bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate affects neighbour‐induced changes in leaf chemical defences and tree diversity–herbivory relationships
Authors: Poeydebat Charlotte , Jactel Hervé , Moreira Xoaquín , Koricheva Julia , Barsoum Nadia , Bauhus Jürgen , Eisenhauer Nico , Ferlian Olga , Francisco Marta , Gottschall Felix , Gravel Dominique , Mason Bill , Muiruri Evalyne , Muys Bart , Nock Charles , Paquette Alain , Ponette Quentin , Scherer‐Lorenzen Michael , Stokes Victoria , Staab Michael , Verheyen Kris , Castagneyrol Bastien
Published: October 2020

Associational resistance theory predicts that insect herbivory decreases with increasing tree diversity in forest ecosystems. However, the generality of this effect and its underlying mechanisms are still debated, particularly since evidence has accumulated that climate may influence the direction and strength of the relationship between diversity and herbivory.

We quantified insect leaf herbivory and leaf chemical defences (phenolic compounds) of silver birchBetula pendulain pure and mixed plots with different tree species composition across 12 tree diversity experiments in different climates. We investigated whether the effects of neighbouring tree species diversity on insect herbivory in birch, that is, associational effects, were dependent on the climatic context, and whether neighbour‐induced changes in birch chemical defences were involved in associational resistance to insect herbivory.

We showed that herbivory on birch decreased with tree species richness (i.e. associational resistance) in colder environments but that this relationship faded as mean annual temperature increased.

Birch leaf chemical defences increased with tree species richness but decreased with the phylogenetic distinctiveness of birch from its neighbours, particularly in warmer and more humid environments.

Herbivory was negatively correlated with leaf chemical defences, particularly when birch was associated with closely related species. The interactive effect of tree diversity and climate on herbivory was partially mediated by changes in leaf chemical defences.

Our findings confirm that tree species diversity can modify the leaf chemistry of a focal species, hence its quality for herbivores. They further stress that such neighbour‐induced changes are dependent on climate and that tree diversity effects on insect herbivory are partially mediated by these neighbour‐induced changes in chemical defences.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Genetic variation in resistance and high fecundity impede viral biocontrol of invasive fish
Authors: Mintram Kate S. , van Oosterhout Cock , Lighten Jackie
Published: October 2020

Common carp Cyprinus carpio is one of the top global invasive vertebrates and can cause significant ecological damage. The Australian Government's National Carp Control Program (NCCP) proposes to release Koi herpesvirus (KHV) to eradicate feral carp in one of the largest ecological interventions ever attempted. Ecological and human health risks have been highlighted regarding the release of a highly pathogenic viral biocontrol for an aquatic species. The efficacy of KHV has also been questioned, and it has not been demonstrated to produce lasting population reductions.

We developed an individual‐based model (IBM) to examine the ecological and evolutionary response of a carp population after KHV release. This simulated the interaction between fish life history, viral epidemiology, host genetic resistance and population demography to critically evaluate the impact of KHV release under optimal conditions and a ‘best‐case scenario’ for disease transmission.

KHV will rarely result in prolonged reductions or population extinctions. Crucially, realistic scenarios result in a rapidly rebounding population of resistant individuals. Additional measures aimed to reduce carp population recovery rate (e.g. with genetic engineering) require rapid efficacy to significantly reduce carp numbers alongside KHV.

Fish fecundity has an overwhelming influence on viral efficacy as a biocontrol agent when combined with genetic resistance within a population. A high probability of population extinction is only met when carp fecundity is reduced to 1% of biological observations.

Synthesis and applications. We use an individual‐based model to evaluate the efficacy of Koi herpesvirus biocontrol in Common Carp, and find that high host fecundity combined with genetic resistance results in rapid population rebound after initial large fish kills. Biocontrol approaches relying on natural selection lose efficacy over successive generations as resistance genes increase in frequency. Given the intense logistical effort and risks to ecosystems and human health associated with large fish kills after viral release, we suggest that sustained manual removal, alongside ecological restoration to favour recovery of native species, provides a risk‐free approach to reducing populations.
Common garden experiments to study local adaptation need to account for population structure
Authors: de Villemereuil Pierre , Gaggiotti Oscar E. , Goudet Jérôme
Published: October 2020

Common garden experiments are precious to study adaptive phenomenon and adaptive potential, in that they allow to study local adaptation without the confounding effect of phenotypic plasticity. The QST − FST comparison framework, comparing genetic differentiation at the phenotypic and molecular level, is the usual way to test and measure whether local adaptation influences phenotypic divergence between populations.

Here, we highlight that the assumptions behind the expected equality QST = FST under neutrality correspond to a very simple model of population genetics. While the equality might, on average, be robust to violation of such assumptions, more complex population structure can generate strong evolutionary noise.

