bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of hospital characteristics associated with improved mortality following complex upper gastrointestinal cancer surgery in Queensland
Authors: Narendra Aaditya , Baade Peter D. , Aitken Joanne F. , Fawcett Jonathan , Smithers Bernard M.
Published: September 2019

Background

High hospital‐volume and service capability are associated with improved mortality following complex cancer surgery. Using a population‐based study in Queensland, we assessed differences in mortality following oesophagectomy and pancreaticoduodenectomy, comparing high‐ and low‐volume hospitals stratified by service capability.

Methods

Data on all patients undergoing oesophagectomy and pancreaticoduodenectomy for cancer in Queensland between 2001 and 2015 were obtained from the Queensland Oncology Repository. Hospital service capability was defined using the 2015 Australian Institute of Health and Welfare hospital peer groupings. Hospitals were grouped into ‘high‐volume (≥6 oesophagectomies or pancreaticoduodenectomies annually) with high service capability'; ‘low‐volume (<6) with high service capability' and ‘low‐volume with low service capability'. Multivariate Poisson models were used to estimate differences in 30‐ and 90‐day mortality between hospital groups adjusting for age, sex, socioeconomic status, Charlson and American Society of Anesthesiologists scores, chemotherapy, radiotherapy, stage and time‐period.

Results

For oesophagectomy, adjusted 90‐day mortality was higher in low‐volume compared with high‐volume hospitals, regardless of service capability (low‐volume, high service: incident rate ratio (IRR) 3.86, 95% confidence interval (CI) 1.74–8.57; low‐volume, low service: IRR 3.40, 95% CI 1.16–10.00). For pancreaticoduodenectomy, mortality was higher in low‐volume compared with high‐volume centres regardless of service capability: 30‐day mortality (low‐volume, high service: IRR 2.32, 95% CI 1.07–5.03; low‐volume, low service: IRR 3.92, 95% CI 1.45–10.61); 90‐day mortality (low‐volume, high service: IRR 2.36, 95% CI 1.29–4.30; low‐volume, low service: IRR 3.32, 95% CI 1.64–6.71).

Conclusion

High hospital resection volumes are associated with lower post‐operative mortality following oesophagectomy and pancreaticoduodenectomy regardless of hospital service capability. This data supports centralization of these procedures to high‐volume centres.
Brief Report. A qualitative study of maternal mental health services in New Zealand: Perspectives of Māori and Pacific mothers and midwives
Authors: Holden Gabrielle , Corter Arden L. , Hatters‐Friedman Susan , Soosay Ian
Published: September 2019

Objectives

Suicide is the leading cause of maternal death in New Zealand particularly amongst Māori and Pacific. We explored current maternal mental health (MMH) screening practices and supports.

Methods

Qualitative research included interviews and focus groups with maternity carers and mothers of Māori and Pacific descent. Thematic analysis used a general inductive approach.

Results

Both mothers and carers reported that MMH screening is ad hoc and discussed multilevel barriers that hamper screening and access to supports.

Conclusion

There are gaps in MMH services, and service improvements need to be targeted at patient, provider, and systems levels.
Supporting the mental health of mothers of children with a disability: Health professional perceptions of need, role, and challenges
Authors: Gilson Kim‐Michelle , Johnson Shae , Davis Elise , Brunton Susan , Swift Elena , Reddihough Dinah , Williams Katrina
Published: September 2019

Background

Mothers of children with a disability have a higher risk of mental health difficulties than mothers of typically developing children. Very little is known about how health professionals perceive their role in supporting mothers' mental health. We aimed to explore the perspectives of health professionals working with families of children with a disability about how they provide support for maternal mental health in their roles. Specifically, whether professionals consider it their role and responsibility to provide support, the types of actions that they engage in to do this, and the challenges that they experience.

Methods

This qualitative semi‐structured interview study included 13 health professionals (allied health professionals, general practitioners, and paediatricians) working with families of a child with a disability. Thematic analysis was conducted on transcribed interview data.

Results

Four overlapping themes were identified from the data indicating that professionals knew that mothers needed mental health support but were not always clear about their roles and responsibilities to support maternal mental health. Professionals also found it difficult to address maternal mental health difficulties, were not always aware of the best strategies to support maternal mental health, and faced difficulties that could be overcome with training and system improvements.

Conclusions

Although all health professionals were aware of the frequent occurrence of maternal mental health difficulties and the importance of addressing them, several challenges were identified to managing them successfully. Providing health professionals with training in discussing mental health and clearer referral pathways would contribute to mothers being better supported, in addition to policy change that allows parental support in child health services.
Performance measures in inflammatory bowel disease surveillance colonoscopy: Implementing changes to practice improves performance
Authors: Smith Samuel C. L. , Cannatelli Rosanna , Bazarova Alina , Sharma Neel , McCulloch Adam , Mak Jason , Shivaji Uday N. , Iqbal Tariq , Kane Kate , Ghosh Subrata , Cooney Rachel , Iacucci Marietta
Published: September 2019

Background and Aim

Dye‐based chromoendoscopy (DCE) with targeted biopsies is recommended for inflammatory bowel disease (IBD) surveillance. However, DCE has not yet been widely adopted into clinical practice. We evaluated quality indicators in IBD surveillance following introduction of structured changes in service delivery.

