bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of elective switching to vedolizumab in inflammatory bowel disease patients under tumor necrosis factor antagonist‐maintained clinical remission
Authors: Wang Yunwei , Wang Jennifer , Pekow Joel , Dalal Sushila , Cohen Russell D , Ollech Jacob , Israel Amanda , Shogan Benjamin D , Micic Dejan , Cannon Lisa , Umanskiy Konstantin , Hurst Roger , Hyman Neil , Rubin David T , Sakuraba Atsushi
Published: June 2019

Background and Aim

Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti‐tumor necrosis factor (TNF) therapy. This study was to examine long‐term outcome of IBD patients switching to VDZ from anti‐TNF agents for reasons other than failure of therapy.

Methods

Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti‐TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan–Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6–12 months after switching to VDZ therapy was analyzed.

Results

A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7–52) of VDZ therapy, 34 (82.9%) were in VDZ‐maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow‐up colonoscopy.

Conclusions

Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti‐TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti‐TNF remitters to VDZ treatment is a safe practice in specific patient populations.
Rhythm processing in cochlear implant−mediated music perception
Authors: Jiam Nicole T. , Limb Charles J.
Published: June 2019

Cochlear implants (CIs) are biomedical devices that provide sound to people with severe‐to‐profound hearing loss by direct electrical stimulation of auditory neurons in the cochlea. Despite the remarkable achievements with respect to speech perception in quiet environments, music perception with CIs remains generally poor due to the degradation of auditory input. Prior studies have shown that both pitch perception and timbre discrimination are poor in CI users, whereas the performance on rhythmic tasks is nearly equivalent to normal hearing participants. There are several caveats, however, to this generalization regarding rhythm processing for CI users. The purpose of this article is to summarize the literature on rhythmic perception for CI users while highlighting important limitations within these studies. We will also identify areas for future research and development of CI‐mediated music processing. It is likely that rhythm processing will continue to advance as our understanding of electrical current delivery to the auditory nerve improves.
Genetic analysis of photosynthesis‐related traits in faba bean (Vicia faba) for crop improvement
Authors: Khazaei Hamid , Wach Damian , Pecio Alicja , Vandenberg Albert , Stoddard Frederick L.
Published: June 2019

Increasing productivity through improvement of photosynthesis in faba bean breeding programmes requires understanding of the genetic control of photosynthesis‐related traits. Hence, we investigated the gene action of leaf area, gas exchange traits, canopy temperature, chlorophyll content, chlorophyll fluorescence parameters and biomass. We chose inbred lines derived from cultivars 'Aurora' (Sweden) and 'Mélodie' (France) along with an Andean accession, ILB 938, crossed them (Aurora/2 × Mélodie/2, ILB 938/2 × Aurora/2 and Mélodie/2 × ILB 938/2), and prepared the six standard generations for quantitative analysis (P1, P2, F1, F2, B1, and B2). Gene action was complex for each trait, involving additive and dominance gene actions and interactions. Additive gene action was important for SPAD, photosynthetic rate, stomatal conductance and Fv/Fm. Dominance effect was important for biomass production. It is suggested that breeders selecting for productivity can maximize genetic gain by selecting early generations for canopy temperature, SPAD and Fv/Fm, then later generations for biomass. The information on genetics of various contributing traits of photosynthesis will assist plant breeders in choosing an appropriate breeding strategy for enhancing productivity in faba bean.
Prospective study on changes in the donor gallbladder contraction function after left lateral lobe hepatectomy
Authors: Wei Lin , Zhi Xin , He Enhui , Qian Linxue , Sun Liying , Zhu Zhijun , Zeng Zhigui , Qu Wei
Published: June 2019

This study aimed to evaluate the feasibility of donor gallbladder preservation in liver transplantation. Conventional removal of the donor gallbladder is applied in a majority of pediatric liver transplantation. A total of 42 donors who underwent gallbladder preservation in liver transplantation from October 2013 to December 2015 at the Beijing Friendship Hospital, China, were enrolled for the study. The changes in gallbladder volume and the gallbladder EF of donors before and after surgery were measured through ultrasound, and the changes in the donor gallbladder contraction function before and after surgery were evaluated to help verify the feasibility of gallbladder preservation in living donor left lateral lobe hepatectomy. The gallbladder emptying index dropped to 42.67% in 2 weeks after surgery and gradually increased with the length of recovery time, which could reach 69.14% in 3 months after surgery. At that time, 97.6% of the donors were considered to have recovered their gallbladder contraction function. The gallbladder contraction function at an early stage after gallbladder preservation in liver transplantation is not obviously improved, but it can recover to a normal level in 1 month after surgery, indicating that the gallbladder preservation in hepatectomy of living donor can effectively guarantee the gallbladder contraction function.
Risk–Risk Tradeoff Analysis of Nuclear Explosives for Asteroid Deflection
Authors: Baum Seth D.
Published: June 2019

