bluuebunny/crossref_metadata_2025 huggingface dataset:
External Hazard Coinciding With Small Break LOCA—Thermohydraulic Calculation With System Code ATHLET
Authors: Kosowski Kai , Seidl Marcus
Published: October 2019

The safety behaviors of a nuclear power plant (NPP) after an external hazard-initiated event, as well as after a small break (SB) loss of coolant accident (LOCA), are already well known as part of the analyses made for standard license application. The coincidence of both events leads to a beyond-design basis consideration. Such a combination of both event categories is investigated by means of the thermohydraulic system code ATHLET. The scenario assumes an external event with a LOCA caused by induced vibrations on a small pipe attached to the primary circuit, although all pipes are designed to withstand the loads created by such an external event. Furthermore, in the context of both robustness and enveloping analyses, both a loss of offsite power (LOOP) and an unavailability of the emergency diesel power supply are postulated. The NPP in the scenario considered only has access to the passive accumulators and to systems supplied via the safeguard emergency diesel engines (second quartet of emergency diesel engines), which are housed in the bunkered emergency feed building. The dedicated type of external event itself is not in focus, but rather the thermohydraulic behavior of the NPP is considered. Apart from the model's assumptions, the accident sequence is explained in detail. The remaining systems for emergency core cooling are capable of handling the LOCA under such demanding boundary conditions. Long-term cooling can be ensured. Furthermore, heat removal out of the core is always sufficient. Eventually, all safety protection objectives have been complied for this beyond-design basis scenario.
Method Based on Characteristic Ray Information for Arbitrary Geometry Volume Calculation in NECP-X
Authors: Zhou Xinyu , Liu Zhouyu , Cao Lu , Cao Liangzhi , Wu Hongchun , Han Yu , Tang Chuntao
Published: October 2019

The constructive solid geometry (CSG) method is widely used in the Monte Carlo community because of its geometry flexibility. As the requirements of designing new reactors and development of deterministic methods, the CSG method is adopted for the geometry modeling in the deterministic numerical nuclear reactor physics codes to construct complex geometries in recent years. In the new developed numerical nuclear reactor physics code NECP-X, the CSG method is also implemented to expand its geometric modeling capability, but it is difficult to efficiently calculate the volume of complex geometries. This work develops a new efficient method for calculating volume of arbitrarily complex geometries for NECP-X. Rather than implementing the sampling method, the new developed method is based on the characteristic ray information, which is used for the method of characteristics (MOC) sweeping in NECP-X. The implementation shows that this method is very convenient to be applied to the MOC codes. A set of cases such as pin-cell and hexagonal rod-bundle assembly problems are tested to show the accuracy and performance.
Hull Shape Actuation for Speed Regulation in an Underwater Vehicle
Authors: DeVries Levi , Kutzer Michael D. M. , Bass Archie , Richmond Rebecca
Published: October 2019

Autonomous underwater vehicles (AUVs) have shown great promise in fulfilling surveillance, scavenging, and monitoring tasks. Traditional gliders and streamlined AUVs are designed for long-term operational efficiency in expansive environments but are limited in cluttered spaces due to their shape and control authority; agile AUVs can penetrate cluttered or sensitive environments but are limited in operational endurance at large spatial scales. This paper presents the dynamic modeling and control design of an underwater hull capable of actuating its shape morphology. The prototype hull incorporates flexible, buckled fiberglass ribs to ensure a rigid shape that is actuated by modulating the length of the body’s semi-major axis. We represent the vehicle shape using a single control input actuating the vehicle’s length-to-diameter ratio. Hydrodynamic modeling of the flexible hull suggests that dynamic shape actuation can modulate the mass and drag properties of the hull to improve control of the vehicle’s forward speed. Using tools from nonlinear control theory, this paper presents the derivation of a shape-actuating autonomous control algorithm regulating the vehicle speed to a time-varying reference speed, subject to the actuator limits. The theoretical control results are illustrated using numerical simulations of the vehicle model.
Ultrasound Imaging Characterization of Soft Tissue Dynamics of the Seated Human Body
Authors: Yamada Daisuke , Değirmenci Alperen , Howe Robert D.
Published: October 2019

To characterize the dynamics of internal soft organs and external anatomical structures, this paper presents a system that combines medical ultrasound imaging with an optical tracker and a vertical exciter that imparts whole-body vibrations on seated subjects. The spatial and temporal accuracy of the system was validated using a phantom with calibrated internal structures, resulting in 0.224 mm maximum root-mean-square (r.m.s.) position error and 13 ms maximum synchronization error between sensors. In addition to the dynamics of the head and sternum, stomach dynamics were characterized by extracting the centroid of the stomach from the ultrasound images. The system was used to characterize the subject-specific body dynamics as well as the intrasubject variabilities caused by excitation pattern (frequency up-sweep, down-sweep, and white noise, 1–10 Hz), excitation amplitude (1 and 2 m/s2 r.m.s.), seat compliance (rigid and soft), and stomach filling (empty and 500 mL water). Human subjects experiments (n = 3) yielded preliminary results for the frequency response of the head, sternum, and stomach. The method presented here provides the first detailed in vivo characterization of internal and external human body dynamics. Tissue dynamics characterized by the system can inform design of vehicle structures and adaptive control of seat and suspension systems, as well as validate finite element models for predicting passenger comfort in the early stages of vehicle design.
Generation of Recombinant Rotavirus Expressing NSP3-UnaG Fusion Protein by a Simplified Reverse Genetics System
Authors: Philip Asha A. , Perry Jacob L. , Eaton Heather E. , Shmulevitz Maya , Hyser Joseph M. , Patton John T.
Published: October 2019