Synthesis. We highlight recent methodological developments aimed at overcoming this issue and at providing a more general framework to detect local adaptation, using less restrictive assumptions. We invite empiricists to look into these methods and theorists to continue developing even more general methods.
Product differentiation and cost pass‐through: industry‐wide versus firm‐specific cost shocks
Authors: Bittmann Thomas , Loy Jens‐Peter , Anders Sven
Published: October 2020

This paper investigates the impact of product differentiation on firm‐specific and industry‐wide cost pass‐through in grocery retailing. We use attribute distance measures to model product differentiation based on a unique set of retail scanner data for ready‐to‐eat soup products in the Canadian market. Results from a panel error correction model suggest that product differentiation explains a significant share of the variation in the rate of cost pass‐through across products. More differentiated products are associated with lower rates of cost pass‐through of industry‐wide and higher pass‐through of firm‐specific costs shocks. The findings validate an oligopolistic model of product differentiation, where firms use differentiation as a non‐price competitive factor in strategic pricing decisions.
Evidence‐based juvenile justice programs and practices: A critical review
Authors: Elliott Delbert S. , Buckley Pamela R. , Gottfredson Denise C. , Hawkins J. David , Tolan Patrick H.
Published: October 2020

There is growing critical commentary and debate about the relative effectiveness of individual program and generic practice approaches to identifying evidence‐based interventions and their impact on the operation of the juvenile justice system. The central issue is whether both of these approaches to identifying evidence‐based interventions provide a valid and reliable guide to improving juvenile justice programming and, if so, what are the relative advantages and disadvantages of each? From a public policy perspective, should we be investing more heavily in one or the other, or treating them as effective complementary approaches and encourage both? We address each of these questions and offer some suggestions for improving the effectiveness of each approach.
Wetland Flowpaths Mediate Nitrogen and Phosphorus Concentrations across the Upper Mississippi River Basin
Authors: Mengistu Samson G. , Golden Heather E. , Lane Charles R. , Christensen Jay R. , Wine Michael L. , D’Amico Ellen , Prues Amy , Leibowitz Scott G. , Compton Jana E. , Weber Marc H. , Hill Ryan A.
Published: October 2020

Eutrophication, harmful algal blooms, and human health impacts are critical environmental challenges resulting from excess nitrogen and phosphorus in surface waters. Yet we have limited information regarding how wetland characteristics mediate water quality across watershed scales. We developed a large, novel set of spatial variables characterizing hydrological flowpaths from wetlands to streams, that is, “wetland hydrological transport variables,” to explore how wetlands statistically explain the variability in total nitrogen (TN) and total phosphorus (TP) concentrations across the Upper Mississippi River Basin (UMRB) in the United States. We found that wetland flowpath variables improved landscape‐to‐aquatic nutrient multilinear regression models (from R2 = 0.89 to 0.91 for TN; R2 = 0.53 to 0.84 for TP) and provided insights into potential processes governing how wetlands influence watershed‐scale TN and TP concentrations. Specifically, flowpath variables describing flow‐attenuating environments, for example, subsurface transport compared to overland flowpaths, were related to lower TN and TP concentrations. Frequent hydrological connections from wetlands to streams were also linked to low TP concentrations, which likely suggests a nutrient source limitation in some areas of the UMRB. Consideration of wetland flowpaths could inform management and conservation activities designed to reduce nutrient export to downstream waters.
Rapture‐ready darters: Choice of reference genome and genotyping method (whole‐genome or sequence capture) influence population genomic inference in Etheostoma
Authors: Reid Brendan N. , Moran Rachel L. , Kopack Christopher J. , Fitzpatrick Sarah W.
Published: October 2020

Researchers studying nonmodel organisms have an increasing number of methods available for generating genomic data. However, the applicability of different methods across species, as well as the effect of reference genome choice on population genomic inference, remain difficult to predict in many cases. We evaluated the impact of data type (whole‐genome vs. reduced representation) and reference genome choice on data quality and on population genomic and phylogenomic inference across several species of darters (subfamily Etheostomatinae), a highly diverse radiation of freshwater fish. We generated a high‐quality reference genome and developed a hybrid RADseq/sequence capture (Rapture) protocol for the Arkansas darter (Etheostoma cragini). Rapture data from 1,900 individuals spanning four darter species showed recovery of most loci across darter species at high depth and consistent estimates of heterozygosity regardless of reference genome choice. Loci with baits spanning both sides of the restriction enzyme cut site performed especially well across species. For low‐coverage whole‐genome data, choice of reference genome affected read depth and inferred heterozygosity. For similar amounts of sequence data, Rapture performed better at identifying fine‐scale genetic structure compared to whole‐genome sequencing. Rapture loci also recovered an accurate phylogeny for the study species and demonstrated high phylogenetic informativeness across the evolutionary history of the genus Etheostoma. Low cost and high cross‐species effectiveness regardless of reference genome suggest that Rapture and similar sequence capture methods may be worthwhile choices for studies of diverse species radiations.
msGBS: A new high‐throughput approach to quantify the relative species abundance in root samples of multispecies plant communities
Authors: Wagemaker Cornelis A. M. , Mommer Liesje , Visser Eric J. W. , Weigelt Alexandra , van Gurp Thomas P. , Postuma Maarten , Smit‐Tiekstra Annemiek E. , de Kroon Hans
Published: October 2020