To prevent catastrophic asteroid–Earth collisions, it has been proposed to use nuclear explosives to deflect away earthbound asteroids. However, this policy of nuclear deflection could inadvertently increase the risk of nuclear war and other violent conflict. This article conducts risk–risk tradeoff analysis to assess whether nuclear deflection results in a net increase or decrease in risk. Assuming nonnuclear deflection options are also used, nuclear deflection may only be needed for the largest and most imminent asteroid collisions. These are low‐frequency, high‐severity events. The effect of nuclear deflection on violent conflict risk is more ambiguous due to the complex and dynamic social factors at play. Indeed, it is not clear whether nuclear deflection would cause a net increase or decrease in violent conflict risk. Similarly, this article cannot reach a precise conclusion on the overall risk–risk tradeoff. The value of this article comes less from specific quantitative conclusions and more from providing an analytical framework and a better overall understanding of the policy decision. The article demonstrates the importance of integrated analysis of global risks and the policies to address them, as well as the challenge of quantitative evaluation of complex social processes such as violent conflict.
Resonances in bounded media: Nonlinear and boundary effects
Authors: Shatnawi Taqi A. M. , Amundsen David E.
Published: June 2019

We study the response of nonlinear wave systems in bounded domains at or near resonance. There are typically two qualitatively distinct types of response which may be observed relating to whether or not higher harmonics are themselves resonant. We introduce a variety of nonlinear model problems at or near resonance and study the subsequent response. We explain how the features of this problem such as the form of nonlinearity, boundary conditions, and the nature of spectrum play a fundamental role in the qualitative nature of the response. Numerical simulations are carried out to provide further explanation and comparison with analytic approximations. The results of this study provide a better understanding of the impact and interplay between nonlinear and boundary effects and thus in turn will contribute to providing new insights into various physically motivated problems in acoustics and other settings.
Path segmentation for movement trajectories with irregular sampling frequency using space‐time interpolation and density‐based spatial clustering
Authors: Song Ying , Song Tianci , Kuang Rui
Published: June 2019

Path segmentation methods have been developed to distinguish stops and moves along movement trajectories. However, most studies do not focus on handling irregular sampling frequency of the movement data. This article proposes a four‐step method to handle various time intervals between two consecutive records, including parameter setting, space‐time interpolation, density‐based spatial clustering, and integrating the geographic context. The article uses GPS tracking data provided by HOURCAR, a non‐profit car‐sharing service in Minnesota, as a case study to demonstrate our method and present the results. We also implement the DB‐SMoT algorithm as a comparison. The results show that our four‐step method can handle various time intervals between consecutive records, group consecutive stops close to each other, and distinguish different types of stops and their inferred activities. These results can provide novel insights into car‐sharing behaviors such as trip purposes and activity scheduling.
Wealth Effects on Consumption in Malta: Evidence from Household Level Data
Authors: Georgakopoulos Ilias
Published: June 2019

This paper attempts to examine for the first time the effects of household wealth on consumption in Malta, based on household level data from the 2017 Household Finance and Consumption Survey (HFCS). The estimation of the log-log consumption function is performed using OLS regression, after taking into account the survey design. The results provide evidence in support of the existence of a wealth effect on consumption, stemming from housing and financial wealth. In particular, the housing wealth effect on consumption is positive and higher than the financial wealth effect for the whole sample size, especially for homeowners. In addition, comparisons in the differences in wealth effects across age groups confirm the existence of a life-cycle pattern in consumption.
Commissioning of vacuum system for SuperKEKB positron damping ring
Authors: Shibata Kyo , Suetsugu Yusuke , Ishibashi Takuya , Shirai Mitsuru , Terui Shinji , Kanazawa Ken-ichi , Hisamatsu Hiromi
Published: June 2019

The first stage commissioning of the new positron damping ring, which was constructed in the upgraded injector system of the SuperKEKB, was carried out from February to July 2018. Vacuum scrubbing in the arc sections, which occupy most of the ring, progressed smoothly, and a beam lifetime of 1000 s was obtained with a stored beam current of 10 mA and a beam dose of 0.7 A h. However, the beam lifetime did not increase with subsequent vacuum scrubbing because the beam lifetime was primarily determined by the Touschek effect. The residual gas composition during beam operation was typical of what would be expected for a vacuum system pumped by nonevaporable getter pumps. Rough Molflow+-based estimates of the photon-stimulated desorption yields of the beam pipe at the arc sections revealed that they decreased to 1.4 × 10−4 molec. photon−1 for H2 and to 2.3 × 10−5 molec. photon−1 for CO at a beam dose of 2 A h, which corresponds to a photon dose of 1 × 1023 photons m−1.
New pentaquarks hint at zoo of exotic matter
Authors: Cho Adrian
Published: June 2019

Short-lived particles made of five quarks may resemble molecules in their structure.
Bipartisan bill proposes forum on U.S. academic espionage
Authors: Mervis Jeffrey
Published: June 2019

Congress asked to set up National Academies roundtable.
Cancer modeling meets human organoid technology
Authors: Tuveson David , Clevers Hans
Published: June 2019

