bluuebunny/crossref_metadata_2025 huggingface dataset:
The overlooked role of taphonomy in ecology: post‐mortem processes can outweigh recruitment effects on community functions
Authors: Liversage Kiran , Kotta Jonne , Fraser Clarissa M. L. , Figueira Will F. , Coleman Ross A.
Published: November 2019

Biogenic structures that persist post‐mortem are ubiquitous, but rarely considered as key ecological features. Post‐mortem structures in many ecological systems exert community‐level effects and thus the dynamics of their degradation (i.e. taphonomy) become important in affecting community functions and ecosystem services, and these often‐overlooked effects may rival the influence of recruitment and typical post‐recruitment processes. Moreover, in some highly researched habitat types, post‐mortem structures may be mistaken for living organisms, thus introducing significant error into our understanding of population processes. We examined widespread patterns and processes in marine assemblages with calcareous tubeworms and brackish‐water assemblages with bryozoans, in order to test the importance of taphonomy for populations and communities. In tubeworm assemblages, taphonomic variability caused differential accumulation of post‐mortem structures, exerting community‐level influence, and importantly it negated effects from recruitment on the community functions. For tubeworms and bryozoans, proportions of post‐mortem structures varied between sheltered and exposed habitats with overall distributional variability being caused by the share of post‐mortem structures, not living animals. Population‐level inferences in such systems would be extremely problematic without careful differentiation of dead/living structures. Dynamics emerging from the interaction of taphonomic processes and recruitment ecology are relevant for many other important biogenic habitats, especially coral reefs with death assemblages of bleached corals; a failure to consider variability in processes acting on the death assemblages, alongside the living, may severely distort understanding of patterns and processes in populations and communities.
Metaecosystem dynamics drive community composition in experimental, multi‐layered spatial networks
Authors: Harvey Eric , Gounand Isabelle , Fronhofer Emanuel A. , Altermatt Florian
Published: November 2019

Cross‐ecosystem subsidies are studied with a focus on resource exchange at local ecosystem boundaries. This perspective ignores regional dynamics that can emerge via constraints imposed by the landscape, potentially leading to spatially‐dependent effects of subsidies and spatial feedbacks. Using miniaturized landscape analogues of river dendritic and terrestrial lattice spatial networks, we manipulated and studied resource exchange between the two whole networks. We found community composition in dendritic networks depended on the resource pulse from the lattice network, with the strength of this effect declining in larger downstream patches. In turn, this spatially‐dependent effect imposed constraints on the lattice network with populations in that network reaching higher densities when connected to more central patches in the dendritic network. Consequently, localized cross‐ecosystem fluxes, and their respective effects on recipient ecosystems, must be studied in a perspective taking into account the explicit spatial configuration of the landscape.
Governance, federalism and organizing institutions to manage complex problems
Authors: Fowler Luke
Published: November 2019

In managing complex policy problems in the federal system, state and local governments are organized into different arrangements for translating policy goals into policy outcomes. Air quality management is used as a test case to understand these variations and their impact on policy outcomes. With data from Clean Air Act implementation plans and a survey of state and local air quality managers, five separate institutional designs are identified: (1) central agencies; (2) top‐down; (3) donor–recipient; (4) regional agencies; and (5) emergent governance. Findings indicate that some arrangements (donor–recipient and emergent governance) result in notably better air quality than others (central agencies, top‐down). Specifically, when designed to allow bargaining between state and local officials, intergovernmental management is still the most effective approach to complex policy problems; but, in absence of this, conventional federalism arrangements are less effective than public agencies self‐organizing around shared policy goals.
Stability not change: Improving frontline employee motivation through organizational reform is harder than it looks
Authors: van Loon Nina M. , Baekgaard Martin , Moynihan Donald P.
Published: November 2019

As evidence mounts about the positive effects of autonomous motivation such as public service motivation, there is a growing case for public organizations to design reforms to better support public employees’ inherent desire to help others. But how feasible is this in reality? Most experimental evidence on autonomous motivation stems from interventions at the individual level, possibly exaggerating what government reforms can achieve in reality. We present a longitudinal study that analyses a three‐year trial in Danish hospitals in which incentives and autonomy were changed to encourage autonomous motivation. This set‐up offers a rare opportunity to observe the potential malleability of intrinsic, public service, user and external motivation. The results show little observable change in motivation due to the reform. We explore the practical difficulties of translating evidence about motivation into reforms given implementation challenges, contextual factors and a recognition that motivation might be less malleable than implied by research.
Does the Office of Patient Experience Matter in Improving Delivery of Care?
Authors: Sharma Luv , Chandrasekaran Aravind , Bendoly Elliot
Published: November 2019

This research examines the performance benefits of the Office of Patient Experience (OPX), a new administrative innovation in the health care industry. OPX is an independent structure within a hospital, having its own annual budget and full‐time staff, and is responsible for improving patient experience during the hospital stay. We specifically investigate the effectiveness of OPXs in improving experiential quality (EQ), measured as the quality of interactions between hospital's caregivers and patients. In addition, we look at how the operation of these offices help hospitals manage variability during the delivery of care, which introduces additional challenges to maintaining high EQ. Specifically, we investigate the impact of variability in care delivery introduced due to two factors—patient case mix index (CMI) and resident intensity. CMI is an indicator of patient acuity and their care burden on hospitals while resident intensity is measured as a ratio of residents to beds at a hospital and is a proxy for variability introduced due to disruptions in caregiver teams due to the presence of residents who are getting trained at the hospital. Our empirical analyses involve tracking the operation of these offices across 3615 US acute care hospitals for the years 2007–2014. To account for endogeneity, we used an instrumental variable fixed effects regression model with a least absolute shrinkage and selection operator (LASSO) on the first‐stage to identify and select the strongest instruments. Findings suggest that the OPX is associated with 1.95% higher EQ for each year of its operation. Furthermore, we find that an OPX is more effective in improving EQ for hospitals that deal with high CMI patients (6.5% for high vs. −0.3% for low) or high resident intensity (1.8% for high vs. 0.9% low). Moreover, we find evidence of operating efficiencies associated with OPXs, with a 1.4% reduction in operating cost for each year of its operation. Preliminary evidence also suggests that Chief Patient Experience Officers (CXOs), leaders of OPX, with medical backgrounds (i.e., MD or nursing degree) are more effective at improving EQ. Finally, we validate our findings through interviews with OPX and hospital staff at a prominent teaching hospital with an active OPX.
Standard and alternative error theories about moral reasons
Authors: Lofitis Kipros
Published: November 2019

An error theory about moral reasons is the view that ordinary thought is committed to error, and that the alleged error is the thought that moral norms (expressing alleged moral requirements) invariably supply agents with sufficient normative reasons (for action). In this paper, I sketch two distinct ways of arguing for the error theorist's substantive conclusion that moral norms do not invariably supply agents with sufficient normative reasons. I am primarily interested in the somewhat neglected way, which I callthe alternative route. A reason for this is because it seems a genuine question whether the alternative route towards the substantive conclusion need be as troubling to the moralist as the standard route. My hunch is that it is not. Though the alternative error theory denies justification from genuinely moral acts, it also does so from acts born out of self‐interest or immorality. If the alternative theory is true, the moralist can at least hold on to the claim that if genuinely moral considerations fail to provide agents with reasons for action, nothing else (of the sort) does.
Step‐down from non‐invasive ventilation to continuous positive airway pressure: A better phenotyping is required – Reply
Authors: Arellano‐Maric María P. , Windisch Wolfram
Published: November 2019

See Letter
Normative health‐related fitness values for French children: The Diagnoform Programme
Authors: Vanhelst Jérémy , Ternynck Camille , Ovigneur Hervé , Deschamps Thibault
Published: November 2019

The primary objective of this study was to establish sex‐ and age‐specific physical fitness percentiles for French children. The secondary aim was to assess sex, weight status, and age differences for physical fitness levels in French children. A sample of 31 484 children (16 023 boys, 15 461 girls) aged 6‐11 years participated in the Diagnoform programme. Cardiorespiratory fitness, muscular endurance, speed, flexibility, and agility were assessed in this national programme. Percentile values were estimated as a function of age stratified by sex using a parametric method providing smooth centile curves and explicit formulae for the centile estimates. Values from the 10th to the 90th percentile are reported. The influence of body weight according to sex on the physical fitness level was also examined using an analysis of covariance adjusted for age. Physical fitness levels were slightly better in boys, except for agility and flexibility, in which girls performed better (Cohen's coefficient, 0.20‐0.45; P < .001). All physical fitness tests were significantly associated with age (P < .0001). In general, overweight and obese children had a significantly poorer physical fitness level compared with their normal‐weight counterparts (P < .05). No difference was found between thin and normal‐weight boys and girls, except for agility (P < .05). Reference values provide normative data for French children, and these data should be useful for identifying special needs for appropriate intervention programmes.
Tempus volat, hora fugit: A survey of tie‐oriented dynamic network models in discrete and continuous time
Authors: Fritz Cornelius , Lebacher Michael , Kauermann Göran
Published: November 2019

Given the growing number of available tools for modeling dynamic networks, the choice of a suitable model becomes central. The goal of this survey is to provide an overview of tie‐oriented dynamic network models. The survey is focused on introducing binary network models with their corresponding assumptions, advantages, and shortfalls. The models are divided according to generating processes, operating in discrete and continuous time. First, we introduce the temporal exponential random graph model (TERGM) and the separable TERGM (STERGM), both being time‐discrete models. These models are then contrasted with continuous process models, focusing on the relational event model (REM). We additionally show how the REM can handle time‐clustered observations, that is, continuous‐time data observed at discrete time points. Besides the discussion of theoretical properties and fitting procedures, we specifically focus on the application of the models on two networks that represent international arms transfers and email exchange, respectively. The data allow to demonstrate the applicability and interpretation of the network models.
Multiple xylosyltransferases heterogeneously xylosylate proteinN‐linked glycans inChlamydomonas reinhardtii
Authors: Lucas Pierre‐Louis , Mathieu‐Rivet Elodie , Song Philippe C.T. , Oltmanns Anne , Loutelier‐Bourhis Corinne , Plasson Carole , Afonso Carlos , Hippler Michael , Lerouge Patrice , Mati‐Baouche Narimane , Bardor Muriel
Published: November 2019

Summary

Nowadays, little information is available regarding theN‐glycosylation pathway in the green microalgaChlamydomonas reinhardtii.Recent investigation demonstrated thatC. reinhardtiisynthesizes linear oligomannosides. Maturation of these oligomannosides results inN‐glycans that are partially methylated and carry one or two xylose residues. One xylose residue was demonstrated to be a core β(1,2)‐xylose. Recently,N‐glycoproteomic analysis performed on glycoproteins secreted byC. reinhardtiidemonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)‐xylose. Furthermore, another xylosyltransferase candidate named XTB was suggested to be involved in the xylosylation inC. reinhardtii. In the present study, we focus especially on the characterization of the structures of the xylosylatedN‐glycans fromC. reinhardtiitaking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double‐mutant. The combination of mass spectrometry approaches allowed us to identify the majorN‐glycan structures bearing one or two xylose residues. They confirm that XTA is responsible for the addition of the core β(1,2)‐xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of theN‐glycan as well as in the partial addition of the core β(1,2)‐xylose suggesting that this transferase exhibits a low substrate specificity. Analysis of the double‐mutant suggests that an additional xylosyltransferase is involved in the xylosylation process inC. reinhardtii. Additional putative candidates have been identified in theC. reinhardtiigenome. Altogether, these results pave the way for a better understanding of theC. reinhardtii N‐glycosylation pathway.
Association of meniscal injury to joint space width on standard tibial plateau leveling osteotomy lateral radiographic projections of the canine stifle
Authors: Won Wylen Wade , Lee Alison M. , Butler James Ryan , Wills Robert W. , Brinkman Erin L.
Published: November 2019

Up to 70% of dogs with cranial cruciate ligament tears have concurrent meniscal injury, and these injuries can increase the risk of developing osteoarthritis and persistent lameness. Studies assessing joint space width on knee radiographs in people have indicated associations between joint space width and meniscal injuries. The aim of this prospective analytical study was to determine if there was an association between stifle joint space width on three different radiographic projections (the standard tibial plateau leveling osteotomy projections and a standing lateral projection) and meniscal injuries identified at surgery in dogs. There was a significant association between dogs with a meniscal tear and the corresponding joint space width on standard tibial plateau leveling osteotomy lateral radiographic projections (P‐value = .0028). Based on receiver operator characteristic curve analysis, joint space widths measuring less than 3.43 mm may indicate a meniscal tear, with a corresponding 89.5% specificity and 40.5% sensitivity in dogs weighing 31 kg. Joint space narrowing is seen with meniscal tears in dogs, and radiography may be a noninvasive way to identify meniscal tears prior to surgery.
Validity of thermography for measuring burn wound healing potential
Authors: Carrière Michelle E. , de Haas Louise E. M. , Pijpe Anouk , Meij‐de Vries Annebeth , Gardien Kim L. M. , van Zuijlen Paul P. M. , Jaspers Mariëlle E. H.
Published: November 2019

Accurate assessment of burn wound depth and the associated healing potential is vital in determining the need for surgical treatment in burns. Infrared thermography measures the temperature of the burn wound noninvasively, thereby providing indirect information on its blood flow. Previous research demonstrated that a small, low‐priced, handheld thermal imager has an excellent reliability, but a moderate validity for measuring burn wound healing potential. A new and more sensitive version of this convenient device has become available. The aim of this study was to evaluate the validity of thermography for measuring burn wound healing potential, compared to Laser Doppler Imaging (LDI) as a reference standard. Thermal images and LDI scans were obtained from burn wounds between 2 and 5 days postburn. Temperature differences between burned and nonburned skin (ΔT) were calculated. To evaluate validity, ΔT values were compared to the healing potential categories assessed by LDI. Two receiver operating characteristic curves were created and two ΔT cutoff values were calculated to illustrate the ability to discriminate between burn wounds that heal in a time period of less than 14 days, between 14 and 21 days, and more than 21 days. Between June and October 2018, 43 burn wounds in 32 patients were measured. ΔT cutoff values of 0.6°C (sensitivity 68%, specificity 95%) and −2.3°C (sensitivity 30%, specificity 95%) were calculated to discriminate between burn wounds that heal in <14 and ≥14 days, and burn wound that heal in ≤21 and >21 days, respectively. This study shows a good validity of the feasible thermal imager for the assessment of burn wound healing potential. Therefore, we consider it a promising technique to be used for triage in local hospitals and general practices, and as a valuable addition to clinical evaluation in burn centers.
Comparing Canadian Generalist and Specialist Elementary School Teachers’ Self-Efficacy and Barriers Related to Physical Education Instruction
Authors: Truelove Stephanie , Johnson Andrew M. , Burke Shauna M. , Tucker Patricia
Published: November 2019