Previous studies generated recombinant rotaviruses that express FPs by inserting reporter genes into the NSP1 ORF of genome segment 5. Unfortunately, NSP1 is expressed at low levels in infected cells, making viruses expressing FP-fused NSP1 less than ideal probes of rotavirus biology. Moreover, FPs were inserted into segment 5 in such a way as to compromise NSP1, an interferon antagonist affecting viral growth and pathogenesis. We have identified an alternative approach for generating rotaviruses expressing FPs, one relying on fusing the reporter gene to the NSP3 ORF of genome segment 7. This was accomplished without interrupting any of the viral ORFs, yielding recombinant viruses that likely express the complete set of functional viral proteins. Given that NSP3 is made at moderate levels in infected cells, rotaviruses encoding NSP3-based FPs should be more sensitive probes of viral infection than rotaviruses encoding NSP1-based FPs.
Estimation of cost-based prices for injectable medicines in the WHO Essential Medicines List
Authors: Gotham Dzintars , Barber Melissa Joy , Hill Andrew M
Published: October 2019

Objectives

Challenges remain in ensuring universal access to affordable essential medicines. We previously estimated the expected generic prices based on cost of production for medicines in solid oral formulations (ie, capsules or tablets) on the WHO Model List of Essential Medicines (EML). The objectives of this analysis were to estimate cost-based prices for injectable medicines on the EML and to compare these to lowest current prices in England, South Africa, and India.

Design

Data on the cost of active pharmaceutical ingredients (APIs) exported from India were extracted from an online database of customs declarations (www.infodriveindia.com). A formula was designed to use API price data to estimate a cost-based price, by adding the costs of converting API to a finished pharmaceutical product, including the cost of formulation in vials or ampoules, transportation and an average profit margin.

Results

For injectable formulations on the WHO EML, medicines had prices above the estimated cost-based price in 77% of comparisons in England (median ratio 2.54), and 62% in South Africa (median ratio 1.48), while 85% of medicines in India had prices below estimated cost-based price (median ratio 0.30). 19% of injectable medicines in England, 9% in South Africa, and 5% in India had prices more than 10 times the estimated cost-based price. Medicines that appeared in the top 20 by ratio of lowest current price to estimated cost-based price for more than one country included numerous oncology medicines—irinotecan, leuprorelin, ifosfamide, daunorubicin, filgrastim and mesna—as well as valproic acid and ciclosporin.

Conclusions

Estimating manufacturing costs can identify cases in which profit margins for medicines may be set significantly higher than average.
Pragmatic cluster randomised double-blind pilot and feasibility trial of an active behavioural physiotherapy intervention for acute non-specific neck pain: a mixed-methods protocol
Authors: Wiangkham Taweewat , Uthaikhup Sureeporn , Rushton Alison B
Published: October 2019

Introduction

Non-specific neck pain causes pain and disability and contributes substantial socioeconomic burden internationally. Up to 50% of adults experience neck pain annually, leading to reduced the quality of life. An active behavioural physiotherapy intervention (ABPI) may be feasible to manage patients with acute non-specific neck pain to prevent transition to chronicity. A recent pilot and feasibility trial investigating an acute whiplash-associated disorder population found potential value of the ABPI with 95% of participants fully recovered (Neck Disability Index: NDI ≤4, compared with 17% in the standard physiotherapy arm); supporting a definitive trial. Qualitative findings from the physiotherapists supported the potential of the ABPI in a non-specific neck pain population.

Methods and analysis

Two phases: (1) Pragmatic cluster randomised double-blind, parallel 2-arm (ABPI vs standard physiotherapy intervention) pilot and feasibility trial to evaluate the procedures and feasibility of the ABPI for the management of acute non-specific neck pain. Six physiotherapy departments from six public hospitals in Thailand will be recruited and cluster randomised by a computer-generated randomisation sequence with block sampling. Sixty participants (30 each arm, 10 per hospital) will be assessed at baseline and 3 months following baseline for NDI, Numerical Rating Scale for pain intensity, cervical range of motion, fear-avoidance beliefs questionnaire and EuroQol-5 dimensions 5 levels outcomes, and (2) Embedded qualitative study using semistructured interviews to explore acceptability of the ABPI to participants (n=12) and physiotherapists (n=3). Descriptive analysis of the quantitative data and interpretative phenomenological analysis to code and analyse qualitative data (deductive and inductive) will inform feasibility for a future definitive trial.

Ethics and dissemination

This trial is approved by the Naresuan University Institutional Review Board (NUIRB_0380/61).