Organoids are microscopic self-organizing, three-dimensional structures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to create indefinitely expanding organoids starting from tumor tissue of individuals suffering from a range of carcinomas. Alternatively, CRISPR-based gene modification allows the engineering of organoid models of cancer through the introduction of any combination of cancer gene alterations to normal organoids. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting. Here, we review the current state and future prospects of the rapidly evolving tumor organoid field.
Organoids-on-a-chip
Authors: Park Sunghee Estelle , Georgescu Andrei , Huh Dongeun
Published: June 2019

Recent studies have demonstrated an array of stem cell–derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology.
Ethics of inclusion: Cultivate trust in precision medicine
Authors: Lee Sandra Soo-Jin , Fullerton Stephanie M. , Saperstein Aliya , Shim Janet K.
Published: June 2019

We must explore how studies enhance diversity, inclusion
David A. Hamburg (1925–2019)
Authors: Fineberg Harvey V.
Published: June 2019

Renowned physician-psychiatrist and humanitarian
A new narrative for the ocean
Authors: Lubchenco Jane , Gaines Steven D.
Published: June 2019

Narratives help frame our thinking and action. On the eve of World Oceans Day and in anticipation of the United Nations Decade of Ocean Science for Sustainable Development (2021–2030), a new narrative for the ocean is warranted—one that reflects current scientific knowledge and inspires new science and effective action.
Sequential Open-Label Study of the Safety, Tolerability, and Pharmacokinetic Interactions between Dihydroartemisinin-Piperaquine and Mefloquine in Healthy Thai Adults
Authors: Hanboonkunupakarn Borimas , van der Pluijm Rob W. , Hoglund Richard , Pukrittayakamee Sasithon , Winterberg Markus , Mukaka Mavuto , Waithira Naomi , Chotivanich Kesinee , Singhasivanon Pratap , White Nicholas J. , Dondorp Arjen M. , Tarning Joel , Jittamala Podjanee
Published: June 2019

Artemisinin-based combination therapies (ACTs) have contributed substantially to the global decline in
Plasmodium falciparum
morbidity and mortality, but resistance to artemisinins and their partner drugs is increasing in Southeast Asia, threatening malaria control. New antimalarial compounds will not be generally available soon.
Food Microstructure and Fat Content Affect Growth Morphology, Growth Kinetics, and Preferred Phase for Cell Growth of
Listeria monocytogenes
in Fish-Based Model Systems
Authors: Verheyen Davy , Xu Xiang Ming , Govaert Marlies , Baka Maria , Skåra Torstein , Van Impe Jan F.
Published: June 2019

Listeria monocytogenes
is one of the most hazardous foodborne pathogens due to the high fatality rate of the disease (i.e., listeriosis). In this study, the growth behavior of
L. monocytogenes
was investigated at a microscopic scale in food model systems that mimic processed fish products (e.g., fish paté and fish soup), and the results were related to macroscopic growth parameters. Many studies have previously focused on the food microstructural influence on microbial growth. The novelty of this work lies in (i) the microscopic investigation of products with a complex composition and/or structure using confocal laser scanning microscopy and (ii) the direct link to the macroscopic level. Growth behavior (i.e., concerning bacterial growth morphology and preferred phase for growth) was more complex than assumed in common macroscopic studies. Consequently, the effectiveness of industrial antimicrobial food preservation technologies (e.g., thermal processing) might be overestimated for certain products, which may have critical food safety implications.
A Potent and Effective SuicidalListeriaVaccine Platform
Authors: Hanson William G. , Benanti Erin L. , Lemmens Edward E. , Liu Weiqun , Skoble Justin , Leong Meredith L. , Rae Chris S. , Fassò Marcella , Brockstedt Dirk G. , Chen Chen , Portnoy Daniel A. , Dubensky Thomas W. , Lauer Peter
Published: June 2019

Live-attenuatedListeria monocytogeneshas shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenesrecombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens.
CD28 Costimulation Is Required for Development of Herpetic Stromal Keratitis but Does Not Prevent Establishment of Latency
Authors: Yin Xiao-Tang , Baugnon Nicholas K. , Potter Chloe A. , Tai Shannon , Keadle Tammie L. , Stuart Patrick M.
Published: June 2019

We study the pathogenesis of herpes simplex virus-mediated corneal disease. T cells play a critical role both in disease and in the maintenance of latency in neurons. Consequently, the focus of this study was to evaluate the role that T cell costimulation plays both in corneal disease and in controlling the ability of the virus to maintain a stable infection of the ganglia that innervate the cornea. We demonstrate that in the absence of costimulation with CD28, corneal disease does not take place. However, this costimulation does not prevent the ability of CD8+T cells to develop and, thus, control latent infection of neurons. We conclude from these studies that CD28 costimulation is required for corneal destructive immune responses but that CD8+T cells develop over time and help to maintain latency.
Draft Genome Sequence of Streptococcus suis S10, a Virulent Strain Used in Experimental Pig Infections
Authors: Gaiser Rogier A. , Zomer Aldert L. , Wells Jerry M. , van Baarlen Peter
Published: June 2019

