bluuebunny/crossref_metadata_2025 huggingface dataset:
Graph-Theoretical Formulation of the Generalized Epitope-based Vaccine Design Problem
Authors: Dorigatti Emilio , Schubert Benjamin
Published: November 2019

Epitope-based vaccines have revolutionized vaccine research in the last decades. Due to their complex nature, bioinformatics plays a pivotal role in their development. However, existing algorithms address only specific parts of the design process or are unable to provide formal guarantees on the quality of the solution. Here we present a unifying formalism of the general epitope vaccine design problem that tackles all phases of the design process simultaneously and combines all prevalent design principles. We then demonstrate how to formulate the developed formalism as an integer linear program which guarantees optimality of the designs. This makes it possible to explore new regions of the vaccine design space, analyze the trade-offs between the design phases, and balance the many requirements of vaccines.
Global transcriptome analysis reveals circadian control of splicing events in Arabidopsis thaliana
Authors: Romanowski Andrés , Schlaen Rubén G. , Perez-Santangelo Soledad , Mancini Estefanía , Yanovsky Marcelo J.
Published: November 2019

The circadian clock of Arabidopsis thaliana controls many physiological and molecular processes, allowing plants to anticipate daily changes in their environment. However, developing a detailed understanding of how oscillations in mRNA levels are connected to oscillations in post-transcriptional processes, such as splicing, has remained a challenge.

Here we applied a combined approach using deep transcriptome sequencing and bioinformatics tools to identify novel circadian regulated genes and splicing events.

Using a stringent approach, we identified 300 intron retention, 8 exon skipping, 79 alternative 3’ splice site usage, 48 alternative 5’ splice site usage, and 350 multiple (more than one event type) annotated events under circadian regulation. We also found 7 and 721 novel alternative exonic and intronic events. Depletion of the circadian regulated splicing factor AtSPF30 homolog, resulted in the disruption of a subset of clock controlled splicing events.

Altogether, our global circadian RNA-seq coupled with an in silico, event centred, splicing analysis tool offers a new approach for studying the interplay between the circadian clock and the splicing machinery at a global scale. The identification of many circadian regulated splicing events broadens our current understanding of the level of control that the circadian clock has over this posttranscriptional regulatory layer.
Using MAP-Elites to Optimize Self-Assembling Behaviors in a Swarm of Bio-micro-robots
Authors: Cazenille Leo , Bredeche Nicolas , Aubert-Kato Nathanael
Published: November 2019

We are interested in programming a swarm of molecular robots that can perform self-assembly to form specific shapes at a specific location. Programming such robot swarms is challenging for two reasons. First, the goal is to optimize both the parameters and the structure of chemical reaction networks. Second, the search space is both high-dimensional and deceptive. In this paper, we show that MAP-Elites, an algorithm that searches for both high-performing and diverse solutions, outperforms previous state-of-the-art optimization methods.
Behavioral traits that define social dominance are the same that reduce social influence in a consensus task
Authors: Rodriguez-Santiago Mariana , Nührenberg Paul , Derry James , Deussen Oliver , Garrison Linda K , Garza Sylvia F , Francisco Fritz , Hofmann Hans A , Jordan Alex
Published: November 2019

In many species, cultures, and contexts, social dominance reflects the ability to exert influence over others, and the question of what makes an effective leader is pertinent to a range of disciplines and contexts. While dominant individuals are often assumed to be most influential, the behavioral traits that make them dominant may also make them socially aversive and thereby reduce their influence. Here we examine the influence of dominant and subordinate males on group behavior in different social contexts using the cichlid fish Astatotilapia burtoni. We find that phenotypically dominant males display behavioral traits that typify leadership across taxonomic systems – aggressive, social centrality, and movement leadership, while subordinate males are passive, socially peripheral, and have little influence over movement. However, in a more complex group-consensus task involving visual cue associations, subordinate males become the most effective agents of social change. We find that dominant males are spatially distant and have lower signal-to-noise ratios of informative behavior in the association task, potentially interfering with their ability to generate group-consensus. In contrast, subordinate males are physically close to other group members, have high signal-to-noise behaviors in the association task, and visual connectivity to other group members equal to that of dominant males. The attributes that define effective social influence are therefore highly context-specific, with socially and phenotypically dominant males being influential in routine but not complex social scenarios. These results demonstrate that behavioral traits that are typical of socially dominant individuals may actually reduce their social influence in other contexts.

