bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probe dependence of allosteric enhancers on the binding affinity of adenosine A1‐receptor agonists at rat and human A1‐receptors measured using NanoBRET
Authors: Cooper Samantha L. , Soave Mark , Jörg Manuela , Scammells Peter J. , Woolard Jeanette , Hill Stephen J. 
Published: January 2019

Background and PurposeAdenosine is a local mediator that regulates a number of physiological and pathological processes via activation of adenosine A1‐receptors. The activity of adenosine can be regulated at the level of its target receptor via drugs that bind to an allosteric site on the A1‐receptor. Here, we have investigated the species and probe dependence of two allosteric modulators on the binding characteristics of fluorescent and nonfluorescent A1‐receptor agonists.Experimental ApproachA Nano‐luciferase (Nluc) BRET (NanoBRET) methodology was used. This used N‐terminal Nluc‐tagged A1‐receptors expressed in HEK293T cells in conjunction with both fluorescent A1‐receptor agonists (adenosine and NECA analogues) and a fluorescent antagonist CA200645.Key ResultsPD 81,723 and VCP171 elicited positive allosteric effects on the binding affinity of orthosteric agonists at both the rat and human A1‐receptors that showed clear probe dependence. Thus, the allosteric effect on the highly selective partial agonist capadenoson was much less marked than for the full agonists NECA, adenosine, and CCPA in both species. VCP171 and, to a lesser extent, PD 81,723, also increased the specific binding of three fluorescent A1‐receptor agonists in a species‐dependent manner that involved increases in Bmax and pKD.Conclusions and ImplicationsThese results demonstrate the power of the NanoBRET ligand‐binding approach to study the effect of allosteric ligands on the binding of fluorescent agonists to the adenosine A1‐receptor in intact living cells. Furthermore, our studies suggest that VCP171 and PD 81,723 may switch a proportion of A1‐receptors to an active agonist conformation (R*).
Switch of psoriasis therapy from a fumaric acid ester mixture to dimethyl fumarate monotherapy: Results of a prospective study
Authors: Falkvoll Sandra , Gerdes Sascha , Mrowietz Ulrich 
Published: January 2019

SummaryBackgroundFumaric acid esters (FAEs) are used for systemic therapy of moderate to severe psoriasis. Until recently, only a mixture of dimethyl fumarate (DMF) and three salts of ethyl hydrogen fumarate was available. However, a drug containing DMF as the sole ingredient was registered for the same indication in 2017. This prospective study aimed to investigate the switch from the currently used FAE mixture to DMF alone.Patients and methodsForty patients were consecutively recruited, for whom the FAE mixture was switched to DMF alone on the basis of the last DMF‐equivalent dose without interrupting treatment. At the first check‐up after switching, the efficacy and tolerability of the DMF drug was compared with that of the previous treatment.ResultsThe data show that the efficacy remained unchanged in the majority of patients. Tolerability (e.g. gastrointestinal complaints and flushing) of the DMF drug was rated equal or better in most patients than with the previous treatment.ConclusionsThe results show that it is possible to switch psoriasis patients under stable therapy with the FAE mixture to the DMF drug directly and without interruption.
Supply Chain Contracts and Inventory Shrinkage: An Empirical Analysis in the Grocery Retailing Industry
Authors: Choi Min , Rabinovich Elliot , Richards Timothy J. 
Published: January 2019