Here, we report the draft whole-genome sequence of
Streptococcus suis
strain S10, isolated from the tonsils of a healthy pig.
S. suis
S10 belongs to the highly virulent serotype 2, which includes isolates that cause infectious diseases, including meningitis, in pigs and human.
Draft Genome Sequences of Antibiotic-Resistant Escherichia coli Isolates from U.S. Wastewater Treatment Plants
Authors: Gomez-Alvarez Vicente , Hoelle Jill
Published: June 2019

The spread of antibiotic-resistant microorganisms is a major public health concern. Here, we report the draft genome sequences of three
Escherichia coli
isolates from primary effluent collected from geographically dispersed U.S.
Complete Chloroplast Genome Sequence of a White Spruce (Picea glauca, Genotype WS77111) from Eastern Canada
Authors: Lin Diana , Coombe Lauren , Jackman Shaun D. , Gagalova Kristina K. , Warren René L. , Hammond S. Austin , Kirk Heather , Pandoh Pawan , Zhao Yongjun , Moore Richard A. , Mungall Andrew J. , Ritland Carol , Jaquish Barry , Isabel Nathalie , Bousquet Jean , Jones Steven J. M. , Bohlmann Joerg , Birol Inanc
Published: June 2019

Here, we present the complete chloroplast genome sequence of white spruce (
Picea glauca
, genotype WS77111), a coniferous tree widespread in the boreal forests of North America. This sequence contributes to genomic and phylogenetic analyses of the
Picea
genus that are part of ongoing research to understand their adaptation to environmental stress.
Genome Sequences of Three Cruciviruses Found in the Willamette Valley (Oregon)
Authors: de la Higuera Ignacio , Torrance Ellis L. , Pratt Alyssa A. , Kasun George W. , Maluenda Amberlee , Stedman Kenneth M.
Published: June 2019

Cruciviruses are single-stranded DNA (ssDNA) viruses whose genomes suggest the possibility of gene transfer between DNA and RNA viruses. Many crucivirus genome sequences have been found in metagenomic data sets, although no crucivirus has been isolated.
Delayed calcareous nannoplankton boom-bust successions in the earliest Paleocene Chicxulub (Mexico) impact crater
Authors: Jones Heather L. , Lowery Christopher M. , Bralower Timothy J.
Published: June 2019

The Cretaceous-Paleogene (K-Pg; 66 Ma) mass extinction was caused by a bolide impact on the Yucatán platform near modern Chicxulub, Mexico. Calcareous nannoplankton, a dominant group of primary producers, were almost eradicated at this time. Post-impact nannoplankton assemblages from Northern Hemisphere sites were characterized by a short-lived series of high-dominance, low-diversity acmes (“boom-bust” successions), which likely represent an unstable post-impact environment. Although these boom-bust successions are a global signal, the mechanisms that controlled the taxonomic switchovers between acmes are currently unknown. Here, we present detailed analyses of calcareous nannoplankton and planktic foraminiferal assemblages in a new K-Pg section from the peak ring of the Chicxulub crater. We show that although nannoplankton assemblages resemble the typical series of acmes at Tethyan sites, the termination of the “disaster” acme in the crater is delayed by at least 500 k.y. The coincidence between shifts in the dominant planktic foraminiferal trophic group and switchovers in nannoplankton boom-bust taxa suggests that this series of acmes may represent a gradual trend toward oligotrophy driven by the global restoration of biological pump efficiency. Thus, the global diachroneity of boom-bust successions likely reflects the differential pacing of biological pump restoration between oceanic basins and settings.
Assessing the knowledge, attitudes and perceptions of tobacco-associated diseases and how it is influenced by tobacco products advertisement, promotion and sponsorship while enforcing a strong and comprehensive ban in Panama: a cross-sectional study
Authors: Quintana Hedley Knewjen , Herrera Víctor , Niño Cecilio , Gómez Beatriz , Roa Reina
Published: June 2019

Objectives

Assessing the knowledge, attitudes and perceptions (KAP) of tobacco-associated diseases, and how it is influenced by tobacco products' advertisement, promotion and sponsorship (TAPS) while enforcing a strong and comprehensive ban.

Design

The Panamanian implementation of the Global Adult Tobacco Survey: an international standardised cross-sectional survey study.

Setting

National Panamanian population aged between 15 years and 29 years old.

Participants

There were 4796 responding participants (n=905 830 in the expanded sample).

Primary and secondary outcomes

An index was developed using factorial analysis using TAPS and KAP variables. The primary outcomes were: (1) The national median index value. (2) The index value stratified by sex, age, occupation, income quintile and geographical areas. (3) The first and second factor loadings (FFL and SFL, respectively) for variables included in the KAP index.

