bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible evidence of a supermassive black hole binary with two radio jets in blazar 3C279
Authors: Qian S. J. , Britzen S. , Krichbaum T. P. , Witzel A.
Published: August 2018

Context. Studies of periodic and quasi-periodic phenomena in optical and radio bands are important for understanding the physical processes in quasars. Investigation of periodic/quasi-periodic behavior of the relativistic jets in blazars is particularly significant because it can provide unique information about the formation, collimation, and acceleration of the jets and the properties of the central engines (black hole/accretion disk systems) in blazars.

Aims. We investigate the parsec-scale kinematics of the 31 superluminal components observed in blazar 3C279 and attempt to search for evidence of its jet precession and double-jet structure.

Methods. The previously suggested precessing jet nozzle model is applied to model-fit the kinematics of its superluminal components observed during the 1981–2015 period. It is shown that the parsec-scale kinematics of the entire source can be interpreted in terms of a double-jet scenario.

Results. The superluminal components observed in 3C279 can be divided into two groups that are ejected from two relativistic jets. The two jets have different orientations in space and jet-cone shapes, but both jets precess with the same precession period of 25 yr (16.3 yr in the source frame). The kinematic features of all the superluminal knots (trajectory, core separation, and apparent velocity) can be consistently explained. Their innermost trajectories follow the respective precessing common parabolic patterns with trajectory curvatures that occurred in the outer jet regions at different core separations. The bulk Lorentz factor, Doppler factor, and viewing angle of their motion are derived. The unusual jet-direction change of ∼100° observed in 2010–2011 can be naturally explained.

Conclusions. We propose a double-jet structure scenario for 3C279 and suggest that there may be a supermassive black hole binary in the center of 3C279 ejecting two precessing relativistic jets, resulting in its very complex structure and kinematics on parsec scales, and with extremely variable emission across the electromagnetic spectrum. Because the two jets have the same precession period, the precession of the double jet may have originated from the modulation of their jet orientation by the change in their orbital velocity direction relative to the observer. In this case the mass ratio m/M of the binary is approximately equal to the ratio of the jet cone widths, being on the order of ∼0.5.
Prothrombotic State Induced by Middle-Distance Endurance Exercise in Middle-Aged Athletes
Authors: Salvagno Gian , Tarperi Cantor , Gelati Matteo , Montagnana Martina , Danese Elisa , Festa Luca , Sanchis-Gomar Fabian , Favaloro Emmanuel , Schena Federico , Lippi Giuseppe
Published: August 2018

Since the impact of possible prothrombotic factors on blood coagulation resulting from exercise remains elusive, this study investigated the acute effects of middle-distance endurance running on blood coagulation parameters in middle-aged athletes. The study population consisted of 33 male endurance runners who were engaged in a 21.1 km run under competitive conditions. Blood samples were collected before the run, immediately after the run, and 3 hours after run completion. Samples were assessed for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area under the curve of thrombin generation [TGA-AUC]), and peak thrombin generation (TGA-PK). Post-run variations were expressed as delta (Δ). At baseline, APTT was found to be significantly associated with ABO blood group, VWF:Ag, and FVIII; fibrinogen with age; VWF:Ag with BMI, training regimen, and ABO blood group; APTT with FVIII; FVIII with VWF:Ag and ABO blood group; APTT with VWF:Ag; and TGA-PK with ABO blood group, PT, and TGA-AUC. Immediately after the run, statistically significant increases were observed for PT, D-dimer, VWF:Ag, and FVIII, while statistically significant reductions could be observed for APTT, TGA-AUC, and TGA-PK. Fibrinogen values remained unchanged. Significant correlations were observed between Δ VWF:Ag and Δ FVIII, Δ APTT and Δ VWF:Ag, Δ APTT and Δ FVIII, Δ TGA-AUC and Δ TGA-PK, and between Δ D-dimer and Δ TGA-AUC and Δ TGA-PK. No Δ variation was associated with running time. The results of this study seemingly suggest that middle-distance competitive running may evoke several prothrombotic changes in blood coagulation.
Nahrungsmittelallergien und Anaphylaxie
Authors: Happle C.
Published: August 2018

Nahrungsmittelallergien sind der häufigste Auslöser für Anaphylaxien im Kindesalter. Auch wenn es in den vergangenen Jahren neue Daten zur Ätiologie und interessante Ansätze zur spezifischen Immuntherapie von Nahrungsmittelallergien gab, gibt es bisher keine Heilung. Die Behandlung besteht primär in Allergenkarenz und symptomatischer Medikation. Dabei kommt der Notfalltherapie eine besondere Bedeutung zu. Das Risiko plötzlich auftretender schwerer Symptome mit potenziell fatalem Ausgang kann für betroffene Patienten und ihre Familien eine starke Einschränkung ihrer Lebensqualität bedeuten. Schulungen im Erkennen und Umgang von Anaphylaxien und in der Anwendung eines Adrenalin-Autoinjektors sind für gefährdete Patienten essenziell. Der vorliegende Artikel gibt nach einer kurzen Einführung zu Pathophysiologie, Epidemiologie und Behandlung von Nahrungsmittelallergien einen aktuellen Überblick zur Literatur und zu Handlungsempfehlungen bei Nahrungsmittel-assoziierter Anaphylaxie. Er soll als Entscheidungshilfe im Hinblick auf die Verordnung eines Adrenalin-Autoinjektors bei Nahrungsmittelallergie dienen und gibt Empfehlungen für das Notfalltraining von Kindern und Familien mit Anaphylaxierisiko.
Rohmilch für Kinder – Gefahr für schwere hämolytisch-urämische Syndrome
Authors: Lang M. , Kunkel J. , Kabesch M. , Melter M. , Kittel J.
Published: August 2018