Significance Statement

The attributes that allow individuals to attain positions of social power and dominance are common across many vertebrate social systems – aggression, intimidation, coercion. Yet these traits are socially aversive, and can make dominant individuals poor agents of social change. In a vertebrate system (social cichlid fish) we show that dominant males are aggressive, socially central, and lead group movement. Yet dominant males are poor effectors of consensus in an more sophisticated association task compared with passive, socially-peripheral subordinate males. The most effective agents of social influence possess behavioral traits opposite of those typically found in position of social dominance, suggesting the behavioral processes that generate social dominance may simultaneously place the most ineffective leaders in positions of power.
Full Water‐Cycle Monitoring in an Urban Catchment Reveals Unexpected Water Transfers (Detroit MI, USA)
Authors: Hoard Christopher J. , Haefner Ralph J. , Shuster William D. , Pieschek Rachel L. , Beeler Stephanie
Published: November 2019

A goal in urban water management is to reduce the volume of stormwater runoff in urban systems and the effect of combined sewer overflows into receiving waters. Effective management of stormwater runoff in urban systems requires an accounting of various components of the urban water balance. To that end, precipitation, evapotranspiration (ET), sewer flow, and groundwater in a 3.40‐hectare sewershed in Detroit, Michigan were monitored to capture the response of the sewershed to stormwater flow prior to implementation of stormwater control measures. Monitoring results indicate that stormflow in sewers was not initiated unless rain depth was 3.6 mm or greater. ET removed more than 40% of the precipitation in the sewershed, whereas pipe flow accounted for 19%–85% of the losses. Flows within the sewer that could not be associated with direct precipitation indicate an unexpected exchange of water between the leaky sewer and the groundwater system, pathways through abandoned or failing residential infrastructure, or a combination of both. Groundwater data indicate that groundwater flows into the leaky combined sewer rather than out. This research demonstrates that urban hydrologic fluxes can modulate the local water cycle in complex ways which affect the efficiency of the wastewater system, effectiveness of stormwater management, and, ultimately, public health.
Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey
Authors: Barrière David André , Boumezbeur Fawzi , Dalmann Romain , Cadeddu Roberto , Richard Damien , Pinguet Jérémy , Daulhac Laurence , Sarret Philippe , Whittingstall Kevin , Keller Matthieu , Mériaux Sébastien , Eschalier Alain , Mallet Christophe
Published: November 2019

Background and Purpose

We previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N‐(4‐hydroxyphenyl)‐5Z,8Z,11Z,14Z‐eicosatetraenamide) to activate CB1 receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms supporting paracetamol‐induced analgesia remain unknown.

Experimental Approach

The effects of paracetamol on brain function in Sprague‐Dawley rats were determined by functional MRI. Levels of neurotransmitters in the periaqueductal grey (PAG) were measured using in vivo 1H‐NMR and microdialysis. Analgesic effects of paracetamol were assessed by behavioural tests and challenged with different inhibitors, administered systemically or microinjected in the PAG.

Key Results

Paracetamol decreased the connectivity of major brain structures involved in pain processing (insula, somatosensory cortex, amygdala, hypothalamus, and the PAG). This effect was particularly prominent in the PAG, where paracetamol, after conversion to AM404, (a) modulated neuronal activity and functional connectivity, (b) promoted GABA and glutamate release, and (c) activated a TRPV1 channel‐mGlu5 receptor‐PLC‐DAGL‐CB1 receptor signalling cascade to exert its analgesic effects.

Conclusions and Implications

The elucidation of the mechanism of action of paracetamol as an analgesic paves the way for pharmacological innovations to improve the pharmacopoeia of analgesic agents.
IFN‐γ +874T/A polymorphism increases susceptibility to post‐traumatic osteomyelitis
Authors: Zhao Xing‐qi , Jiang Nan , Hu Yan‐jun , Yu Bin
Published: November 2019

Immunological inflammatory reaction is one of the key links in the occurrence and development of post‐traumatic osteomyelitis after microbial invasion. Growing evidence suggests complex interactions between IFN‐γ and bone remodelling cells. However, potential association of IFN‐γ gene polymorphism with susceptibility to post‐traumatic osteomyelitis remains unclear. This study aimed to investigate the potential link between IFN‐γ +874T/A polymorphism and risk of developing post‐traumatic osteomyelitis. A total of 189 patients with post‐traumatic osteomyelitis and 200 healthy controls were enrolled for genotyping using the SNaPshot genotyping method. Statistically significant associations were found between the gene polymorphism and the risk of post‐traumatic osteomyelitis by dominant model (AA + AT vs. TT, OR = 1.820, p = .017) and heterozygous model (AT vs. TT, OR = 1.781, p = .029). Moreover, the frequency of mutant allele A was significantly higher in the patients than that in the healthy controls (15.07% vs. 9.25%, OR = 1.742, p = .013). IFN‐γ +874T/A polymorphism may contribute to the increased susceptibility to post‐traumatic osteomyelitis.
Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence
Authors: Wei Shupei , Liu Lili , Chen Zhiyu , Yin Wenli , Liu Yingzi , Ouyang Qianying , Zeng Feiyue , Nie Yingjie , Chen Tao
Published: November 2019