Methods

In August 2016, we introduced a number of changes to IBD surveillance practice in our endoscopy unit. These included training using interactive videos/images in a structured module, DCE as standard by using a foot‐pedal operated pump jet, allocation of 45‐minute procedure timeslots, targeted biopsies (except in high‐risk patients), scoring of endoscopic disease activity, and lesion detection/morphology characterization. All IBD surveillance colonoscopies were allocated to a small team of four DCE‐trained endoscopists. We compared quality measures for surveillance procedures carried out pre‐ and post‐August 2016. The two groups were compared using chi‐squared statistics

Results

A total of 598 IBD surveillance procedures (277 pre‐August 2016 and 321 post‐August 2016) were done and included in the study. Use of DCE increased (54.2% vs 76.0% P < 0.0005) whereas random biopsy surveillance decreased (12.3% vs 3.1% P < 0.0005). Use of Paris classification (26.1% vs 57.0% P < 0.0005) and Kudo pit pattern increased (21.7% vs 59.0% P < 0.0005). There was also an increase in lesion detection rate (24.9% vs 33.1% P < 0.05).

Conclusions

Implementation of extensive changes in practice of surveillance colonoscopy resulted in significant improvement in quality indicators within a short period of time. Training, education and audit may continue to facilitate the adoption of DCE and further improve quality of performance in IBD surveillance.
Crack closure in friction stir weldment using non‐linear model for fatigue crack propagation
Authors: Lepore Marcello Antonio , Maligno Angelo Rosario , Berto Filippo
Published: September 2019

The fatigue crack propagation in a friction stir‐welded sample has been simulated herein by means of two 3‐dimensional finite element method (FEM)‐based analyses. Numerical simulations of the fatigue crack propagation have been carried out by assuming a residual stress field as a starting condition. Two initial cracks, observed in the real specimen, have been assessed experimentally by performing fatigue tests on the welded sample. Hence, the same cracks have been placed in the corresponding FE model, and then a remote load with boundary conditions has been applied on the welded specimen. The material behaviour of the welded joint has been modelled by means of the Ramberg‐Osgood equation, while the non‐linear Kujawski‐Ellyin (KE) model has been adopted for the fatigue crack propagation under small‐scale yielding (SSY) conditions. Owing to the compressive nature of the residual stress field that acts on a part of the cracked regions, the crack closure phenomenon has also been considered. Then, the original version of the KE law has been modified to fully include the closure effect in the analysis. Later, the crack closure effect has also been assessed in the simulation of fatigue propagation of three cracks. Finally, an investigation of the fracture process zone (FPZ) extension as well as the cyclic plastic zone (CPZ) and monotonic plastic zone (MPZ) extensions have been assessed.
Political connections and informed trading: Evidence from TARP
Authors: Akin Ozlem , Coleman Nicholas S. , Fons‐Rosen Christian , Peydró José‐Luis
Published: September 2019

We study insider trading behavior surrounding the largest bank bailout in history: Troubled Asset Relief Program (TARP). In politically connected banks, insider buying during the pre‐TARP period is associated with increases in abnormal returns around bank‐specific TARP announcement; for unconnected banks, trading and returns are uncorrelated. Results hold across insiders within the same bank and are stronger for finance‐related government connections. Through a Freedom of Information Act request, we obtained the previously undisclosed TARP funds requested; the ratio of received to requested funds correlates both with abnormal returns and insider buying behavior in connected banks.
Morphological, immunophenotypical and molecular features of hypermutation in colorectal carcinomas with mutations in DNA polymerase ε (POLE)
Authors: Forgó Erna , Gomez Adam J , Steiner David , Zehnder James , Longacre Teri A
Published: September 2019

Aims

Colorectal carcinomas (CRC) with mismatch repair (MMR) deficiency have increased tumour mutation burden and respond to immune check‐point inhibitor therapy. The Cancer Genome Atlas identified hypermutated CRCs with somatic mutations in DNA polymerase ε (POLE) with mutation burdens exceeding that of MMR‐deficient CRCs.

Methods and results

To identify the morphological, immunophenotypical and molecular features of POLE‐mutated CRCs, 63 consecutive MMR‐intact CRCs were evaluated by Sanger sequencing for POLE exonuclease domain mutations in exons 9, 11, 13 and 14 and confirmed by next‐generation sequencing. Tumour immune microenvironment and IMMUNOSCORE®1 were assessed in POLE‐mutated CRCs using immunohistochemistry to detect CD3+/CD8+ tumour‐infiltrating lymphocytes and compared to 59 non‐POLE mutated MMR‐intact CRC, 10 non‐POLE mutated MMR‐deficient CRCs and 223 normal colonic mucosa.