Plant interactions are as important belowground as aboveground. Belowground plant interactions are however inherently difficult to quantify, as roots of different species are difficult to disentangle. Although for a couple of decades molecular techniques have been successfully applied to quantify root abundance, root identification and quantification in multispecies plant communities remains particularly challenging. Here we present a novel methodology, multispecies genotyping by sequencing (msGBS), as a next step to tackle this challenge. First, a multispecies meta‐reference database containing thousands of gDNA clusters per species is created from GBS derived High Throughput Sequencing (HTS) reads. Second, GBS derived HTS reads from multispecies root samples are mapped to this meta‐reference which, after a filter procedure to increase the taxonomic resolution, allows the parallel quantification of multiple species. The msGBS signal of 111 mock‐mixture root samples, with up to 8 plant species per sample, was used to calculate the within‐species abundance. Optional subsequent calibration yielded the across‐species abundance. The within‐ and across‐species abundances highly correlated (R2 range 0.72–0.94 and 0.85–0.98, respectively) to the biomass‐based species abundance. Compared to a qPCR based method which was previously used to analyse the same set of samples, msGBS provided similar results. Additional data on 11 congener species groups within 105 natural field root samples showed high taxonomic resolution of the method. msGBS is highly scalable in terms of sensitivity and species numbers within samples, which is a major advantage compared to the qPCR method and advances our tools to reveal hidden belowground interactions.
Inclusive Biomedical Innovation during the COVID‐19 Pandemic
Authors: Pannu Jaspreet
Published: October 2020

CEPI represents the first step towards Joseph Stiglitz’s vision, cited by Gubby, of a fund which provides large rewards for cures to common diseases such as malaria, and smaller rewards for rarer diseases or less innovative ‘me‐too’ drugs (Stiglitz, BMJ, 333, 2006, pp. 1279–1280). As a fledgling organization facing a Goliath, it deserves international support in its dual goals of incentivizing innovation and ensuring equitable access to biomedical advances.
Washington's liquor license system and alcohol‐related adverse health outcomes
Authors: Phillips Aryn Z. , Rodriguez Hector P. , Kerr William C. , Ahern Jennifer A.
Published: October 2020

Background and Aims

In June 2012, Washington state (USA) implemented Initiative 1183, privatizing liquor sales. As a result, off‐premises outlets increased from 330 to over 1400 and trading hours lengthened. Increased availability of liquor may lead to increased consumption. This study examines the impact of Initiative 1183 on alcohol‐related adverse health outcomes, measured by inpatient hospitalizations for alcohol‐related disorders and accidental injuries. It further assesses heterogeneity by urbanicity, because outlets increased most in metropolitan‐urban areas.

Design

County‐by‐quarter difference‐in‐difference linear regression models, estimated statewide and within metropolitan/rural strata.

Setting and Participants

Data are from AHRQ Healthcare Cost and Utilization State Inpatient Database 2010–2014 and HHS Area Health Resource File 2010–2014. Changes in the rates of hospitalizations in the 2.5 years following Initiative 1183 in Washington (n = 39 counties) are compared with changes in Oregon (n = 36 counties).

Measurements

County rates of hospitalizations per 1000 residents, including all records with any‐listed ICD‐9 Clinical Classification Software code denoting an alcohol‐related disorder, and all records with any‐listed external cause of injury code denoting an accidental injury.

Findings

The increase in the rate of accidental injury hospitalizations in Washington's metropolitan‐urban counties was on average 0.289 hospitalizations per 1000 county residents per quarter greater than the simultaneous increase observed in Oregon (P = 0.017). This result was robust to alternative specifications using a propensity score matched sample and synthetic control methods with data from other comparison states. The evidence did not suggest that Initiative 1183 was associated with differential changes in the rate of hospitalizations for alcohol‐related disorders in metropolitan‐urban (P = 0.941), non‐metropolitan‐urban (P = 0.162), or rural counties (P = 0.876).

Conclusions

Implementing Washington's Initiative 1183 (privatizing liquor sales) appears to have been associated with a significant increase in the rate of accidental injury hospitalizations in urban counties in that state but does not appear to be significantly associated with changes in the rate of hospitalizations specifically for alcohol‐related disorders within 2.5 years.
What is it like to live with a functional movement disorder? An interpretative phenomenological analysis of illness experiences from symptom onset to post‐diagnosis
Authors: Dosanjh Mandip , Alty Jane , Martin Carol , Latchford Gary , Graham Christopher D.
Published: October 2020

Objectives

With few empirically supported treatments, functional movement disorders (FMD) can be challenging to manage. To enable service providers to better support people with FMD, this study sought to understand the lived experience of FMD: to gain insight into how individuals make sense of their experience from symptom onset through medical evaluation and diagnosis to post‐diagnostic adaptation.

Design

An interpretative phenomenological analysis (IPA) of patient accounts of living with FMD.

