient case definitions to account for potential imprecision in the progression proxies. RESULTS: Of nearly 9 million study-eligible patients, 17,136 were identified with non-IPF fibrosing ILD. The prevalence of disease progression per 10,000 (95% confidence interval) ranged from 12.14 (11.74-12.54) to 29.05 (28.43-29.67) over a mean observation time of 1.44 years for MAPD enrollees (n = 14,686), and from 0.89 (0.81-0.97) to 2.36 (2.24-2.48) over a mean observation time of 1.29 years for commercial enrollees (n = 2,450). Prevalence estimates increased with age for both insurance types. Among patients with progression, 4,097 met at least two progression proxies not considering OCS (strict case definition) and 9,946 met at least one progression proxy (lenient case definition). The mean (standard deviation) number of proxies met was 2.1 (1.3), and the most common individual proxies met (alone or in combination with other proxies) were OCS use (48.9%), respiratory hospitalization (44.2%), and oxygen therapy (44.1%). CONCLUSIONS: This is among the first claims-based estimates of the prevalence of non-IPF chronic fibrosing ILD with a progressive phenotype. Our analysis indicates that this phenotype is rare in the overall population but increases substantially with increasing age.

A complete object database containing a model (representing geometric and texture information) of every possible workpiece is a common necessity e.g. for different object recognition or task planning approaches. The generation of these models is often a tedious process. In this paper we present a fully automated approach to tackle this problem by generating complete workpiece models using a robotic manipulator. A workpiece is recorded by a depth sensor from multiple views for one side, then turned, and captured from the other side. The resulting point clouds are merged into one complete model. Additionally, we represent the information provided by the object’s texture using keypoints. We present a proof of concept and evaluate the precision of the final models. In the end we conclude the usefulness of our approach showing a precision of around 1 mm for the resulting models.

Metabarcoding approaches are exponentially increasing our understanding of soil biodiversity, with a major focus on the bacterial part of the microbiome. Part of the soil diversity are also eukaryotes that include fungi, algae, protists and Metazoa. Nowadays, soil eukaryotes are targeted with the same approaches developed for bacteria and archaea (prokaryotes). However, fundamental differences exist between domains. After providing a short historical overview of the developments of metabarcoding applied to environmental microbiology, we compile the most important differences between domains that prevent direct method transfers between prokaryotic and eukaryotic soil metabarcoding approaches, currently dominated by short-read sequencing. These include the existence of divergent diversity concepts and the variations in eukaryotic morphology that affect sampling and DNA extraction. Furthermore, eukaryotes experienced much more variable evolutionary rates than prokaryotes, which prevent capturing the entire eukaryotic diversity in a soil with a single amplification protocol fit for short-read sequencing. In the final part we focus on future potentials for optimization of eukaryotic metabarcoding that include superior possibility of functionally characterizing eukaryotes and to extend the current information obtained, such as by adding a real quantitative component. This review should optimize future metabarcoding approaches targeting soil eukaryotes and kickstart this promising research direction.

Ancestral adaptations to tropical-like climates drive most multicellular biogeography and macroecology. Observational studies suggest that this niche conservatism could also be shaping unicellular biogeography and macroecology, although evidence is limited to Acidobacteria and testate amoebae. We tracked the phylogenetic signal of this niche conservatism in far related and functionally contrasted groups of common soil protists (Bacillariophyta, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida) along a humid but increasingly cold elevational gradient in Switzerland. Protist diversity decreased, and the size of the geographic ranges of taxa increased with elevation and associated decreasing temperature (climate), which is consistent with a macroecological pattern known as the Rapoport effect. Bacillariophyta exhibited phylogenetically overdispersed communities assembled by competitive exclusion of closely related taxa with shared (conserved) niches. By contrast, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida exhibited phylogenetically clustered communities assembled by habitat filtering, revealing the coexistence of closely related taxa with shared (conserved) adaptations to cope with the humid but temperate to cold climate of the study site. Phylobetadiversity revealed that soil protists exhibit a strong phylogenetic turnover among elevational sites, suggesting that most taxa have evolutionary constraints that prevent them from colonizing the colder and higher sites of the elevation gradient. Our results suggest that evolutionary constraints determine how soil protists colonize climates departing from warm and humid conditions. We posit that these evolutionary constraints are linked to an ancestral adaptation to tropical-like climates, which limits their survival in exceedingly cold sites. This niche conservatism possibly drives their biogeography and macroecology along latitudinal and altitudinal climatic gradients.