Conclusions

A total of 4.8% CRC (four MMR‐intact primary and one MMR‐intact metastasis) harboured POLE mutations in amino acid 286 in exon 9 (p.P286R) or exon 13 (p.V411L). POLE‐mutated CRCs arose in the transverse colon and rectum, were male‐predominant, younger and showed increased tumour‐infiltrating lymphocytes and immune cells at the tumour–stromal interface. The patient with metastatic POLE‐mutated CRC was placed on PD‐1 inhibitor treatment with marked and sustained response. These data indicate that POLE‐mutated CRCs have hypermutated phenotypes despite MMR‐intact status, with mutation burdens higher than that in microsatellite‐unstable CRCs. Given the recent approval for treatment of microsatellite‐unstable cancer with immune check‐point inhibitors, assessment of POLE status may help to guide therapeutic decisions for hypermutated tumours with intact MMR that would otherwise be missed by routine testing.
Application of a decision tree to establish factors associated with a nomogram of aortic stiffness
Authors: Vallée Alexandre , Safar Michel E. , Blacher Jacques
Published: September 2019

Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular (CV) diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. A nomogram of aortic stiffness was evaluated by the calculation of PWV index. Theoretical PWV can be calculated according to age, gender, mean blood pressure, and heart rate, allowing to form an individual PWV index [(measured PWV – theoretical PWV)/theoretical PWV]. The purpose of the present cross‐sectional study was to investigate the determinants of the PWV index, by applying a decision tree. A cross‐sectional study was conducted from 2012 to 2017, and 597 individuals were included. A training decision tree was constructed based on seventy percent of these subjects (N = 428). The remaining 30% (N = 169) were used as the testing dataset to evaluate the performance of the decision trees. The input variables for the models were clinical and biochemical parameters. The different input variables remained in the model were diabetes, tobacco status, carotid plaque, albuminuria, C‐reactive protein, total cholesterol, BMI, and previous CV diseases. For the validation decision model, the sensitivity, specificity, and accuracy values for identifying the related risk factors of PWV index were 70%, 78%, and 0.73. Since determinants of PWV index were all well‐accepted CV risk factors, a nomogram of aortic stiffness could be considered as an integrator of CV risk factors on their duration of exposure and could be utilized to develop future programs for CV risk assessment and reduction strategies.
Serial exposure to ethanol drinking and methamphetamine enhances glutamate excitotoxicity
Authors: Blaker Amanda L. , Moore Elizabeth R. , Yamamoto Bryan K.
Published: September 2019

A significant comorbidity exists between alcohol and methamphetamine (Meth) abuse but the neurochemical consequences of this co‐abuse are unknown. Alcohol and Meth independently and differentially affect glutamatergic transmission but the unique effects of their serial exposure on glutamate signaling in mediating damage to dopamine neurons are unknown. Sprague–Dawley rats had intermittent voluntary access to 10% ethanol (EtOH) every other day and water over 28 days and were then administered a binge injection regimen of Meth or saline. EtOH drinking decreased the glutamate aspartate transporter and increased basal extracellular concentrations of glutamate within the striatum when measured after the last day of drinking. Ceftriaxone is known to increase the expression and/or activity of glutamate transporters in the brain and prevented both the decreases in glutamate aspartate transporter and the increases in basal extracellular glutamate when administered during EtOH drinking. EtOH drinking also exacerbated the acute increases in extracellular glutamate observed upon Meth exposure, the subsequent increases in spectrin proteolysis, and the long‐term decreases in dopamine content in the striatum, all of which were attenuated by ceftriaxone administration during EtOH drinking only. These results implicate EtOH‐induced increases in extracellular glutamate and corresponding decreases in glutamate uptake as mechanisms that contribute to the vulnerability produced by EtOH drinking and the unique neurotoxicity observed after serial exposure to Meth that is not observed with either drug alone.

image

Open Science: This manuscript was awarded with the Open Materials Badge

For more information see: https://cos.io/our-services/open-science-badges/
miRNAs as biomarkers of orofacial clefts: A systematic review
Authors: Mendes Sissy Maria Dos Anjos , Espinosa Daybelis Del Socorro González , Moreira Paulo Eliezer De Oliveira , Marques Diego , Fagundes Nathalia Carolina Fernandes , Ribeiro‐dos‐Santos Ândrea
Published: September 2019

Orofacial clefts are facial malformations caused by the improper development of the lips and palate. Many genetic and epigenetic molecules have been involved in the mechanisms of orofacial clefts, one of which are miRNAs. This systematic review aimed to identify miRNAs associated to non‐syndromic orofacial clefts in humans. After applying a series of criteria, four studies were selected for analysis. In total, one hundred miRNAs were observed in the literature, of which 57 were reported as upregulated and 43 as downregulated in all orofacial cleft classifications. Moreover, nine miRNAs were differentially expressed only in cleft palate patients, which might suggest distinct regulatory mechanisms for the etiology of cleft lips and palates. We suggest broader population sampling in order to include diverse ethnic groups in the future, as well as analyses toward identifying miRNA target genes and pathways. We highlight the need for experimental validation and of these results to allow further translational approaches and clinical applications.
Alcohol Expectancies Moderate the Association Between School Connectedness and Alcohol Consumption
Authors: Cummins Kevin M. , Diep Sherry A. , Brown Sandra A.
Published: September 2019

BACKGROUND

In this study, we investigate the moderated association of school connectedness and alcohol expectancies with adolescent drinking.