Trial registration number and status

TCTR20180607001; Recruiting commenced 1 February 2019.
Current therapy for the upper limb after stroke: a cross-sectional survey of UK therapists
Authors: Stockley Rachel , Peel Rosemary , Jarvis Kathryn , Connell Louise
Published: October 2019

Objectives

To survey the reported content, frequency and duration of upper limb treatment provided by occupational and physiotherapists for people after stroke in the UK.

Design

A cross-sectional online survey was used. Description and analysis of the data were based on items from the Template for Intervention Description and Replication (Who, Where, What and How much).

Setting

The online survey was distributed via professional and social networks to UK-based therapists.

Participants

Respondents were occupational or physiotherapists currently working clinically in the UK with people after stroke. Over the 6 week data collection period, 156 respondents opened the survey, and 154 completed it. Respondents comprised 85 physiotherapists and 69 occupational therapists.

Results

Respondents reported treating the upper limb a median of three times a week (range: 1 to 7) for a mean of 29 min (SD: 18). Most (n=110) stated this was supplemented by rehabilitation assistants, family and/or carers providing additional therapy a median of three times a week (range 1 to 7). Functional training was the most commonly reported treatment for people with mild and moderate upper limb deficits (>40%). There was much less consistency in treatments reported for people with severe upper limb deficits with less than 20% (n=28) reporting the same treatments.

Conclusions

This study provides a contemporaneous description of reported therapy in the UK for people with upper limb deficits after stroke and a detailed template to inform standard therapy interventions in future research. Several evidence-based therapies were reported to be used by respondents (eg, constraint induced movement therapy), but others were not (eg, mental imagery). The findings also highlight that the current reported provision of upper limb therapy is markedly less than what is likely to be effective. This underlines an urgent need to configure and fund services to empower therapists to deliver greater amounts of evidence-based treatment for people with upper limb deficits after stroke.
The Upper Gastrointestinal Cancer Registry (UGICR): a clinical quality registry to monitor and improve care in upper gastrointestinal cancers
Authors: Maharaj Ashika D , Holland Jennifer F , Scarborough Ri O , Evans Sue M , Ioannou Liane J , Brown Wendy , Croagh Daniel G , Pilgrim Charles H C , Kench James G , Lipton Lara R , Leong Trevor , McNeil John J , Nikfarjam Mehrdad , Aly Ahmad , Burton Paul R , Cashin Paul A , Chu Julie , Duong Cuong P , Evans Peter , Goldstein David , Haydon Andrew , Hii Michael W , Knowles Brett P F , Merrett Neil D , Michael Michael , Neale Rachel E , Philip Jennifer , Porter Ian W T , Smith Marty , Spillane John , Tagkalidis Peter P , Zalcberg John R
Published: October 2019

Purpose

The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia.

Participants

It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation.

Findings to date

The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile.

Future plans

The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.
Health and wellbeing of people with intellectual disability in New South Wales, Australia: a data linkage cohort
Authors: Reppermund Simone , Heintze Theresa , Srasuebkul Preeyaporn , Reeve Rebecca , Dean Kimberlie , Smith Melinda , Emerson Eric , Snoyman Phillip , Baldry Eileen , Dowse Leanne , Szanto Tracey , Sara Grant , Florio Tony , Johnson Anina , Clements Melissa , McKenzie Kathryn , Trollor Julian
Published: October 2019

Purpose

People with intellectual disability (ID) experience high rates of physical and mental health problems, while access to appropriate healthcare is often poor. This cohort was established to develop an epidemiological profile related to the health, health service use, disability services, mortality and corrective services records of people with ID.

Participants

The cohort contains 92 542 people with ID (40% females) with a median age of 23 years (IQR: 12–43 years) and 2 004 475 people with a neuropsychiatric or developmental disorder diagnosis (50% females) with a median age of 51 years (IQR: 29–73 years) from New South Wales, Australia. The whole sample contains records for 2 097 017 individuals with most data sets spanning financial years 1 July 2001 to 30 June 2016. A wide range of data from linked population data sets are included in the areas of disability, health, corrective services and targeted specialist support services in public schools, Public Guardian and Ombudsman services.

Findings to date

This study includes one of the largest cohorts of people with ID internationally. Our data have shown that the presence of ID is significantly associated with emergency department presentations and psychiatric readmissions after the first psychiatric admission based on a subcohort of people with a psychiatric admission. Adults with ID experience premature mortality and over-representation of potentially avoidable deaths compared with the general population.

Future plans

Within the health service system, we will examine different components, that is, inpatient, emergency adult services, children and younger people services and costs associated with healthcare as well as mortality, cause and predictors of death. The neuropsychiatric and developmental disorders comparison cohort allows comparisons of the physical health, mental health and service use profiles of people with ID and those with other neuropsychiatric disorders.
Osteosarcoma affecting multiple bones in a dog
Authors: Wyatt Eleanor , Piviani Martina , Rich Andrew F , Mortier Jeremy Raphael , Comerford Eithne , Finotello Riccardo
Published: October 2019