Methods

Eight participants were recruited from a UK teaching hospital adult neurology service: seven females, varying in age (20s‐70s), FMD symptom type (tremor, dystonia, and tics), and time to diagnosis (10 ‐ 192 months). Semi‐structured interviews facilitated participant accounts of key events. Interviews lasted 75‐125 minutes and were transcribed verbatim.

Results

Three super‐ordinate themes were apparent. The first covered the experiences of onset (‘Something is wrong with me’), including loss of control ‐ with the affected body part often described as a separate entity ‐ threats to identity and disturbance in relationships. ‘At last! What now?’ outlined the bittersweet experience of diagnosis and of treatments. Third, ‘Living my life with it’ incorporated ongoing experiences of coping with symptoms. While some continued to struggle with the emotional impact of symptoms, others developed a compassionate relationship with their self and maintained satisfying activities.

Conclusions

FMD has a significant impact on patients’ relationships with themselves and others, which in turn affects well‐being. These findings suggest some nuanced additions to interventions (diagnosis, psychotherapy, physiotherapy, public education.)
Artificial intelligence and machine learning for protein toxicity prediction using proteomics data
Authors: Vishnoi Shubham , Matre Himani , Garg Prabha , Pandey Shubham Kumar
Published: October 2020

Instead of only focusing on the targeted drug delivery system, researchers have a great interest in developing peptide‐based therapies for the procurement of numerous class of diseases. The main idea behind this is to anchor the properties of the receptor to design peptide‐based therapeutics. As these macromolecules have distinct physicochemical properties over small molecules, it becomes an obligatory field for the treatment of diseases. For this, various in silico models have been developed to speculate the proteins by virtue of the application of machine learning and artificial intelligence. By analysing the properties and structural alert of toxic proteins, researchers aim to dissert some of the mechanisms of protein toxicity from which therapeutic insights may be drawn. Numerous models already exist worldwide emphasizing themselves as leading paramount for toxicity prediction in protein macromolecules. Few of them comparatively compete with the other predictive protein toxicity models and convincingly give a high‐performance result in terms of accuracy. But their foundation is quite ambiguous, and varying approaches are found at the level of toxicoproteomic data utilization while building a machine learning model. In this review work, we present the contribution of artificial intelligence and machine learning approaches in prediction of protein toxicity using proteomics data.
Outcomes following repeat exenteration for locally advanced pelvic malignancy
Authors: Blake Joshua , Koh Cherry E. , Steffens Daniel , De Robles Marie Shella , Brown Kilian , Lee Peter , Austin Kirk , Solomon Michael J.
Published: October 2020

Aim

This study aims to assess surgical outcomes and survival following first, second and third pelvic exenterations for pelvic malignancy.

Method

Consecutive patients undergoing pelvic exenteration for pelvic malignancy at a quaternary referral centre from January 1994 and December 2017 were included. Demographics and surgical outcomes were compared between patients who underwent first, second and third pelvic exenterations by generalized mixed modelling with repeated measures. Survival was assessed using Cox proportional hazards models and Kaplan–Meier plots.

Results

Of the 642 exenterations reviewed, 29 (4.5%) were second and 6 (0.9%) were third exenterations. Patients selected for repeat exenteration were more likely to have asymptomatic local recurrences detected on routine surveillance (P < 0.001). Postoperative wound complications increased with repeat exenteration (6%, 17%, 33%; P = 0.003, respectively). Additionally, postoperative length of stay increased from 27 to 38 and 48 days, respectively (P = 0.004). Median survival from first exenteration was 4.75, 5.30 and 8.14 years respectively amongst first, second and third exenteration cohorts (P = 0.849). Median survival from the most recent exenteration was 4.75 years after a first exenteration, 2.02 years after a second exenteration and 1.45 years after a third exenteration (P = 0.0546).

Conclusion

This study demonstrates that repeat exenteration for recurrent pelvic malignancy is feasible but is associated with increased complication rates and length of admission and reduced likelihood of attaining R0 margin. Moreover, these data indicate that repeat exenteration does not afford a survival advantage compared with patients having a single exenteration. These data suggest that repeat exenteration for recurrent pelvic malignancy may be of questionable therapeutic value.
How colour‐deficient observers see things, or not.
Authors: Eschbach Reiner
Published: October 2020

Colour deficiency or, colloquially, colour blindness, is common and has been observed and described in the scientific literature for ca. 200 years. In more recent times, algorithms have been developed that simulate the effect of colour deficiency to a colour‐normal observer. Sometimes these algorithms are used to indicate potential problems in the colour design, but often the implicit assumption is that a colour‐deficient observer actually sees things that way. But do they? This paper questions some of the underlying assumptions of the algorithms.
Deciphering the COVID‐19 cytokine storm: Systematic review and meta‐analysis
Authors: Mulchandani Rubina , Lyngdoh Tanica , Kakkar Ashish Kumar
Published: October 2020

Introduction

The coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine storm, contributing to ARDS, multiple‐organ failure and, in the most severe cases, death. We aimed to quantify the differences in the circulating levels of major inflammatory and immunological markers between severe and nonsevere COVID‐19 patients.