Results

Fifteen out of the 16 variables comprising the index were variables related to KAP and one variable was related to TAPS. The top three variables according to their FFL were ‘KAP that cigarette is associated to …’: (1) ‘… bladder cancer’. (2) ‘… breast cancer’. (3) ‘… stomach cancer’. The top three variables according to the SFL were ‘KAP that cigarette is associated to …’: (1)‘… chronic bronchitis’. (2) ‘… myocardial infarction’. (3) ‘… lung cancer’. Illegal tobacco advertisement in posters was the only TAPS variable included in the index. The national KAP index value was 0.26. Our results show that current smokers, teens, men, people with the lowest income quintile, and those living in Guna Yala Indigenous Territory (health region with the highest smoking prevalence) had a lower median value than the national median.

Conclusions

Men, young adults and deprived youth had the lowest median KAP index. Illegal TAPS had no influence on the KAP of tobacco-associated diseases when a strong and comprehensive ban is enforced.
PRIME (Positive Transitions Through the Menopause) Study: a protocol for a mixed-methods study investigating the impact of the menopause on the health and well-being of women living with HIV in England
Authors: Tariq Shema , Burns Fiona M , Gilson Richard , Sabin Caroline
Published: June 2019

Introduction

Advances in antiretroviral therapy have transformed HIV into a long-term condition with near-normal life expectancy for those in whom viral replication is well controlled on treatment. This means that age-related events, including menopause, is of increasing importance in the care of people living with HIV. The PRIME (Positive Transitions Through the Menopause) Study aims to explore the impact of the menopause on the health and well-being of women living with HIV (WLHIV).

Methods and analysis

The PRIME Study is a multicentre, mixed-methods observational study deploying a multiphase sequential design with explanatory and exploratory phases. Phase 1 comprised three focus group discussions with WLHIV. In phase 2 we aimed to administer questionnaires comprising detailed assessment of menopausal status and symptoms to 1500 WLHIV aged 45–60 attending HIV clinics in England. Phase 3 comprised semistructured interviews with a subsample of phase 2 participants. Ongoing quantitative follow-up of 100 participants is planned between October 2018 and September 2019. Qualitative and quantitative data will be kept analytically distinct and analysed using appropriate methods. We will integrate quantitative and qualitative findings using coding matrices.

Ethics and dissemination

The PRIME Study has ethical approval from the South East Coast-Surrey Research Ethics Committee on behalf of all National Health Service (NHS) sites, and approval from University College London Research Ethics Committee for qualitative work conducted in non-NHS sites. In conjunction with the study Expert Advisory Group (which includes WLHIV), we have drafted a dissemination strategy that takes into account a wide range of stakeholders, including patients, policy makers and healthcare providers. This includes at least five empirical research papers to be submitted to peer-reviewed journals, as well as an accessible report aimed primarily at a non-technical audience (published in May 2018 and launched at a live-streamed event). Both quantitative and qualitative data are held by the PRIME Study team and are available by request.
Clitoral surgery on minors: an interview study with clinical experts of differences of sex development
Authors: Liao Lih-Mei , Hegarty Peter , Creighton Sarah , Lundberg Tove , Roen Katrina
Published: June 2019

Objectives

Clitoral surgery on minors diagnosed with differences of sex development is increasingly positioned as a violation of human rights. This qualitative study identified how health professionals (HPs) navigate the contentious issues as they offer care to affected families.

Design

Qualitative analysis of audio-recorded semistructured interviews with HPs. All of the interviews were transcribed verbatim for theoretical thematic analysis.

Setting

Twelve specialist multidisciplinary care centres for children, adolescents and adults diagnosed with a genetic condition associated with differences of sex development.

Participants

Thirty-two medical, surgical, psychological and nursing professionals and clinical scientists in 12 specialist centres in Britain and Sweden formed the interview sample.

Results

All interviewees were aware of the controversial nature of clitoral surgery and perceived themselves and their teams as non-interventionist compared with other teams. Data analyses highlighted four strategies that the interviewees used to navigate their complex tasks: (1) engaging with new thinking, (2) holding on to historical assumptions, (3) reducing the burden of dilemmas and (4) being flexible. In response to recent reports and debates that challenge clitoral surgery on minors, HPs had revised some of their opinions. However, they struggled to reconcile their new knowledge with the incumbent norms in favour of intervention as they counsel care users with variable reactions and expectations. The flexible approach taken may reflect compromise, but the interviewees were often trapped by the contradictory values and assumptions.

Conclusions

If the pathology-based vocabularies and narratives about genital diversity could be modified, and normative assumptions are questioned more often, clinicians may be more adept at integrating their new knowledge into a more coherent model of care to address the psychosocial concerns that genital surgery purports to overcome.
Guided or self-guided internet-based cognitive–behavioural therapy (iCBT) for depression? Study protocol of an individual participant data network meta-analysis
Authors: Karyotaki Eirini , Furukawa Toshi A , Efthimiou Orestis , Riper Heleen , Cuijpers Pim
Published: June 2019

Introduction

Although guided forms of internet-based cognitive–behavioural therapy (iCBT) result in a substantial reduction in depression, it seems that the most scalable way to deliver iCBT is without guidance. However, direct evidence on the comparison between guided and self-guided iCBT is scarce. Moreover, it is unclear which types of patients may benefit more from each of these two forms of iCBT. Network meta-analysis (NMA) using individual participant data (IPD) offers a way to assess the relative efficacy of multiple (>2) interventions. Moreover, it maximises our power to detect patient-level characteristics (covariates) that have an important effect on the efficacy of interventions. This protocol describes the procedures of an IPD-NMA, which aims at examining the relative efficacy of guided compared with self-guided iCBT and at identifying predictors and moderators of treatment outcome.