A 9 years and 5 months old, neutered male, Rottweiler was presented for referral at the Small Animal Teaching Hospital, University of Liverpool, for investigations following a fracture of the left femur, which had occurred after minor trauma. Radiographs at the primary veterinary practice revealed a closed, slightly displaced, comminuted, proximal diaphyseal fracture, which had cortical thinning around the fracture site, suggestive of a pathological fracture. Advanced imaging (computed tomography) revealed polyostotic osteolytic lesions which contained contrast enhancing, soft tissue attenuating tissue, associated with cortical destruction throughout the appendicular and axial skeleton. Ultrasound‐guided fine needle aspirates of four lesions (right scapular, right femoral, left pelvic and vertebral lesions) were assessed by a boarded clinical pathologist, confirmed diagnosis of a polyostotic osteosarcoma. The patient was euthanased and postmortem examination confirmed the diagnosis.
Effectiveness of multigenerational transfer of Sumai 3 Fusarium head blight resistance in hard red spring wheat breeding populations
Authors: Berraies S. , Knox R.E. , DePauw R.M. , Clarke F.R. , Martin A.R. , Xue A.G. , Gilbert J.A. , Brûlé-Babel A.L. , Savard M. , Blackwell B. , Cuthbert R. , Ruan Y. , Campbell H.L.
Published: October 2019

Several quantitative trait loci (QTL) have been identified for Fusarium head blight (FHB) resistance in the cultivar Sumai 3. Wheat breeders need to know which Sumai 3 loci are present in derived lines used as parents for effective marker-assisted selection for genetic improvement. This study was conducted to identify the loci in Sumai 3 derived parents that contribute FHB resistance in breeding populations. Three doubled haploid (DH) populations utilizing Sumai 3 derived parents, ND3085, ND744, and Alsen, were evaluated during 2007 and 2008 in FHB nurseries near Carman, MB, Ottawa, ON and Charlottetown, PE. The percentage of incidence, severity, Fusarium-damaged kernels (FDK), and deoxynivalenol (DON) accumulation were measured, and FHB index calculated. DNA markers at six FHB resistance loci detected in Sumai 3 were evaluated on the populations. For each trait, a t test was applied to means of observations pooled by parental type of each marker to determine which loci contributed to resistance. The alleles at 3BS and 5AS most frequently contributed to Type I and Type II FHB resistance, as well as to reduced FDK and DON in all three populations. Markers revealed resistance on 3BS and 5AS in Alsen, ND3085, and ND744, on 3BSc, 4D, and 6BS in ND744, on 4D in ND3085, and on 6BS in Alsen. In some environments, the susceptible parent Infinity contributed minor QTL on 2D, 3BSc, and 6BS. Likewise, Helios contributed minor QTL on 5AS and 6BS.
Multiplicative factorization in numerical semigroups
Authors: Baeth Nicholas R. , Enlow Matthew
Published: October 2019

A numerical semigroup is a nonempty additively closed subset [Formula: see text] with [Formula: see text]. The arithmetic, that is the additive factorization properties, of numerical semigroups has been well studied. Their multiplicative properties, on the other hand, have received little, if any, attention. If [Formula: see text] or [Formula: see text], then multiplicative factorization (as products of primes) in [Formula: see text] is unique. However, if there is [Formula: see text] with [Formula: see text], then multiplicative factorization in [Formula: see text] is no longer unique. The purpose of this paper is to introduce this previously unstudied structure of numerical semigroups. Specifically, we classify the irreducible elements and provide a description of how non-unique multiplicative factorization can be in numerical semigroups. In addition, we show that multiplicative numerical semigroups belong to the class of [Formula: see text]-monoids, but yet are not Krull.
A Framework for Integrating Domain Knowledge in Logistic Regression with Application to Hospital Readmission Prediction
Authors: Radovanović Sandro , Delibašić Boris , Jovanović Miloš , Vukićević Milan , Suknović Milija
Published: October 2019

It is commonly understood that machine learning algorithms discover and extract knowledge based on data at hand. However, a huge amount of knowledge is available which is in machine-readable format and ready for inclusion in machine learning algorithms and models. In this paper, we propose a framework that integrates domain knowledge in form of ontologies/hierarchies into logistic regression using stacked generalization. Namely, relations from ontology/hierarchy are used in stacking manner in order to obtain higher, more abstract concepts. Obtained concepts are further used for prediction. The problem we solved is unplanned 30-days hospital readmission, which is considered as one of the major problems in healthcare. Proposed framework yields better results compared to Ridge, Lasso, and Tree Lasso Logistic Regression. Results suggest that the proposed framework improves AUC by up to 9.5% on pediatric datasets and up to 4% on morbidly obese patients’ datasets and also improves AUPRC by up to 5.7% on pediatric datasets and up to 2.6% on morbidly obese patients’ datasets on average. This indicates that the inclusion of domain knowledge improves the predictive performance of Logistic Regression.
Some results of left and right α-commutators of groups
Authors: Haghparast Marziyeh , Moghaddam Mohammad Reza R. , Rostamyari Mohammad Amin
Published: October 2019

In 1904, Schur proved his famous result which says that if the central factor group of a given group [Formula: see text] is finite, then so is its derived subgroup. In 1994, Hegarty showed that if the absolute central factor group, [Formula: see text], is finite, then so is its autocommutator subgroup, [Formula: see text].