In unserer Klinik wurden innerhalb einer Woche drei Patienten mit hämolytisch-urämischem Syndrom (HUS) aufgenommen. Alle Kinder stammten aus einer Großfamilie. Sie hatten bei Aufnahme eine schwere Anämie und Thrombozytopenie sowie Zeichen eines Nierenversagens, zwei Kinder mussten dialysiert werden, ein Kind erlitt im Rahmen des HUS neurologische Komplikationen und behält eine schwere Beeinträchtigung. Es kann auch ein Jahr nach dem HUS weder laufen noch sprechen. Anamnestisch hatten alle Kinder Rohmilch verzehrt, welche direkt von ein und demselben Bauernhof bezogen wurde. Bei allen Patienten gelang der Keimnachweis von enterohämorrhagischen E. coli (EHEC) im Stuhl, bei einem Patient konnte der gleiche E. coli O80:H2 mittels Pulsfeldgelelektrophorese sowohl im Stuhl als auch in der Rohmilchprobe vom Bauernhof nachgewiesen werden.

Aufgrund eines geänderten ökologischen Bewusstseins in Teilen der deutschen Bevölkerung, kam es in den letzten Jahren wieder zu vermehrter Nachfrage nach Rohmilch „frisch vom Bauernhof”. Unter anderem wegen der Gefahr von Infektionen ist der Verkauf der Rohmilch in Deutschland prinzipiell verboten, er kann jedoch unter bestimmten Voraussetzungen erlaubt werden. Das Bewusstsein dafür, dass durch den Konsum von Rohmilch für den Menschen durch die Übertragung von Bakterien wie EHEC, Listerien, Salmonellen oder anderen Erregern eine Gesundheitsgefahr ausgehen kann, ist in den letzten Jahren in Zeiten der industriellen Milchaufbereitung zunehmend verschwunden.
Nanoscale cavitation in perforation of cellular membrane by shock-wave induced nanobubble collapse
Authors: Nan Nan , Si Dongqing , Hu Guohui
Published: August 2018

The collapse of the bubble induced by the shock wave leads to nano-jet, which is able to perforate cellular membranes. This phenomenon is investigated by Martini coarse-grained molecular dynamic (CG-MD) simulations in the present study. It is found that the occurrence of cavitation nucleation at the nanoscale can be observed during the perforation process. The cavitation locates near the puncture of the cell membrane and its ultimate evolutionary form presents a ring-like structure. The volume of the cavitation is calculated for different initial bubble sizes, and it is found that the maximum volume of the cavitation area has a correlation with the initial bubble size. To understand the underlying physics of the cavitation phenomenon, the classical nucleation theory based on the Rayleigh-Plesset equation is applied to the non-equilibrium nanoscale system after the pressure field is obtained by using the Irving-Kirkwood-Noll procedure. The consistence between the results of CG-MD and the theory reveals that the average pressure of the local environment plays a crucial role in cavitation occurrence on the non-equilibrium system subjected to strong inertia, e.g., shock wave and nano-jet.
Critically slow learning in flashcard learning models
Authors: Nishimura Joel
Published: August 2018

Algorithmic education theory examines, among other things, the trade-off between reviewing old material and studying new material: time spent learning the new comes at the expense of reviewing and solidifying one’s understanding of the old. This trade-off is captured in the “Slow Flashcard System” (SFS)—a system that has been studied not only for its applications in educational software but also for its critical properties; it is a simple discrete deterministic system capable of remarkable complexity, with standing conjectures regarding its longterm behavior. Here, we introduce a probabilistic model of SFS and further derive a continuous time, continuous space partial differential equation model. These two models of SFS shed light on the longterm behavior of SFS and open new avenues of research.
Semitransparent organic solar cells based on the gasochromism of WO3
Authors: Long Yongbing , Zhong Jinyao , Liang Wenyue , Shen Liang , Xu Haitao , Deng Haidong
Published: August 2018

