'Calving laws', 'sliding laws' and the stability of tidewater glaciers

A new calving criterion is introduced, which predicts calving where the depth of surface crevasses equals ice height above sea level. Crevasse depth is calculated from strain rates, and terminus position and calving rate are therefore functions of ice velocity, strain rate, ice thickness and water depth. We couple the calving criterion with three 'sliding laws', in which velocity is controlled by (1) basal drag, (2) lateral drag and (3) a combination of the two. In model 1, velocities and strain rates are dependent on effective pressure, and hence ice thickness relative to water depth. Imposed thinning can lead to acceleration and terminus retreat, and ice shelves cannot form. In model 2, ice velocity is independent of changes in ice thickness unless accompanied by changes in surface gradient. Velocities are strongly dependent on channel width, and calving margins tend to stabilize at flow-unit widenings. Model 3 exhibits the combined characteristics of the other two models, and suggests that calving glaciers are sensitive to imposed thickness changes if basal drag provides most resistance to flow, but stable if most resistance is from lateral drag. ice shelves can form if reduction of basal drag occurs over a sufficiently long spatial scale. In combination, the new calving criterion and the basal-lateral drag sliding function (model 3) can be used to simulate much of the observed spectrum of behaviour of calving glaciers, and present new opportunities to model ice-sheet response to climate change.</p

Study on serious road traffic injuries in the EU

The general objective of this study is to collect knowledge that will enable the future identification of measures for effective prevention of serious road traffic injuries. The specific objective is to provide fact-based analysis on the most common circumstances and types of road traffic crashes leading to serious injuries of MAIS3+ severity. More specifically, the study is directed at providing an understanding of the main circumstances and factors that affect the emergence of serious road traffic injuries, medically coded as MAIS3+, for the following road traffic modes in the EU: pedestrians, bicyclists, motorcyclists and car occupants

Modeling what we sample and sampling what we model: challenges for zooplankton model assessment

Zooplankton are the intermediate trophic level between phytoplankton and fish, and are an important component of carbon and nutrient cycles, accounting for a large proportion of the energy transfer to pelagic fishes and the deep ocean. Given zooplankton's importance, models need to adequately represent zooplankton dynamics. A major obstacle, though, is the lack of model assessment. Here we try and stimulate the assessment of zooplankton in models by filling three gaps. The first is that many zooplankton observationalists are unfamiliar with the biogeochemical, ecosystem, size-based and individual-based models that have zooplankton functional groups, so we describe their primary uses and how each typically represents zooplankton. The second gap is that many modelers are unaware of the zooplankton data that are available, and are unaccustomed to the different zooplankton sampling systems, so we describe the main sampling platforms and discuss their strengths and weaknesses for model assessment. Filling these gaps in our understanding of models and observations provides the necessary context to address the last gap—a blueprint for model assessment of zooplankton. We detail two ways that zooplankton biomass/abundance observations can be used to assess models: data wrangling that transforms observations to be more similar to model output; and observation models that transform model outputs to be more like observations. We hope that this review will encourage greater assessment of zooplankton in models and ultimately improve the representation of their dynamics

Clinical and Pathological Findings in SARS-CoV-2 Disease Outbreaks in Farmed Mink (Neovison vison)

SARS-CoV-2, the causative agent of COVID-19, caused respiratory disease outbreaks with increased mortality in 4 mink farms in the Netherlands. The most striking postmortem finding was an acute interstitial pneumonia, which was found in nearly all examined mink that died at the peak of the outbreaks. Acute alveolar damage was a consistent histopathological finding in mink that died with pneumonia. SARS-CoV-2 infections were confirmed by detection of viral RNA in throat swabs and by immunohistochemical detection of viral antigen in nasal conchae, trachea, and lung. Clinically, the outbreaks lasted for about 4 weeks but some animals were still polymerase chain reaction–positive for SARS-CoV-2 in throat swabs after clinical signs had disappeared. This is the first report of the clinical and pathological characteristics of SARS-CoV-2 outbreaks in mink farms

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours. Methods: We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. The starting doses were berzosertib 18 mg/m2, gemcitabine 875 mg/m2 and cisplatin 60 mg/m2. Results: Fifty-two patients received berzosertib + gemcitabine and eight received berzosertib + gemcitabine + cisplatin. Four patients receiving berzosertib + gemcitabine had a total of seven dose-limiting toxicities (DLTs) and three receiving berzosertib + gemcitabine + cisplatin had a total of three DLTs. Berzosertib 210 mg/m2 (days 2 and 9) + gemcitabine 1000 mg/m2 (days 1 and 8) Q3W was established as the recommended Phase 2 dose (RP2D); no RP2D was determined for berzosertib + gemcitabine + cisplatin. Neither gemcitabine nor cisplatin affected berzosertib PK. Most patients in both arms achieved a best response of either partial response or stable disease. Conclusions: Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs. Clinical trial identifier: NCT02157792

Translation of clinical problems in osteoarthritis into pathophysiological research goals

Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the 'European League Against Rheumatism study group on OA' and People with Arthritis/Rheumatism across Europe (PARE) representatives

Height at diagnosis and birth-weight as risk factors for osteosarcoma

OBJECTIVES: Osteosarcoma typically occurs during puberty. Studies of the association between height and/or birth-weight and osteosarcoma are conflicting. Therefore, we conducted a large pooled analysis of height and birth-weight in osteosarcoma. METHODS: Patient data from seven studies of height and three of birth-weight were obtained, resulting in 1,067 cases with height and 434 cases with birth-weight data. We compared cases to the 2000 US National Center for Health Statistics Growth Charts by simulating 1,000 age- and gender-matched controls per case. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between height or birth-weight and risk of osteosarcoma for each study were estimated using logistic regression. All of the case data were combined for an aggregate analysis. RESULTS: Compared to average birth-weight subjects (2,665-4,045 g), individuals with high birth-weight (≥ 4,046 g) had an increased osteosarcoma risk (OR 1.35, 95% CI 1.01-1.79). Taller than average (51st - 89th percentile) and very tall individuals (≥ 90th percentile) had an increased risk of osteosarcoma (OR 1.35, 95% CI 1.18-1.54 and OR 2.60, 95% CI 2.19-3.07, respectively; P (trend) < 0.0001). CONCLUSIONS: This is the largest analysis of height at diagnosis and birth-weight in relation to osteosarcoma. It suggests that rapid bone growth during puberty and in utero contributes to OS etiology

Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans

Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms

Customer emotions in service failure and recovery encounters

Emotions play a significant role in the workplace, and considerable attention has been given to the study of employee emotions. Customers also play a central function in organizations, but much less is known about customer emotions. This chapter reviews the growing literature on customer emotions in employee–customer interfaces with a focus on service failure and recovery encounters, where emotions are heightened. It highlights emerging themes and key findings, addresses the measurement, modeling, and management of customer emotions, and identifies future research streams. Attention is given to emotional contagion, relationships between affective and cognitive processes, customer anger, customer rage, and individual differences

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions