bluuebunny/crossref_metadata_2025 huggingface dataset:
Nalmefene in alcohol‐dependent patients with a high drinking risk: Randomized controlled trial
Authors: Miyata Hisatsugu , Takahashi Masayoshi , Murai Yoshiyuki , Tsuneyoshi Kana , Hayashi Takako , Meulien Didier , Sørensen Per , Higuchi Susumu
Published: July 2019

Aims

Reducing alcohol consumption is one treatment approach for alcohol‐dependent patients. This study compared nalmefene 20 mg and 10 mg with placebo, combined with psychosocial support, in alcohol‐dependent Japanese patients with a high or very high drinking risk level (DRL).

Methods

This was a multicenter, randomized, double‐blind, phase 3 study conducted in alcohol‐dependent patients with a high or very high DRL. Patients were randomized to 24 weeks of treatment with as‐needed nalmefene 20 mg, 10 mg, or placebo with psychosocial support. The primary endpoint was change in heavy drinking days (HDD) from baseline to week 12. A key secondary endpoint was the change in total alcohol consumption (TAC) from baseline to week 12.

Results

At week 12, 234, 206, and 154 patients who received placebo, nalmefene 20 mg, and 10 mg were included in the primary endpoint analysis. Compared with placebo, nalmefene was associated with significant reductions in HDD at week 12 (difference in 20 mg group, −4.34 days/month; 95% confidence interval [CI]: −6.05 to −2.62; P < 0.0001; difference in 10 mg group, −4.18 days/month; 95%CI: −6.05 to −2.32; P < 0.0001), as well as a significant reduction in TAC at week 12 (P < 0.0001). The incidence of treatment‐emergent adverse events was 87.9%, 84.8%, and 79.2% in the groups receiving nalmefene 20 mg, 10 mg, and placebo, respectively. These events were mostly of mild or moderate severity.

Conclusions

Nalmefene 20 mg or 10 mg effectively reduced alcohol consumption and was well tolerated in alcohol‐dependent patients with a high or very high DRL.
Amie Thomasson's Easy Approach to Ontology
Authors: Schiffer Stephen
Published: July 2019

Philosophers have long debated whether abstract objects such as numbers and properties exist, but in recent years philosophical debate about what things exist has been ratcheted up more than a notch to question whether even ordinary objects such as pineapples and tables exist. One view has it that all existence questions are difficult questions whose answers hang on achieving an ontological theory that succeeds in carving nature at its joints. Some proponents of this view further claim to have succeeded in that carving, even without the benefit of any instrument sharper than the a priori arguments conjured in their armchairs, and to have discovered, alas, that no ordinary concrete objects exist. Naturally, many of us have been made to wonder what premise in the argument for that conclusion enjoys a plausibility greater than that of the negation of the argument's conclusion. In her remarkable new book, Ontology Made Easy, Amie Thomasson strives to do much more than that in defense of common‐sense ontology. But not only for common‐sense ontology. She propounds a unified approach to all existence questions—whether about the existence of dogs, shoes or tables, or about the existence of numbers, propositions or fictional characters—according to which existence questions “are not deep and difficult subjects for metaphysical dispute, but rather questions to be resolved straightforwardly by employing our conceptual competence, often combining this with empirical investigations” (20). Thomasson calls her way of resolving existence questions the easy approach to ontology, and to that I now turn.
Foreign Human Capital and Total Factor Productivity: A Sectoral Approach
Authors: Fassio Claudio , Kalantaryan Sona , Venturini Alessandra
Published: July 2019

We analyze the role of migrants in productivity growth in the three largest European countries—France, Germany and the United Kingdom—in the years 1994–2007, using Total Factor Productivity. Unlike previous research, which mainly employs a regional approach, our analysis is at the sectoral level: this allows to distinguish the real contribution of migrants to productivity from possible inter‐sectoral complementarities, which might also foster growth. We control for the share of migrants and the different components of human‐capital, such as education, age and diversity, and adopt instrumental variables strategies to address the possible endogeneity of migration. The results show that migrants contribute to the productivity of the sectors in which they are employed, but with important differences: highly‐educated migrants show a larger positive effect in high‐tech sectors, and to a lesser extent in services sector. The diversity of countries of origin contributes to productivity growth only in the services sectors.
Stored platelet number and viscoelastic maximum amplitude are not altered by warming or rapid infusion
Authors: Hess Aaron S. , Ramamoorthy Jagan , Connor Joseph , Raife Thomas , Hess John R.
Published: July 2019

BACKGROUND

Platelet transfusion is an important aspect of hemostatic resuscitation. Leading textbooks recommend never infusing platelets through warmers or rapid infusers, but there is no evidence to justify this position.

MATERIALS AND METHODS

We obtained units of apheresis platelets in plasma from our hospital blood bank and drew a baseline sample from every unit. In the warmer arm, an aliquot from each unit was injected into a fluid warmer heated to 41°C (Ranger, 3M Corporation). After 5 minutes' incubation, the aliquot was withdrawn and sampled. In the infuser arm, we ran the remainder of the unit through a rapid infuser (RI‐2, Belmont Instrument Corporation) at 500 mL/min while warmed, and obtained a sample from the outflow line. A platelet count and viscoelastic maximum amplitude (Haemonetics) was measured from every sample.

RESULTS

We observed no clotting or device malfunctions. Average postwarmer temperature was 41.8°C (range, 41.0–43.0). There was no significant difference in postwarmer platelet count or viscoelastic maximum amplitude. Average postinfuser temperature was 37.4°C (range, 36.1–39.0). All units reached the goal infusion rate of 500 mL/min. There was a small increase in postinfuser platelet count. There was no significant change in postinfuser viscoelastic maximum amplitude.

CONCLUSION

We were unable to detect any effect of warming or rapid infusion on the number or viscoelastic maximum amplitude of stored apheresis platelets. Contrary to common teaching, these results suggest that rapid infusion and warming does not meaningfully harm apheresis platelets.
Internal fixation of a complete ventral luxation of the dens axis in an American quarter horse yearling
Authors: Schulze Nicole , Ehrle Anna , Noguera Cender Andrea C. , Lischer Christoph
Published: July 2019

Objective

To report surgical treatment of a complete luxation of the atlantoaxial articulation with a 4.5‐mm T‐locking compression plate (T‐LCP) in a horse.

Study design

Case report.

Animals

A one‐year‐old American quarter horse filly.

Methods

A one‐year‐old American quarter horse filly presented with a complete luxation of the atlantoaxial articulation. Closed and open reduction of the luxation were attempted under general anesthesia with the aid of a pulley system. Because the manual reduction was unsuccessful, the dens axis was excised, and the atlas and axis were stabilized with a 4.5‐mm T‐LCP. Four 5.5‐mm cortex screws were placed across the atlantoaxial articulation in lag fashion to provide additional stability.

Results

The horse made an uneventful recovery from surgery and remained comfortable thereafter. Nine months postsurgery, the filly had developed normally and did not show any sign of ataxia or reduced mobility of the cranial neck.

Conclusion

The described surgical approach resulted in the successful stabilization of a complete luxation of the atlantoaxial articulation in an American quarter horse yearling, with a favorable outcome.

Clinical significance

Complete atlantoaxial luxation is associated with a poor prognosis for survival in horses. This is the first report of a favorable outcome after surgical stabilization. The described approach presents a valuable alternative to the manual reduction of atlantoaxial luxation in horses.
Cine y representaciones nacionales: la imagen de España en la ficción internacional
Authors: Francescutti Luis Pablo
Published: July 2019

En este artículo se analizan las imágenes sobre la España actual en el cine de ficción extranjero. Las películas retratan un país moderno, próspero y culturalmente homogéneo a través de Barcelona, Madrid, Andalucía y la costa del Mediterráneo; y soslayan las regiones interiores y atlánticas, su diversidad cultural y las tensiones identitarias. Las anglosajonas, europeas y asiáticas enfatizan su atractivo turístico, la mezcla de tradición y modernidad y estereotipos como la tauromaquia, el flamenco o el carácter festivo, orgulloso y pasional de los españoles; las latinoamericanas se centran en las relaciones laborales y afectivas entre españoles y latinos. Las ópticas se complementan: anglosajones, europeos y asiáticos proyectan una mirada equiparable a la de turistas venidos de países ricos; los latinoamericanos adoptan la perspectiva de los inmigrantes de países pobres. Entre ambas iluminan las percepciones externas sobre los españoles y el imaginario latinoamericano acerca de la madre patria.
Imaginario social, crisis y miedo en King Kong (1933)
Authors: Roche Cárcel Juan A.
Published: July 2019

La primera proyección de la película King Kong, en 1933, causó en los miles de espectadores un extraordinario efecto, pues les provocó una reacción situada entre el terror y la fascinación. En efecto, el éxito de la película fue fulminante debido a la calidad del filme, a los espectaculares efectos especiales y a la profunda e intensa conexión emocional entre el imaginario de los espectadores del periodo y la temática de la cinta. En este sentido, tal vínculo se halla en la ambivalente y dialéctica interrelación que se produce entre esta primera versión de King Kong, la crisis del 29 –y los miedos que esta genera– y el imaginario norteamericano de los años 30. Pero, como se comprobará en el artículo, en el imaginario del filme se entremezclan, contaminándose mutuamente, entre otros, la realidad y la ficción, la verdad y la mentira, la seguridad y el peligro, el consciente y el subconsciente y la racionalidad y las emociones. Así, se concluirá que el imaginario norteamericano de los años treinta refleja no solamente la crisis económica del 29, sino también representa su sueño, sus temores y esperanzas, sus recuerdos y olvidos, así como oblitera su pasado, revigoriza su presente y ansía un porvenir mejor.
Relative Contributions of Matrix and Myocytes to Biaxial Mechanics of the Right Ventricle in Pulmonary Arterial Hypertension
Authors: Vélez-Rendón Daniela , Pursell Erica R. , Shieh Justin , Valdez-Jasso Daniela
Published: July 2019

Pulmonary arterial hypertension (PAH) commonly leads to right ventricular (RV) hypertrophy and fibrosis that affect the mechanical properties of the RV myocardium (MYO). To investigate the effects of PAH on the mechanics of the RV MYO and extracellular matrix (ECM), we compared RV wall samples, isolated from rats in which PAH was induced using the SuHx protocol, with samples from control animals before and after the tissues were decellularized. Planar biaxial mechanical testing, a technique first adapted to living soft biological tissues by Fung, was performed on intact and decellularized samples. Fung's anisotropic exponential strain energy function fitted the full range of biaxial test results with high fidelity in control and PAH samples both before and after they were decellularized. Mean RV myocardial apex-to-outflow tract and circumferential stresses during equibiaxial strain were significantly greater in PAH than control samples. Mean RV ECM circumferential but not apex-to-outflow tract stresses during equibiaxial strain were significantly greater in the PAH than control group. The ratio of ECM to myocardial stresses at matched strains did not change significantly between groups. Circumferential stresses were significantly higher than apex-to-outflow tract stresses for all groups. These findings confirm the predictions of a mathematical model based on changes in RV hemodynamics and morphology in rat PAH, and may provide a foundation for a new constitutive analysis of the contributions of ECM remodeling to changes in RV filling properties during PAH.
Sound exposure level as a metric for analyzing and managing underwater soundscapes
Authors: Martin S. Bruce , Morris Corey , Bröker Koen , O'Neill Caitlin
Published: July 2019

The auditory frequency weighted daily sound exposure level (SEL) is used in many jurisdictions to assess possible injury to the hearing of marine life. Therefore, using daily SEL to describe soundscapes would provide baseline information about the environment using the same tools used to measure injury. Here, the daily SEL from 12 recordings with durations of 18–97 days are analyzed to: (1) identify natural soundscapes versus environments affected by human activity, (2) demonstrate how SEL accumulates from different types of sources, (3) show the effects of recorder duty cycling on daily SEL, (4) make recommendations on collecting data for daily SEL analysis, and (5) discuss the use of the daily SEL as an indicator of cumulative effects. The autocorrelation of the one-minute sound exposure is used to help identify soundscapes not affected by human activity. Human sound sources reduce the autocorrelation and add low-frequency energy to the soundscapes. To measure the daily SEL for all marine mammal auditory frequency weighting groups, data should be sampled at 64 kHz or higher, for at least 1 min out of every 30 min. The daily autocorrelation of the one-minute SEL provides a confidence interval for the daily SEL computed with duty-cycled data.
Intelligibility of conversational and clear speech in young and older talkers as perceived by young and older listeners
Authors: Tuomainen Outi , Hazan Valerie , Davis Chris , Kim Jeesun
Published: July 2019

A related paper [Hazan, Tuomainen, Tu, Kim, Davis, Brungart, and Sheffield. (2018b). Hear. Res. 369, 33–41] showed that, for young adult listeners, speech produced by older adults was less intelligible than the speech of young adults but both talker groups improved the intelligibility of their speech via clear speech modifications. Here, this study was extended to include older listeners with/without presbycusis. The results showed that for older listeners, speech produced by older adults was less intelligible than the speech of young adults and scores improved in the clear speech condition. The best predictor of intelligibility was the amount of energy in the mid-frequency range of the spectrum.
Commensal Microbes Affect Host Humoral Immunity to
Bordetella pertussis
Infection
Authors: Zhang Youyi , Ran Zihan , Tian Miaomiao , Zhou Yang , Yang Jingcheng , Yin Juan , Lu Daru , Li Rui , Zhong Jiang
Published: July 2019

As important players in the host defense system, commensal microbes and the microbiota influence multiple aspects of host physiology.
Bordetella pertussis
infection is highly contagious among humans. However, the roles of the microbiota in
B. pertussis
pathogenesis are poorly understood. Here, we show that antibiotic-mediated depletion of the microbiota results in increased susceptibility to
B. pertussis
infection during the early stage.
Biochemical Analysis of Coronavirus Spike Glycoprotein Conformational Intermediates during Membrane Fusion
Authors: Kawase Miyuki , Kataoka Michiyo , Shirato Kazuya , Matsuyama Shutoku
Published: July 2019

Recent studies using single-particle cryo-electron microscopy (cryoEM) revealed the mechanism underlying activation of viral fusion protein at the priming stage. However, characterizing the subsequent triggering stage underpinning transition from pre- to postfusion structures is difficult because single-particle cryoEM excludes unstable structures that appear as heterogeneous shapes. Therefore, population-based biochemical analysis is needed to capture features of unstable proteins. Here, we analyzed protease digestion products of a coronavirus fusion protein during activation; their sizes appear to be affected directly by the conformational state. We propose a model for the viral fusion protein in the intermediate state, which involves a compact structure and conformational changes that overcome steric hindrance within the three fusion protein subunits.
Genetics of Lactococci
Authors: Gaudu Philippe , Yamamoto Yuji , Jensen Peter Ruhdal , Hammer Karin , Lechardeur Delphine , Gruss Alexandra
Published: July 2019

Lactococcus lactis
is the best characterized species among the lactococci, and among the most consumed food-fermenting bacteria worldwide. Thanks to their importance in industrialized food production, lactococci are among the lead bacteria understood for fundamental metabolic pathways that dictate growth and survival properties. Interestingly, lactococci belong to the Streptococcaceae family, which includes food, commensal and virulent species. As basic metabolic pathways (e.g., respiration, metal homeostasis, nucleotide metabolism) are now understood to underlie virulence, processes elucidated in lactococci could be important for understanding pathogen fitness and synergy between bacteria. This chapter highlights major findings in lactococci and related bacteria, and covers five themes: distinguishing features of lactococci, metabolic capacities including the less known respiration metabolism in Streptococcaceae, factors and pathways modulating stress response and fitness, interbacterial dialogue
via
metabolites, and novel applications in health and biotechnology.
Rifting of the northern margin of the Indian craton in the Early Cretaceous: Insight from the Aulis Trachyte of the Lesser Himalaya (Nepal)
Authors: Bhandari Saunak , Xiao Wenjiao , Ao Songjian , Windley Brian F. , Zhu Rixiang , Li Rui , Wang Hao Y.C. , Esmaeili Rasoul
Published: July 2019