METHODS

Two large community samples were obtained with 2 repeated attempted censuses of all students attending a large suburban school district. Participants completed a self‐administered questionnaire that assessed substance use, alcohol expectancies, and school connectedness. We used logistic regression analyses on the training sample and confirmed with Bayesian test intervals with the test sample.

RESULTS

Party related alcohol expectancies and school connectedness interacted in their explanatory association with recent drinking and binging, such that school connectedness had a protective association only for youth with lower positive expectancies. These findings were the result of pre‐planned exploratory analysis, which were confirmed with out‐of‐sample test data.

CONCLUSIONS

The potential benefits for student health behaviors resulting from improved school connectedness may be dependent on at least one dimension of alcohol expectancies, at the individual level.
Associations between estimated foetal weight discordance and clinical characteristics within dichorionic twins: The NICHD Fetal Growth Studies
Authors: Amyx Melissa M. , Albert Paul S. , Bever Alaina M. , Hinkle Stefanie N. , Owen John , Grobman William A. , Newman Roger B. , Chien Edward K. , Gore‐Langton Robert E. , Buck Louis Germaine M. , Grantz Katherine L.
Published: September 2019

Background

Birthweight discordance is well studied, with less known about longitudinal inter‐twin differences in foetal growth.

Objective

To examine inter‐twin per cent differences in EFW (EFW%), head (HC%) and abdominal circumference (AC%), and femur length (FL%) across gestation in dichorionic twin gestations and explore associated characteristics.

Methods

Foetal biometrics were assessed by ultrasound and EFW calculated at ≤6 study visits among women with dichorionic twin pregnancies enrolled in the NICHD Fetal Growth Studies cohort (US, 2012‐2013). Inter‐twin per cent difference was defined: ([Sizelarger twin − Sizesmaller twin]/Sizelarger twin × 100). Linear mixed models evaluated per cent differences in foetal biometrics at 15 weeks and their change per week overall and by maternal/neonatal characteristics in unadjusted and adjusted models.

Results

In 140 pregnancies, inter‐twin per cent differences increased across gestation for EFW (0.18%/week, 95% confidence interval [CI] 0.10, 0.27), HC (0.03%/week, 95% CI 0.00, 0.06), and AC (0.03%/week, 95%CI −0.01, 0.08) but decreased for FL (−0.03%/week, 95% CI −0.09, 0.02). After adjustment, change in EFW% difference across gestation differed by pre‐pregnancy body mass index (BMI [kg/m2]; underweight [<18.5]; normal weight [18.5‐24.9]; overweight [25.0‐29.9]; obese [≥30.0]; Pinteraction = .022); and conception method (in vitro fertilisation [IVF], intrauterine insemination, ovulation induction medication, donor egg/embryo, none; Pinteraction = .060). While EFW% difference increased with normal pre‐pregnancy BMI (0.24%/week, 95% CI 0.12, 0.37), little change was noted with pre‐pregnancy obesity (0.01%/week, 95% CI −0.15, 0.17). EFW% difference increased in conceptions without fertility treatments (0.23%/week, 95% CI 0.11, 0.34) but not IVF conceptions (−0.00%/week, 95% CI −0.16, 0.16). Similar patterns of differences across gestation were noted for HC% by conception method (Pinteraction = .026) and AC% by pre‐pregnancy BMI (Pinteraction = .071); changes in HC% differed by parity (nulliparous, multiparous; Pinteraction = .004).

Conclusions

EFW% difference increased across gestation in dichorionic twins, but remained stable with pre‐pregnancy obesity or IVF conception, patterns mirrored for HC and AC. Research is needed to understand pathologic versus physiologic differential twin growth trajectories.
Generalized and Institutional Trust: Their Impacts on First‐ and Second‐Order Environmental Cooperation
Authors: Irwin Kyle
Published: September 2019

Environmental issues remain problematic, but a growing body of work shows that trust is a solution. Yet, studies offer competing arguments on what type of trust promotes cooperation, generalized versus institutional trust. Further, previous studies use a variety of measures to define environmental cooperation, including membership in environmental groups, recycling garbage, and purchasing green products. These measures are unalike but often considered as analogous. I argue that environmental measures fit within one of two frameworks: first‐order cooperation or second‐order cooperation. To address these discrepancies, I use 2000 and 2010 General Social Survey waves to determine how generalized trust and institutional trust differently affect first‐ and second‐order environmental cooperation. The findings indicate that generalized trust is strongly linked to both forms of environmental cooperation, but the relationship of institutional trust on first‐ and second‐order cooperation is inconsistent.
Implementation of Nurse‐Driven HIV Screening Targeting Key Populations in Emergency Departments: A Multilevel Analysis From the DICI‐VIH Trial
Authors: Leblanc Judith , Côté José , Pagé M. Gabrielle , Piquet Hélène , Simon Tabassome , Crémieux Anne‐Claude ,   the DICI‐VIH (Dépistage Infirmier CIblé du VIH) Group
Published: September 2019

Background

In countries with concentrated HIV epidemics, optimizing screening to reach individuals with undiagnosed infection is essential. The DICI‐VIH study, a cluster‐randomized crossover trial conducted in eight French emergency departments (EDs), found that a strategy combining nurse‐driven targeted HIV screening with routine diagnostic testing was effective.