In this paper, we introduce the concept of left and right [Formula: see text]-commutator, [Formula: see text], and [Formula: see text], where [Formula: see text] is an automorphism of the group [Formula: see text]. Then under some condition, we prove that the finiteness of [Formula: see text] implies that [Formula: see text] is also finite. We also construct an upper bound for the order of [Formula: see text] in terms of the order of [Formula: see text].
Modular Riesz bases versus Riesz bases in Hilbert C∗-modules
Authors: Hasannasab Marzieh
Published: October 2019

In this paper, we give new characterizations of modular Riesz bases in Hilbert [Formula: see text]-modules. We prove that modular Riesz bases share many properties with Riesz bases in Hilbert spaces. Moreover, we show that there are also important differences; for example, there exist exact frames that are not modular Riesz bases.
Improving Named Entity Recognition in Vietnamese Texts by a Character-Level Deep Lifelong Learning Model
Authors: Nguyen Ngoc-Vu , Nguyen Thi-Lan , Thi Cam-Van Nguyen , Tran Mai-Vu , Nguyen Tri-Thanh , Ha Quang-Thuy
Published: October 2019

Named entity recognition (NER) is a fundamental task which affects the performance of its dependent task, e.g. machine translation. Lifelong machine learning (LML) is a continuous learning process, in which the knowledge base accumulated from previous tasks will be used to improve future learning tasks having few samples. Since there are a few studies on LML based on deep neural networks for NER, especially in Vietnamese, we propose a lifelong learning model based on deep learning with a CRFs layer, named DeepLML–NER, for NER in Vietnamese texts. DeepLML–NER includes an algorithm to extract the knowledge of “prefix-features” of named entities in previous domains. Then the model uses the knowledge in the knowledge base to solve the current NER task. Preprocessing and model parameter tuning are also investigated to improve the performance. The effect of the model was demonstrated by in-domain and cross-domain experiments, achieving promising results.
Digging deeper: The influence of historical mining on Glasgow's subsurface thermal state to inform geothermal research
Authors: Watson Sean M. , Westaway Rob , Burnside Neil M.
Published: October 2019

Studies of the former NE England coalfield in Tyneside demonstrated that heat flow perturbations in boreholes were due to the entrainment and lateral dispersion of heat from deeper in the subsurface through flooded mine workings. This work assesses the influence of historical mining on geothermal observations across Greater Glasgow. The regional heat flow for Glasgow is 60 mW m
−2
and, after correction for palaeoclimate, is estimated as
c
. 80 mW m
−2
. An example of reduced heat flow above mine workings is observed at Hallside (
c
. 10 km SE of Glasgow), where the heat flow through a 352 m deep borehole is
c
. 14 mW m
−2
. Similarly, the heat flow across the 199 m deep GGC01 borehole in the Glasgow Geothermal Energy Research Field Site is
c
. 44 mW m
−2
. The differences between these values and the expected regional heat flow suggest a significant component of horizontal heat flow into surrounding flooded mine workings. This deduction also influences the quantification of deeper geothermal resources, as extrapolation of the temperature gradient above mine workings would underestimate the temperature at depth. Future projects should consider the influence of historical mining on heat flow when temperature datasets such as these are used in the design of geothermal developments.

Supplementary material
: Background information on the chronology of historical mining at each borehole location and a summary of groundwater flow in mine workings beneath Glasgow are available at
https://doi.org/10.6084/m9.figshare.c.4681100

Thematic collection:
This article is part of the ‘Early Career Research’ available at:
https://www.lyellcollection.org/cc/SJG-early-career-research
Resting Level of Insulin-Like Growth Factor-1 Is Not at Play in Cardiac Enlargement in Endurance-Trained Adolescents
Authors: Rundqvist Louise , Engvall Jan , Blomstrand Peter , Carlsson Emma , Faresjö Maria
Published: October 2019

Purpose. The study aimed to investigate resting levels of several selected growth and metabolic hormones in a group of 24 endurance-trained adolescents (aged 13–19 years) compared with 24 untrained age- and sex-matched controls, and to investigate if increased cardiac dimensions were related to these hormones at rest with emphasis on insulin-like growth factor-1 (IGF-1). Methods. The hormones (cortisol, IGF-1, IGF-2, follicle-stimulating hormone, growth hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone) were analysed with chemiluminescence microparticle immunoassay (CMIA) or multiplex fluorochrome (Luminex) technique. Cardiac dimensions were assessed by echocardiographic examination at rest. Peak oxygen uptake was obtained by a maximal cardiopulmonary exercise test on a treadmill. Results. Circulating levels of analysed hormones at rest did not differ between the groups. A correlation was found between increased cardiac dimensions and IGF-1 in the controls, but not in the active group. This correlation declined also among the controls when the cardiac parameters were indexed for body surface area. Conclusion. Increased cardiac dimensions in endurance-trained adolescents could not be related to resting levels of hormones associated with growth and metabolism, including IGF-1 and GH. In addition, the resting levels of these hormones seem not to be affected by intense regular endurance exercise in adolescents. These findings may contribute to the knowledge about cellular signaling that trigger growth as well as cardiac adaptation to endurance training in young athletes.
Bringing Oncohistones into the Fold
Authors: Sarthy Jay F. , Henikoff Steven
Published: October 2019

Identification of cancer-associated mutations in core histone genes has proved challenging due to these genes' highly conserved nature and presence in large arrays. Recent analyses of cancer genomes, including one in this issue of Cancer Discovery, show that mutations in the histone fold can affect nucleosome stability, providing a novel mechanism by which oncohistones contribute to tumorigenesis.