Purpose: We aimed to explore and compare generalist and physical education (PE) specialist (males and females) elementary teachers’ self-efficacy to teach and the barriers perceived when teaching PE.Methods: Canadian elementary school teachers completed the validated online survey, Teacher Efficacy Scale in PE, with 11 additional questions examining the perceived strength of barriers related to teaching quality PE.Results: Specialist teachers’ self-efficacy (n = 296) was significantly higher (p < .05) than that of generalist teachers (n = 818). Gender was found to predict teachers’ self-efficacy, with female generalists reporting the lowest scores on the Teacher Efficacy Scale in PE. There was a statistically significant difference between the perceived strength of nine out of the 11 listed barriers, with generalist teachers reporting barriers as more inhibitory than specialists.Discussion/Conclusion: This study highlights the gap between generalists’ and specialists’ self-efficacy to teach and the perceived barriers when teaching PE. Efforts specifically targeted to supporting female generalists teaching PE are necessary.
Detecting and quantifying causal associations in large nonlinear time series datasets
Authors: Runge Jakob , Nowack Peer , Kretschmer Marlene , Flaxman Seth , Sejdinovic Dino
Published: November 2019

A novel causal discovery method for estimating nonlinear interdependency networks from large time series datasets.
A multihost bacterial pathogen overcomes continuous population bottlenecks to adapt to new host species
Authors: Bacigalupe Rodrigo , Tormo-Mas María Ángeles , Penadés José R. , Fitzgerald J. Ross
Published: November 2019

A model of bacterial host switching provides a window into the population dynamics of host adaptation.
Modeling other minds: Bayesian inference explains human choices in group decision-making
Authors: Khalvati Koosha , Park Seongmin A. , Mirbagheri Saghar , Philippe Remi , Sestito Mariateresa , Dreher Jean-Claude , Rao Rajesh P. N.
Published: November 2019

A Bayesian model suggests that when interacting with a group, humans simulate the “mind of the group” to choose an action.
The commonness of rarity: Global and future distribution of rarity across land plants
Authors: Enquist Brian J. , Feng Xiao , Boyle Brad , Maitner Brian , Newman Erica A. , Jørgensen Peter Møller , Roehrdanz Patrick R. , Thiers Barbara M. , Burger Joseph R. , Corlett Richard T. , Couvreur Thomas L. P. , Dauby Gilles , Donoghue John C. , Foden Wendy , Lovett Jon C. , Marquet Pablo A. , Merow Cory , Midgley Guy , Morueta-Holme Naia , Neves Danilo M. , Oliveira-Filho Ary T. , Kraft Nathan J. B. , Park Daniel S. , Peet Robert K. , Pillet Michiel , Serra-Diaz Josep M. , Sandel Brody , Schildhauer Mark , Šímová Irena , Violle Cyrille , Wieringa Jan J. , Wiser Susan K. , Hannah Lee , Svenning Jens-Christian , McGill Brian J.
Published: November 2019

A large fraction of Earth’s plant species are faced with increased chances of extinction.
Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation
Authors: Tang Alan T. , Sullivan Katie R. , Hong Courtney C. , Goddard Lauren M. , Mahadevan Aparna , Ren Aileen , Pardo Heidy , Peiper Amy , Griffin Erin , Tanes Ceylan , Mattei Lisa M. , Yang Jisheng , Li Li , Mericko-Ishizuka Patricia , Shen Le , Hobson Nicholas , Girard Romuald , Lightle Rhonda , Moore Thomas , Shenkar Robert , Polster Sean P. , Rödel Claudia J. , Li Ning , Zhu Qin , Whitehead Kevin J. , Zheng Xiangjian , Akers Amy , Morrison Leslie , Kim Helen , Bittinger Kyle , Lengner Christopher J. , Schwaninger Markus , Velcich Anna , Augenlicht Leonard , Abdelilah-Seyfried Salim , Min Wang , Marchuk Douglas A. , Awad Issam A. , Kahn Mark L.
Published: November 2019

Loss of PDCD10 signaling in brain endothelium and gut epithelium contribute to cerebral cavernous malformation in a mouse model.
Leukotrienes fuel fibrosis
Authors: Dakin Stephanie G.
Published: November 2019

Senescent fibroblasts are a key source of profibrotic leukotrienes during pulmonary fibrosis.
A two-step program preventing bone metastatic relapse
Authors: Kerr Bethany A.
Published: November 2019

Treating bone metastatic prostate cancer with docetaxel nanoparticles and denosumab averts tumor regrowth.
Pathways That Synthesize Phosphatidylethanolamine Impact Candida albicans Hyphal Length and Cell Wall Composition through Transcriptional and Posttranscriptional Mechanisms
Authors: Tams Robert N. , Wagner Andrew S. , Jackson Joseph W. , Gann Eric R. , Sparer Timothy E. , Reynolds Todd B.
Published: November 2019

Candida albicans
is a leading cause of systemic bloodstream infections, and synthesis of the phospholipid phosphatidylethanolamine (PE) is required for virulence. The
psd1
Δ/Δ
psd2
Δ/Δ mutant, which cannot synthesize PE by the cytidine diphosphate diacylglycerol (CDP-DAG) pathway, is avirulent in the mouse model of systemic candidiasis.
ZBTB7B (ThPOK) Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis
Authors: Kennedy James M. , Georges Anna , Bassenden Angelia V. , Vidal Silvia M. , Berghuis Albert M. , Taniuchi Ichiro , Majewski Jacek , Lathrop Mark , Behr Marcel A. , Langlais David , Gros Philippe
Published: November 2019