To reconstruct the early tectonic history of the Himalayan orogen before final India-Asia collision, we carried out geochemical and geochronological studies on the Early Cretaceous Aulis Trachyte of the Lesser Himalaya. The trace-element geochemistry of the trachytic lava flows suggests formation in a rift setting, and zircon U-Pb ages indicate that volcanism occurred in Early Cretaceous time. The felsic volcanics show enrichment of more incompatible elements and rare earth elements, a pattern that is identical to the trachyte from the East African Rift (Kenya rift), with conspicuous negative anomalies of Nb, P, and Ti. Although much of the zircon age data are discordant, they strongly suggest an Early Cretaceous eruption age, which is in agreement with the fossil age of intravolcanic siltstones. The Aulis Trachyte provides the first corroboration of Cretaceous rifting in the Lesser Himalaya as suggested by paleomagnetic data associated with the concept that the northern margin of India separated as a microcontinent and drifted north in the Neo-Tethys before terminal collision of India with Asia.
Guillain-Barre syndrome with concurrent posterior reversible encephalopathy syndrome and hyponatraemia: mere coincidence or rare coexistence
Authors: Drye Carley , Bose Subhasish , Pathireddy Samata , Aeddula Narothama Reddy
Published: July 2019

A 61-year-old Caucasian woman with a history of hypertension presented with a week’s history of confusion falls and back pain was found to have hyponatraemia from secretion of antidiuretic hormone and treated appropriately. Given her persistent symptoms, despite a normal CT head on presentation, an MRI head was obtained, showing vasogenic oedema in line with posterior reversible encephalopathy syndrome (PRES). Despite aggressive antihypertensives and supportive measures, unfortunately, her condition deteriorated, with increased confusion, new left-sided flaccid paresis, paraesthesias and worsening of the back pain. Following further testing including a cerebrospinal fluid analysis, finally diagnosed with an atypical presentation of Guillain-Barre syndrome (GBS), and prompt management with intravenous immunoglobulins was initiated. She recovered clinically and returned to near-normal function on follow-up. We use this case to suggest the importance of dysautonomia in GBS and various clinical manifestations it can present with, including PRES and hyponatraemia.
Hamstring rehabilitation in elite track and field athletes: applying the British Athletics Muscle Injury Classification in clinical practice
Authors: Macdonald Ben , McAleer Stephen , Kelly Shane , Chakraverty Robin , Johnston Michael , Pollock Noel
Published: July 2019

Rationale

Hamstring injuries are common in elite sports. Muscle injury classification systems aim to provide a framework for diagnosis. The British Athletics Muscle Injury Classification (BAMIC) describes an MRI classification system with clearly defined, anatomically focused classes based on the site of injury: (a) myofascial, (b) muscle–tendon junction or (c) intratendinous; and the extent of the injury, graded from 0 to 4. However, there are no clinical guidelines that link the specific diagnosis (as above) with a focused rehabilitation plan.

Objective

We present an overview of the general principles of, and rationale for, exercise-based hamstring injury rehabilitation in British Athletics. We describe how British Athletics clinicians use the BAMIC to help manage elite track and field athletes with hamstring injury. Within each class of injury, we discuss four topics: clinical presentation, healing physiology, how we prescribe and progress rehabilitation and how we make the shared decision to return to full training. We recommend a structured and targeted diagnostic and rehabilitation approach to improve outcomes after hamstring injury.
Poor health, physical workload and occupational social class as determinants of health-related job loss: results from a prospective cohort study in the UK
Authors: Sewdas Ranu , van der Beek Allard J , Boot Cecile R L , D’Angelo Stefania , Syddall Holly E , Palmer Keith T , Walker-Bone Karen
Published: July 2019

Objectives

The aims of the present study were to assess the association and interactions of physical workload and poor health with health-related job loss (HRJL) among older workers, and the association and interactions of occupational social class and poor health with HRJL.

Methods

Data were used from an existing prospective cohort study, Health and Employment after Fifty, where employed or self-employed workers aged 50–64 years (n=4909) were followed-up between 2014 and 2016. Associations between potential determinants (self-perceived health status, physical workload and occupational social class) and 2-year HRJL were examined by Cox regression analyses. To study whether physical workload or occupational social class moderates the influence of poor health on HRJL, additive and multiplicative interactions were calculated.

Results

Older workers with poor self-perceived health status had increased risk of HRJL during the 2-year follow-up period (men: HR 2.57 (95%CI: 1.68 to 3.92); women: HR 3.26 (95%CI: 2.33 to 4.55)). Furthermore, men with high physical workload were at increased risk for HRJL (HR 1.63 (95%CI: 1.09 to 2.43)). No significant interactions (p<0.05) were identified between poor health and high physical workload, nor between poor health and lower occupational social class.