Semitransparent organic solar cells (ST-OSCs) based on the gasochromism of WO3 are theoretically proposed by capping a WO3 and a Pt layer on the transparent Ag electrode of the devices. Transfer matrix method is used to investigate the effects of the gaschromism of the WO3 layer on the transmission, short-circuit current density (Jsc), and color of the devices. It is revealed that the gaschromism can reduce the average transmission of the device from 33.4 % to 21.5% and a reduction of 35.6% is achieved for the ST-OSC with a 270nm-thick WO3 layer. This occurs because the gaschromism can change the reflection of Ag/WO3/Pt multilayer and improve light absorption in the WO3 layer. The superposed effects of these two factors lead to reduction in light transmission of the device. Meanwhile, the effects of the gaschromism on the Jsc and color coordinates of the devices are relatively small.
Nonlinear neoclassical two-fluid theory of response of tokamak plasma to resonant error-field
Authors: Fitzpatrick Richard
Published: August 2018

A nonlinear, neoclassical, two-fluid theory of the interaction of a single-helicity magnetic island chain with a resonant error-field in a quasi-cylindrical, low-β, tokamak plasma is presented. In particular, the analysis of Fitzpatrick [Phys. Plasmas 25, 042503 (2018)] is generalized to take explicit time dependence into account. Aside from the ability to more accurately treat time-varying problems, the main physical effect that is introduced into the theory by the incorporation of explicit time dependence is ion inertia. The formalism developed in the paper is used to analyze two time-varying problems. First, the interaction of a pre-existing magnetic island chain with a resonant error-field. Second, an error-field-maintained magnetic island chain. The latter problem is of direct relevance to experiments in which deliberately applied, multi-harmonic, resonant magnetic perturbations are used to suppress edge localized modes (ELMs) in tokamak plasmas. Indeed, the predictions of the theory are strikingly similar to data recently obtained from ELM suppression experiments in the DIII-D tokamak [R. Nazikian et al., Nucl. Fusion 58, 106010 (2018)].
Nanometer scale thermal response of polymers to fast thermal perturbations
Authors: Minakov Alexander A. , Schick Christoph
Published: August 2018

Nanometer scale thermal response of polymers to fast thermal perturbations is described by linear integro-differential equations with dynamic heat capacity. The exact analytical solution for the non-equilibrium thermal response of polymers in plane and spherical geometry is obtained in the absence of numerical (finite element) calculations. The solution is different from the iterative method presented in a previous publication. The solution provides analytical relationships for fast thermal response of polymers even at the limit t → 0, when the application of the iterative process is very problematic. However, both methods give the same result. It was found that even fast (ca. 1 ns) components of dynamic heat capacity greatly enhance the thermal response to local thermal perturbations. Non-equilibrium and non-linear thermal response of typical polymers under pulse heating with relaxation parameters corresponding to polystyrene and poly(methyl methacrylate) is determined. The obtained results can be used to analyze the heat transfer process at the early stages of crystallization with fast formation of nanometer scale crystals.
Low-temperature helium plasma generated at atmospheric pressures by non-standard field applicator
Authors: DeJarnette Drew
Published: August 2018

Low-temperature helium plasmas were sustained using radio frequency excitation waveforms in a cylindrical glass tube, both in steady state and flowing conditions.
Considering centrifugal force improves ice accretion simulation on helicopter rotors
Authors: Cockbill Louisa
Published: August 2018

A new 3D model of ice accretion offers more realistic modeling of a helicopter rotors’ rotating surfaces, based on the analysis of mass-, momentum-, and energy-conservation of the unfrozen water film.
A probabilistic system helps understand the transition between models of learning
Authors: Cockbill Louisa
Published: August 2018

Through bypassing the complexity of the slow flashcard system of learning, the trade-off between bounded and unbounded learning has been captured on a familiarity curve.
Synthesis of a Highly Functionalised and Homochiral 2-Iodocyclohexenone Related to the C-Ring of the Polycyclic, Indole Alkaloids Aspidophytine and Haplophytine
Authors: Dlugosch Michael , Banwell Martin G.
Published: August 2018

The enzymatically-derived and enantiomerically pure (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (7) has been elaborated over 10 steps into cyclohexenone 8. The latter compound embodies the enantiomeric form of the C-ring associated with the hexacyclic framework of the alkaloid aspidophytine (2). As such, this work sets the stage for effecting the conversion of the enantiomeric metabolite ent-7 into compound ent-8, and thence, through previously established protocols, including a palladium-catalysed Ullmann cross-coupling reaction, into the title alkaloids.
Quick approximation of threshold values for genome-wide association studies
Authors: Hao Zhiyu , Jiang Li , Gao Jin , Ye Jinhua , Zhao Jingli , Li Shuling , Yang Runqing
Published: August 2018

Standard normal statistics, chi-squared statistics, Student’s t statistics and F statistics are used to map quantitative trait nucleotides for both small and large sample sizes. In genome-wide association studies (GWASs) of single-nucleotide polymorphisms (SNPs), the statistical distributions depend on both genetic effects and SNPs but are independent of SNPs under the null hypothesis of no genetic effects. Therefore, hypothesis testing when a nuisance parameter is present only under the alternative was introduced to quickly approximate the critical thresholds of these test statistics for GWASs. When only the statistical probabilities are available for high-throughput SNPs, the approximate critical thresholds can be estimated with chi-squared statistics, formulated by statistical probabilities with a degree of freedom of two. High similarities in the critical thresholds between the accurate and approximate estimations were demonstrated by extensive simulations and real data analysis.
Polygenic approaches to detect gene–environment interactions when external information is unavailable
Authors: Lin Wan-Yu , Huang Ching-Chieh , Liu Yu-Li , Tsai Shih-Jen , Kuo Po-Hsiu
Published: August 2018