We used a genome-wide screen inN-ethyl-N-nitrosourea (ENU)-mutagenized mice to identify genes in which recessive loss-of-function mutations protect against pathological neuroinflammation. We identified an R367Q mutation in the ZBTB7B (ThPOK) protein in which homozygosity causes protection against experimental cerebral malaria (ECM) caused by infection withPlasmodium bergheiANKA.
Evidence of Robustness in a Two-Component System Using a Synthetic Circuit
Authors: Dutta Arkajyoti , Rudra Paulami , Banik Suman Kumar , Mukhopadhyay Jayanta
Published: November 2019

Robustness in essential biological circuits is an important feature of the living organism. A few pieces of evidence support the existence of robustness
in vivo
in the two-component system (TCS) with a bifunctional sensor kinase (SK). The assays were done under physiological conditions in which the SK was much lower than the response regulator (RR). Here, using a synthetic circuit, we varied the concentrations of the SK and RR of a representative TCS to monitor output robustness
in vivo. In vitro
assays were also performed under conditions where the concentration of the SK was greater than that of the RR. Our results demonstrate the extent of output robustness in the TCS signaling pathway with respect to the concentrations of the two components.
pH Sensing in Bacillus subtilis: a New Path to a Common Goal
Authors: Manson Michael D.
Published: November 2019

pH is one of the most fundamental properties of the environments in which microorganisms live. It is, therefore, not surprising that bacteria have evolved mechanisms to sense and respond to pH. One aspect of this response for motile bacteria is to migrate to areas of optimal pH. The paper by P. Tohidifar, M. J. Plutz, G. W. Ordal, and C.
Fifteen-minute consultation: The infant with a neck lump
Authors: Reynolds Sarah , Yap Darren , Marikar Dilshad , Roland Damian
Published: November 2019

Studying head and neck anatomy may be a distant memory and clinicians can struggle with how to approach neck lumps diagnostically. This article gives a brief guide to common (and rare but serious) causes of neck lumps in infancy, their identification and management.
Treatment of atypical pulmonary carcinoid with combination ipilimumab and nivolumab
Authors: Nestor Jacquelyn , Barnaby Keara , Esposito Michael , Seetharamu Nagashree
Published: November 2019

Atypical pulmonary carcinoid (APC) is a lung neuroendocrine neoplasm (NEN), whose treatment draws from management of gastrointestinal NENs and small-cell lung carcinoma. We present a patient with recurrent metastatic APC and persistent mediastinal lymphadenopathy refractory to cisplatin and etoposide. After pursuing alternative treatments, he returned with significant progression, including diffuse subcutaneous nodules, weight loss and worsening cough. New biopsy analysis demonstrated APC with low mutational burden, low Ki-67 and Programmed Death-Ligand 1 (PD-L1), and without microsatellite instability. We pursued combination nivolumab and ipilimumab treatment based on success of CheckMate 032 in small-cell lung cancer. The patient’s symptoms dramatically responded within a month, with almost complete resolution of lymphadenopathy following four cycles. He has been successfully maintained on nivolumab for the last 18 months. This suggests combination immunotherapy may be beneficial in the treatment of metastatic APC, and that PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors may be valuable in treating tumours lacking traditional biomarkers.
Persistent type 2 respiratory failure on background of advanced thymoma with lung metastases
Authors: Munir Abrar , Khan Mohsin Ijaz , Cheong Jason Kah Chun
Published: November 2019

We report a patient in her 60s with history of end-stage thymoma with bilateral lung metastases on palliative chemotherapy presented to the hospital with sudden shortness of breath initially treated for probable pulmonary embolism (PE) pending CT of the pulmonary arteries which was subsequently negative for PE. During this admission, she developed transient right-sided facial droop and slurred speech which resolved spontaneously; however, the patient became unresponsive and desaturated with severe decompensated type 2 respiratory failure. Patient was supported with non-invasive ventilation (biphasic positive airway pressure) for few days. Myasthenia gravis was suspected due to clinical features and confirmed by the high titre of acetylcholine receptor antibody titre.
Anastrozole-induced liver injury after a prolonged latency: a very rare complication of a commonly prescribed medication
Authors: Xie Chencheng , Abdullah Hafez Mohammad Ammar , Abdallah Mohamed , Quist Erin , Niazi Mumtaz
Published: November 2019

Anastrozole is an aromatase inhibitor that has been used more frequently over the last decade especially for oestrogen receptor-positive breast cancer. It has a relatively safe side effect profile. However, occasionally it has been associated with serious adverse events. Here, we present the case of a 58-year-old woman who presented with significantly elevated liver enzymes 4 years after starting anastrozole. She was not taking any other medications and an extensive workup did not reveal any other cause for her liver injury. The patient’s liver enzymes normalised after discounting the anastrozole. She scored 4 on the updated Roussel Uclaf Causality Assessment Method grading system which was possible for drug-induced liver injury. A review of the literature revealed six prior cases of anastrozole-related liver injury. Anastrozole should be considered as a possible culprit in patients who develop an unexplained acute liver injury.
Short axial length and hyperopic refractive error are risk factors of central serous chorioretinopathy
Authors: Terao Nobuhiro , Koizumi Hideki , Kojima Kentaro , Kusada Natsuki , Nagata Kenji , Yamagishi Tetsuya , Yoneda Kazuhito , Yoshii Kengo , Kinoshita Shigeru , Sotozono Chie
Published: November 2019

Background/aims

To evaluate the axial length (AL) and refractive status in central serous chorioretinopathy (CSC).