Methods

Relevant studies were identified from PubMed, EMBASE, Web of Science, SCOPUS and preprint servers. Risk of bias was assessed for each study, using appropriate checklists. All studies were described qualitatively and a subset was included in the meta‐analysis, using forest plots.

Results

Based on 23 studies, mean cytokine levels were significantly higher (IL‐6: MD, 19.55 pg/mL; CI, 14.80, 24.30; IL‐8: MD, 19.18 pg/mL; CI, 2.94, 35.43; IL‐10: MD, 3.66 pg/mL; CI, 2.41, 4.92; IL‐2R: MD, 521.36 U/mL; CI, 87.15, 955.57; and TNF‐alpha: MD, 1.11 pg/mL; CI, 0.07, 2.15) and T‐lymphocyte levels were significantly lower (CD4+ T cells: MD, −165.28 cells/µL; CI, −207.58, −122.97; CD8+ T cells: MD, −106.51 cells/µL; CI, −128.59, −84.43) among severe cases as compared to nonsevere ones. There was heterogeneity across studies due to small sample sizes and nonuniformity in outcome assessment and varied definitions of disease severity. The overall quality of studies was sub‐optimal.

Conclusion

Severe COVID‐19 is characterized by significantly increased levels of pro‐inflammatory cytokines and reduced T lymphocytes. Well‐designed and adequately powered prospective studies are needed to amplify the current evidence and provide definitive answers to dilemmas regarding timing and type of anti‐COVID‐19 therapy particularly in severe patients.
The Recovering Quality of Life 10‐item (ReQoL‐10) scale in a first‐episode psychosis population: Validation and implications for patient‐reported outcome measures (PROMs)
Authors: Chua Yi Chian , Wong Horng Hien , Abdin Edimansyah , Vaingankar Janhavi , Shahwan Shazana , Cetty Laxman , Yong Yee Huei , Hon Charlene , Lee Helen , Tang Charmaine , Verma Swapna , Subramaniam Mythily
Published: October 2020

Aim

This study aimed to examine the psychometric performance of the Recovering Quality of Life scale 10‐item version (ReQoL‐10) using a sample from a Singapore first‐episode psychosis intervention program, to explore its clinical and sociodemographic correlates, and to discuss its utility as a patient‐reported outcome measure (PROM).

Methods

Sociodemographic data, duration of untreated psychosis (DUP), and diagnosis were collected from 300 participants. Clinical data, which included baseline and current scores on the Patient Health Questionnaire 9‐item version, EuroQoL‐5 Dimension 3‐level version, Positive and Negative Syndrome Scale, and Global Assessment of Functioning scale, were extracted. The ReQoL‐10 was tested for structural validity, internal consistency, and construct validity, and a multiple linear regression determined if any of the baseline factors were statistically significant predictors of the total ReQoL‐10 scores.

Results

The mean (SD) total ReQoL‐10 score of the sample was 27.8 (7.8). Confirmatory factor analysis confirmed the bifactor model structure of the ReQoL‐10. The instrument demonstrated good internal consistency and adequate construct validity. Being older was associated with higher total ReQoL‐10 scores, while being married, having a highest educational level of vocational/diploma, longer DUP, and a diagnosis of affective psychosis were associated with lower total ReQoL‐10 scores.

Conclusions

This study has validated the ReQoL‐10 as suitable for routine use to measure recovery‐specific quality of life in a psychiatric setting among patients with first‐episode psychosis, and is a potential tool to initiate recovery conversations. As a PROM, it can facilitate shared decision making, in line with efforts to evaluate and improve quality of care.
Which factors delay treatment in bipolar disorder? A nationwide study focussed on duration of untreated illness
Authors: Buoli Massimiliano , Cesana Bruno Mario , Fagiolini Andrea , Albert Umberto , Maina Giuseppe , de Bartolomeis Andrea , Pompili Maurizio , Bondi Emi , Steardo Luca , Amore Mario , Bellomo Antonello , Bertolino Alessandro , Di Nicola Marco , Di Sciascio Guido , Fiorillo Andrea , Rocca Paola , Sacchetti Emilio , Sani Gabriele , Siracusano Alberto , Di Lorenzo Giorgio , Tortorella Alfonso , Altamura Alfredo Carlo , Dell'Osso Bernardo ,   ISBD Italian Chapter Epidemiologic Group
Published: October 2020

Aim

The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD).

Method

A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one‐way analyses of variance or Kruskal‐Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another.

Results

An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = −.52, P < .001). DUI resulted to be longer in patients with: at least one lifetime marriage/partnership (P = .009), a first psychiatric diagnosis of major depressive disorder or substance abuse (P < .001), a depressive polarity of first episode (P < .001), no lifetime psychotic symptoms (P < .001), BD type 2 (P < .001), more lifetime depressive/hypomanic episodes (P < .001), less lifetime manic episodes (P < .001), presence of suicide attempts (P = .004), depressive episodes (P < .001), hypomanic episodes (P = .004), hospitalizations (P = .011) in the last year.