OBJECTIVES Generalized pustular psoriasis (GPP) is a rare and severe, inflammatory skin disease. GPP is characterized by recurrent flares that consist of disseminated erythematous skin rash with sterile neutrophil-filled pustules that can result in an emergency department (ED) visit or hospital stay due to systemic complications. This study characterizes hospitalizations, ED visits, and inpatient treatment due to GPP in the United States (US). METHODS A descriptive, retrospective cross-sectional analysis was conducted in Cerner Health Facts, a US electronic medical record database. Hospitalizations and ED visits were identified between 1 October 2015 and 1 July 2017. Visits were included in the study if they were GPP-related, defined as a GPP diagnosis (ICD-10-CM code: L40.1) in the first or second position at admission or discharge, and if the discharge date was within the study period. Hospitalizations and ED visits were the units of analysis. Demographics, comorbidities, medication use, and outcomes were characterized with descriptive statistics. Outcomes included length of stay, intensive care unit (ICU) admission, and death. RESULTS A total of 71 GPP-related hospitalizations and 64 GPP-related ED visits were included in the study. Other specified inflammatory skin conditions (OSICS)/skin and subcutaneous tissue infections (54%/34%), fluid and electrolyte disorders (46%), hypertension (30%), septicemia (24%), and acute renal failure (18%) were the most frequently coded conditions accompanying a GPP-related hospitalization. OSICS/skin and subcutaneous tissue infections (47%/42%) were the most commonly coded conditions accompanying a GPP-related ED visit. Medication use during GPP-related hospitalizations included topicals (triamcinolone (42%); clobetasol (17%)), systemic corticosteroids (prednisone (20%); methylprednisolone (11%)), and non-biologic and biologic immunosuppressants (cyclosporine (6%); methotrexate (4%); etanercept (1%)). Analgesics (acetaminophen 67%; morphine 24%), and antibiotics (vancomycin 21%) were also common. The median length of stay for hospitalizations was 5 days. Three hospitalizations included an ICU admission and two hospitalizations resulted in death. CONCLUSIONS The presence of concurrent immune-mediated conditions, and frequent prescribing of analgesics, including opioids, illustrate the burden of GPP in patients requiring acute and inpatient care.

Aim: To evaluate Medicaid spending and healthcare resource utilization (HRU) in treatment-resistant depression (TRD). Materials & methods: TRD beneficiaries were identified from Medicaid claims databases (January 2010–March 2017) and matched 1:1 with major depressive disorder (MDD) beneficiaries without TRD (non-TRD-MDD) and randomly selected patients without MDD (non-MDD). Differences in HRU and per-patient-per-year costs were reported in incidence rate ratios (IRRs) and cost differences (CDs), respectively. Results: TRD beneficiaries had higher HRU than 1:1 matched non-TRD-MDD (e.g., inpatient visits: IRR = 1.41) and non-MDD beneficiaries (N = 14,710 per cohort; e.g., inpatient visits: IRR = 3.42, p Conclusion: TRD is associated with higher HRU and costs versus non-TRD-MDD and non-MDD. TRD poses a significant burden to Medicaid.

Sphagnum-dominated ecosystem plays major roles as carbon sinks at the global level. Associated microbial communities, in particular, eukaryotes, play significant roles in nutrient fixation and turnover. In order to understand better the ecological processes driven by these organisms, the first step is to characterise these associated organisms. We characterised the taxonomic diversity, and from this, inferred the functional diversity of microeukaryotes in Sphagnum mosses in tropical, subtropical and temperate climatic zones through an environmental DNA diversity metabarcoding survey of the V9 region of the gene coding for the RNA of the small subunit of the ribosomes (SSU rRNA). As microbial processes are strongly driven by temperatures, we hypothesised that saprotrophy would be highest in warm regions, whereas mixotrophy, an optimal strategy in oligotrophic environments, would peak under colder climates. Phylotype richness was higher in tropical and subtropical climatic zones than in the temperate region, mostly due to a higher diversity of animal parasites (i.e. Apicomplexa). Decomposers, and especially opportunistic yeasts and moulds, were more abundant under warmer climates, while mixotrophic organisms were more abundant under temperate climates. The dominance of decomposers, suggesting a higher heterotrophic activity under warmer climates, is coherent with the generally observed faster nutrient cycling at lower latitudes; this phenomenon is likely enhanced by higher inputs of nutrients most probably brought in the system by Metazoa, such as arthropods. Fil: Singer, David. Universidade de Sao Paulo; Brasil. Universite de Neuchatel; Suiza Fil: Metz, Sebastián Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Unrein, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Shimano, Satoshi. Hosei University; Japón Fil: Mazei, Yuri. Universidad Estatal de Moscú ; Rusia Fil: Mitchell, Edward A. D.. Jardin Botanique de Neuchâtel; Suiza Fil: Lara Pandis, Enrique Miguel. Consejo Superior de Investigaciones Científicas. Real Jardín Botánico; España