Conclusion

Our study indicates that older workers in poor health, and older workers with a physically demanding job, are at increased risk of HRJL. Having a physically demanding job or working in routine/manual occupations does not moderate the association between poor health and HRJL.
Development of hypotension in patients newly diagnosed with heart failure in UK general practice: retrospective cohort and nested case–control analyses
Authors: Martín-Pérez Mar , Michel Alexander , Ma Mark , García Rodríguez Luis Alberto
Published: July 2019

Objectives

Hypotension is of particular relevance for patients with heart failure (HF), since almost all HF drugs cause lowering of blood pressure (BP) and it is associated with a poor prognosis. We aimed to investigate hypotension incidence and risk factors in patients with incident HF in the UK.

Design

Retrospective cohort study including nested case–control analyses.

Setting

The Health Improvement Network UK primary care database.

Participants

18 677 adult patients with incident HF during 2000–2005 were followed and cases of hypotension (systolic BP ≤90 mm Hg) were identified. Controls were age-matched, sex-matched and date-matched to cases (1:2).

Primary and secondary outcome measures

We estimated hypotension incidence in the full study population and relevant subgroups (eg, sex and age). Potential risk factors for hypotension overall and for multiple versus single hypotensive episodes were evaluated using conditional logistic regression and unconditional regression models, respectively.

Results

During a mean follow-up of 3.31 years, 2565 patients (13.7%) developed hypotension. The incidence of hypotension was 3.17 cases per 100 patient years (95% confidence interval (CI): 3.05–3.30), and was markedly increased in women aged 18–39 years (n=32; 17.72 cases per 100 patient-years; 95% CI: 9.69–29.73). Hypotension risk factors included high healthcare utilisation (proxy measure for HF severity and general comorbidity; eg, ≥10 primary care physician visits versus none, odds ratio (OR): 2.29; 95% CI: 1.34–3.90), previous hypotensive episodes (OR: 2.32; 95% CI: 1.84–2.92), renal failure and use of aldosterone antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Risk factors identified for hypotension generally overlapped with those for multiple versus single hypotensive episodes.

Conclusions

Hypotension occurs frequently in patients with incident HF. Our findings may help identify patients most likely to benefit from close BP monitoring. The increased incidence of hypotension in young women with HF requires investigation.
External validation of the quick Sequential Organ Failure Assessment score for mortality and bacteraemia risk evaluation in Japanese patients undergoing haemodialysis: a retrospective multicentre cohort study
Authors: Nishiwaki Hiroki , Sasaki Sho , Hasegawa Takeshi , Sasai Fumihiko , Kawarazaki Hiroo , Minatoguchi Shun , Uchida Daisuke , Koitabashi Kenichiro , Ozeki Takaya , Koiwa Fumihiko
Published: July 2019

Objectives

We aimed to examine the validity of the quick Sequential Organ Failure Assessment (qSOFA) score for mortality and bacteraemia risk assessment in Japanese haemodialysis patients.

Design

This is a retrospective multicentre cohort study.

Setting

The six participating hospitals are tertiary-care institutions that receive patients on an emergency basis and provide primary, secondary and tertiary care. The other participating hospital is a secondary-care institution that receives patients on an emergency basis and provides both primary and secondary care.

Participants

This study included haemodialysis outpatients admitted for bacteraemia suspicion, who had blood drawn for cultures within 48 hours of their initial admission.

Primary and secondary outcome measures

The primary outcome measure was overall in-hospital mortality. Secondary outcomes included 28-day in-hospital mortality and the incidence of bacteraemia diagnosed based on blood culture findings. The discrimination, calibration and test performance of the qSOFA score were assessed. Missing data were handled using multiple imputation.

Results

Among the 507 haemodialysis patients admitted with bacteraemia suspicion between August 2011 and July 2013, the overall in-hospital mortality was 14.6% (74/507), the 28-day in-hospital mortality was 11.1% (56/507) and the incidence of bacteraemia, defined as a positive blood culture, was 13.4% (68/507). For predicting in-hospital mortality among haemodialysis patients, the area under the receiver operating characteristic curve was 0.61 (95% CI 0.56–0.67) for a qSOFA score ≥2. The Hosmer-Lemeshow χ2statistics for the qSOFA score as a predictor of overall and 28-day in-hospital mortality were 5.72 (p=0.02) and 7.40 (p<0.01), respectively.