Conclusions

Different factors resulted to increase the length of DUI in a nationwide sample of bipolar patients. In addition, the DUI was found to show a negative long‐term effect in terms of more suicidal behaviour, more probability of hospitalization and depressive/hypomanic episodes.
Magnetization transfer ratio: a quantitative imaging biomarker for 5q spinal muscular atrophy
Authors: Kollmer J. , Kessler T. , Sam G. , Hayes J. M. , Lentz S. I. , Heiland S. , Bendszus M. , Wick W. , Weiler M.
Published: October 2020

Background and purpose

We quantified peripheral nerve lesions in adults with 5q‐linked spinal muscular atrophy (SMA) type 3 by analysing the magnetization transfer ratio (MTR) of the sciatic nerve, and tested its potential as a novel biomarker for macromolecular changes.

Methods

Eighteen adults with SMA 3 (50% SMA 3a, 50% SMA 3b) and 18 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging in a 3‐Tesla magnetic resonance scanner. Two axial three‐dimensional gradient echo sequences, with and without an off‐resonance saturation rapid frequency pulse, were performed at the right distal thigh. Sciatic nerve regions of interest were manually traced on 10 consecutive axial slices in the images generated without off‐resonance saturation, and then transferred to corresponding slices generated by the sequence with the off‐resonance saturation pulse. Subsequently, MTR and cross‐sectional areas (CSAs) of the sciatic nerve were analysed. In addition, detailed neurologic, physiotherapeutic and electrophysiologic examinations were conducted in all patients.

Results

Sciatic nerve MTR and CSA reliably differentiated between healthy controls and SMA 3, 3a or 3b. MTR was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0020) than in respective controls. In patients with SMA 3, MTR correlated with all clinical scores, and arm nerve compound motor action potentials (CMAPs). CSA was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0006) than in controls, but did not correlate with clinical scores or electrophysiologic results.

Conclusions

Magnetization transfer ratio is a novel imaging marker that quantifies macromolecular nerve changes in SMA 3, and positively correlates with clinical scores and CMAPs.
Detection of disability worsening in relapsing‐remitting multiple sclerosis patients: a real‐world roving Expanded Disability Status Scale reference analysis from the Italian Multiple Sclerosis Register
Authors: Lepore V. , Bosetti C. , Santucci C. , Iaffaldano P. , Trojano M. , Mosconi P. ,   the Italian Multiple Sclerosis Register Centers Group, the Scientific Committee of Italian SM Register
Published: October 2020

Background and purpose

In relapsing‐remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6‐month confirmed disability‐worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real‐world setting.

Methods

A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability‐worsening events and of confirmed disability‐worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months.

Results

Using a fixed baseline EDSS reference, the cumulative probability of 6‐year overall confirmed disability‐worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability‐worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability‐worsening events).

Conclusions

In a real‐world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability‐worsening events unrelated to relapse in RRMS patients.
Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis
Authors: Raftopoulos R. , Kuhle J. , Grant D. , Hickman S. J. , Altmann D. R. , Leppert D. , Blennow K. , Zetterberg H. , Kapoor R. , Giovannoni G. , Gnanapavan S.
Published: October 2020

Background

A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses.

Methods

Eighty‐six acute ON cases were randomized to receive phenytoin (4–6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL).

Results

Sixty‐four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo – phenytoin was −44 pg/ml at 3 months (P = 0.019) and −27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and −1.6 pg/ml at 6 months (P = 0.766).

Conclusions

At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized.
Effect of artificial aging on high translucent dental zirconia: simulation of early failure
Authors: Skjold Anneli , Schriwer Christian , Gjerdet Nils R. , Øilo Marit
Published: October 2020

Higher yttria content enhances the translucency and appearance of dental zirconia materials. Alterations in material composition also affect mechanical properties. The aim of this study was to compare the fracture load after artificial short‐term aging of monolithic, full‐contour zirconia crowns with different amounts of yttria‐stabilization. Sixty crowns (thirty super high translucent crowns (5Y‐Z) and thirty high translucent crowns (3Y‐Z)) were produced to fit a model of a premolar with a shallow chamfer preparation. The crowns were cemented with self‐adhesive resin cement on composite abutments. For each zirconia type, three groups of crowns (n = 10) were allocated to: (i) cyclic loading (200 N, 1 Hz, 30,000 cycles), (ii) hydrothermal aging (3 × 20 min, 134°C 3.2 bar), or (iii) no treatment (control). Surviving crowns from the aging process were quasistatically loaded until fracture. The 3Y‐Z crowns had statistically significantly higher fracture values (3,449 N) than the 5Y‐Z crowns (1,938 N). The aging procedures did not affect load at fracture. Fractographic analysis showed that fractures started either at the crown margin or at the occlusal intaglio area. Higher yttria content leads to a reduction in material strength and damage tolerance, and this should be reflected in recommendations for clinical use.
Defending, prospecting or reacting? Strategic management during cutbacks in the Dutch penitentiary sector
Authors: Schmidt Eduard , Van de Walle Steven
Published: October 2020