The exploration of ‘gene–environment interactions’ (G × E) is important for disease prediction and prevention. The scientific community usually uses external information to construct a genetic risk score (GRS), and then tests the interaction between this GRS and an environmental factor (E). However, external genome-wide association studies (GWAS) are not always available, especially for non-Caucasian ethnicity. Although GRS is an analysis tool to detect G × E in GWAS, its performance remains unclear when there is no external information. Our ‘adaptive combination of Bayes factors method’ (ADABF) can aggregate G × E signals and test the significance of G × E by a polygenic test. We here explore a powerful polygenic approach for G × E when external information is unavailable, by comparing our ADABF with the GRS based on marginal effects of SNPs (GRS-M) and GRS based on SNP × E interactions (GRS-I). ADABF is the most powerful method in the absence of SNP main effects, whereas GRS-M is generally the best test when single-nucleotide polymorphisms main effects exist. GRS-I is the least powerful test due to its data-splitting strategy. Furthermore, we apply these methods to Taiwan Biobank data. ADABF and GRS-M identified gene × alcohol and gene × smoking interactions on blood pressure (BP). BP-increasing alleles elevate more BP in drinkers (smokers) than in nondrinkers (nonsmokers). This work provides guidance to choose a polygenic approach to detect G × E when external information is unavailable.
The Relationship Between Blood Sample Volume and Diagnostic Sensitivity of Blood Culture for Typhoid and Paratyphoid Fever: A Systematic Review and Meta-Analysis
Authors: Antillon Marina , Saad Neil J , Baker Stephen , Pollard Andrew J , Pitzer Virginia E
Published: August 2018

Background

Blood culture is the standard diagnostic method for typhoid and paratyphoid (enteric) fever in surveillance studies and clinical trials, but sensitivity is widely acknowledged to be suboptimal. We conducted a systematic review and meta-analysis to examine sources of heterogeneity across studies and quantified the effect of blood volume.

Methods

We searched the literature to identify all studies that performed blood culture alongside bone marrow culture (a gold standard) to detect cases of enteric fever. We performed a meta-regression analysis to quantify the relationship between blood sample volume and diagnostic sensitivity. Furthermore, we evaluated the impact of patient age, antimicrobial use, and symptom duration on sensitivity.

Results

We estimated blood culture diagnostic sensitivity was 0.59 (95% confidence interval [CI], 0.54–0.64) with significant between-study heterogeneity (I2, 76% [95% CI, 68%–82%]; P < .01). Sensitivity ranged from 0.51 (95% CI, 0.44–0.57) for a 2-mL blood specimen to 0.65 (95% CI, 0.58–0.70) for a 10-mL blood specimen, indicative of a relationship between specimen volume and sensitivity. Subgroup analysis showed significant heterogeneity by patient age and a weak trend towards higher sensitivity among more recent studies. Sensitivity was 34% lower (95% CI, 4%–54%) among patients with prior antimicrobial use and 31% lower after the first week of symptoms (95% CI, 19%–41%). There was no evidence of confounding by patient age, antimicrobial use, symptom duration, or study date on the relationship between specimen volume and sensitivity.

Conclusions

The relationship between the blood sample volume and culture sensitivity should be accounted for in incidence and next-generation diagnostic studies.
Effectiveness of Pelvic Floor Muscle Training Alone and in Combination With Biofeedback, Electrical Stimulation, or Both Compared to Control for Urinary Incontinence in  Men Following Prostatectomy: Systematic Review and Meta-Analysis
Authors: Kannan P , Winser S J , Fung B , Cheing G
Published: August 2018

Background

The efficacy of pelvic floor muscle training (PFMT) alone and in combination with biofeedback (BFB), electrical stimulation (ES), or both for urinary incontinence in men following prostatectomy is inconclusive.

Purpose

The purpose of this study was to determine whether PFMT works well alone or in combination with BFB, ES, or both in comparison with a control.

Data Sources

The databases Ovid Medline, EMBASE, CENTRAL, Scopus, and Web of Science, and the specialized register of the Citroen Incontinence Review Group were searched from study inception to August 2017. Abstract proceedings from urological meetings, including the European Association of Urology and the American Urological Association, were also searched.

Study Selection

Randomized controlled trials that compared PFMT alone and PFMT with ES, BFB, or both and no treatment, placebo, or sham were included in the review.

Data Extraction, Synthesis, and Quality

Two independent reviewers completed data extraction and quality appraisal. The Grading of Recommendations, Assessment, Development, and Evaluation tool was used for quality appraisal. Meta-analysis was done with software used for preparing and maintaining Cochrane reviews.

Limitations

Methodological flaws in the included studies limited internal validity.