ABSTRACTContracts in grocery supply chains based on Scan‐Based Trading (SBT) have recently emerged as alternatives to contracts based on Vendor‐Managed Inventory (VMI) as governance mechanisms between retailers and vendors. In contrast to VMI, vendors under SBT remain the owners of inventory delivered to retailers until it is sold to consumers. While SBT contracts offer clear benefits to retailers and suppliers, they also carry unique inventory risks which result from retailers marketing and selling supplier‐owned inventory without bearing all the cost of mismanagement. Further risks in both of these arrangements arise from vendors’ contracting out store deliveries to third party logistics (3PL) providers as opposed to taking on the responsibility for deliveries themselves. This paper examines the effect of SBT on inventory shrink relative to VMI using data from a supplier delivering directly to stores using a combination of 3PL and supplier employees. We find that shrink levels tend to be higher under SBT relative to VMI. We also observe that supplier decisions to contract store deliveries out to 3PL providers yield higher shrink levels under SBT and VMI contracts. Based on average inventory replenishment amounts at retail stores, SBT contracts account for 10.20% in shrink relative to VMI contracts. In addition, 3PL contracts account for 2.92% in shrink relative to the amounts observed when the vendor bears responsibility for store deliveries. Our findings highlight potential losses in efficiency in grocery supply chains reflected in higher shrink under SBT and 3PL contracts that may undercut the promised benefits from these arrangements.
Motor development in children with Dravet syndrome
Authors: Verheyen Karen , Verbecque Evi , Ceulemans Berten , Schoonjans An‐Sofie , Van De Walle Patricia , Hallemans Ann 
Published: January 2019

AimThe aim of this study is to describe the course of motor development in children with Dravet syndrome.MethodForty‐three participants (21 males, 22 females; mean age at last assessment 53.89mo±42.50mo) met the inclusion criteria of having a confirmed diagnosis of Dravet syndrome and presence of data on motor development. All data between 1985 and 2018 were derived retrospectively from their medical records. Gross motor milestones and motor age equivalents were used to describe motor development. Standardized neurodevelopmental assessment and the Bayley Scales of Infant Development defined the overall motor development. Peabody Developmental Motor Scales, Bruininks‐Oseretsky Test of Motor Proficiency, and the Beery‐Buktenica Developmental Test of Visual‐Motor Integration were used to describe development in specific motor domains.ResultsChildren with Dravet syndrome showed a delay in both sitting (seven out of 14) and walking independently (11 out of 25). Overall motor age equivalents revealed a delay in 29 out of 38 assessments (age 9–115mo). All assessments of children older than 2 years (16 out of 16) showed a delay. Gross motor delay was present in seven out of seven and fine motor delay in 10 out of 13 assessments (age 19–167mo).InterpretationMotor development is delayed in the majority of children with Dravet syndrome older than 2 years and increases with age.What this paper addsA delay in motor development is present in most children with Dravet syndrome older than 2 years.Large diversity in early gross motor milestones confirms heterogeneity in Dravet syndrome.
Aid‐supported governance reforms in Solomon Islands: Piecemeal progress or persistent stalemate?
Authors: Sahin Selver B. , Shahin Evgeniia 
Published: January 2019

AbstractMotivationDespite seeming donor–recipient consensus on the importance of effective governance, aid‐linked reforms often fall short of the expected outcomes. Solomon Islands provides a highly relevant case to explore the dynamics of institutional reform processes, and understand why, even in a relatively favourable operating environment, structural reforms are difficult to implement.PurposeThis article aims to provide empirically grounded analysis of key factors that hinder institutional change in fragile aid‐receiving countries by addressing the reciprocal (rather than unilateral) constraints and trade‐offs faced by both recipients and donors, and examining their implications for the emerging institutional trajectories in host states.Approach and MethodsThis study is based on the use of a single case study that involves in‐depth review of related academic and policy literature, and media reports through the lens of “mutual dependencies.”FindingsSolomon Islands’ recent experience with the regulation of Constituency Development Funds and tertiary scholarships makes it clear that by continuously postponing the implementation of relevant policies, domestic authorities try to avoid the potential costs institutional reforms are likely to create. Similarly, donors concerned about their own strategic interests and power relationships with other actors remain unable to enforce full implementation of such reforms. The process in Solomon Islands further confirms that political trade‐offs facing all actors in different forms have a constraining effect on the achievement of desired policy objectives.Policy ImplicationsPolicy reforms require domestic authorities to develop specific mechanisms that have the potential to secure popular support in favour of proposed structural changes. Donors need new and more evidence‐based approaches that may help balance between their strategic concerns and the achievement of institutional outcomes.
Quantifying uncertainty in the wild‐caught fisheries goal of the Ocean Health Index
Authors: Afflerbach Jamie C. , Frazier Melanie , Froehlich Halley E. , Anderson Sean C. , Halpern Benjamin S. 
Published: January 2019