Glioma is a common brain malignancy for which new drug development is urgently needed because of radiotherapy and drug resistance. Recent studies have demonstrated that artemisinin (ARS) compounds can display antiglioma activity, but the mechanisms are poorly understood. Using cell lines and mouse models, we investigated the effects of the most soluble ARS analogue artesunate (ART) on glioma cell growth, migration, distant seeding and senescence and elucidated the underlying mechanisms. Artemisinin effectively inhibited glioma cell growth, migration and distant seeding. Further investigation of the mechanisms showed that ART can influence glioma cell metabolism by affecting the nuclear localization of SREBP2 (sterol regulatory element‐binding protein 2) and the expression of its target gene HMGCR (3‐hydroxy‐3‐methylglutaryl coenzyme A reductase), the rate‐limiting enzyme of the mevalonate (MVA) pathway. Moreover, ART affected the interaction between SREBP2 and P53 and restored the expression of P21 in cells expressing wild‐type P53, thus playing a key role in cell senescence induction. In conclusion, our study demonstrated the new therapeutic potential of ART in glioma cells and showed the novel anticancer mechanisms of ARS compounds of regulating MVA metabolism and cell senescence.
Fundic gland polyp prevalence according toHelicobacter pyloriinfection status
Authors: Notsu Takumi , Adachi Kyoichi , Mishiro Tomoko , Ishimura Norihisa , Ishihara Shunji
Published: November 2019

Background and Aim

The prevalence of fundic gland polyp (FGP) occurrence has not been clarified in individuals withHelicobacter pyloriinfection post‐eradicated status. This study was performed to examine the relationship between FGP prevalence andH.pyloriinfection status.

Methods

We enrolled 3400 subjects (2185 male subjects and 1215 female subjects; mean age 54.7 ± 9.5 years) with knownH. pyloriinfection status and who underwent an upper gastrointestinal endoscopy examination as part of an annual check‐up. Subjects without and withH.pyloriinfection numbered 1617 and 239, respectively, while 1544 had a post‐eradication status. The presence of FGP and degree of gastric mucosal atrophy were determined in each subject using an endoscopic method.

Results

Endoscopy findings showed FGPs in 1029 (30.3%) of all subjects. The prevalence ratio of FGP positivity inH.pylori‐negative,H.pylori‐positive, and post‐eradicated subjects was 51.9%, 1.7%, and 12.0%, respectively. Multiple logistic regression analysis revealed that female gender, older age, milder gastric mucosal atrophy, and anti‐secretory therapy were significant risk factors for FGP occurrence. As compared withH.pylori‐positive subjects, the odds ratios forH.pylori‐negative and post‐eradication status were 48.3 and 6.6, respectively (P< 0.001). In the post‐eradication status subjects, longer duration following bacterial eradication was a significant risk factor for occurrence of FGPs.

Conclusion

The risk of FGP occurrence in individuals who have undergoneH.pylorieradication treatment is lower as compared with those who have never been infected. However, that risk increases over time following eradication.
Real‐world experience with Grazoprevir/Elbasvir in the treatment of previously “difficult to treat” patients infected with hepatitis C virus genotype 1 and 4
Authors: Zarębska‐Michaluk Dorota , Jaroszewicz Jerzy , Buczyńska Iwona , Simon Krzysztof , Lorenc Beata , Tudrujek‐Zdunek Magdalena , Tomasiewicz Krzysztof , Sitko Marek , Garlicki Aleksander , Janczewska Ewa , Dybowska Dorota , Halota Waldemar , Pawłowska Małgorzata , Pabjan Paweł , Mazur Włodzimierz , Czauż‐Andrzejuk Agnieszka , Berak Hanna , Horban Andrzej , Socha Łukasz , Klapaczyński Jakub , Piekarska Anna , Blaszkowska Maria , Belica‐Wdowik Teresa , Dobracka Beata , Tronina Olga , Deroń Zbigniew , Białkowska‐Warzecha Jolanta , Laurans Łukasz , Flisiak Robert
Published: November 2019

Background and Aim

Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real‐world experience, particularly in previously “difficult‐to‐treat” patients with chronic kidney diseases, human immunodeficiency virus‐coinfected, cirrhotics, and treatment‐experienced.

Methods

The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer‐2 database, large national real‐world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online.

Results

A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV‐coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent‐to‐treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult‐to‐treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation.

Conclusions

GZR/EBR treatment carried‐out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult‐to‐treat populations.
A symptom severity questionnaire for patients suffering from functional gastrointestinal disorder: FGI‐Checklist
Authors: Chan Yawen , Cheong Pui Kuan , Fang Fanny Fan , Cheung Cynthia K Y , Lan Lin Lin , Yuen Kay Wing Ki , Ching Jessica Yuet Ling , Mak Arthur Dun Ping , Wu Justin Che‐yuen
Published: November 2019

Background and Aim

A well‐validated, comprehensive checklist of functional gastrointestinal (FGI) disorder (FGID) symptom severity for tracking symptom profile changes over time is lacking. We aim to develop and validate a comprehensive symptom severity checklist for FGID.