Aim

The aim was to investigate factors associated with the implementation of HIV screening targeting key populations in EDs.

Methods

A self‐administered questionnaire was distributed at registration to patients aged 18–64 years and able to give consent during the DICI‐VIH intervention. Based on their responses, those belonging to key populations were offered a rapid test by triage nurses. Two key stages of the process were evaluated: questionnaire distribution by providers and test acceptance by patients. Patient information, daily workload, and ED characteristics were collected. The associations between these variables and (a) the proportion of questionnaires distributed and (b) the proportion of tests accepted were evaluated using multilevel modeling in order to examine differences in screening implementation between EDs.

Results

Questionnaire distribution proportions varied from 23% to 48% across EDs. They were higher on weekdays than weekends (odds ratio, OR: 3.77; 95% CI: 3.57–3.99) and when research staff participated (OR: 1.31; 95% CI: 1.26–1.37). They decreased over time (OR: 0.76; 95% CI: 0.71–0.82; 4th [Q3] vs. 1st quartile [Q0] of intervention days) and with increased patient flow (OR: 0.61; 95% CI: 0.56–0.67; Q3 vs. Q0 of eligible patients). Test acceptance varied from 64% to 77% across EDs, increased with research staff participation (OR 1.20; 95% CI: 1.03–1.40), and decreased over time (OR: 0.75; 95% CI: 0.60–0.92; Q3 vs. Q0). Patients who accepted were more likely to be younger (OR: 0.76; 95% CI: 0.61–0.96; 50–64‐year‐old vs. 30–39‐year‐old patients).

Linking Evidence to Action

Patient flow, intervention duration, weekdays, and research staff participation were important determinants of targeted screening implementation. These findings could help guide future implementation in similar settings.
Face Recognition on Bag Locking Mechanism
Authors: Ishak Mohamad Hafis Izran , Idris Nurul Hawani , Sahlan Shafishuhaza
Published: September 2019

With the emergent of biometric technology, people are no longer afraid to keep their important things in the safe box or room or even facility. This is because; human beings have unique features that distinguish them with other people. The scheme is based on an information theory approach that decomposes face images into a small set of characteristic feature images called ‘Eigenfaces’, which are actually the principal components of the initial training set of face images. In this report, thorough explanation on design process of face recognition on bags locking mechanism will be elucidated. The results and analysis of the proposed design prototype also presented and explained. The platform for executing the algorithm is on the Raspberry Pi. There are two artificial intelligent techniques applied to manipulate and processing data which is fuzzy logic and neural networks. Both systems are interdependent with each other, so that it can calculate and analyse data precisely. The receive image from the camera is analysed through the Eigenfaces algorithm. The algorithm is using Principal Component Analysis (PCA) method which comprise of artificial neural network paradigm and also statistical paradigm.
Millimeter Wave Fifth Generation (5G) Antenna for Smartphone Application
Authors: Azmi Fatin Iswani , Zubir Farid , Muhamad Nadzir Norsaidah
Published: September 2019

In this paper, a single element antenna is designed at millimeter-wave frequency bands for future 5G smartphone applications. The configuration of proposed antenna is multiple L-slots on the ground plane which is designed on a low cost FR4 board. The antenna covers a frequency range between 28 to 35 GHz with a higher bandwidth 4.7 GHz. The antenna shows an excellent performance when integrated with the mobile phone application. The single element antenna exhibits a maximum radiation pattern around 5.945 dBi.
Trajectory Measurement of Radial Jet Drilling Wells: Improved Tool and Data Processing
Authors: Huang Zhe , Huang Zhongwei , Wu Long , Su Yinao , Hong Chunyang
Published: September 2019