17 pages, 6 figures, 3 tables, supplementary information https://doi.org/10.1007/s00300-021-02850-3, Previous studies conducted in summer in the lakes at Hope Bay (Antarctic Peninsula) between 1991 and 2007 showed a large numerical contribution of flagellated Chrysophyceae to the phytoplankton communities, particularly in the oligotrophic lakes, as evidenced by light microscopy observations and molecular fingerprinting. Given the ecological relevance of this group in these Antarctic microbial foodwebs, we carried out further molecular analyses (clone libraries and 18S Illumina high throughput sequencing) to characterize their phylogenetic diversity. The results of this study significantly increased the retrieved Chrysophyceae biodiversity. Clone libraries in two selected lakes (one oligotrophic and one mesotrophic) yielded 12 different chrysophycean OTUs, whereas 81 Swarm OTUs were recovered from six lakes using Illumina HiSeq. With the combination of both methods, we observed sequences of all the chrysophyte known clades, although most of the diversity belonged to Clade D, a group comprising mixotrophic and heterotrophic species. The percentage of reads for this clade in Illumina HiSeq ranged from 30% to 96% of the total Chrysophyceae reads. Based on experiments and observations, we also describe the main ecological traits of this group: the dominant taxa were small pigmented flagellates, well adapted to survive in oligotrophic systems, sometimes abundant under ice-cover subjected to low light intensities, and that have phagotrophic behavior. The used combination of methods allowed us to characterize the biodiversity and ecology of the Chrysophyceae, the dominant phytoplankton group in the oligotrophic lakes of this Maritime Antarctic region, The Antarctic expeditions were supported by the Dirección Nacional del Antártico (DNA) of Argentina, within the framework of a cooperative project between this institution, University of Buenos Aires and the Institut de Ciències del Mar (ICM)-CSIC. The investigations were financed by grants of the Argentinean Funds for Technical and Scientific Investigation (FONCYT, PICT 04440 and PICT 32732); the Spanish projects MIXANTAR (REN2002-11396-E/ANT) and MICRODIFF (DGICYT REN2001-2120/MAR) grant SB2001-0166 from the Spanish MECyD; the grant "Atracción de talento investigador" from the Community of Madrid (2017-T1/AMB- 5210); and the Swiss NSF (P2NEP3-178543), With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

To estimate healthcare resource utilization (HCRU) and economic burden of generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) in a commercially insured population the United States (US).Adult patients with a GPP or PPP diagnosis were identified between April 1, 2016 and August 1, 2019 in the IQVIA PharMetrics Plus database. Patients required continuous enrollment in medical and pharmacy benefits 6 months before and ≥2 months after the index diagnosis. GPP and PPP cohorts were exactly matched 1:3 on demographics and index date to a plaque psoriasis and a control cohort of the general population. All-cause HCRU and cost measures (direct medical and pharmacy) were reported as per patient per month (PPPM). Generalized linear models estimated adjusted cost ratios between matched cohorts, controlling for comorbidities.HCRU was high among GPP and PPP patients. Rates of inpatient visits were 4 times higher in GPP patients and 2 times higher in PPP patients compared to their matched cohorts. GPP patients experienced significantly higher total healthcare costs compared to matched cohorts (GPP vs plaque psoriasis: cost ratio 1.36, 95% confidence interval (1.22, 1.50); GPP vs control: 5.58 (3.73, 8.36)). PPP patients had significantly higher total healthcare costs compared to the general population (4.11 (3.31, 5.11)), while costs were comparable to plaque psoriasis patients (1.06 (0.97, 1.16)).GPP and PPP patients have significant economic burden due to higher direct medical and pharmacy costs. Further investigation is needed to better understand the drivers of economic burden in patients with GPP and PPP, and how HCRU and costs are impacted by disease severity.

1. The relative importance of global versus local environmental factors for growth and thus carbon uptake of the bryophyte genus Sphagnum—the main peat‐former and ecosystem engineer in northern peatlands—remains unclear. 2. We measured length growth and net primary production (NPP) of two abundant Sphagnum species across 99 Holarctic peatlands. We tested the importance of previously proposed abiotic and biotic drivers for peatland carbon uptake (climate, N deposition, water table depth and vascular plant cover) on these two responses. Employing structural equation models (SEMs), we explored both indirect and direct effects of drivers on Sphagnum growth. 3. Variation in growth was large, but similar within and between peatlands. Length growth showed a stronger response to predictors than NPP. Moreover, the smaller and denser Sphagnum fuscum growing on hummocks had weaker responses to climatic variation than the larger and looser Sphagnum magellanicum growing in the wetter conditions. Growth decreased with increasing vascular plant cover within a site. Between sites, precipitation and temperature increased growth for S. magellanicum. The SEMs indicate that indirect effects are important. For example, vascular plant cover increased with a deeper water table, increased nitrogen deposition, precipitation and temperature. These factors also influenced Sphagnum growth indirectly by affecting moss shoot density. 4. Synthesis. Our results imply that in a warmer climate, S. magellanicum will increase length growth as long as precipitation is not reduced, while S. fuscum is more resistant to decreased precipitation, but also less able to take advantage of increased precipitation and temperature. Such species‐specific sensitivity to climate may affect competitive outcomes in a changing environment, and potentially the future carbon sink function of peatlands.