Methods

A 20‐item scale, including both upper and lower gastrointestinal symptoms, was generated to measure the symptom severity commonly found in FGID. Patients who experienced at least monthly symptoms of FGID with negative endoscopy findings were invited to complete the FGI‐Checklist, Patient Health Questionaire‐9 for assessing depressive symptoms, and Patient Health Questionnaire‐15 for assessing somatic symptoms at baseline. A subset of patients who met Rome III diagnostic criteria of gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome received medication treatment for 8–12 weeks and completed the FGI‐Checklist again at a follow‐up visit. Exploratory factor analysis was performed for subscales formation and psychometric properties were measured.

Results

Six hundred and forty‐one patients were recruited for current study and 108 (16.8%) of them completed the FGI‐Checklist again at follow‐up. Exploratory factor analysis identified a five‐factor solution accounting for 66.8% of the total variance. The five factors are named esophageal syndrome, reflux syndrome, functional dyspepsia syndrome, nausea and vomiting syndrome, and abdominal and bowel syndrome. The FGI‐Checklist total score correlated with Patient Health Questionaire‐9 and Patient Health Questionnaire‐15 (all P < 0.001), which demonstrated good construct validity. Good item‐internal consistency was found (Cronbach's alphas: 0.69–0.87). Responsiveness for reflux syndrome subscale, functional dyspepsia syndrome subscale, and abdominal and bowel syndrome subscale after medication treatment was significant (paired‐t‐test: all P < 0.01).

Conclusion

The instrument, Checklist, is valid and reliable.
Late Palaeozoic red beds elucidate fluvial architectures preserving large woody debris in the seasonal tropics of central Pangaea
Authors: Trümper Steffen , Gaitzsch Birgit , Schneider Jörg W. , Ehling Bodo‐Carlo , Kleeberg Reinhard , Rößler Ronny
Published: November 2019

Fluvial red beds containing anatomically preserved large woody debris shed new light on seasonally dry biomes of the Pennsylvanian–Permian transition and elucidate the concurrence of river depositional systems and vegetation. As a result, the occurrence, distribution and preservation of petrified large woody debris accumulations are considered crucial to understanding the role of arborescent vegetation in shaping fluvial environments. This study reports sizeable silicified trunks and corresponding fluvial architectures from the uppermost Pennsylvanian (upper Gzhelian) Siebigerode Formation (Kyffhäuser, central Germany). The origin, taphonomy and depositional environment of the fossil woods are elucidated by using a multidisciplinary approach including geological mapping, lithofacies analysis, sediment petrography, wood anatomical studies and microstructure analyses. Results reflect the gradual burial of a gentle basement elevation by sand‐bed to gravel‐bed braided rivers at the north‐western margin of the perimontane Saale Basin. Facies architectures resulted from a complex interplay of syndepositional tectonics, repeated palaeorelief rejuvenation, high‐frequency channel avulsion, seasonally dry climate and woody debris–sediment interactions. The alluvial influx and cut‐bank erosion recruited trunks from adjacent semi‐riparian slope habitats vegetated by up to 40 m tall cordaitaleans and conifers. High discharge in wide braids facilitated uncongested transport of large woody debris. Trunk entombment and initial preservation resulted from grounding on barforms, anchoring by attached roots and subsequent burial. The post‐depositional two‐phase silicification was influenced by hydrothermal hematite mineralization and determined a selective wood preservation pattern known as ‘pointstone’. Large woody debris‐induced sedimentary structures (‘LWDISS’) are introduced as a class of sediment structures formed by the biogenic impact on terrestrial deposition.
Complete Genome Sequences of Eight Methicillin-Resistant Staphylococcus aureus Strains Isolated from Patients in Japan
Authors: Hikichi Miyako , Nagao Miki , Murase Kazunori , Aikawa Chihiro , Nozawa Takashi , Yoshida Akemi , Kikuchi Taisei , Nakagawa Ichiro
Published: November 2019

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a major pathogen causing nosocomial infections, and the clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to soft tissue infection to fulminant invasive disease. Here, we report the complete genome sequences of eight MRSA strains isolated from patients in Japan.
Effect of medical insurance and family financial risk on healthcare utilisation by patients with chronic diseases in China: a cross-sectional study
Authors: Shu Zhan , Han Yu , Xiao Jinguang , Li Jian
Published: November 2019

Objective

To assess the joint cumulative effects of medical insurance and family health financial risk on healthcare utilisation among patients with chronic conditions in China.

Design

A nationwide population-based case–control study with multinomial logistic regression was conducted and used to estimate the ORs of healthcare utilisation against type of medical insurance and family health financial risk using the Anderson model as a theoretical framework.

Setting

China Family Panel Studies (CFPS) database.

Participants

The study sample included 5260 patients with chronic conditions identified from the 2014 CFPS database.