Methods and analysis

We will use an existing database on psychotherapies for adult depression to identify eligible studies. This database has been updated up to 1 January 2018, through literature searches in PubMed, Embase, PsycINFO and Cochrane Library. The outcome of this IPD-NMA is reduction in depressive symptoms severity. We will fit the model in a Bayesian setting. After fitting the model, we will report the relative treatment effects for different types of patients, and we will discuss the clinical implications of our findings. Based on the results from the IPD-NMA model, we will develop and validate a personalised prediction model, aiming to provide patient-level predictions about the effects of the interventions.

Ethics and dissemination

An ethical approval is not required for this study. The results will be published in a peer-review journal. These results will guide clinical decisions about the most efficient way to allocate iCBT resources, thereby increasing the scalability of this innovative therapeutic approach.
Association between continuity of provider-adjusted regularity of general practitioner contact and unplanned diabetes-related hospitalisation: a data linkage study in New South Wales, Australia, using the 45 and Up Study cohort
Authors: Moorin Rachael E , Youens David , Preen David B , Harris Mark , Wright Cameron M
Published: June 2019

Objective

To assess the association between continuity of provider-adjusted regularity of general practitioner (GP) contact and unplanned diabetes-related hospitalisation or emergency department (ED) presentation.

Design

Cross-sectional study.

Setting

Individual-level linked self-report and administrative health service data from New South Wales, Australia.

Participants

27 409 survey respondents aged ≥45 years with a prior history of diabetes and at least three GP contacts between 1 July 2009 and 30 June 2015.

Main outcome measures

Unplanned diabetes-related hospitalisations or ED presentations, associated costs and bed days.

Results

Twenty-one per cent of respondents had an unplanned diabetes-related hospitalisation or ED presentation. Increasing regularity of GP contact was associated with a lower probability of hospitalisation or ED presentation (19.9% for highest quintile, 23.5% for the lowest quintile). Conditional on having an event, there was a small decrease in the number of hospitalisations or ED presentations for the low (−6%) and moderate regularity quintiles (−8%), a reduction in bed days (ranging from −30 to −44%) and a reduction in average cost of between −23% and −41%, all relative to the lowest quintile. When probability of diabetes-related hospitalisation or ED presentation was included, only the inverse association with cost remained significant (mean of $A3798 to $A6350 less per individual, compared with the lowest regularity quintile). Importantly, continuity of provider did not significantly modify the effect of GP regularity for any outcome.

Conclusions

Higher regularity of GP contact—that is more evenly dispersed, not necessarily more frequent care—has the potential to reduce secondary healthcare costs and, conditional on having an event, the time spent in hospital, irrespective of continuity of provider. These findings argue for the advocacy of regular care, as distinct from solely continuity of provider, when designing policy and financial incentives for GP-led primary care.
Missed nursing care in newborn units: a cross-sectional direct observational study
Authors: Gathara David , Serem George , Murphy Georgina A V , Obengo Alfred , Tallam Edna , Jackson Debra , Brownie Sharon , English Mike
Published: June 2019

Background

Improved hospital care is needed to reduce newborn mortality in low/middle-income countries (LMIC). Nurses are essential to the delivery of safe and effective care, but nurse shortages and high patient workloads may result in missed care. We aimed to examine nursing care delivered to sick newborns and identify missed care using direct observational methods.

Methods

A cross-sectional study using direct-observational methods for 216 newborns admitted in six health facilities in Nairobi, Kenya, was used to determine which tasks were completed. We report the frequency of tasks done and develop a nursing care index (NCI), an unweighted summary score of nursing tasks done for each baby, to explore how task completion is related to organisational and newborn characteristics.

Results

Nursing tasks most commonly completed were handing over between shifts (97%), checking and where necessary changing diapers (96%). Tasks with lowest completion rates included nursing review of newborns (38%) and assessment of babies on phototherapy (15%). Overall the mean NCI was 60% (95% CI 58% to 62%), at least 80% of tasks were completed for only 14% of babies. Private sector facilities had a median ratio of babies to nurses of 3, with a maximum of 7 babies per nurse. In the public sector, the median ratio was 19 babies and a maximum exceeding 25 babies per nurse. In exploratory multivariable analyses, ratios of ≥12 babies per nurse were associated with a 24-point reduction in the mean NCI compared with ratios of ≤3 babies per nurse.