Drilling by high-pressure liquid jet, radial jet drilling (RJD) is a cost-effective technology to restimulate the production of old wells and the development of unconventional reservoirs. However, due to the unique process of 90 deg turning in the casing, hardly any traditional tool can be applied in the RJD trajectory measurement. Even minitools have been developed in the last few years; the increasing cost and unpredictable failure risk of lateral re-entrance are still non-negligible as the current design, much less than the huge measuring errors. In this paper, a new tool was proposed. Based on a special-shaped circuit board and separation of the supporting section, a fluid passageway was reserved in the measuring section to realize the measurement while or after the jet drilling without extra trips. It reduces the cost and failure risk of lateral re-entrance. Ample space in the supporting section was also provided, which meets the long-time operation requirements and establishes the base for real-time communication and trajectory control. Based on noise analyses, random walk is the main source of system noise in short-time measurements, and the effective measuring frequency is mostly in the range of 0–5 Hz. Therefore, autoregressive moving average (ARMA) models, Kalman filter, and low-pass filter were established for denoising. It allows us to analyze the data feature in more detail and extract the valid measuring data with improved accuracy. Considering performance tests result, the average errors of reckoned parameters were improved to less than 15%.
The Malaria Cell Atlas: Single parasite transcriptomes across the complete
Plasmodium
life cycle
Authors: Howick Virginia M. , Russell Andrew J. C. , Andrews Tallulah , Heaton Haynes , Reid Adam J. , Natarajan Kedar , Butungi Hellen , Metcalf Tom , Verzier Lisa H. , Rayner Julian C. , Berriman Matthew , Herren Jeremy K. , Billker Oliver , Hemberg Martin , Talman Arthur M. , Lawniczak Mara K. N.
Published: September 2019

Mapping the malaria parasite

Several species of the parasite
Plasmodium
cause human malarial diseases, and, despite determined control efforts, a huge global disease burden remains. Howick
et al.
present a single-cell analysis of transcription across the malaria parasite life cycle (see the Perspective by Winzeler). Single-cell transcriptomes generated from 10 different life-cycle stages of the rodent-model malaria parasite
P. berghei
identified 20 “modules” among 5156 core transcriptome genes. These clusters enabled functional assignment of hypothetical and conserved genes, and they hint at further substructure of established life-cycle stages. The atlas also allowed for
P. falciparum
and
P. malariae
transcriptomes from patient isolates to be deconvoluted and for classification of parasitemia according to developmental stage.

Science
, this issue p.
eaaw2619
; see also p.
753
The slow earthquake spectrum in the Japan Trench illuminated by the S-net seafloor observatories
Authors: Nishikawa T. , Matsuzawa T. , Ohta K. , Uchida N. , Nishimura T. , Ide S.
Published: September 2019

Slow earthquake segmentation

The Japan Trench is responsible for disastrous megathrust earthquakes like the 2011 Tohoku-Oki quake. Nishikawa
et al.
used new observations from the S-net ocean-bottom seismic network to map slow earthquakes—disturbances that do not cause ground shaking—along the Japan Trench (see the Perspective by Houston). They found that the area that ruptured during the 2011 quake was bounded by areas that have large numbers of slow earthquakes. A segmentation likely caused the 2011 rupture to cease, an observation that is important for assessing risk from future major earthquakes.

Science
, this issue p.
808
; see also p.
750
Reducing tropical deforestation
Authors: Seymour Frances , Harris Nancy L.
Published: September 2019

The interventions required to reduce deforestation differ widely across the tropics
Impact of aging on the immune response to traumatic brain injury (AIm:TBI) study protocol
Authors: Thompson Hilaire J , Rivara Frederick , Becker Kyra J , Maier Ronald , Temkin Nancy
Published: September 2019

Background

Traumatic brain injury (TBI) in older adults leads to considerable morbidity and mortality. Outcomes among older adults with TBI are disparately worse than in younger adults. Differences in immunological response to injury may account for at least some of this disparity. Understanding how ageing differentially affects the immune response to TBI and how older age and these immunological changes affect the natural history of recovery following TBI are the goals of this study.

Design/methods

A prospective multiple cohort design is being used to assess the effects of ageing and TBI on immune makers and to test predictors of impairment and disability in older adults following mild TBI. Older adults (>55 years) with mild TBI are enrolled with three comparison groups: younger adults (21–54 years) with mild TBI, non-injured older adults (>55 years) and non-injured young adults (21–54 years). For the primary analysis, we will assess the association between immune markers and Glasgow Outcome Scale-Extended at 6 months, using logistic regression. Predictors of interest will be inflammatory biomarkers. Multivariate linear regression will be used to evaluate associations between biomarkers and other outcomes (symptoms, function and quality of life) at 3 and 6 months. Exploratory analyses will investigate the utility of biomarkers to predict outcome using receiver-operating characteristic curves.

Discussion

A better understanding of the recovery trajectory and biological rationale for disparate outcomes following TBI in older adults could allow for development of specific interventions aimed at reducing or eliminating symptoms. Such interventions could reduce impairment and healthcare costs.
A Crucial Role for Diet in the Relationship Between Gut Microbiota and Cardiometabolic Disease
Authors: Attaye Ilias , Pinto-Sietsma Sara-Joan , Herrema Hilde , Nieuwdorp Max
Published: September 2019

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.
Pancreatic β-cell-specific deletion of insulin-degrading enzyme leads to dysregulated insulin secretion and β-cell functional immaturity
Authors: Fernández-Díaz Cristina M. , Merino Beatriz , López-Acosta José F. , Cidad Pilar , de la Fuente Miguel A. , Lobatón Carmen D. , Moreno Alfredo , Leissring Malcolm A. , Perdomo Germán , Cózar-Castellano Irene
Published: September 2019