Conclusion

On external validation, the qSOFA score exhibited low diagnostic accuracy and miscalibration for in-hospital mortality and bacteraemia among haemodialysis patients.
Timing Of Primary Surgery for cleft palate (TOPS): protocol for a randomised trial of palate surgery at 6 months versus 12 months of age
Authors: Shaw William , Semb Gunvor , Lohmander Anette , Persson Christina , Willadsen Elisabeth , Clayton-Smith Jill , Trindade Inge Kiemle , Munro Kevin J , Gamble Carrol , Harman Nicola , Conroy Elizabeth J , Weichart Dieter , Williamson Paula
Published: July 2019

Introduction

Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, speech, hearing, dental development and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. This has led to palatal closure in one-stage procedures being carried out around the age of 12 months, but in some cases as early as 6 months. The primary objective of the Timing Of Primary Surgery for Cleft Palate (TOPS)trial is to determine whether surgery for cleft palate performed at 6 or 12 months of age is most beneficial for speech outcomes.

Methods and analysis

Infants with a diagnosis of non-syndromic isolated cleft palate will be randomised to receive standardised primary surgery (Sommerlad technique) for closure of the cleft at either 6 months or 12 months, corrected for gestational age. The primary outcome will be perceived insufficient velopharyngeal function at 5 years of age. Secondary outcomes measured across 12 months, 3 years and 5 years will include growth, safety of the procedure, dentofacial development, speech, hearing level and middle ear function. Video and audio recordings of speech will be collected in a standardised age-appropriate manner and analysed independently by multiple speech and language therapists. The trial aims to recruit and follow-up 300 participants per arm. Data will be analysed according to the intention-to-treat principle using a 5% significance level. All analyses will be prespecified within a full and detailed statistical analysis plan.

Ethics and dissemination

Ethical approval has been sought in each participating country according to country-specific procedures. Trial results will be presented at conferences, published in peer-reviewed journals and disseminated through relevant patient support groups.

Trial registration number

NCT00993551; Pre-results.
IBD prevalence in Lothian, Scotland, derived by capture–recapture methodology
Authors: Jones Gareth-Rhys , Lyons Mathew , Plevris Nikolas , Jenkinson Philip W , Bisset Cathy , Burgess Christopher , Din Shahida , Fulforth James , Henderson Paul , Ho Gwo-Tzer , Kirkwood Kathryn , Noble Colin , Shand Alan G , Wilson David C , Arnott Ian DR , Lees Charlie W
Published: July 2019

Objective

IBD prevalence is estimated to be rising, but no detailed, recent UK data are available. The last reported prevalence estimate in the UK was 0.40% in 2003. We aimed to establish the current, and project future, prevalence in Lothian, Scotland.

Design

We conducted an all-age multiparameter search strategy using inpatient IBD international classification of disease (ICD-10) coding (K50/51)(1997–2018), IBD pathology coding (1990–2018), primary and secondary care prescribing data (2009–2018) and a paediatric registry, (1997–2018) to identify ‘possible’ IBD cases up to 31/08/2018. Diagnoses were manually confirmed through electronic health record review as per Lennard-Jones/Porto criteria. Autoregressive integrated moving average (ARIMA) regression was applied to forecast prevalence to 01/08/2028.

Results

In total, 24 601 possible IBD cases were identified of which 10 499 were true positives. The point prevalence for IBD in Lothian on 31/08/2018 was 784/100 000 (UC 432/100 000, Crohn’s disease 284/100 000 and IBD unclassified (IBDU) 68/100 000). Capture–recapture methods identified an additional 427 ‘missed’ cases (95% CI 383 to 477) resulting in a ‘true’ prevalence of 832/100 000 (95% CI 827 to 837).

Prevalence increased by 4.3% per year between 2008 and 2018 (95% CI +3.7 to +4.9%, p<0.0001). ARIMA modelling projected a point prevalence on 01/08/2028 of 1.02% (95% CI 0.97% to 1.07%) that will affect an estimated 1.53% (95% CI 1.37% to 1.69%) of those >80 years of age.