See related article by Bennett et al., p. 1438.
Recurrent Stroke Reduction with Patent Foramen Ovale Closure versus Medical Therapy Based on Patent Foramen Ovale Characteristics: A Meta-Analysis of Randomized Controlled Trials
Authors: Garg Aakash , Thawabi Mohammed , Rout Amit , Sossou Chris , Cohen Marc , Kostis John B.
Published: October 2019

Efficacy of patent foramen ovale (PFO) closure in patients with cryptogenic stroke remains a matter of debate. We performed a comprehensive meta-analysis of available randomized controlled trials (RCTs) to evaluate the efficacy and safety of PFO closure versus medical therapy (MT) based on PFO characteristics. Random-effects meta-analysis was conducted to estimate risk ratio (RR) with 95% confidence intervals (CI) for the primary end points of stroke. After systematic search, six RCTs (3,747 patients) with 1,889 patients randomized to PFO closure and 1,858 patients randomized to the MT group were included in the meta-analysis. Overall, PFO closure was associated with a significant reduction in recurrent stroke compared to MT [RR 0.41; 95% CI 0.20–0.83]. While there were no differences in mortality or major bleeding between the two groups, risk of newly diagnosed atrial fibrillation was higher in the PFO closure group compared to MT [RR 5.29; 95% CI 2.32–12.06]. Further, risk reduction in stroke with PFO closure was significant in patients with high-risk PFO characteristics [RR 0.37; 95% CI 0.16–0.87] but not in low-risk patients [RR 0.73; 95% CI 0.29–1.84]. In conclusion, among patients with cryptogenic stroke, PFO closure is associated with a significantly reduced risk of recurrent stroke compared to MT. Additionally, the benefit of PFO closure might be dependent on certain PFO characteristics.
R5 HIV-1 gp120 Activates p38 MAPK to Induce Rat Cardiomyocyte Injury by the CCR5 Coreceptor
Authors: Gao Rui , Fang Qiujuan , Zhang Xi , Xu Qin , Ye Hanhui , Guo Wenyan , He Jiao , Chen Yahong , Wang Ruixing , Wu Zhijuan , Yu Jing
Published: October 2019

Background: Effective antiretroviral therapy extends the survival of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome, but these patients remain at higher risk for heart diseases compared with the general population. Previous studies have suggested that HIV-1 glycoprotein 120 (gp120) may be associated with heart disease. However, the underlying mechanisms by which HIV-1 gp120-mediated myocardial injury occurs remain unknown. Objective: The current study aimed to uncover the mechanism of C-C chemokine receptor 5 (CCR5) coreceptor (R5) HIV-1 gp120-induced myocardial injury. Methods: Morphology analysis, determination of the percentage of cell apoptosis, as well as lactate dehydrogenase (LDH) and creatine kinase (CK) assays were used to analyze whether R5 HIV-1 gp120 induced myocardial cell injury. We analyzed the phosphorylation of p38 mitogen-activated protein kinase (MAPK) with the CCR5 antagonist D-Ala-peptide T-amide (DAPTA) and NMDA receptor antagonist MK801, detected LDH and CK assays with p38 MAPK antagonist SB203580 (SB), and detected the percentage of cell apoptosis and death with DAPTA to investigate the mechanism of R5 HIV-1 gp120-induced myocardial cell injury. Results: R5 HIV-1 gp120 damaged myocardial cells and induced p38 MAPK phosphorylation. SB blocked R5 HIV-1 gp120-induced myocardial cell injury. DAPTA blocked R5 HIV-1 gp120-mediated p38 MAPK phosphorylation, while MK801 did not. DAPTA inhibited R5 HIV-1 gp120-induced myocardial cell injury. Conclusion: Our data indicate that R5 HIV-1 gp120 activated p38 MAPK to trigger myocardial cell injury by the CCR5 coreceptor.
Perianal Disease and Granulomas: Think Out of the Box…
Authors: Reis-Melo Ana , Espinheira Maria do Céu , Pinto-Pais Isabel , Bonito Vitor Artur , Bustamante Jacinta , Trindade Eunice
Published: October 2019