Inhibition of insulin-degrading enzyme (IDE) has been proposed as a possible therapeutic target for type 2 diabetes treatment. However, many aspects of IDE's role in glucose homeostasis need to be clarified. In light of this, new preclinical models are required to elucidate the specific role of this protease in the main tissues related to insulin handling. To address this, here we generated a novel line of mice with selective deletion of the Ide gene within pancreatic beta-cells, B-IDE-KO mice, which have been characterized in terms of multiple metabolic end points, including blood glucose, plasma C-peptide, and intraperitoneal glucose tolerance tests. In addition, glucose-stimulated insulin secretion was quantified in isolated pancreatic islets and beta-cell differentiation markers and insulin secretion machinery were characterized by RT-PCR. Additionally, IDE was genetically and pharmacologically inhibited in INS-1E cells and rodent and human islets, and insulin secretion was assessed. Our results show that, in vivo, life-long deletion of IDE from beta-cells results in increased plasma C-peptide levels. Corroborating these findings, isolated islets from B-IDE-KO mice showed constitutive insulin secretion, a hallmark of beta-cell functional immaturity. Unexpectedly, we found 60% increase in Glut1 (a high-affinity/low- Km glucose transporter), suggesting increased glucose transport into the beta-cell at low glucose levels, which may be related to constitutive insulin secretion. In parallel, IDE inhibition in INS-1E and islet cells resulted in impaired insulin secretion after glucose challenge. We conclude that IDE is required for glucose-stimulated insulin secretion. When IDE is inhibited, insulin secretion machinery is perturbed, causing either inhibition of insulin release at high glucose concentrations or constitutive secretion.
ATMIN Is a Tumor Suppressor Gene in Lung Adenocarcinoma
Authors: Foster Hanna , Ruiz E. Josue , Moore Christopher , Stamp Gordon W. H. , Nye Emma L. , Li Ningning , Pan Yihang , He Yulong , Downward Julian , Behrens Axel
Published: September 2019

Tumor cells proliferate rapidly and thus are frequently subjected to replication stress and the risk of incomplete duplication of the genome. Fragile sites are replicated late, making them more vulnerable to damage when DNA replication fails to complete. Therefore, genomic alterations at fragile sites are commonly observed in tumors. FRA16D is one of the most common fragile sites in lung cancer, however, the nature of the tumor suppressor genes affected by FRA16D alterations has been controversial. Here, we show that the ATMIN gene, which encodes a cofactor required for activation of ATM kinase by replication stress, is located close to FRA16D and is commonly lost in lung adenocarcinoma. Low ATMIN expression was frequently observed in human lung adenocarcinoma tumors and was associated with reduced patient survival, suggesting that ATMIN functions as a tumor suppressor in lung adenocarcinoma. Heterozygous Atmin deletion significantly increased tumor cell proliferation, tumor burden, and tumor grade in the LSL-KRasG12D; Trp53 F/F (KP) mouse model of lung adenocarcinoma, identifying ATMIN as a haploinsufficient tumor suppressor. ATMIN-deficient KP lung tumor cells showed increased survival in response to replication stress and consequently accumulated DNA damage. Thus, our data identify ATMIN as a key gene affected by genomic deletions at FRA16D in lung adenocarcinoma.

Significance:

These findings identify ATMIN as a tumor suppressor in LUAD; fragility at chr16q23 correlates with loss of ATMIN in human LUAD and deletion of Atmin increases tumor burden in a LUAD mouse model.
Syndecan-Mediated Ligation of ECM Proteins Triggers Proliferative Arrest of Disseminated Tumor Cells
Authors: Shibue Tsukasa , Reinhardt Ferenc , Weinberg Robert A.
Published: September 2019

Systemic dissemination of tumor cells often begins long before the development of overt metastases, revealing the inefficient nature of the metastatic process. Thus, already at the time of initial clinical presentation, many patients with cancer harbor a myriad disseminated tumor cells (DTC) throughout the body, most of which are found as mitotically quiescent solitary cells. This indicates that the majority of DTCs fail, for still unknown reasons, to initiate rapid proliferation after entering foreign tissue, which likely contributes significantly to the inefficiency of metastasis formation. Here, we showed that extracellular matrix (ECM) components of the host parenchyma prevented proliferation of DTCs that had recently infiltrated foreign tissue by binding to syndecan receptors expressed on the surface of these cells. This led to the recruitment of the Par-3:Par-6:atypical PKC protein complex, a critical regulator of cell polarity, to the plasma membrane and release of Par-1 kinase into the cytosol. Cytosolic Par-1 bound, phosphorylated, and inactivated KSR scaffolding proteins ultimately inhibited Ras/ERK signaling and, in turn, cell proliferation. Inhibition of the syndecan-mediated signaling restored the proliferation of otherwise dormant DTCs, enabling these cells to efficiently colonize foreign tissues. Intriguingly, naturally aggressive cancer cells overcame the antiproliferative effect of syndecan-mediated signaling either by shutting down this signaling pathway or by activating a proproliferative signaling pathway that works independent of syndecan-mediated signaling. Collectively, these observations indicate that the proliferative arrest of DTCs is attributable, in part, to the syndecan-mediated ligation of ECM proteins.