Main outcome measures

The participants were classified by their health insurance coverage: urban employee basic medical insurance (UEBMI), Gong Fei Medical Insurance (GFMI), new rural cooperative medical scheme (NCMS) and urban residents basic medical insurance. Healthcare utilisation was measured by assessing the care level provided by the health institutions selected by patients when they were sick. Health financial risk was measured using the cost of medical expenditures and annual family income over the past year.

Results

Patients were more likely to choose hospital care than care from primary health centres. Patients with NCMS preferred primary healthcare, compared with patients with no medical insurance (OR 1.852, 95% CI 1.458 to 2.352). Patients with UEBMI and GFMI made use of hospital healthcare services (OR 2.654, 95% CI 1.85 to 3.81; OR 1.629, 95% CI 1.15 to 2.30, respectively). Patients who had medium or high financial risk were more likely to choose tertiary/specialised hospital care, compared with those at low financial risk (OR 1.629, 95% CI 1.15 to 2.30; OR 1.220, 95% CI 1.04 to 1.43, respectively).

Conclusions

The majority of patients chose hospital care in our sample. There was a joint effect and relationship between degree of family health financial risk and medical insurance on healthcare utilisation.
HOMESIDE: home-based family caregiver-delivered music and reading interventions for people living with dementia: protocol of a randomised controlled trial
Authors: Baker Felicity Anne , Bloska Jodie , Braat Sabine , Bukowska Anna , Clark Imogen , Hsu Ming H , Kvamme Tone , Lautenschlager Nicola , Lee Young-Eun Claire , Smrokowska-Reichmann Agnieszka , Sousa Tanara Vieira , Stensaeth Karette A , Tamplin Jeanette , Wosch Thomas , Odell-Miller Helen
Published: November 2019

Introduction

Pharmacological interventions to address behavioural and psychological symptoms of dementia (BPSD) can have undesirable side effects, therefore non-pharmacological approaches to managing symptoms may be preferable. Past studies show that music therapy can reduce BPSD, and other studies have explored how formal caregivers use music in their caring roles. However, no randomised study has examined the effects on BPSD of music interventions delivered by informal caregivers (CGs) in the home setting. Our project aims to address the need for improved informal care by training cohabiting family CGs to implement music interventions that target BPSD, and the quality of life (QoL) and well-being of people with dementia (PwD) and CGs.

Methods and analysis

A large international three-arm parallel-group randomised controlled trial will recruit a sample of 495 dyads from Australia, Germany, UK, Poland and Norway. Dyads will be randomised equally to standard care (SC), a home-based music programme plus SC, or a home-based reading programme plus SC for 12 weeks. The primary outcome is BPSD of PwD (measured using the Neuropsychiatric Inventory-Questionnaire). Secondary outcomes will examine relationship quality between CG and PwD, depression, resilience, competence, QoL for CG and QoL for PwD. Outcomes will be collected at baseline, at the end of the 12-week intervention and at 6 months post randomisation. Resource Utilisation in Dementia will be used to collect economic data across the life of the intervention and at 6-month follow-up. We hypothesise that the music programme plus SC will generate better results than SC alone (primary comparison) and the reading programme plus SC (secondary comparison).

Ethics and dissemination

Ethical approval has been obtained for all countries. Results will be presented at national and international conferences and published in scientific journals and disseminated to consumer and caregiver representatives and the community.

Trial registration numbers

ACTRN12618001799246p;NCT03907748
Cohort profile: Mental Health Living Longer: a population-wide data linkage to understand and reduce premature mortality in mental health service users in New South Wales, Australia
Authors: Sara Grant , Arumuganathan Myu , Chen Wendy , Wu Fred , Currow David , Large Matthew , Mulder Cornelis , Ramanuj Parashar Pravin , Burgess Philip M
Published: November 2019

Purpose

Health systems must move from recognition to action if we are to address premature mortality in people with mental illness. Population data registers are an essential tool for planning and monitoring improvement efforts. The Mental Health Living Longer (MHLL) programme establishes a population-wide data linkage to support research translation and service reform in New South Wales (NSW), Australia.

Participants

A total of 8.6 million people who have had contact with NSW public and private health services between July 2001 and June 2018 are currently included in the study. Data include more than 120 million linked records from NSW data collections covering public and private hospital care, emergency departments, ambulance, community mental health services, cancer notifications and care, and death registrations. Linkage is occurring with population-wide breast and cervical cancer screening programmes. Data will be updated 6 monthly.

Findings to date

The cohort includes 970 145 people who have received mental healthcare: 79% have received community mental healthcare, 35% a general hospital admission with a primary mental health diagnosis and 25% have received specialist mental health inpatient care. The most frequent pattern of care is receipt of community mental healthcare only (50%). The median age of the mental health cohort is 34 years, and three-quarters are younger than 53 years. Eleven per cent of the mental health cohort had died during the observation period. Their median age at death was 69 years, which was younger than the median age at death for people accessing other health services.