Conclusions

PFMT alone, PFMT plus BFB and ES, and PFMT plus ES were more effective than the control for urinary incontinence following prostatectomy. The effect of PFMT plus BFB on postprostatectomy incontinence remains uncertain.
Risk Factors on Hospital Arrival for Acute Respiratory Distress Syndrome Following Pediatric Trauma*
Authors: Killien Elizabeth Y. , Mills Brianna , Watson R. Scott , Vavilala Monica S. , Rivara Frederick P.
Published: August 2018

Objectives:

To determine risk factors identifiable at hospital arrival associated with acute respiratory distress syndrome development among critically injured children.

Design:

Retrospective cohort study.

Setting:

Level I or II adult or pediatric trauma centers contributing to the National Trauma Data Bank from 2007 to 2016.

Patients:

Patients less than 18 years admitted to an ICU with traumatic injury.

Interventions:

None.

Measurements and Main Results:

We determined associations between patient, injury, and clinical characteristics present at hospital arrival with development of acute respiratory distress syndrome recorded as a hospital complication. Acute respiratory distress syndrome occurred in 1.8% of 146,058 critically injured children (n = 2,590). The only demographic factor associated with higher risk of developing acute respiratory distress syndrome on multivariable analysis was African American race (relative risk, 1.42 vs white; 95% CI, 1.13–1.78). Injury characteristics included firearm injuries (relative risk 1.93; 1.50–2.48) and motor vehicle crashes (relative risk, 1.91; 1.57–2.31) relative to falls; spine (relative risk, 1.39; 1.20–1.60), chest (relative risk, 1.36; 1.22–1.52), or lower extremity injuries (relative risk, 1.26; 1.10–1.44); amputations (relative risk, 2.10; 1.51–2.91); and more severe injury (relative risk, 3.69 for Injury Severity Score 40–75 vs 1–8; 2.50–5.44). Clinical variables included abnormal respiratory status (intubated relative risk, 1.67; 1.23–2.26 and hypopnea relative risk, 1.23; 1.05–1.45 and tachypnea relative risk, 1.26; 1.10–1.44) and lower Glasgow Coma Scale score (relative risk, 5.61 for Glasgow Coma Scale score 3 vs 15; 4.44–7.07).

Conclusions:

We provide the first description of the incidence of and risk factors for acute respiratory distress syndrome among pediatric trauma patients. Improved understanding of the risk factors associated with acute respiratory distress syndrome following pediatric trauma may help providers anticipate its development and intervene early to improve outcomes for severely injured children.
The Statistical Curriculum Within Randomized Controlled Trials in Critical Illness*
Authors: McCullough James P. A. , Lipman Jeffrey , Presneill Jeffrey J.
Published: August 2018

Objectives:

Incomplete biostatistical knowledge among clinicians is widely described. This study aimed to categorize and summarize the statistical methodology within recent critical care randomized controlled trials.

Design:

Descriptive analysis, with comparison of findings to previous work.

Setting:

Ten high-impact clinical journals publishing trials in critical illness.

Subjects:

Randomized controlled trials published between 2011 and 2015 inclusive.

Interventions:

Data extraction from published reports.

Measurements and Main Results:

The frequency and overall proportion of each statistical method encountered, grouped according to those used to generate each trial’s primary outcome and separately according to underlying statistical methodology. Subsequent analysis compared these proportions with previously published reports. A total of 580 statistical tests or methods were identified within 116 original randomized controlled trials published between 2011 and 2015. Overall, the chi-square test was the most commonly encountered (70/116; 60%), followed by the Cox proportional hazards model (63/116; 54%) and logistic regression (53/116; 46%). When classified according to underlying statistical assumptions, the most common types of analyses were tests of 2 × 2 contingency tables and nonparametric tests of rank order. A greater proportion of more complex methodology was observed compared with trial reports from previous work.

Conclusions:

Physicians assessing recent randomized controlled trials in critical illness encounter results derived from a substantial and potentially expanding range of biostatistical methods. In-depth training in the assumptions and limitations of these current and emerging biostatistical methods may not be practically achievable for most clinicians, making accessible specialist biostatistical support an asset to evidence-based clinical practice.
American Football Players in Preseason Training at Risk of Acute Kidney Injury Without Signs of Rhabdomyolysis
Authors: Divine Jon G. , Clark Joseph F. , Colosimo Angelo J. , Detherage John P. , Donaworth Michael A. , Hasselfeld Kimberly A. , Himmler Aaron , Rauch Joseph T. , Mangine Robert E.
Published: August 2018

Objective:

This study was designed to identify changes in blood biomarkers that would indicate excessive muscle breakdown during the initial 10 days of preseason training in collegiate American football players and subsequently increase their risk of acute kidney injury (AKI).

Design:

Prospective cohort study.

Setting:

Preseason, heat acclimatization period.

Participants:

Twenty-five Division I American football players.

Intervention:

Clinical biomarkers for muscle damage were measured during a preseason training camp. Samples were obtained before camp and approximately 5 and 10 days into camp after completion of heat acclimatization training.