Significance:

This study identifies a novel signaling pathway that regulates the proliferative dormancy of individual disseminated tumor cells.
DUBbing Down Translation: The Functional Interaction of Deubiquitinases with the Translational Machinery
Authors: Kapadia Bandish B. , Gartenhaus Ronald B.
Published: September 2019

Cancer cells revamp the regulatory processes that control translation to induce tumor-specific translational programs that can adapt to a hostile microenvironment as well as withstand anticancer therapeutics. Translational initiation has been established as a common downstream effector of numerous deregulated signaling pathways that together culminate in prooncogenic expression. Other mechanisms, including ribosomal stalling and stress granule assembly, also appear to be rewired in the malignant phenotype. Therefore, better understanding of the underlying perturbations driving oncogenic translation in the transformed state will provide innovative therapeutic opportunities. This review highlights deubiquitinating enzymes that are activated/dysregulated in hematologic malignancies, thereby altering the translational output and contributing to tumorigenesis.
HLA Matching in Unrelated Stem Cell Transplantation up to Date
Authors: Fürst Daniel , Neuchel Christine , Tsamadou Chrysanthi , Schrezenmeier Hubert , Mytilineos Joannis
Published: September 2019

Unrelated hematopoietic stem cell transplantation (HSCT) has evolved from an experimental protocol to a potentially curative first-line treatment in certain disease instances. Factors enabling this transformation were the optimization of treatment protocols and supportive care as well as the availability of a large number of donors worldwide along with the higher quality and reliability of HLA typing. The main criterion for donor selection is HLA compatibility. In this review we discuss the current clinical evidence of HLA matching in unrelated HSCT. In this context, we address methodical aspects of transplantation immunobiology research and discuss the impact of locus and resolution of HLA differences. Furthermore, we address special constellations such as unidirectional mismatches or the presence of nonexpressed alleles as well as HLA alloimmunization and describe the perspective for HLA typing and matching strategies in the future, given the implementation of novel complete or near-complete gene typing approaches using next-generation sequencing short read technology, which are now entering the standard of clinical care.
A questão da Soberania em África como uma peça teatral
Authors: Jesus Luciano Mendes de , Pereira Sayonara Sousa
Published: September 2019

Este artigo propõe a articulação de ideias no campo dos estudos das relações internacionais em África em diálogo com as possibilidades do teatro como um campo experimental de observação de fatos sociopolíticos, a partir da oposição entre a visão afrocentrada de Grovogui e a visão ocidental de Jackson sobre as construções sociopolíticas dos Estados e noções de soberania em África, tendo por base um fato histórico envolvendo a figura de Tierno Bokar, líder religioso islâmico do Mali. Partindo deste caso, reflito sobre como a figura histórica do líder malinês foi retratada em cena pelo griot e ator Sotigui Kouyaté (Mali/Burkina Faso), no espetáculo também intitulado Tierno Bokar, dirigido por Peter Brook, com atores de múltiplas nacionalidades do Centre International de Recherche Théâtrale (Cirt). Desta forma o grupo teatral é analisado como um laboratório para se pensar as relações internacionais num jogo transversal envolvendo cultura e política.
1968 – Grupo Teatro Escambray
Authors: Scudeler Camila
Published: September 2019

Fundado em 1968, o Grupo Teatro Escambray é um dos grupos icônicos da América Latina. O trabalho desenvolvido na zona rural de Cuba, no centro da ilha, marca a história do teatro cubano. São cinquenta anos de dedicação sistemática ao teatro, de maneira ininterrupta, criando e dialogando com a comunidade. Neste artigo expomos o contexto cubano que tornou possível essa iniciativa teatral sem precedentes no país.
A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes
Authors: Chew Derek P. , Lambrakis Kristina , Blyth Andrew , Seshadri Anil , Edmonds Michael J.R. , Briffa Tom , Cullen Louise A. , Quinn Stephen , Karnon Jonathan , Chuang Anthony , Nelson Adam J. , Wright Deborah , Horsfall Matthew , Morton Erin , French John K. , Papendick Cynthia
Published: September 2019

Background:

High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED).

Methods:

Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression.

Results:

In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49–70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%,
P
<0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4–6.4] hours versus standard arm: 5.6 (interquartile range, 4.0–7.1) hours,
P
<0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%,
P
<0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 18/1646 [1.1%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53–2.11], noninferiority
P
value=0.001, superiority
P
value=0.744), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0–99.9%) for 30-day death or myocardial infarction.

Conclusions:

This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients.

Clinical Trial Registration:

URL:
https://www.anzctr.org.au
. Unique identifier: ACTRN12615001379505.