Ancestral adaptations to tropical-like climates drive most multicellular biogeography and macroecology. Observational studies suggest that this niche conservatism could also be shaping unicellular biogeography and macroecology, although evidence is limited to Acidobacteria and testate amoebae. We tracked the phylogenetic signal of this niche conservatism in far related and functionally contrasted groups of common soil protists (Bacillariophyta, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida) along a humid but increasingly cold elevational gradient in Switzerland. Protist diversity decreased, and the size of the geographic ranges of taxa increased with elevation and associated decreasing temperature (climate), which is consistent with a macroecological pattern known as the Rapoport effect. Bacillariophyta exhibited phylogenetically overdispersed communities assembled by competitive exclusion of closely related taxa with shared (conserved) niches. By contrast, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida exhibited phylogenetically clustered communities assembled by habitat filtering, revealing the coexistence of closely related taxa with shared (conserved) adaptations to cope with the humid but temperate to cold climate of the study site. Phylobetadiversity revealed that soil protists exhibit a strong phylogenetic turnover among elevational sites, suggesting that most taxa have evolutionary constraints that prevent them from colonizing the colder and higher sites of the elevation gradient. Our results suggest that evolutionary constraints determine how soil protists colonize climates departing from warm and humid conditions. We posit that these evolutionary constraints are linked to an ancestral adaptation to tropical-like climates, which limits their survival in exceedingly cold sites. This niche conservatism possibly drives their biogeography and macroecology along latitudinal and altitudinal climatic gradients.

Protists dominate eukaryotic diversity and play key functional roles in all ecosystems, particularly by catalyzing carbon and nutrient cycling. To date, however, a comparative analysis of their taxonomic and functional diversity that compares the major ecosystems on Earth (soil, freshwater and marine systems) is missing. Here, we present a comparison of protist diversity based on standardized high throughput 18S rRNA gene sequencing of soil, freshwater and marine environmental DNA. Soil and freshwater protist communities were more similar to each other than to marine protist communities, with virtually no overlap of Operational Taxonomic Units (OTUs) between terrestrial and marine habitats. Soil protists showed higher γ diversity than aquatic samples. Differences in taxonomic composition of the communities led to changes in a functional diversity among ecosystems, as expressed in relative abundance of consumers, phototrophs and parasites. Phototrophs (eukaryotic algae) dominated freshwater systems (49% of the sequences) and consumers soil and marine ecosystems (59% and 48%, respectively). The individual functional groups were composed of ecosystem- specific taxonomic groups. Parasites were equally common in all ecosystems, yet, terrestrial systems hosted more OTUs assigned to parasites of macro-organisms while aquatic systems contained mostly microbial parasitoids. Together, we show biogeographic patterns of protist diversity across major ecosystems on Earth, preparing the way for more focused studies that will help understanding the multiple roles of protists in the biosphere.

Assessing the degree to which climate explains the spatial distributions of different taxonomic and functional groups is essential for anticipating the effects of climate change on ecosystems. Most effort so far has focused on above‐ground organisms, which offer only a partial view on the response of biodiversity to environmental gradients. Here including both above‐ and below‐ground organisms, we quantified the degree of topoclimatic control on the occurrence patterns of >1,500 taxa and phylotypes along a c. 3,000 m elevation gradient, by fitting species distribution models. Higher model performances for animals and plants than for soil microbes (fungi, bacteria and protists) suggest that the direct influence of topoclimate is stronger on above‐ground species than on below‐ground microorganisms. Accordingly, direct climate change effects are predicted to be stronger for above‐ground than for below‐ground taxa, whereas factors expressing local soil microclimate and geochemistry are likely more important to explain and forecast the occurrence patterns of soil microbiota. Detailed mapping and future scenarios of soil microclimate and microhabitats, together with comparative studies of interacting and ecologically dependent above‐ and below‐ground biota, are thus needed to understand and realistically forecast the future distribution of ecosystems., The degree to which climate controls the distributions of taxa affects future ecosystems. Including both above‐ and below‐ground organisms, we compare topoclimatic control on >1,500 taxa by fitting SDMs. Differences in model performances suggest that the influence of topoclimate is stronger on above‐ground species than on below‐ground microorganisms. Accordingly, direct climate change effects are predicted to be stronger for above‐ground than for below‐ground taxa, whereas factors expressing local soil conditions are likely more important for soil microbiota. Future scenarios of soil microclimate and microhabitats, together with ecologically dependent biota, are thus needed to understand and realistically forecast the future ecosystems.