AbstractSustainability indices are proliferating, both to help synthesize scientific understanding and inform policy. However, it remains poorly understood how such indices are affected by underlying assumptions of the data and modelling approaches used to compute indicator values. Here, we focus on one such indicator, the fisheries goal within the Ocean Health Index (OHI), which evaluates the sustainable provision of food from wild fisheries. We quantify uncertainty in the fisheries goal status arising from the (a) approach for estimating missing data (i.e., fish stocks with no status) and (b) reliance on a data‐limited method (catch‐MSY) to estimate stock status (i.e., B/BMSY). We also compare several other models to estimate B/BMSY, including an ensemble approach, to determine whether alternative models might reduce uncertainty and bias. We find that the current OHI fisheries goal model results in overly optimistic fisheries goal statuses. Uncertainty and bias can be reduced by (a) using a mean (vs. median) gap‐filling approach to estimate missing stock scores and (b) estimating fisheries status using the central tendency from a simulated distribution of status scores generated by a bootstrap approach that incorporates error in B/BMSY. This multitiered approach to measure and describe uncertainty improves the transparency and interpretation of the indicator and allows us to better understand uncertainty around our OHI fisheries model and outputs for country‐level interpretation and use.
Fish assemblage–environment relationships suggest differential trophic responses to heavy metal contamination
Authors: Krause Kevin P. , Wu Chin‐Lung , Chu Maria L. , Knouft Jason H. 
Published: January 2019

Abstract

While ecotoxicology has long recognised the importance of identifying levels at which contaminants pose threats to biota, most estimates of species responses to toxicants are derived from controlled laboratory studies and may hold limited relevance to natural systems. However, designing appropriate field‐based studies investigating contaminant induced changes in assemblages has been challenging, partially due to the difficulty in identifying comparable uncontaminated reference sites. The aim of this study is to characterise the effects of heavy metal contamination on natural fish assemblages using an ecologically relevant catchment‐scale design. We hypothesise that environmental variables, including discharge, sediment, and landscape variables, can be used to characterise differences in fish species richness and abundances between sites contaminated with heavy metals and uncontaminated reference sites.

We apply a geographic information systems approach that uses assemblage–environment relationships developed using hydrologic model outputs, land cover, and topographic data from uncontaminated reference sites to predict expected fish species richness and abundance at sites contaminated with heavy‐metals within the Big River catchment in south‐eastern Missouri, U.S.A. These predicted levels of richness and abundance are then compared to observed assemblages at contaminated sites to estimate the potential impacts of historical lead mining activities on freshwater taxa.

We developed models that characterised variation in Centrarchidae (bass and sunfish) richness and abundance, Cyprinidae (minnows) abundance, and Percidae (darters) richness using variables including streamflow regime, suspended sediment concentration, and land cover at uncontaminated sites. Using these relationships, we predicted expected fish species richness and abundance at heavy metal contaminated sites across the Big River catchment and found a significant reduction in centrarchid abundance from field‐collected data compared to predicted estimates.

Our results suggest that centrarchids, which tend to occupy a higher trophic level than cyprinids and percids, have lower abundances at sites contaminated with heavy metals than predicted by assemblage–environment relationships. These decreases in abundance are not associated with decreases in centrarchid species richness, cyprinid abundance, or percid richness.