We analyse how public managers interact with external stakeholders during cutbacks. Relying on strategic management scholarship, we develop an argument on why public managers decide for a closed or an open cutback management strategy. In the former, they try to close off the process for external stakeholders, whereas, in the latter, they actively engage with external stakeholders. A multiple qualitative case study of cutbacks in the Dutch prison sector shows that the choice to actively engage with external stakeholders depends on public managers’ position within the organisational hierarchy, their perception of the stakeholder environment and their process goals. The factors that impact public managers strategic stance can be categorised as contextual, institutional and organisational and environmental determinants. The article contributes to the scholarship on cutback management, accounting and strategic management and shows why these perspectives should be bridged in order to understand managerial behaviour during cutbacks
Decline of unionid mussels enhances hybridisation of native and introduced bitterling fish species through competition for breeding substrate
Authors: Hata Hiroki , Uemura Yohsuke , Ouchi Kaito
Published: October 2020

Bitterling fishes (Subfamily: Acheilognathinae) spawn in the gills of living freshwater mussels and obligately depend on the mussels for reproduction. On the Matsuyama Plain, Japan, populations of unionid mussels—Pronodularia japanensis, Nodularia douglasiae, and Sinanodonta lauta—have decreased rapidly over the past 30 years. Simultaneously, the population of a native bitterling fish, Tanakia lanceolata, which depends on the three unionids as a breeding substrate, has decreased. Furthermore, a congeneric bitterling, Tanakia limbata, has been artificially introduced, and hybridisation and genetic introgression occur between them. Here, we hypothesised that decline of the unionids has enhanced this invasive hybridisation through competition for the breeding substrate.

Three study sites were set in three streams on the Matsuyama Plain. We collected adult bitterling fishes (native T. lanceolata, introduced T. limbata, and foreign Rhodeus ocellatus ocellatus) once a week from April to October 2013 to measure their densities in streams and to examine seasonal differences in female ovipositor length, which elongates in the breeding season. Simultaneously, we set quadrats and captured unionids and measured environmental conditions. Each unionid individual was kept separately in its own aquarium to collect ejected bitterling eggs/larvae. Tanakia eggs and larvae were genotyped using six microsatellite markers and the mitochondrial cytochrome b gene.

Introduced T. limbata was more abundant, had a longer breeding period, and produced more juveniles than native T. lanceolata. Hybrids between the two species occurred at all sites, and in total 101 of the 837 juveniles genotyped were hybrids. The density of P. japanensis was low, at most 0.42 individuals/m2. Nodularia douglasiae and S. lauta have nearly or totally disappeared from these sites. Hybrid clutches of Tanakia species occurred more frequently where the local density of P. japanensis was low. Mussels were apparently overused and used simultaneously by three species of bitterlings.

Decline of freshwater unionid populations has enhanced hybridisation of native and invasive bitterling fishes through increasing competition for breeding substrate. We showed that rapid decline of host mussel species and introduction of an invasive congener have interacted to cause a rapid decline of native bitterling fish.

Degradation of habitat and the introduction of invasive species interact to cause a cascade of extinctions in native species. In our study, obligate parasite species are threatened because the host species are disappearing, which means there is a serious threat of coextinction.
Evaluating international Haemophilia Joint Health Score (HJHS) results combined with expert opinion: Options for a shorter HJHS
Authors: Kuijlaars Isolde A.R. , van der Net Janjaap , Feldman Brian M. , Aspdahl Magnus , Bladen Melanie , de Boer Wypke , Cuesta‐Barriuso Rubén , Matlary Ruth E.D. , Funk Sharon M. , Hilliard Pamela , John Judy A. , Kempton Christine L. , de Kleijn Piet , Manco‐Johnson Marilyn , Petrini Pia , Poonnoose Pradeep , St‐Louis Jean , Thomas Sylvia , Timmer Merel A. , Trakymiene Sonata Saulyte , van Vlimmeren Leo , Fischer Kathelijn
Published: October 2020

Introduction

The Hemophilia Joint Health Score (HJHS) was developed to detect early changes in joint health in children and adolescents with haemophilia. The HJHS is considered by some to be too time consuming for clinical use and this may limit broad adoption.

Aim

This study was a first step to develop a shorter and/or more convenient version of the HJHS for the measurement of joint function in children and young adults with haemophilia, by combining real‐life data and expert opinion.

Methods

A cross‐sectional multicenter secondary analysis on pooled data of published studies using the HJHS (0‐124, optimum score 0) in persons with haemophilia A/B aged 4‐30 was performed. Least informative items, scoring options and/or joints were identified. An expert group of 19 international multidisciplinary experts evaluated the results and voted on suggestions for adaptations in a structured meeting (consensus set at ≥ 80%).