Aim - Trends in spatial patterns of diversity in macroscopic organisms can be well predicted from correlative models, using topo‐climatic variables for plants and animals allowing inference over large scales. By contrast, diversity in soil microorganisms is generally considered as mostly driven by edaphic variables and, therefore, difficult to extrapolate on a large spatial scale based on predictive models. Here, we compared the power of topo‐climatic versus edaphic variables for predicting the diversity of various soil protist groups at the regional scale. Location - Swiss western Alps. Taxa - Full protist community and nine clades belonging respectively to three functional groups: parasites (Apicomplexa, Peronosporomycetes and Phytomyxea), phagotrophs (Sarcomonadea, Tubulinea and Spirotrichea) and phototrophs (Chlorophyta, Trebouxiophyceae and Diatomeae). Methods - We extracted soil DNA from 178 sites along a wide range of elevations with a random‐stratified sampling design. We defined protist Operational Taxonomic Units assemblages by metabarcoding of the V4 region of the rRNA small subunit gene. We assessed and modelled the diversity (Shannon index) patterns of all above‐mentioned taxonomic groups based on topo‐climatic (topography, slope southness, slope steepness and average summer temperature) and edaphic (soil temperature, relative humidity, pH, electroconductivity, phosphorus percentage, carbon/nitrogen, loss on ignition and shale percentage) variables in Generalized Additive Models (GAM). Results - The respective significance of topo‐climatic and edaphic variables varied among taxonomic and—to a certain extent—functional groups: while many variables explained significantly the diversity of the three phototrophs this was less the case for the three parasites. Topo‐climatic variables had a better predictive power than edaphic variables, yet predictive power varied among taxonomic groups. Main conclusions - Topo‐climatic variables (particularly slope steepness and summer temperature if we consider their significance in the GAMs) were, on average, better predictors of protist diversity at the landscape scale than edaphic variables. However, the predictive power of these variables on diversity differed considerably among taxonomic groups; such relationships may be due to direct and/or indirect (e.g. biotic) influences (like with parasitic taxa, where low predictive power is most likely explained by the absence of information on the hosts’ distribution). Future prospects include using such spatial models to predict hotspots of diversity and disease outbreaks.

Molecular data have considerably contributed to building the taxonomy of protists. Recently, the systematics of Hyalospheniidae (Amoebozoa; Tubulinea; Arcellinida) has been widely revised, with implications extending to ecological, biogeographical and evolutionary investigations. Certain taxa, however, still have an uncertain phylogenetic position, including the common and conspicuous species Nebela militaris. A phylogenetic reconstruction of the Hyalospheniidae using partial sequences of the mitochondrial Cytochrome Oxidase Subunit 1 (COI) gene shows that N. militaris does not belong to genus Nebela, but should be placed in its own genus. The morphological singularities (strongly curved pseudostome and a marked notch in lateral view) and phylogenetic placement of our isolates motivated the creation of a new genus: Alabasta gen. nov. Based on their morphology, we include in this genus Nebela kivuense and Nebela longicollis. We discuss the position of genus Alabasta within Hyalospheniidae, and the species that could integrate this new genus based on their morphological characteristics.

Background During the COVID-19 pandemic, adult vaccination in the United States (US) decreased substantially in 2020. Unlike other vaccine-preventable diseases where individuals may have experienced reduced risk due to COVID-related mitigation efforts (e.g., lockdown restrictions, use of face masks), individuals remained at risk of herpes zoster (HZ). This study projects the impact of reduced recombinant zoster vaccine (RZV) use on HZ cases and complications in the US. Methods A multi-cohort Markov model estimated the impact of missed RZV vaccinations, by comparing scenarios with and without missed vaccinations between Apr-Dec 2020, on cases of HZ, postherpetic neuralgia (PHN), and quality-adjusted life-years (QALYs) among US adults aged ≥ 50 years. Epidemiology, RZV efficacy, and utility inputs were obtained from standard US sources, clinical trial data, and published literature. Missed doses were estimated using data on RZV doses and an assumed 43% reduction in RZV vaccinations during the pandemic, based on publicly available data. Deterministic sensitivity and scenario analyses were conducted. Results In 2020, approximately 21 million (M) RZV distributed doses were expected, including an estimated 9.2M RZV series initiations in Apr-Dec. An estimated 3.9M RZV series initiations were missed, resulting in 31,945 projected HZ cases, 2,714 PHN cases, and 610 lost QALYs projected over a 1-year follow up. If individuals with missed RZV initiations remain unvaccinated in 2021, avoidable HZ cases will increase to 63,117 over 2 years. Further, if the same number of RZV initiations are missed in 2021, 95,062 avoidable HZ cases are expected. In a sensitivity analysis assuming 30% RZV reduction, 18,020 avoidable HZ cases and 1,531 PHN cases were observed over 1 year. Conclusion Adding to the substantial COVID-19 infection-related morbidity and mortality, reduced RZV use during the pandemic resulted in further burden from avoidable HZ cases. Health care providers should continue to emphasize the importance of vaccination against HZ and other preventable diseases during the pandemic. Funding GlaxoSmithKline Biologicals SA (GSK study identifier: [VEO-000222]). Acknowledgement Business & Decision Life Sciences c/o GSK (Coordination: Quentin Rayée). Disclosures Elizabeth M. La, PhD, The GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder) Ahmed Salem, MSc, The GSK group of companies (Employee) David Singer, PharmD, MS, The GSK group of companies (Employee) Nicolas Lecrenier, Ing, PhD, The GSK group of companies (Employee, Shareholder) Sara Poston, PharmD, The GSK group of companies (Employee, Shareholder)