Methods

This retrospective observational case series involved 140 patients with CSC (180 eyes) and 78 age-matched and gender-matched control subjects. A detailed ophthalmic examination was performed, including an interferometer measurement of AL. Multimodal imaging comprised colour fundus photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence photography and spectral domain optical coherence tomography.

Results

Eighty eyes of 40 patients were categorised into the bilateral-CSC (b-CSC) group and 100 eyes of 100 patients were categorised into the unilateral-CSC (u-CSC) group. AL of the b-CSC (23.19 mm) and u-CSC (23.75 mm) groups was significantly shorter than that of the control (24.85 mm) group (p<0.001 for both). Moreover, AL was significantly shorter in the b-CSC group than in the u-CSC group (p=0.020). Spherical equivalent (SE) in the b-CSC (0.25 D) group was significantly greater than in the u-CSC (−0.81 D) and control (−1.38 D) groups (p<0.001 for both). Gender (male; OR 4.55; 95% CI 1.13 to 18.40; p=0.033), AL (OR 0.38; 95% CI 0.23 to 0.63; p<0.001), area of choroidal vascular hyperpermeability (OR 1.08; 95% CI 1.03 to 1.13; p=0.002) and presence of descending tract (OR 7.22; 95% CI 1.86 to 28.00; p=0.004) were the variables found to be significantly associated with b-CSC via multiple regression analyses.

Conclusion

Anatomical features, such as shorter AL and greater SE, may be associated with the pathogenesis of CSC.
Short term exposure to fine particulate matter and hospital admission risks and costs in the Medicare population: time stratified, case crossover study
Authors: Wei Yaguang , Wang Yan , Di Qian , Choirat Christine , Wang Yun , Koutrakis Petros , Zanobetti Antonella , Dominici Francesca , Schwartz Joel D
Published: November 2019

Objective

To assess risks and costs of hospital admission associated with short term exposure to fine particulate matter with diameter less than 2.5 µm (PM2.5) for 214 mutually exclusive disease groups.

Design

Time stratified, case crossover analyses with conditional logistic regressions adjusted for non-linear confounding effects of meteorological variables.

Setting

Medicare inpatient hospital claims in the United States, 2000-12 (n=95 277 169).

Participants

All Medicare fee-for-service beneficiaries aged 65 or older admitted to hospital.

Main outcome measures

Risk of hospital admission, number of admissions, days in hospital, inpatient and post-acute care costs, and value of statistical life (that is, the economic value used to measure the cost of avoiding a death) due to the lives lost at discharge for 214 disease groups.

Results

Positive associations between short term exposure to PM2.5and risk of hospital admission were found for several prevalent but rarely studied diseases, such as septicemia, fluid and electrolyte disorders, and acute and unspecified renal failure. Positive associations were also found between risk of hospital admission and cardiovascular and respiratory diseases, Parkinson’s disease, diabetes, phlebitis, thrombophlebitis, and thromboembolism, confirming previously published results. These associations remained consistent when restricted to days with a daily PM2.5concentration below the WHO air quality guideline for the 24 hour average exposure to PM2.5. For the rarely studied diseases, each 1 µg/m3increase in short term PM2.5was associated with an annual increase of 2050 hospital admissions (95% confidence interval 1914 to 2187 admissions), 12 216 days in hospital (11 358 to 13 075), US$31m (£24m, €28m; $29m to $34m) in inpatient and post-acute care costs, and $2.5bn ($2.0bn to $2.9bn) in value of statistical life. For diseases with a previously known association, each 1 µg/m3increase in short term exposure to PM2.5was associated with an annual increase of 3642 hospital admissions (3434 to 3851), 20 098 days in hospital (18 950 to 21 247), $69m ($65m to $73m) in inpatient and post-acute care costs, and $4.1bn ($3.5bn to $4.7bn) in value of statistical life.

Conclusions

New causes and previously identified causes of hospital admission associated with short term exposure to PM2.5were found. These associations remained even at a daily PM2.5concentration below the WHO 24 hour guideline. Substantial economic costs were linked to a small increase in short term PM2.5.
Performance of UK National Health Service compared with other high income countries: observational study
Authors: Papanicolas Irene , Mossialos Elias , Gundersen Anders , Woskie Liana , Jha Ashish K
Published: November 2019

Objective

To determine how the UK National Health Service (NHS) is performing relative to health systems of other high income countries, given that it is facing sustained financial pressure, increasing levels of demand, and cuts to social care.