Conclusion

A significant proportion of nursing care is missed with potentially serious effects on patient safety and outcomes in this LMIC setting. Given that nurses caring for fewer babies on average performed more of the expected tasks, addressing nursing is key to ensuring delivery of essential aspects of care as part of improving quality and safety.
Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response
Authors: Wang Ruiping , Song Shumei , Harada Kazuto , Ghazanfari Amlashi Fatemeh , Badgwell Brian , Pizzi Melissa Pool , Xu Yan , Zhao Wei , Dong Xiaochuan , Jin Jiangkang , Wang Ying , Scott Ailing , Ma Lang , Huo Longfei , Vicente Diego , Blum Murphy Mariela , Shanbhag Namita , Tatlonghari Ghia , Thomas Irene , Rogers Jane , Kobayashi Makoto , Vykoukal Jody , Estrella Jeannelyn Santiano , Roy-Chowdhuri Sinchita , Han Guangchun , Zhang Shaojun , Mao Xizeng , Song Xingzhi , Zhang Jianhua , Gu Jian , Johnson Randy L , Calin George Adrian , Peng Guang , Lee Ju-Seog , Hanash Samir M , Futreal Andrew , Wang Zhenning , Wang Linghua , Ajani Jaffer A
Published: June 2019

Objective

Peritoneal carcinomatosis (PC) occurs frequently in patients with gastric adenocarcinoma (GAC) and confers a poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings of PC’s development/progression remain largely unknown. We characterised exome/transcriptome/immune landscapes of PC cells from patients with GAC aiming to identify novel therapeutic targets.

Design

We performed whole-exome sequencing (WES) and whole transcriptome sequencing (RNA-seq) on 44 PC specimens (43 patients with PC) including an integrative analysis of WES, RNA-seq, immune profile, clinical and pathological phenotypes to dissect the molecular pathogenesis, identifying actionable targets and/or biomarkers and comparison with TCGA primary GACs.

Results

We identified distinct alterations in PC versus primary GACs, such as more frequentCDH1 and TAF1mutations, 6q loss and chr19 gain. Alterations associated with aggressive PC phenotypes emerged with increased mutations inTP53, CDH1, TAF1andKMT2C, higher level of ‘clock-like’ mutational signature, increase in whole-genome doublings, chromosomal instability (particularly, copy number losses), reprogrammed microenvironment, enriched cell cycle pathways, MYC activation and impaired immune response. Integrated analysis identified two main molecular subtypes: ‘mesenchymal-like’ and ‘epithelial-like’ with discriminating response to chemotherapy (31% vs 71%). Patients with the less responsive ‘mesenchymal-like’ subtype had high expression of immune checkpoint T-Cell Immunoglobulin And Mucin Domain-Containing Protein 3 (TIM-3), its ligand galectin-9, V-domain Ig suppressor of T cell activation (VISTA) and transforming growth factor-β as potential therapeutic immune targets.

Conclusions

We have uncovered the unique mutational landscape, copy number alteration and gene expression profile of PC cells and defined PC molecular subtypes, which correlated with PC therapy resistance/response. Novel targets and immune checkpoint proteins have been identified with a potential to be translated into clinics.
Cor triatriatum sinistrum diagnosed in the adulthood: a systematic review
Authors: Rudienė Virginija , Hjortshøj Cristel M S , Glaveckaitė Sigita , Zakarkaitė Diana , Petrulionienė Žaneta , Gumbienė Lina , Aidietis Audrius , Søndergaard Lars
Published: June 2019

Background

We performed a systematic review of cor triatriatum sinistrum (CTS) diagnosed in adults. The aim of this review was to describe the clinical presentation, natural history and management of this congenital heart disease.

Methods

A PubMed literature search for ‘cor triatriatum sinistrum’ published since 2005 was performed. Included patients were divided into those with and without obstructive membrane physiology. The clinical course differences were compared.

Results

A total of 171 published cases were included. The median age at diagnosis was 43 years (IQR, 30–60). Obstructive membrane physiology was observed in 70 (41%), and this patient group was younger at presentation (median age 39 (IQR, 28–52) vs 50 years (IQR, 32–64), p=0.003).

Patients with obstructive membrane more frequently had associated cardiac defects (58.6% vs 42.4%, p=0.039). Overall, the most frequent clinical symptom was atrial fibrillation, as this was present in 56 (32.8%) of all patients. CTS-related symptoms were more frequent in patients with obstructive membrane: congestive heart failure (44.3% vs 15.2%, p<0.001), pulmonary hypertension (27.1% vs 6.1%, p<0.001), haemorrhage (8.6% vs 0%, p=0.004) and infections manifestation (8.6% vs 0%, p=0.004).

A total of 71 (41.5%) patients with CTS required interventional treatment, mainly within patients with the obstructive membrane (86.8% vs 12.6%, p<0.001).