Old-growth forests provide valuable habitats for bat and woodpecker species worldwide. However, the abundance of old-growth related habitat features is frequently reduced in managed forests. Bechstein’s Bat (Myotis bechsteinii, Kuhl 1817) is globally restricted to old-growth deciduous forests in Europe and therefore a species of high European conservation priority. Since the species prefers woodpecker cavities for roosting, woodpeckers are keystone species for Bechstein’s Bat. We surveyed woodpecker activity and forest structural features within 16 roost sites of Bechsteins Bat and a random sample from the surrounding managed forest within the centre of the global distribution of Bechsteins Bat. We found above-average quantity of old-growth related habitat features in the roost sites of Bechstein’s Bat. Five of six occurring woodpecker species revealed significantly higher densities in the roost sites of Bechstein’s Bat, demonstrating a distinct preference of the woodpeckers and the bat in managed forests for old, deciduous stands with high basal areas of large living trees (DBH > 50 cm), bearing deadwood structures and highest available tree cavity densities. Furthermore, when comparing the direct surroundings of roost trees to their wider surroundings (16 ha), cavity density and other old-growth features reached their maxima in the direct surroundings of roost trees (mean = 19.3 cavities ha−1), demonstrating a distinct habitat selection of Bechsteins Bat for patches with maximum available cavity density on large and fine spatial scale. We found a close relation between the basal area of trees with limb break offs (>20 cm base diameter) and tree cavity density, which leads us to the conclusion that specifically injured but still vital, large trees play a major role for the development and long-term persistence of tree cavities. Finally, our analyses revealed a threshold of 20 (DBH > 50 cm) or 10 (DBH > 70 cm) large deciduous trees bearing deadwood structures per ha to fulfil the minimum habitat requirements of the woodpeckers and Bechstein’s Bat. Obviously, Bechsteins Bat and the associated woodpeckers explicitly selected forest patches, which most closely resembled primeval forest benchmarks, emphasising the importance of maintaining and developing forest patches, providing the mentioned habitat features within managed forests.

To create healthy public spaces, Philadelphia prohibits smoking in city-owned and operated parks. Identifying the prevalence and characteristics of smoking in Philadelphia Parks would be useful for monitoring purposes; yet no studies have collected this data. This study identified the prevalence and characteristics of smoking among adult patrons entering three Philadelphia Parks (Washington Square Park, Independence Square Park, and Louis Kahn Park). During May and June 2016, we observed patrons entering the parks on Thursday afternoons. We used handheld electronic devices to categorize patrons by smoking status, age, gender, and tobacco product. We used logistic regression to assess the association of these variables with smoking. We observed 4822 people, of which 10.6% were children. Smoking was noted among 2.6% of adults in Washington Square Park, 2.6% of adults in Independence Square Park, and 7.7% of adults in Louis Kahn Park. Patronizing Louis Kahn Park was associated with greater likelihood of smoking (OR 3.11, CI 1.77-5.46) compared to Washington Square. Males were more likely than females to smoke (OR 1.45, CI 1.01-2.09). Higher likelihood of smoking among males concurs with previous studies. Higher prevalence in Louis Kahn Park may be due to differences in park patron demographics compared to other parks. Results could be used as a baseline for periodic monitoring of smoking in parks in order to inform implementation of the smoke-free park policy in Philadelphia.

High-throughput sequencing (HTS) of soil environmental DNA (eDNA) allows assessing the full diversity of soil micro-eukaryotes. The resulting operational taxonomic units (OTUs) can be assigned to potential taxonomic and functional identities using increasingly complete reference databases. HTS of soil eDNA is revealing a high diversity and abundance of potential eukaryovorous protists, thus challenging the paradigm of the predominantly bacterivorous function of soil phagotrophic protists (i.e. microbial loop). Using Illumina sequencing of soil eDNA and targeting the V9 region of the SSU rRNA gene, we investigated the taxonomic and functional diversities, distribution and co-occurrence patterns of soil micro-eukaryotes in three land-use categories: forests, meadows and croplands located in Switzerland. Each OTU was assigned to a broad functional category (phototrophs, phagotrophs, osmotrophs, or parasites). Total OTU richness was similar in the three land-use categories, but community composition differed significantly between forests and other land-uses. The proportion of fungal sequences (especially Basidiomycota) was highest, and phototroph (i.e. soil microalgae) sequences least abundant in forests. Seven OTUs representing phagotrophic protists, together accounting for >25% of all phagotroph sequences, were significantly correlated to the total number of phototroph sequences, thus suggesting algivory. At least three of these OTUs corresponded to known algal predators. These results suggest that beyond plants, soil microalgae represent a functionally significant but rarely considered input of carbon in soils that should be taken into account when modelling soil nutrient cycling.