Background: Chronic granulomatous disease (CGD) is a primary immunodeficiency due to a malfunction of NADPH oxidase. It is characterized by recurrent and severe infections caused by catalase-positive microorganisms and autoinflammatory manifestations. Recently, there has been described an NCF4 gene variant that causes a deficiency of p40phox, a subunit of NADPH oxidase. Patients with this deficiency appear to have a less severe clinical form as compared to classic CGD. Case: A 15-year-old girl with vulvar lichen planus since she was 2 years old and suspected Crohn’s disease (CD) was first seen at our hospital. At the age of 12 years, she had been submitted to sacrococcygeal cyst exeresis, without cicatrization of the surgical wound and extension of the lesion to the perianal area. The diagnosis of CD was questioned, and the patient underwent an endoscopic and radiologic assessment, which was normal. A skin biopsy from the perianal area revealed a granuloma; thus, CD with isolated perianal disease was assumed. After several different treatments including antibiotics, infliximab, and adalimumab, the perianal lesion persisted, with no associated gastrointestinal symptoms. Therefore, the hypothesis of an immunodeficiency was considered. An immunologic and genetic study revealed reduced oxidative burst in the phorbol myristate acetate test, with diminished reactive oxygen species production and a homozygous mutation in the NCF4 gene. The adolescent started prophylactic trimethoprim-sulfamethoxazole and became asymptomatic. Conclusions: The present case highlights that alternative diagnoses to CD must be considered in the presence of isolated perianal disease with granulomatous inflammation, especially when the disease is refractory to conventional CD therapy.
Postthrombectomy Systolic Blood Pressure and Clinical Outcome among Patients with Successful Recanalization
Authors: Chang Jun Young , Han Moon-Ku
Published: October 2019

Background: Optimal blood pressure (BP) management after intraarterial thrombectomy (IAT) has yet to be thoroughly elucidated. We assessed whether maintaining a systolic BP (SBP) of ≤130 mm Hg for 24 h following IAT was associated with better outcomes in patients with successful recanalization. Methods: Patients presenting with large vessel occlusion within 4 h from symptom onset underwent IAT based on multiphase computed tomography angiography, and those achieving successful recanalization were included in this retrospective analysis. Patients were dichotomized based on a 24-h mean SBP after IAT >130 or ≤130 mm Hg, and functional outcomes were compared at 3 months. At 3 months, 24-h mean SBPs were compared based on recanalization degree, baseline collateral status, stroke mechanism, and occlusion site. Results: The proportion of favorable outcomes at 3 months (modified Rankin Scale [mRS] 0–2) was significantly lower in patients with a mean SBP >130 mm Hg over the 24 h after IAT (40.5 vs. 66.7%, p = 0.02). The distribution of mRS varied significantly among patients with complete recanalization, poor baseline collateral status (pial arterial filling score 0–3), cardioembolic stroke, or middle cerebral artery occlusion, with higher mRS values associated with higher mean SBPs. A mean SBP >130 mm Hg during the 24 h after IAT was associated with worse functional outcomes after multivariable adjustment (OR 2.66; 95% CI 1.11–6.41; p= 0.03). Conclusion: Stricter BP control during the 24 h following IAT may improve clinical outcomes in patients with large vessel occlusion who achieved successful recanalization.
Shear Stress Attenuates Inward Remodeling in Cultured Mouse Thoracodorsal Arteries in an eNOS-Dependent, but Not Hemodynamic Manner, and Increases Cx37 Expression
Authors: Looft-Wilson Robin C. , Billig Janelle E. , Sessa William C.
Published: October 2019

Background: Arteries chronically constricted in culture remodel to smaller diameters. Conversely, elevated luminal shear stress (SS) promotes outward remodeling of arteries in vivo and prevents inward remodeling in culture in a nitric oxide synthase (NOS)-dependent manner. Objectives: To determine whether SS-induced prevention of inward remodeling in cultured arteries is specifically eNOS-dependent and requires dilation, and whether SS alters the expression of eNOS and other genes potentially involved in remodeling. Methods: Female mouse thoracodorsal arteries were cannulated, pressurized to 80 mm Hg, and cultured for 2 days with low SS (<7 dyn/cm2), high SS (≥15 dyn/cm2), high SS + L-NAME (NOS inhibitor, 10–4 M), or high SS in arteries from eNOS–/– mice. In separate arteries cultured 1 day with low or high SS, eNOS and connexin (Cx) 37, Cx40, and Cx43 mRNA were assessed with real-time PCR. Results: High SS caused little change in passive diameters after culture (–4.7 ± 2.0%), which was less than low SS (–18.9 ± 1.4%; p < 0.0001), high SS eNOS–/– (–18.0 ± 1.5; p < 0.001), or high SS + L-NAME (–12.0 ± 0.6%; nonsignificant) despite similar constriction during culture. Cx37 mRNA expression was increased (p < 0.05) with high SS, but other gene levels were not different. Conclusions: eNOS is involved in SS-induced prevention of inward remodeling in cultured small arteries. This effect does not require NO-mediated dilation. SS increased Cx37.
Prognostic Factors in HER2-Positive Primary Breast Cancer Patients Treated Using Neoadjuvant Chemotherapy Plus Trastuzumab
Authors: Fujita Noriko , Enomoto Yukie , Inakami Keiko , Yanagisawa Tetsu , Iguchi Chikage , Aono Toyokazu , Nomura Takashi , Yamamoto Hitoshi , Kasugai Tsutomu , Shiba Eiichi
Published: October 2019