Conclusion

The natural history of CTS most often manifests with symptoms of congestive heart failure. Patients with obstructive membrane most often have associated cardiac defects and higher risk for infections and haemorrhage. The interventional treatment of CTS remains the first choice for obstructive membrane.
Calcification and extracellular matrix dysregulation in human postmortem and surgical aortic valves
Authors: Gomez-Stallons M Victoria , Tretter Justin T , Hassel Keira , Gonzalez-Ramos Osniel , Amofa Dorothy , Ollberding Nicholas J , Mazur Wojciech , Choo Joseph K , Smith J Michael , Kereiakes Dean J , Yutzey Katherine E
Published: June 2019

Objectives

Calcific aortic valve disease (CAVD) is a progressive disease ranging from aortic valve (AoV) sclerosis to AoV stenosis (AS), characterised by severe calcification with impaired leaflet function. Due to the lack of early symptoms, the pathological progression towards valve dysfunction is poorly understood. The early patterns of AoV calcification and altered extracellular matrix (ECM) organisation were analysed in individuals postmortem without clinical AS compared with clinical AS.

Methods

Histological patterns of calcification and ECM organisation in postmortem AoV leaflets without clinical AS obtained from a tissue repository and surgical specimens obtained from individuals with clinical AS were compared with in vivo imaging prior to transcatheter AoV implantation.

Results

AoV calcification was detected in all samples from individuals >50 years old, with severity increasing with age, independent of known CAVD risk factors. Two distinct types of calcification were identified: ‘Intrinsic’, primarily found at the leaflet hinge of postmortem leaflets, accompanied by abnormal collagen and proteoglycan deposition; and ‘Nodular’, extending from the middle to the tip regions in more severely affected postmortem leaflets and surgical specimens, associated with increased elastin fragmentation and loss of elastin integrity. Even in the absence of increased thickening, abnormalities in ECM composition were observed in postmortem leaflets without clinical AS and worsen in clinical AS.

Conclusions

Two distinct phenotypes of AoV calcification are apparent. While the ‘nodular’ form is recognised on in vivo imaging and is present with CAVD and valve dysfunction, it is unclear if the ‘intrinsic’ form is pathological or detected on in vivo imaging.
Initial layer and incompressible limit for Euler–Poisson equation in nonthermal plasma
Authors: Luo Tao , Wang Shu , Wang Yan-Lin
Published: June 2019

The singular limit from compressible Euler–Poisson equation in nonthermal plasma to incompressible Euler equation with an ill-prepared initial data is investigated in this paper by constructing approximate solutions of the appropriate order via an asymptotic expansion. Nonlinear asymptotic stability of initial layer approximation is established with the convergence rate.
Flood Risk Analysis on Terrains
Authors: Rav Mathias , Lowe Aaron , Agarwal Pankaj K.
Published: June 2019

An important problem in terrain analysis is modeling how water flows across a terrain and creates floods by filling up depressions. In this article, we study the
flooding query
problem: Preprocess a given terrain Σ, represented as a triangulated
xy
-monotone surface with
n
vertices, into a data structure so that for a query rain region
R
and a query point
q
on Σ, one can quickly determine how much rain has to fall in
R
so that
q
is flooded. Available terrain data is often subject to uncertainty, which must be incorporated into the terrain analysis. For instance, the digital elevation models of terrains have to be refined to incorporate underground pipes, tunnels, and waterways under bridges, but there is often uncertainty in their existence. By representing the uncertainty in the terrain data explicitly, we can develop methods for flood risk analysis that properly incorporate terrain uncertainty when reporting what areas are at risk of flooding.

We present two results. First, we present an
O
(
n
log
n
)-time algorithm for preprocessing Σ with a linear-size data structure that can answer a flooding query in
O
(|
R
| +
m
log
n
) time, where |
R
| is the number of vertices in
R
,
m
is the number of so-called tributaries of
q
at which rain is falling, and
n
is the number of vertices of the terrain. Next, we extend this data structure to handle “uncertain” terrains using a standard Monte Carlo method. Given a probability distribution on terrain data, our data structure returns the probability of a query point being flooded if a specified amount of rain falls on a query region. We implement our data structure and test it on real terrains, showing that a small number of samples suffice to accurately estimate the flood risk.
Interactive Mapping Specification with Exemplar Tuples
Authors: Bonifati Angela , Comignani Ugo , Coquery Emmanuel , Thion Romuald
Published: June 2019

While schema mapping specification is a cumbersome task for data curation specialists, it becomes unfeasible for non-expert users, who are unacquainted with the semantics and languages of the involved transformations.

In this article, we present an interactive framework for schema mapping specification suited for non-expert users. The underlying key intuition is to leverage a few exemplar tuples to infer the underlying mappings and iterate the inference process via simple user interactions under the form of Boolean queries on the validity of the initial exemplar tuples. The approaches available so far are mainly assuming pairs of complete universal data examples, which can be solely provided by data curation experts, or are limited to poorly expressive mappings.

We present a quasi-lattice-based exploration of the space of all possible mappings that satisfy arbitrary user exemplar tuples. Along the exploration, we challenge the user to retain the mappings that fit the user’s requirements at best and to dynamically prune the exploration space, thus reducing the number of user interactions. We prove that after the refinement process, the obtained mappings are correct and complete. We present an extensive experimental analysis devoted to measure the feasibility of our interactive mapping strategies and the inherent quality of the obtained mappings.