Rain fed granite rock basins are ancient geological landforms of worldwide distribution and structural simplicity. They support habitats that can switch quickly from terrestrial to aquatic along the year. Diversity of animals and plants, and the connexion between communities in different basins have been widely explored in these habitats, but hardly any research has been carried out on microorganisms. The aim of this study is to provide the first insights on the diversity of eukaryotic microbial communities from these environments. Due to the ephemeral nature of these aquatic environments, we predict that the granitic basins should host a high proportion of dormant microeukaryotes. Based on an environmental DNA diversity survey, we reveal diverse communities with representatives of all major eukaryotic taxonomic supergroups, mainly composed of a diverse pool of low abundance OTUs. Basin communities were very distinctive, with alpha and beta diversity patterns non-related to basin size or spatial distance respectively. Dissimilarity between basins was mainly characterised by turnover of OTUs. The strong microbial eukaryotic heterogeneity observed among the basins may be explained by a complex combination of deterministic factors (diverging environment in the basins), spatial constraints, and randomness including founder effects. Most interestingly, communities contain organisms that cannot coexist at the same time because of incompatible metabolic requirements, thus suggesting the existence of a pool of dormant organisms whose activity varies along with the changing environment. These organisms accumulate in the pools, which turns granitic rock into high biodiversity microbial islands whose conservation and study deserve further attention.

In the Local Health Authority (LHA) of Parma, Emilia Romagna, Italy, 16 medical homes were established between 2011 and 2014. The authors implemented a 1-year (January 1, 2015, to December 31, 2015) cross-sectional population-based design to compare utilization and processes of care between medical homes and comparison practices using the Parma LHA administrative health care database. Residents (n = 372 396) attributed to a primary care physician practicing in a medical home as of January 1, 2015, were considered exposed to medical homes. Adjusted rates of emergency department (ED) use (incidence rate ratio [IRR] = 0.86; 95% CI = 0.82-0.90), potentially avoidable ED use (IRR = 0.78; 95% CI = 0.72-0.84), and hospitalization for chronic ambulatory care sensitive conditions (ACSCs; IRR = 0.87, 95% CI = 0.78-0.97) were lower among patients in medical homes. Performance on process of care measures favored the medical home group; however, associations were generally weak. Receipt of care in medical homes in Parma LHA was associated with lower rates of avoidable ED visits and hospitalizations for chronic ACSCs.

Objective Our objective was to assess healthcare resource utilization (HRU) and costs among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD) and those without MDD in US Integrated Delivery Networks (IDNs). Methods This was a retrospective matched-cohort study. The Optum© Integrated Claims Electronic Health Record de-identified database was used to identify adult patients with TRD (January 2011–June 2017) across US IDNs. TRD patients were propensity score matched 1:1 with non-TRD MDD and non-MDD patients on demographics. Rates of HRU and costs were compared up to 2 years following the first antidepressant pharmacy claim (or randomly imputed date for non-MDD patients) using negative binomial and ordinary least squares regressions, respectively, with 95% confidence intervals (CIs) from nonparametric bootstraps (costs only) adjusted for baseline comorbidity index and costs. Results All 1582 TRD patients were matched to non-TRD MDD and non-MDD patients and evaluated. TRD patients were on average 46 years old, and 67% were female. Mean duration of observation was 20.1, 19.6, and 17.9 months in the TRD, non-TRD MDD, and non-MDD cohorts, respectively. Patients with TRD had significantly higher rates of HRU than did non-TRD MDD patients (inpatient visits 0.35 vs. 0.16 per patient per year [PPPY]; adjusted incidence rate ratio [IRR] 2.04 [95% CI 1.74–2.39]) and non-MDD patients (0.35 vs. 0.09 PPPY, adjusted IRR 3.05 [95% CI 2.54–3.66]). TRD patients incurred significantly higher costs PPPY than did non-TRD MDD patients ($US25,807 vs. 13,701, adjusted cost difference $US9479 [95% CI 7071–11,621]) and non-MDD patients ($US25,807 vs. 8500, adjusted cost difference $US11,433 [95% CI 8668–13,876]). Conclusions HRU and costs associated with TRD are significant in US IDNs. Electronic supplementary material The online version of this article (10.1007/s41669-019-0154-z) contains supplementary material, which is available to authorized users.