Future plans

The MHLL programme will examine (i) all-cause mortality, (ii) suicide, (iii) cancer mortality and (iv) medical mortality. Within each theme, the programme will quantify the problem in mental health service users compared with the NSW population, describe the people most affected, describe the care received, identify predictors of premature mortality, and identify variation and opportunities for change.
ANTECEDENTS OF SUCCESS IN A RESEARCH AND DEVELOPMENT CONSORTIUM
Authors: DOMINGUEZ-BLANCO JORGE , CASTRO-ABANCÉNS IGNACIO , CEPEDA-CARRION GABRIEL
Published: November 2019

This study explores and examines the relationship between the success of Research and Development (R&D) consortia and the factors that determine this success. Most studies of R&D consortium success are based on a set of observable variables as antecedents of this success. In our study, we recognise the complexity of the problem and use latent variables as a set of weighted observable variables, rather than classical variables. Empirical insights are provided by applying a second-generation technique, namely the PLS-SEM algorithm, to analyse the data gathered from R&D consortia in Spain. The results demonstrate the existence of constructs (partner attributes, alliance attributes, environment attributes and leadership) that encompass the determinant factors for success, and also show that the attributes of the partners and the characteristics of the project alliances exert a positive influence on the success of the joint R&D project.
African Swine Fever Epidemiology and Control
Authors: Dixon Linda K. , Stahl Karl , Jori Ferran , Vial Laurence , Pfeiffer Dirk U.
Published: November 2019

African swine fever is a devastating disease that can result in death in almost all infected pigs. The continuing spread of African swine fever from Africa to Europe and recently to the high–pig production countries of China and others in Southeast Asia threatens global pork production and food security. The African swine fever virus is an unusual complex DNA virus and is not related to other viruses. This has presented challenges for vaccine development, and currently none is available. The virus is extremely well adapted to replicate in its hosts in the sylvatic cycle in East and South Africa. Its spread to other regions, with different wildlife hosts, climatic conditions, and pig production systems, has revealed unexpected epidemiological scenarios and different challenges for control. Here we review the epidemiology of African swine fever in these different scenarios and methods used for control. We also discuss progress toward vaccine development and research priorities to better understand this complex disease and improve control.
Convergence Diagnostics for Markov Chain Monte Carlo
Authors: Roy Vivekananda
Published: November 2019

Markov chain Monte Carlo (MCMC) is one of the most useful approaches to scientific computing because of its flexible construction, ease of use, and generality. Indeed, MCMC is indispensable for performing Bayesian analysis. Two critical questions that MCMC practitioners need to address are where to start and when to stop the simulation. Although a great amount of research has gone into establishing convergence criteria and stopping rules with sound theoretical foundation, in practice, MCMC users often decide convergence by applying empirical diagnostic tools. This review article discusses the most widely used MCMC convergence diagnostic tools. Some recently proposed stopping rules with firm theoretical footing are also presented. The convergence diagnostics and stopping rules are illustrated using three detailed examples.
3D Digital Image Correlation Analysis of the Shrinkage Strain in Four Dual Cure Composite Cements
Authors: Mitrović Aleksandra , Antonović Dušan , Tanasić Ivan , Mitrović Nenad , Bakić Gordana , Popović Dejana , Milošević Miloš
Published: November 2019

The introduction of resin-based cements and an adhesive-bonding system in daily dental practice has given the opportunity to increase the retention of previously conventional cemented restorations and the optimal results in esthetic. This experimental study employed the 3D Digital Image Correlation Method (3D-DIC) for detecting shrinkage strain in four dual cured composite cements. The aim was to visualize measure, analyze, and compare strain fields in four resin-based cements using the 3D-DIC method. A total of 72 samples were divided into 4 groups considering variations in sample types, diameter, and thickness. Four types of composite cements: RelyX U200 (3 M ESPE, St. Paul, MN, USA), MaxCem Elite (Kerr, Orange, CA, USA), Multilink Automix (Ivoclar Vivadent, Schaan, Liechtenstein), and SeT PP (SDI, Australia) were used. Each type had diameters of 3 mm, 4 mm, and 5 mm, respectively, combined with two different values of thickness: 1 mm and 2 mm. Thickness had an important role on strain detected in all tested materials showing higher strain in samples with 2 mm thickness compared to 1 mm samples. Shrinkage strain values were the highest in Set PP samples indicated the possibility of undesirable de-bonding.
Physical Activity, Mental Health, and Wellbeing among Older Adults in South and Southeast Asia: A Scoping Review
Authors: Kadariya Shanti , Gautam Rupesh , Aro Arja R.
Published: November 2019