Background: It is unclear for whom new anti-human epidermal growth factor receptor 2 (anti-HER2) agents, such as pertuzumab and T-DM1, should be considered. We investigated prognostic factors before neoadjuvant chemotherapy (NAC) among HER2-positive invasive breast cancer patients and those after NAC among patients who did not achieve pathological complete response (pCR) using conventional adjuvant trastuzumab. Methods: HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and June 2017 at the Osaka Breast Clinic. Patients with distant metastasis or using NAC containing pertuzumab were excluded. The main outcome was disease-free survival (DFS). We investigated pre- and post-NAC prognostic factors using the log-rank test and Cox proportional hazards model. Results: In total, 157 patients were included. Among the pre-NAC prognostic factors, younger age (under 40 years old) and positive clinical nodal status were significantly poorer prognostic factors (hazard ratio [HR] 3.47, 95% CI 1.06–10.12, p = 0.041 and HR 3.32, 95% CI 1.03–14.78, p = 0.045) by multivariate analysis. Among the post-NAC prognostic factors, patients with non-pCR (3-year DFS; 85 vs. 96%, p = 0.022) had a poorer DFS than patients with pCR. DFS was assessed for non-pCR patients (n = 64). High post-NAC Ki-67 status (≥20%; HR 6.73, 95% CI 1.82–31.93, p = 0.004) was a significant and large post-NAC tumor size (≥2 cm; HR 3.65, 95% CI 0.97–14.71, p = 0.056) was a marginally significant prognostic factor by multivariate analysis. After having combined them, high post-NAC Ki-67 status or large post-NAC tumor size was also a significant prognostic factor (HR 5.75, 95% CI 1.32–16.12, p = 0.017). Conclusions: Positive clinical nodal status and young age were found to be prognostic factors before NAC in HER2-postive invasive breast cancer patients. A high post-NAC Ki-67 status and large post-NAC tumor size were significant and marginally significant prognostic factors, respectively, after NAC in patients who did not achieve pCR. New anti-HER2 agents, such as pertuzumab and T-DM1, should be considered for the patients with those prognostic factors.
Exacerbation of Portal Hypertensive Enteropathy after Endoscopic Injection Sclerotherapy for Esophageal Varices
Authors: Otani Ichiro , Oka Shiro , Aikata Hiroshi , Iio Sumio , Tsuboi Akiyoshi , Kunihara Sayoko , Nagaoki Yuko , Tanaka Shinji , Chayama Kazuaki
Published: October 2019

Introduction: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. Methods: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. Results: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. Conclusions: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.
William Barnett Warrington (1869–1919)
Authors: Bracewell R. Martyn , Larner Andrew J.
Published: October 2019

William Barnett Warrington (1869–1919) was a physician and physiologist working in Liverpool, United Kingdom, at the end of the 19th and beginning of the 20th centuries. His training included periods at the National Hospital for the Paralysed and Epileptic, Queen Square, London, and in the Liverpool laboratory of Charles Scott Sherrington. He investigated structural alterations in nerve cells following various nerve lesions and helped to develop laboratory facilities to support clinical practice through the Pathological Diagnosis Society of Liverpool. His clinical interests were broad, but his main focus seems to have been in disorders of the peripheral nervous system. He published many papers, encompassing descriptions of Charcot-Marie-Tooth disease, brachial plexus paralyses (possibly including neuralgic amyotrophy), and, in the context of the First World War, traumatic peripheral nerve injuries. He may have described cases of Guillain-Barré syndrome prior to the eponymous description but despite being familiar with the technique of lumbar puncture, he did not report cerebrospinal fluid findings in these patients.
Aderência intertalâmica e Alzheimer
Authors: Belkovsky Mikhael , Souza Isabela C. B. , Akamatsu Flávia Emi , Hojaij Flavio C. , Jacomo Alfredo Luiz
Published: October 2019

OBJETIVO: Descrever dimensões e prevalência da Aderência Intertalâmica (AI) em cadáveres do Serviço de Verificação de Óbitos da Capital - USP, considerando idade, sexo, peso, altura e histórico pessoal de doença de Alzheimer (DA). MÉTODOS: Cinquenta e sete cadáveres (31H/26M) foram incluídos no estudo, com média de idade de 66,2 anos (variando entre 15 e 91 anos). A análise da AI foi feita após secção transversal da calota craniana e incisão axial no limite inferior do tronco encefálico seguida de retirada do encéfalo de sua cavidade. Cinquenta e quatro encéfalos foram submetidos a incisão sagital mediana, dois encéfalos foram submetidos a cortes axiais, e um encéfalo a secção coronal. Dados quantitativos foram comparadas pelo teste t de student, e dados qualitativos pelo teste de Qui Quadrado. A análise idade vs área foi feita por regressão linear. RESULTADOS: A prevalência de AI foi de 79%, não havendo diferença significativa entre os sexos (p=0,68).  Observou-se associação entre menores áreas de secção sagital e idades mais avançadas (p=0,02). Não houve diferença significativa na prevalência de AI nem na área de secção transversal em pacientes com DA. DISCUSSÃO: Ao contrário de estudos prévios, que associaram maior prevalência e tamanho de AI com sexo feminino, isso não foi observado em nossa casuística. Apesar de não ser estatisticamente significativa nota-se uma diferença importante nas áreas médias de secção sagital dos grupos com e sem DA, o que aponta para a necessidade de estudos subsequentes com amostras maiores.