WHAT IS KNOWN AND OBJECTIVE The application of biologics to treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is well established. Our aim was to characterize the most recent five years of data on rates of adherence, persistence, switching and dose escalations with biologics used to treat IBD in the United States. METHODS We systematically reviewed electronic databases MEDLINE, MEDLINE In-Process, EMBASE and Cochrane Library for 2012-2017 as well as conference proceedings for 2016-2017 published in English. RESULTS AND DISCUSSION Of 449 records identified, 41 met all screening criteria. Published studies varied greatly in methodology, data sources, population studied, follow-up time and endpoint definitions, preventing meaningful comparisons across studies. Based on studies using a medication possession rate threshold of

Daratumumab was initially approved by the US Food and Drug Administration to be given intravenously over the course of several hours during each administration. Because the duration of the first dose can exceed 7 h, the US Oncology Network developed a split first dose schedule to administer the first administration (dose) over 2 consecutive days.This trial was a retrospective cohort study of adult multiple myeloma (MM) patients who initiated daratumumab within the US Oncology Network between November 1, 2015, and June 30, 2017. Descriptive analyses were conducted to compare split dose versus single-dose groups, and a multivariable linear regression model was developed to identify factors associated with total administration time.In total, 622 patients were included in the analysis (364 split first dose patients and 258 single-dose patients). Infusion reactions to the first administration were documented for 47.8% of split first dose patients and 48.3% of single-dose patients. Among the total study population, the most common reactions were lower respiratory tract-related reactions (26.1%), upper respiratory tract-related reactions (17.2%), and gastrointestinal adverse events (12.5%), with no statistically significant differences between groups. The median infusion duration was 4.5 h for day 1 of the split first dose and 6.5 h for the single dose (P 0.0001); the total median infusion time was 8.7 h for the split first dose. In multivariable regression, the only factor associated with infusion time was dosing schedule.These results provide real-world evidence regarding the safety and infusion time of the first infusion of daratumumab. Although the total administration time was longer among patients receiving a split first dose, the shorter day 1 infusion for this dosing schedule without increased infusion reactions may be an option for community oncology clinics.

Trebouxiophyceae are a ubiquitous class of Chlorophyta encountered in aquatic and terrestrial environments. Most taxa are photosynthetic, and many acts as photobionts in symbiotic relationships, while others are free-living. Trebouxiophyceae have also been widely investigated for their use for biotechnological applications. In this work, we aimed at obtaining a comprehensive image of their diversity by compiling the information of 435 freshwater, soil and marine environmental DNA samples surveyed with Illumina sequencing technology in order to search for the most relevant environments for bioprospecting. Freshwater and soil were most diverse and shared more than half of all operational taxonomic units (OTUs), however, their communities were significantly distinct. Oceans hosted the highest genetic novelty, and did not share any OTUs with the other environments; also, marine samples host more diversity in warm waters. Symbiotic genera usually found in lichens such as Trebouxia, Myrmecia and Symbiochloris were also abundantly detected in the ocean, suggesting either free-living lifestyles or unknown symbiotic relationships with marine planktonic organisms. Altogether, our study opens the way to new prospection for trebouxiophycean strains, especially in understudied environments like the ocean., EL wishes to acknowledge the program ‘Atracción de talentos de la Comunidad de Madrid’ (grant 2017-T1/AMB-5210 4) and Swiss National Fund project SNF 31003A_163254 for funding. The project was funding by the ANPCyT ‘Agencia Nacional de Promoción Científica y Tecnológica’ (PICT-2014-1290; PICT-2016-1079). The Swiss NSF (P2NEP3_178543) to D.S.

Summary Microbial eukaryotes play important roles in aquatic ecosystem functioning. Unravelling their distribution patterns and biogeography provides important baseline information to infer the underlying mechanisms that regulate the biodiversity and complexity of ecosystems. We studied the distribution patterns and factors driving diversity gradients in microeukaryote communities (total, abundant, uncommon and rare community composition) along a latitudinal gradient of lakes distributed from Argentinean Patagonia to Maritime Antarctica using both denaturing gradient gel electrophoresis (DGGE) and high-throughput sequencing (IlluminaHiSeq). DGGE and abundant Illumina operational taxonomic units (OTUs) showed both decreasing richness with latitude and significant differences between Patagonian and Antarctic lakes communities. In contrast, total richness did not change significantly across the latitudinal gradient, although evenness and diversity indices were significantly higher in Patagonian lakes. Beta-diversity was characterized by a high species turnover, influenced by both environmental and geographical descriptors, although this pattern faded in the rare community. Our results suggest the co-existence of a ‘core biosphere' containing reduced number of abundant/dominant OTUs on which classical ecological rules apply, together with a much larger seedbank of rare OTUs driven by stochastic and reduced dispersal processes. These findings shed new light on the biogeographical patterns and forces structuring inland microeukaryote composition across broad spatial scales. This article is protected by copyright. All rights reserved.