Main Outcomes:

Creatine kinase, myoglobin, lactate dehydrogenase, and creatinine were measured. Glomerular filtration rate (GFR) was calculated. Urine was collected at each blood draw to qualitatively identify hematuria and red blood cells.

Results:

A high percentage of athletes had an asymptomatic reduction in kidney function over the 10-day period. Ten of 23 athletes did have a significant, 31.6%, mean reduction in GFR, placing each at risk of AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification. The plasma myoglobin for the at risk of AKI group had a mean value 8× above their baseline mean on day 5 and statistically significant mean 13× higher on day 10 than baseline. The not at risk of AKI group did not have significant differences between days 0, 5, and 10.

Conclusions:

A relatively high percentage of athletes had an asymptomatic reduction in kidney function during the intense preseason training period. 43.4% of athletes in this study had a significant 31.6% mean reduction in GFR over the 10 days. According to RIFLE classification, this placed each athlete “at risk” of AKI.
Does Weekend Hospital Admission Affect Upper Gastrointestinal Hemorrhage Outcomes?
Authors: Liu Lina , Hao Dongxia , Liu Wei , Wang Lianfu , Wang Xudong
Published: August 2018

Background:

Compared with weekday admissions, weekend admissions are consistently associated with worse patient outcomes, known as the “weekend effect.” The weekend effect may have adverse health consequences, including death. To determine the potential impact of the weekend effect on primary (ie, mortality) and secondary outcomes of patients with upper gastrointestinal hemorrhage (UGIH).

Materials and Methods:

This was a network meta-analysis based on cohort studies. Databases were searched for studies published up to April 2018. The predefined primary outcome was mortality (30-d mortality and in-hospital mortality). The secondary efficacy outcomes were rebleeding rates, use of endoscopic therapy, need for surgery or angiography, mean length of hospital stay, and time to endoscopy. The study protocol was registered with PROSPERO (No. CRD42018094660).

Results:

In total, 25 studies, including 28 analyses (N=1,203,202 patients), were eligible. The results revealed a tendency toward increased 30-day mortality and increased in-hospital mortality among weekend admissions. In a subgroup analysis, there were significance differences in mortality according to the study location (ie, Europe) and UGIH type (ie, variceal UGIH), with these subgroups having elevated mortality rates. Moreover, weekday admissions were associated with a significant decrease in rebleeding rates. In the network meta-analysis, the study location (in Europe or Asia) and type of UGIH (ie, variceal UGIH) were associated with an increased likelihood of high in-hospital mortality among weekend admissions.

Conclusions:

The evidence derived from this network meta-analysis supports the idea that weekend admissions are associated with an increased risk of death, especially among variceal UGIH patients in European hospitals.
Caring for survivors of childhood cancer: it takes a village
Authors: Song Ailin , Fish Jonathan D.
Published: August 2018

Purpose of review

Over 80% of children diagnosed with cancer are now cured. The burgeoning population of survivors of childhood cancer experiences high rates of morbidity and mortality due to ‘late-effects’ of treatment. These can be defined as any consequence of treatment that persists beyond or develops after the completion of cancer therapy. Awareness of late-effects is critically important for pediatricians and adult providers alike, as late-effects impact children in proximity to cancer treatment, as well as adults many decades removed. This review presents the importance of lifelong follow-up care for survivors, highlights existing screening guidelines, and reviews various models of survivor care.

Recent findings

National and international guidelines have been developed to standardize screening for survivors, and multiple models of survivorship care exist. The optimal model likely depends on individual factors, including the survivor's needs and preferences, as well as local resources. Key strategies for the successful care of survivors include accurate risk-stratification for specific late-effects, individualized screening plans, education of survivors and professionals, clear communication between providers, and well coordinated transition of care across services.

Early identification and management of late-effects are important for survivors of childhood cancer. Providers should be familiar with the risks for specific late-effects and have access to screening guidelines. The strengths and weaknesses of care models, along with individual circumstances, should be considered in designing the optimal approach to care for each survivor.
Urea-mediated anomalous diffusion in supported lipid bilayers
Authors: Weatherill E. E. , Coker H. L. E. , Cheetham M. R. , Wallace M. I.
Published: August 2018

Diffusion in biological membranes is seldom simply Brownian motion; instead, the rate of diffusion is dependent on the time scale of observation and so is often described as anomalous. In order to help better understand this phenomenon, model systems are needed where the anomalous diffusion of the lipid bilayer can be tuned and quantified. We recently demonstrated one such model by controlling the excluded area fraction in supported lipid bilayers (SLBs) through the incorporation of lipids derivatized with polyethylene glycol. Here, we extend this work, using urea to induce anomalous diffusion in SLBs. By tuning incubation time and urea concentration, we produce bilayers that exhibit anomalous behaviour on the same scale as that observed in biological membranes.
K-mer based classifiers extract functionally relevant features to support accurate Peroxiredoxin subgroup distinction
Authors: Xiao Jiajie , Turkett William H.
Published: August 2018

Background

The Peroxiredoxins (Prx) are a family of proteins that play a major role in antioxidant defense and peroxide-regulated signaling. Six distinct Prx subgroups have been defined based on analysis of structure and sequence regions in proximity to the Prx active site. Analysis of other sequence regions of these annotated proteins may improve the ability to distinguish subgroups and uncover additional representative sequence regions beyond the active site.