This geographic information systems‐based approach provides a useful and ecologically relevant framework for understanding the response of taxa to the presence of contaminants without assuming habitat equivalence across sites. Our findings also suggest the need for further research regarding how heavy metals impact fishes of varying trophic levels in natural settings.
Full‐genome characterization of the RIVM‐HAV16‐090‐like hepatitis A virus strains recovered from Japanese men who have sex with men, with sporadic acute hepatitis A
Authors: Watanabe Shunji , Morimoto Naoki , Miura Kouichi , Takaoka Yoshinari , Nomoto Hiroaki , Tsukui Mamiko , Isoda Norio , Ohnishi Hiroshi , Nagashima Shigeo , Takahashi Masaharu , Okamoto Hiroaki , Yamamoto Hironori 
Published: January 2019

AimThe major transmission mode of hepatitis A virus (HAV) in Japan is the fecal–oral route by contaminated foods. In contrast, HAV infection is well documented as a sexually transmitted disease in Europe and North America. The present study was undertaken to determine the full‐genome sequence of HAV and trace the transmission route of HAV in Japanese men who have sex with men (MSM).MethodsIn 2018, we encountered three Japanese MSM with acute hepatitis A co‐infected with HIV for 4–12 years. Serum samples obtained from these patients were used for HAV full‐genome analyses.ResultsIsolated HAV strains were segregated into subgenotype IA. The three HAV strains shared 100% identity within the 481‐nucleotide partial sequence. The entire nucleotide sequence showed that the three strains were 99.97% similar to each other with only two nucleotide substitutions. At the amino acid level, the three strains differed from each other by only one or two amino acids. All three strains obtained in the present study were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries during 2015–2017. In addition, these 66 strains include the RIVM‐HAV16‐090 (EuroPride) strain, which has been involved in HAV outbreaks among MSM worldwide.ConclusionsWe determined for the first time the full‐genome sequence of HAV isolated from Japanese MSM with acute hepatitis A and found that the strains were identical to those from MSM worldwide. Thus, these HAV strains were imported to Japan from foreign countries through MSM.
DNA damage repair alterations are frequent in prostatic adenocarcinomas with focal pleomorphic giant‐cell features
Authors: Lotan Tamara L , Kaur Harsimar B , Alharbi Abdullah M , Pritchard Colin C , Epstein Jonathan I 
Published: January 2019

AimsProstatic adenocarcinomas with focal pleomorphic giant‐cell features constitute a rare tumour subtype with abysmal clinical outcomes. More than one‐third of patients with this histology die within a year of the initial diagnosis of prostate cancer. We aimed to perform molecular profiling of these tumors to identify potential therapeutic targets.Methods and resultsHere, we performed next‐generation sequencing with a highly validated targeted panel (UW‐OncoPlex) on somatic tumour DNA extracted from eight cases of prostatic adenocarcinoma with focal pleomorphic giant‐cell features, including cases with and without prior treatment for prostate cancer. We found that DNA damage repair mutations are common in this rare subset of prostate tumours, with two of eight having bi‐allelic pathogenic mutations in homologous DNA repair genes (including BRCA2 and NBN) and two of eight having bi‐allelic pathogenic mutations in mismatch repair genes (including MSH2 and MLH1).ConclusionThese data are consistent with emerging data showing that DNA repair alterations are enriched among castration‐resistant prostate cancer and aggressive subsets of primary tumours. Given that these patients are potential candidates for poly(ADP‐ribose) polymerase inhibitor and/or immune checkpoint blockade, and have a poor prognosis with standard therapy, we recommend that tumour and germline DNA sequencing with or without mismatch repair protein immunohistochemistry be considered for all prostatic adenocarcinomas with focal pleomorphic giant‐cell features.
The experience and role of partners in helping to meet the support needs of adolescents and young adults with cancer
Authors: Davies Jane 
Published: January 2019