Background. Physical activity is believed to enhance body functions and sense of wellbeing in general population. Objectives. This study aimed to explore physical activity measures; and the association between those measures, and mental wellbeing among older adults in South and Southeast Asia. Methods. A systematic search was made in CINHAL, EMBASE, PubMed, and PsycINFO. Articles published between 2008 and 2018 were selected with participants aged 60 years and above, living at home, community, supported housing, or residential care homes, with no diagnosed/limiting illness. Results. Five observational and four interventional studies on physical activity were analysed. Depression and sleep quality were the commonest outcome variables. Exercise frequency, regularity, and duration were found to positively impact mental wellbeing. Conclusion. Physical activity was generally found protecting against depression and improved sleep quality of older adults from South and Southeast Asia. Future studies should focus on more objective measures of physical activity.
The Crucial Role of CXCL8 and Its Receptors in Colorectal Liver Metastasis
Authors: Bie Yaqin , Ge Wei , Yang Zhibin , Cheng Xianshuo , Zhao Zefeng , Li Shengjie , Wang Wenchao , Wang Yu , Zhao Xiaofeng , Yin Zhengfeng , Li Yunfeng
Published: November 2019

CXCL8 (also known as IL-8) can produce different biological effects by binding to its receptors: CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC). CXCL8 and its receptors are associated with the development of various tumor types, especially colorectal cancer and its liver metastases. In addition to promoting angiogenesis, proliferation, invasion, migration, and the survival of colorectal cancer (CRC) cells, CXCL8 and its receptors have also been known to induce the epithelial-mesenchymal transition (EMT) of CRC cells, to help them to escape host immunosurveillance as well as to enhance resistance to anoikis, which promotes the formation of circulating tumor cells (CTCs) and their colonization of distant organs. In this paper, we will review the established roles of CXCL8 signaling in CRC and discuss the possible strategies of targeting CXCL8 signaling for overcoming CRC drug resistance and cancer progression, including direct targeting of CXCL8/CXCR1/2 or indirect targeting through the inhibition of CXCL8-CXCR1/2 signaling.
Campylobacter fetus Meningitis and Pyogenic Spondylodiscitis in a Healthy Young Woman
Authors: Ikeda Kenta , Manabe Yasuhiro , Fujiwara Shunya , Omote Yoshio , Narai Hisashi , Abe Koji
Published: November 2019

We report a rare case of Campylobacter fetus meningitis and pyogenic spondylodiscitis in a healthy young woman. A 35-year-old woman without significant medical history presented with fever, headache, and low back pain. C. fetus was detected from the blood culture. Cerebrospinal fluid analysis showed bacterial meningitis 2 days after onset. Although initial magnetic resonance imaging (MRI) did not reveal abnormal findings, repeated MRI showed a low-signal-intensity lesion on T1-weighted image (T1WI) and a high-signal-intensity lesion on T2WI between the L5 and S1 vertebral bodies 11 days after onset. The mode of infection was considered to be the consumption of raw chicken meat. After antibiotic treatment with 12 g/day ampicillin following 6 g/day meropenem, she was discharged 51 days after onset. As the inflammatory signs on MRI improved, oral antibiotic therapy was discontinued 85 days after onset. Although the initial MRI showed no abnormal findings, repeat MRI should be performed for patients who have persistent low back pain and fever.
Hepatic Encephalopathy Mimicking Acute Dominant Middle Cerebral Artery Ischemic Stroke: A Case Report
Authors: Younes Kyan , Gonzales Nicole R. , Sarraj Amrou , Bonfante Eliana , Jagolino-Cole Amanda
Published: November 2019

Hepatic encephalopathy and hyperammonemia are common in the setting of liver disease and have been associated with both generalized and focal neurological deficits. We report a case of hepatic encephalopathy with transaminitis in the setting of hyperammonemia clinically mimicking acute dominant middle cerebral artery (MCA) syndrome. A 59-year-old right-handed woman had new-onset expressive aphasia, left gaze deviation, and right hemiparesis consistent with MCA stroke. Her symptoms began 12 h after transarterial chemoembolization, a procedure to embolize blood supply and provide cytotoxic agents to a hepatocellular carcinoma tumor. Thrombocytopenia and age-indeterminate hypodensities on brain CT precluded intravenous thrombolytic administration. MRI revealed predominantly dominant hemisphere subcortical restricted diffusion with no cortical involvement. Due to a mismatch between the MRI findings and the neurological symptoms, she underwent digital subtraction cerebral angiography to assess candidacy for intra-arterial thrombectomy, which revealed completely patent MCAs with intact filling of the distal branches. Liver enzymes and ammonia were elevated. The patient was treated with lactulose and intravenous fluids. After normalization of liver enzymes, the patient’s neurological deficits resolved. Reversal of this patient’s focal symptoms with medical management could potentially be explained by the recovery of blood flow-metabolic demand mismatch caused by worsening liver dysfunction and hyperammonemia. As acute stroke therapies and interventions increase in utility for large artery acute ischemic stroke, it is vital to recognize hepatic encephalopathy and liver failure as part of the differential diagnosis for patients presenting with MCA syndrome.
The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support
Authors: Amin Amit P. , Spertus John A. , Curtis Jeptha P. , Desai Nihar , Masoudi Frederick A. , Bach Richard G. , McNeely Christian , Al-Badarin Firas , House John A. , Kulkarni Hemant , Rao Sunil V.
Published: November 2019

Background:

Impella was approved for mechanical circulatory support (MCS) in 2008, but large-scale, real-world data on its use are lacking. Our objective was to describe trends and variations in Impella use, clinical outcomes, and costs across US hospitals in patients undergoing percutaneous coronary intervention (PCI) treated with MCS (Impella or intra-aortic balloon pump).