Results

The space of Prx subgroup classifiers is surveyed to highlight similarities and differences in the available approaches. Exploiting the recent growth in annotated Prx proteins, a whole sequence-based classifier is presented that employs support vector machines and a k-mer (k=3) sequence representation.

Distinguishing k-mers are extracted and located relative to published active site regions.

Conclusions

This work demonstrates that the 3-mer based classifier can attain high accuracy in subgroup annotation, at rates similar to the current state-of-the-art. Analysis of the classifier’s automatically derived models show that the classification decision is based on a combination of conserved features, including a significant number of residue regions that have not been previously suggested as informative by other classifiers but for which there is evidence of functional relevance.
Nuclear TARBP2 drives oncogenic dysregulation of RNA splicing and decay
Authors: Fish Lisa , Nguyen Hoang C.B. , Zhang Steven , Hochman Myles , Dill Brian D. , Molina Henrik , Najafabadi Hamed S. , Alarcon Claudio , Goodarzi Hani
Published: August 2018

Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe a regulatory program, mediated by the double-stranded RNA binding protein TARBP2, that controls RNA stability in the nucleus. TARBP2 binding to pre-mRNAs results in increased intron retention, subsequently leading to targeted degradation of TARBP2-bound transcripts. This is mediated by TARBP2 recruitment of the m6A RNA methylation machinery to its target transcripts, where deposition of m6A marks influences the recruitment of splicing regulators, inhibiting efficient splicing. Interactions between TARBP2 and the nucleoprotein TPR then promote degradation of these TARBP2-bound transcripts by the nuclear exosome. Additionally, analysis of clinical gene expression datasets revealed a functional role for this TARBP2 pathway in lung cancer. Using xenograft mouse models, we find that TARBP2 impacts tumor growth in the lung, and that this function is dependent on TARBP2-mediated destabilization of ABCA3 and FOXN3. Finally, we establish the transcription factor ZNF143 as an upstream regulator of TARBP2 expression.

RESEARCH HIGHLIGHTS

The RNA-binding protein TARBP2 controls the stability of its target transcripts in the nucleus

Nuclear TARBP2 recruits the methyltransferase complex to deposit m6A marks on its target transcripts

TARBP2 and m6A-mediated interactions with splicing and nuclear RNA surveillance complexes result in target transcript intron retention and decay.

Increased TARBP2 expression is associated with lung cancer and promotes lung cancer growthin vivo.

The transcription factor ZNF143 drives oncogenic TARBP2 upregulation in lung cancer.
Unified single-cell analysis of testis gene regulation and pathology in 5 mouse strains
Authors: Jung Min , Wells Daniel , Rusch Jannette , Ahmed Suhaira , Marchini Jonathan , Myers Simon , Conrad Donald F.
Published: August 2018

By removing the confounding factor of cellular heterogeneity, single cell genomics can revolutionize the study of development and disease, but methods are needed to simplify comparison among individuals. To develop such a framework, we assayed the transcriptome in 62,600 single cells from the testes of wildtype mice, and mice with gonadal defects due to disruption of the genes Mlh3, Hormad1, Cul4a or Cnp. The resulting expression atlas of distinct cell clusters revealed novel markers and new insights into testis gene regulation. By jointly analysing mutant and wildtype cells using a model-based factor analysis method, SDA, we decomposed our data into 46 components that identify novel meiotic gene regulatory programmes, mutant-specific pathological processes, and technical effects. Moreover, we identify, de novo, DNA sequence motifs associated with each component, and show that SDA can be used to impute expression values from single cell data. Analysis of SDA components also led us to identify a rare population of macrophages within the seminiferous tubules of Mlh3-/- and Hormad1-/- testes, an area typically associated with immune privilege. We provide a web application to enable interactive exploration of testis gene expression and components at http://www.stats.ox.ac.uk/~wells/testisAtlas.html
Deep convolutional neural networks for accurate somatic mutation detection
Authors: Sahraeian Sayed Mohammad Ebrahim , Liu Ruolin , Lau Bayo , Mohiyuddin Marghoob , Lam Hugo Y.K.
Published: August 2018

We present NeuSomatic, the first convolutional neural network approach for somatic mutation detection, which significantly outperforms previous methods on different sequencing platforms, sequencing strategies, and tumor purities. NeuSomatic summarizes sequence alignments into small matrices and incorporates more than a hundred features to capture mutation signals effectively. It can be used universally as a stand-alone somatic mutation detection method or with an ensemble of existing methods to achieve the highest accuracy.
Boreal marine fauna from the Barents Sea disperse to Arctic Northeast Greenland
Authors: Andrews Adam J. , Christiansen Jørgen S. , Bhat Shripathi , Lynghammar Arve , Westgaard Jon-Ivar , Pampoulie Christophe , Præbel Kim
Published: August 2018