AbstractAimTo explore the experiences and needs of partners who are supporting adolescents and young adults with cancer.The diagnosis of cancer at any age is significant. Uniquely, in adolescents and young adults this is set against the backdrop of early adult development. This is at a time when young people may be embarking on new experiences and the development of romantic relationships is no exception. There is limited evidence of how partners cope during this time and what their role is alongside how the relationship may change over time.DesignAn exploratory qualitative study using narrative enquiry.MethodsThe protocol was approved in February 2018 and data will be collected between May – December 2018. The theoretical approach will incorporate positioning theory by considering the contextual situation of the partner with reference to their stories, including their rights and duties. Two interviews will be undertaken which will be approximately 2 months apart, where participants will be asked to share their stories. They will also be given a diary at the end of the first interview to record their thoughts about their role and relationship. The diary and interview data will be thematically analysed.DiscussionIt is envisaged that the study will culminate in the identification of key themes which will illuminate the experiences, needs and roles of partners of adolescents and young adults with cancer.ImpactThese findings will inform the development of guidance which will help partners in the future in this area of practice.
Changes in health behaviours and health status of novice nurses during the first 2 years of work
Authors: Han Kihye , Kim Yeon‐Hee , Lee Hye Young , Cho Hyeonmi , Jung Young Sun 
Published: January 2019

AbstractAimsTo explore changes in health behaviours and health status of novice nurses during the first 2 years of work.BackgroundNovice nurses experience many difficulties in maintaining healthy behaviours while adapting to clinical settings. However, studies about the health of novice nurses have not focused on changes over time.DesignLongitudinal descriptive study with self‐reported questionnaires.MethodsData were collected from 493 novice nurses who started work between September 2014 ‐ December 2015 at a tertiary hospital in Seoul. Dietary behaviours, sleep, depressive symptoms, perceived stress and health status were measured at six time points during the first 2 years of work (the first day of orientation before ward placement, 6 weeks after starting work and 6, 12, 18 and 24 months of work). Changes were examined using means or percentages and 95% confidence intervals.ResultsUnhealthy dietary behaviours increased across 6 months, continuing for 2 years. Sleep quality and quantity, depressive symptoms, perceived stress and health status first worsened and then improved; however, they were worse than at baseline.ConclusionOrganizational support for novice nurses is urgently needed. Workplace health education programmes will help them adjust to rotating shift work and maintain better health status.
Intervention fidelity in postintensive care follow‐up consultations at ten sites in the RAPIT‐trial: A mixed‐methods evaluation
Authors: Jensen Janet F. , Overgaard Dorthe , Bestle Morten H. , Christensen Doris F. , Rattray Janice , Egerod Ingrid 
Published: January 2019

AbstractAimThe aim of the study was to evaluate intervention fidelity of nurses’ delivery of the RAPIT recovery program for postintensive care patients.BackgroundInterventions addressing patient problems after intensive care lack description of the process of delivery and the evidence of their effectiveness. This is needed to understand how these interventions work.DesignMultistage intervention framework in a mixed‐methods design. Intervention fidelity strategies were assessed for intervention design, training, delivery, receipt, and enactment with quantitative and qualitative methods inspired by the Medical Research Council and the National Institutes of Health Fidelity Framework.MethodsData collection was embedded in a multicenter randomized controlled trial to explore intervention fidelity of a recovery program (December 2012–February 2017). Ten Danish intensive care units participated in the RAPIT‐trial including 386 patients and 27 nurses. Quantitative data covered training and delivery. Qualitative data explored design, quality of delivery, receipt, and enactment seen from nurses’ and patients’ perspectives. Data were analysed statistically and by systematic deductive‐inductive thematic analysis.FindingsA framework for participatory enactment of a complex intervention was developed and demonstrated delivery with high consistent fidelity across sites. Low delivery doses and variations were related to the program, patient, provider nurses and context.ConclusionOur study provides insight into the process of intervention fidelity of a nurse‐led postintensive care recovery program and potentially enables professionals to understand key factors in cross‐site implementation. Although we demonstrate consistent delivery and variations suggest that some patients may benefit more than others.