Design

Observational study using secondary data from key international organisations such as Eurostat and the Organization for Economic Cooperation and Development.

Setting

Healthcare systems of the UK and nine high income comparator countries: Australia, Canada, Denmark, France, Germany, the Netherlands, Sweden, Switzerland, and the US.

Main outcome measures

79 indicators across seven domains: population and healthcare coverage, healthcare and social spending, structural capacity, utilisation, access to care, quality of care, and population health.

Results

The UK spent the least per capita on healthcare in 2017 compared with all other countries studied (UK $3825 (£2972; €3392); mean $5700), and spending was growing at slightly lower levels (0.02% of gross domestic product in the previous four years, compared with a mean of 0.07%). The UK had the lowest rates of unmet need and among the lowest numbers of doctors and nurses per capita, despite having average levels of utilisation (number of hospital admissions). The UK had slightly below average life expectancy (81.3 years compared with a mean of 81.7) and cancer survival, including breast, cervical, colon, and rectal cancer. Although several health service outcomes were poor, such as postoperative sepsis after abdominal surgery (UK 2454 per 100 000 discharges; mean 2058 per 100 000 discharges), 30 day mortality for acute myocardial infarction (UK 7.1%; mean 5.5%), and ischaemic stroke (UK 9.6%; mean 6.6%), the UK achieved lower than average rates of postoperative deep venous thrombosis after joint surgery and fewer healthcare associated infections.

Conclusions

The NHS showed pockets of good performance, including in health service outcomes, but spending, patient safety, and population health were all below average to average at best. Taken together, these results suggest that if the NHS wants to achieve comparable health outcomes at a time of growing demographic pressure, it may need to spend more to increase the supply of labour and long term care and reduce the declining trend in social spending to match levels of comparator countries.
Going to extremes: the Goldilocks/Lagom principle and data distribution
Authors: Leese Henry J , Sathyapalan Thozhukat , Allgar Victoria , Brison Daniel R , Sturmey Roger
Published: November 2019

Numerical data in biology and medicine are commonly presented as mean or median with error or confidence limits, to the exclusion of individual values. Analysis of our own and others’ data indicates that this practice risks excluding ‘Goldilocks’ effects in which a biological variable falls within a range between ‘too much’ and ‘too little’ with a region between where its function is ‘just right’; a concept captured by the Swedish term ‘Lagom’. This was confirmed by a narrative search of the literature using the PubMed database, which revealed numerous relationships of biological and clinical phenomena of the Goldilocks/Lagom form including quantitative and qualitative examples from the health and social sciences. Some possible mechanisms underlying these phenomena are considered. We conclude that retrospective analysis of existing data will most likely reveal a vast number of such distributions to the benefit of medical understanding and clinical care and that a transparent approach of presenting each value within a dataset individually should be adopted to ensure a more complete evaluation of research studies in future.
Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction)
Authors: Moncrieff Joanna , Lewis Glyn , Freemantle Nick , Johnson Sonia , Barnes Thomas R E , Morant Nicola , Pinfold Vanessa , Hunter Rachael , Kent Lyn J , Smith Ruth , Darton Katherine , Horne Robert , Crellin Nadia E , Cooper Ruth E , Marston Louise , Priebe Stefan
Published: November 2019

Introduction

Antipsychotic medication is effective in reducing acute symptoms of psychosis, but it has a range of potentially serious and debilitating adverse effects and is often disliked by patients. It is therefore essential it is only used when benefits outweigh harms. Although multiple trials conducted with people with schizophrenia indicate an increased risk of relapse in the short-term following abrupt antipsychotic discontinuation, there is little evidence about the long-term outcome of a gradual process of reduction and discontinuation on social functioning, relapse and other outcomes.

Methods and analysis

This is a multicentre, randomised controlled trial involving people with schizophrenia and related disorders who have had more than one episode. Participants are randomised to have a clinically-supervised, gradual reduction of antipsychotic medication, leading to discontinuation when possible, or to continue with maintenance treatment. Blinded follow-up assessments are conducted at 6, 12 and 24 months and the primary outcome is social functioning, measured by the Social Functioning Scale at 24 months. A minimum of 134 evaluable participants provides 90% power to detect a five-point difference, and 206 to detect a four-point difference. Secondary outcomes include severe relapse (admission to hospital) and the study is also intended to detect a minimum 10% difference in severe relapse, which requires 402 participants, assuming a 15% loss to follow-up. Other secondary outcomes include all relapses, as identified by an independent and blinded endpoint committee, symptoms measured by the Positive and Negative Syndrome Scale, quality of life, adverse effects, self-rated recovery and neuropsychological measures. Enrolment started in 2016. The trial is scheduled to finish in June 2022.

Ethics and dissemination

Ethical approval was initially obtained on 27 October 2016 (UK Research Ethics Committee reference 16/LO/1507). Results will be published in peer-reviewed journals and disseminated to the public.