As a result of ocean warming, the species composition of the Arctic seas has begun to shift in a boreal direction. One ecosystem prone to fauna shifts is the Northeast Greenland shelf. The dispersal route taken by boreal fauna to this area is, however, not known. This knowledge is essential to predict to what extent boreal biota will colonise Arctic habitats. Using population genetics, we show that Atlantic cod (Gadus morhua), beaked redfish (Sebastes mentella), and deep-sea shrimp (Pandalus borealis) specimens recently found on the Northeast Greenland shelf originate from the Barents Sea, and suggest that pelagic offspring were dispersed via advection across the Fram Strait. Our results indicate that boreal invasions of Arctic habitats can be driven by advection, and that the fauna of the Barents Sea can project into adjacent habitats with the potential to colonise putatively isolated Arctic ecosystems such as Northeast Greenland.
Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic forms of autism in post-mortem human brain tissue
Authors: Wong Chloe C.Y. , Smith Rebecca G. , Hannon Eilis , Ramaswami Gokul , Parikshak Neelroop N. , Assary Elham , Troakes Claire , Poschmann Jeremie , Schalkwyk Leonard C. , Sun Wenjie , Prabhakar Shyam , Geschwind Daniel H. , Mill Jonathan
Published: August 2018

Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behavior. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular etiology of ASD, we quantified genome-wide patterns of DNA methylation in 233 post-mortem tissues samples isolated from three brain regions (prefrontal cortex, temporal cortex and cerebellum) dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the cerebellum. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically-defined subtype of ASD, were characterized by striking differences in DNA methylation across a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.
Characterization of osteoarthritis phenotypes by global metabolomic profiling of human synovial fluid
Authors: Carlson Alyssa K. , Rawle Rachel A. , Wallace Cameron W. , Brooks Ellen G. , Adams Erik , Greenwood Mark C. , Olmer Merissa , Lotz Martin K. , Bothner Brian , June Ronald K.
Published: August 2018

Objective

Osteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolic phenotypes of OA from human synovial fluid.

Design

Post mortemsynovial fluids (n=75) were analyzed by high performance-liquid chromatography mass spectrometry (HPLC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression.

Results

Global metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Phenotypes of OA exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid.

Conclusion

These results revealed distinct metabolic phenotypes of OA in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers and assist in developing personalized interventions for subgroups of OA patients.
The role of familial socio-political forces on new venture creation in family business
Authors: Bhatnagar Navneet , Ramachandran Kavil , Ray Sougata
Published: August 2018

Purpose

New venture (NV) creation is critical to the growth and long-term survival of business groups. The purpose of this paper is to investigate the NV creation process in family business (FB) context and examine the influence of familial socio-political considerations and dynamics on venture creation processes.

Design/methodology/approach

The paper employs a triangulation technique drawing from the extant literature, observations from 25 in-depth interviews of FB leaders and insights from two FB practitioners and abductive reasoning to theorize on the NV creation process and the influence of socio-political considerations and dynamics within family.

Findings

The results show that there are four distinct stages of the NV creation process in FB context. Familial socio-political considerations and dynamics greatly influence the NV creation process. These considerations and dynamics vary according to the socio-political clout enjoyed by the proposer. Leadership’s predisposition to the proposer and the proposer’s socio-political clout in the family determine whether an NV proposal leads to venture creation.

Research limitations/implications

The study extends NV creation literature by suggesting that in addition to the economic rationale, socio-political considerations play a critical role in venture creation decisions. Future research can validate the findings with quantitative analysis.

Practical implications

FB members must garner strong socio-political support for their NV proposal. FB leaders must ensure that their NV proposal evaluation and resource allocation decisions are not unduly influenced by the proposer’s socio-political clout.

Originality/value

The study views the NV creation process in FB context from the lens of familial forces at play. It identifies four distinct stages of the NV creation process and examines the role played by familial socio-political considerations and dynamics during each stage.
Embedded order reduction of hierarchical systems within an mCCM framework
Authors: Popp Michael , Mathis Wolfgang
Published: August 2018

Purpose

The purpose of this paper is to present the embedding of linear and nonlinear order reduction methods in a theoretical framework for handling hierarchically interconnected dynamical systems.

Design/methodology/approach

Based on the component connection modeling (CCM), a modified framework called mCCM for describing interconnected dynamic systems especially with hierarchical structures is introduced and used for order reduction purposes. The balanced truncation method for linear systems and the trajectory piecewise linear reduction scheme are used for the order reduction of systems described within the mCCM framework.

Findings

It is shown that order reduction methods can be embedded into the context of interconnected dynamical systems with the benefit of having a further degree of freedom in form of the hierarchical level, on which the order reduction is performed.

Originality/value

The aspect of hierarchy within system descriptions is exploited for order reduction purposes. This distinguishes the presented approach from common methods, which already start with single large-scale systems without explicitly considering hierarchical structures.