Results

Original data on 499 persons with haemophilia from 7 studies were evaluated. Median age was 15.0 years [range 4.0‐29.9], 83.2% had severe haemophilia and 61.5% received prophylaxis. Median (IQR) HJHS total was 6.0 (1.0‐17.0). The items 'duration swelling' and 'crepitus' were identified as clinically less informative and appointed as candidates for reduction.

Conclusion

Analysis of 499 children and young adults with haemophilia showed that the HJHS is able to discriminate between children and adults and different treatment regimens. Reduction of the items 'duration swelling' and 'crepitus' resulted in the HJHSshort, which had the same discriminative ability. Additional steps are needed to achieve a substantially shorter HJHS assessment.
MiR‐590‐3p regulates cardiomyocyte P19CL6 proliferation, apoptosis and differentiation in vitro by targeting PTPN1 via JNK/STAT/NF‐kB pathway
Authors: Wang Fanshun , Zhang Hongqiang , Wang Chunsheng
Published: October 2020

Cardiomyocyte differentiation is a multi‐step process which involves a number of signalling pathways. microRNAs exhibit regulatory functions in various diseases and are involved in the signalling pathways in multiple physiological processes, but the specific functions of particular mRNAs is often not fully understood. of an example of this is that the role of miR‐590‐3p in the differentiation of cardiomyocytes remains unclear. In the current study, RT‐qPCR was used to determine the expression of miR‐590‐3p in cardiomyocytes differentiated from the embryonic carcinoma cell line P19CL6. MTT, EdU, caspase‐3 activity and flow cytometry assays were performed to examine the influence of miR‐590‐3p on cell behaviour. A luciferase assay was used to confirm binding between miR‐590‐3p and PTPN1. Western blotting was used to determine the relationship between the JNK/STAT/NF‐kB pathway and PTPN1. The results inferred that miR‐590‐3p became heavily expressed in differentiated P19CL6. Knockdown miR‐590‐3p suppressed the cell proliferation while at the same time, accelerated apoptosis. Moreover, PTPN1 was identified as the target of miR‐590‐3p. More importantly, PTPN1 overexpression activated the JNK/STAT/NF‐kB pathway and limited the differentiation of P19CL6. Thus the conclusions from this study are that miR‐590‐3p has the potential to regulate the proliferation, apoptosis and differentiation of cardiomyocyte P19CL6 in vitro by targeting PTPN1 via the JNK/STAT/NF‐kB pathway.
Labor‐eliminating technical change in a developing economy
Authors: Gilbert John , Oladi Reza
Published: October 2020

Developing countries face significant challenges arising from automation. While the trade theory literature has tended to focus on factor‐neutral and factor‐augmenting technical change, automation processes suggest another form of technical change is relevant: factor‐eliminating. We explore the impact of a labor‐eliminating technical change in the context of a small developing economy. Unlike labor‐augmenting technical changes, labor‐eliminating technical changes are not necessarily cost‐reducing, and thus will not necessarily be adopted. A manufacturing wage held artificially higher than at the market‐clearing level, as in the Harris–Todaro framework, increases the incentive to automate. We establish the conditions under which firms will adopt a labor‐eliminating technology, and describe the resulting changes in equilibrium outcomes. Under plausible circumstances, automation can actually lower output, and may raise both the rate and level of unemployment. Immiserizing growth becomes a possibility, and can be tied directly to the underlying wage distortion.
Utility of FLAER and CD157 in a five‐color single‐tube high sensitivity assay, for diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)—A standalone flow cytometry laboratory experience
Authors: Seth Neha , Mahajan Vidisha , Kedia Shweta , Sutar Archana , Sehgal Kunal
Published: October 2020

Background

FLAER‐based flow cytometry assay is considered the gold standard for diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). CD157 is a recently reported marker for GPI‐anchored protein found both on neutrophils and monocytes. This study highlights the robustness of FLAER and CD157 combination to identify PNH clones in a high sensitivity assay. Though rare, the data shown highlight the presence of CD157 negativity in few cases re‐emphasizing the importance of FLAER for PNH diagnosis.

Methods

A single 5‐color tube—FLAER Alexa488/ CD157PE/ CD15PECy5/ CD64PE‐Cy7 & CD45APCH7—was used for a high sensitivity PNH assay.

Results

Of 364 cases, 59(16.2%) cases had PNH clone in both granulocytes and monocytes. PNH clone sizes ranged from 0.02% to 96.6% in granulocytes and 0.07% to 96.3% in monocytes based on their FLAER‐negative, CD157‐negative phenotype. Twenty‐two of the 59 PNH cases (37.3%) had WBC clone size of <1%. In addition, there were 10 cases which showed absence of CD 157 expression on both granulocytes and monocytes but on FLAER staining showed normal staining patterns. Three of these ten cases also showed a PNH clone based on absence of FLAER expression on both granulocytes and monocytes.

Conclusion

FLAER and CD157 is a robust combination for diagnosis of clinical and subclinical PNH. Absence of CD157 expression in normal WBCs, though rare, should be kept in mind and re‐emphasizes the importance of FLAER for the high sensitivity PNH assay.