Methods:

From the Premier Healthcare Database, we analyzed 48 306 patients undergoing PCI with MCS at 432 hospitals between January 2004 and December 2016. Association analyses were performed at 3 levels: time period, hospital, and patient. Hierarchical models with propensity adjustment were used for association analyses. We examined trends and variations in the proportion of Impella use, and associated clinical outcomes (in-hospital mortality, bleeding requiring transfusion, acute kidney injury, stroke, length of stay, and hospital costs).

Results:

Among patients undergoing PCI treated with MCS, 4782 (9.9%) received Impella; its use increased over time, reaching 31.9% of MCS in 2016. There was wide variation in Impella use across hospitals (>5-fold variation). Specifically, among patients receiving Impella, there was a wide variation in outcomes of bleeding (>2.5-fold variation), and death, acute kidney injury, and stroke (all ≈1.5-fold variation). Adverse outcomes and costs were higher in the Impella era (years 2008–2016) versus the pre-Impella era (years 2004–2007). Hospitals with higher Impella use had higher rates of adverse outcomes and costs. After adjustment for the propensity score, and accounting for clustering of patients by hospitals, Impella use was associated with death: odds ratio, 1.24 (95% CI, 1.13–1.36); bleeding: odds ratio, 1.10 (95% CI, 1.00–1.21); and stroke: odds ratio, 1.34 (95% CI, 1.18–1.53), although a similar, nonsignificant result was observed for acute kidney injury: odds ratio, 1.08 (95% CI, 1.00–1.17).

Conclusions:

Impella use is rapidly increasing among patients undergoing PCI treated with MCS, with marked variability in its use and associated outcomes. Although unmeasured confounding cannot be ruled out, when analyzed by time periods, or at the hospital level or the patient level, Impella use was associated with higher rates of adverse events and costs. More data are needed to define the appropriate role of MCS in patients undergoing PCI.
Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age
Authors: Martinez Felipe A. , Serenelli Matteo , Nicolau Jose C. , Petrie Mark C. , Chiang Chern-En , Tereshchenko Sergey , Solomon Scott D. , Inzucchi Silvio E. , Køber Lars , Kosiborod Mikhail N. , Ponikowski Piotr , Sabatine Marc S. , DeMets David L. , Dutkiewicz-Piasecka Monika , Bengtsson Olof , Sjöstrand Mikaela , Langkilde Anna Maria , Jhund Pardeep S. , McMurray John J.V.
Published: November 2019

Background:

The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozin according to age, given potential concerns about the efficacy and safety of therapies in the elderly.

Methods:

Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure <95 mm Hg and estimated glomerular filtration rate <30 mL·min
−1
·1.73 m
−2
. The primary outcome was the composite of an episode of worsening heart failure (heart failure hospitalization or urgent heart failure visit) or cardiovascular death, whichever occurred first.

Results:

A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were <55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4–17.9), 15.7 (95% CI, 13.2–18.7), 15.1 (95% CI, 13.1–17.5), and 18.0 (95% CI, 15.2–21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60–1.28), 0.71 (95% CI, 0.55–0.93), 0.76 (95% CI, 0.61–0.95), and 0.68 (95% CI, 0.53–0.88;
P
for interaction=0.76). Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and symptoms. Although adverse events and study drug discontinuation increased with age, neither was significantly more common with dapagliflozin in any age group.

Conclusions:

Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03036124.
Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction
Authors: McMurray John J.V. , Jackson Alice M. , Lam Carolyn S.P. , Redfield Margaret M. , Anand Inder S. , Ge Junbo , Lefkowitz Marty P. , Maggioni Aldo P. , Martinez Felipe , Packer Milton , Pfeffer Marc A. , Pieske Burkert , Rizkala Adel R. , Sabarwal Shalini V. , Shah Amil M. , Shah Sanjiv J. , Shi Victor C. , van Veldhuisen Dirk J. , Zannad Faiez , Zile Michael R. , Cikes Maja , Goncalvesova Eva , Katova Tzvetana , Kosztin Anamaria , Lelonek Malgorzata , Sweitzer Nancy , Vardeny Orly , Claggett Brian , Jhund Pardeep S. , Solomon Scott D.
Published: November 2019

Background:

Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men.

Methods:

In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes.

Results:

Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro–B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59–0.90) in women and 1.03 (95% CI, 0.84–1.25) in men (
P
interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men.

Conclusions:

As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding.

Clinical Trial Registration:

https://www.clinicaltrials.gov
. Unique identifier: NCT01920711.