Trial registration number

ISRCTN90298520. EudraCT: 2016-000709-36. Pre-results.
Challenges in making standardisation work in healthcare: lessons from a qualitative interview study of a line-labelling policy in a UK region
Authors: Kriznik Natasha Marie , Lamé Guillaume , Dixon-Woods Mary
Published: November 2019

Objective

To identify and learn from efforts to design and implement a standardised policy for labelling of invasive tubing and lines across a regional health system.

Design

Single case study involving qualitative interviews and documentary analysis.

Setting

A devolved health system in the UK National Health Service (NHS).

Participants

NHS staff (n=10) and policy-makers (n=8) who were involved in the design and/or implementation of the standardised policy.

Results

Though standardising labelling of invasive tubing and lines was initially seen as a common-sense technical change, challenges during the process of developing and implementing the policy were multiple and sociotechnical in nature. Major challenges related to defining the problem and the solution, limited sustained engagement with stakeholders and users, prototyping/piloting of the solution, and planning for implementation. Some frontline staff remained unconvinced of the need for or value of the policy, since they either did not believe that there was a problem or did not agree that standardised labelling was the right solution. Mundane practical issues such authorisation and resourcing, supply chains for labels, the need to restructure work practices to accommodate the new standard, and the physical features of the labels in specific clinical settings all had important impacts.

Conclusions

Newly standardised tools and practices have to fit within a system of pre-existing norms, practices and procedures. We identified a number of practical, social and cultural challenges when designing and implementing a standardised policy in a regional healthcare system. Taking account of both sociocultural and technical aspects of standardisation, combined with systems thinking, could lead to more effective implementation and increase acceptability and usability of new standards.
Combined health risks of cigarette smoking and low levels of physical activity: a prospective cohort study in England with 12-year follow-up
Authors: Jackson Sarah E , Brown Jamie , Ussher Michael , Shahab Lion , Steptoe Andrew , Smith Lee
Published: November 2019

Objectives

To (1) estimate the combined risks of cigarette smoking and physical inactivity for chronic disease, disability and depressive symptoms and (2) determine whether risks associated with these behaviours are additive or synergistic.

Design and setting

Longitudinal observational population study using data from Waves 2 (2004/2005) through 8 (2016/2017) of the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults in England.

Participants

6425 men and women aged ≥52 years (mean (SD) 65.88 (9.34) years) at baseline.

Main outcome measures

Smoking status (never, former, current) and level of physical activity (high, defined as moderate/vigorous physical activity (MVPA) more than once a week; low, defined as MVPA once a week or less) were self-reported at Wave 2 baseline. Self-rated health, limiting long-standing illness, chronic conditions (coronary heart disease (CHD), stroke, cancer, chronic lung disease) and depressive symptoms were reported in each biennial wave.

Results

Both smoking and low levels of physical activity were associated with increased risk of incident health problems over the 12-year follow-up period. Current smokers with low levels of physical activity had especially high risks of developing fair/poor self-rated health, CHD, stroke, cancer and chronic lung disease compared with highly active never smokers (adjusted relative risk range 1.89–14.00). While additive effects were evident, tests of multiplicative interactions revealed no evidence of large synergistic effects of smoking and low physical activity (Bayes factor range 0.04–0.61), although data were insensitive to detect smaller effects.

Conclusions

Among older adults in England, there was no evidence of large synergistic effects of smoking and low levels of physical activity on risk of developing chronic disease or depressive symptoms over 12 years. However, additive effects of smoking and low levels of physical activity were evident, underscoring the importance of each of these lifestyle risk behaviours for disease onset.
Sedatives and sedation at the end of life: a nursing home retrospective cohort study
Authors: Schildmann Eva , Bolzani Anna , Meesters Sophie , Grüne Bettina , Marheineke Alina , Remi Constanze , Bausewein Claudia
Published: November 2019

Objectives

Sedatives are frequently used at the end of life in specialist palliative care. There is scarce information about their use in nursing homes. Therefore, we aimed to assess the use of (1) sedatives generally and (2) ‘sedatives with continuous effect’, based on objective operational criteria, within the last week of life in a nursing home.

Methods

This was a retrospective cohort study of residents who died in a German nursing home between 1/2015 and 12/2017, using the nursing home’s medical records, which contained drug sheets and nurses’ notes. Sedatives analysed were those recommended by guidelines for ‘palliative sedation’: benzodiazepines, levomepromazine, haloperidol (≥5 mg/day) and propofol. Exploratory statistical analysis was conducted using R V.3.6.1.

Results

46/165 (28%) deceased residents received a sedative during the last week of life, all without use of the term ‘sedation’. 26/165 residents (16%) received ‘sedatives with continuous effect’, for median 4 days (range 1–7). Oral lorazepam was used most frequently, mainly for agitation, anxiety and dyspnoea, but also due to palliative status and patients wish. The median total daily dose of lorazepam within the last week of life was 1.5 mg (range 0.5–7.5). The term ‘palliative’ was significantly more often used for residents receiving sedatives (p=0.001).

Conclusions

Compared with published data on continuous deep sedation, moderate or deep sedation was less frequent in this nursing home and never labelled as ‘sedation’. Multicentre mixed-methods research is needed to gain representative and more detailed data on sedation practices at the end of life in nursing homes.