Conclusions

We report a rigorously validated IBD cohort with all-age point prevalence on 31/08/2018 of 1 in 125, one of the highest worldwide.
Genetic variants and copy number changes in soft tissue leiomyosarcoma detected by targeted amplicon sequencing
Authors: Rao Uma , Schoedel Karen Elizabeth , Petrosko Patricia , Sakai Nozomi , LaFramboise William
Published: July 2019

Aims

Leiomyosarcomas (LMSs) occur in various tissues and harbour potential for metastases. The genomic landscape of LMS is poorly understood. In an effort to improve understanding of the LMS genome, we analysed 11 LMSs of somatic soft tissue including matching tissue of normal phenotype.

Methods

DNA derived from microdissected tumour domains and matching normal tissue underwent amplicon sequencing of 409 tumour suppressors and oncogenes using the Ion Torrent Comprehensive Cancer Panel.

Results

Genomic changes were heterogeneous with few recurrent abnormalities detected. Coding variants were identified in genes involved in signal transduction, transcriptional regulation and DNA repair. There were variants in several genes related to angiogenesis andGPR124variants (TEM5) were confirmed by immunohistochemical analysis of a LMS tissue microarray. Surprisingly, there were shared coding variants in tumour and corresponding normal tissue.

Conclusions

LMSs are a very heterogeneous population lacking recurrent somatic abnormalities. The presence of damaging mutations in normal tissue may reflect either a germline predisposition or field effect rather than tissue contamination. Hopeful therapeutic targets appear to be those related toAKT/MTORpathway.
RASA1mosaic mutations in patients with capillary malformation-arteriovenous malformation
Authors: Revencu Nicole , Fastre Elodie , Ravoet Marie , Helaers Raphaël , Brouillard Pascal , Bisdorff-Bresson Annouk , Chung Clara W T , Gerard Marion , Dvorakova Veronika , Irvine Alan D , Boon Laurence M , Vikkula Miikka
Published: July 2019

Background

Capillary malformation-arteriovenous malformation is an autosomal dominant disorder, characterised by capillary malformations and increased risk of fast-flow vascular malformations, caused by loss-of-function mutations in theRASA1orEPHB4genes. Around 25% of the patients do not seem to carry a germline mutation in either one of these two genes. Even if other genes could be involved, some individuals may have mutations in the known genes that escaped detection by less sensitive techniques. We tested the hypothesis that mosaic mutations could explain some of previously negative cases.

Methods

DNA was extracted from peripheral blood lymphocytes, saliva or vascular malformation tissues from four patients.RASA1andEPHB4coding regions and exon/intron boundaries were analysed by targeted custom gene panel sequencing. A second panel and/or Sanger sequencing were used to confirm the identified mutations.

Results

Four distinct mosaicRASA1mutations, with an allele frequency ranging from 3% to 25%, were identified in four index patients with classical capillary malformation-arteriovenous malformation phenotype. Three mutations were known, one was novel. In one patient, a somatic second hit was also identified. One index case had three affected children, illustrating that the mosaicism was also present in the germline.

Conclusion

This study shows thatRASA1mosaic mutations can cause capillary malformation-arteriovenous malformation. Thus, highly sensitive sequencing techniques should be considered as diagnostic tools, especially for patients with no family history. Even low-level mosaicism can cause the classical phenotype and increased risk for offspring. In addition, our study further supports the second-hit pathophysiological mechanism to explain the multifocality of vascular lesions in this disorder.
CCMG practice guideline: laboratory guidelines for next-generation sequencing
Authors: Hume Stacey , Nelson Tanya N , Speevak Marsha , McCready Elizabeth , Agatep Ron , Feilotter Harriet , Parboosingh Jillian , Stavropoulos Dimitri J , Taylor Sherryl , Stockley Tracy L
Published: July 2019

Purpose

The purpose of this document is to provide guidance for the use of next-generation sequencing (NGS, also known as massively parallel sequencing or MPS) in Canadian clinical genetic laboratories for detection of genetic variants in genomic DNA and mitochondrial DNA for inherited disorders, as well as somatic variants in tumour DNA for acquired cancers. They are intended for Canadian clinical laboratories engaged in developing, validating and using NGS methods.

Methods of statement development

The document was drafted by the Canadian College of Medical Geneticists (CCMG) Ad Hoc Working Group on NGS Guidelines to make recommendations relevant to NGS. The statement was circulated for comment to the CCMG Laboratory Practice and Clinical Practice committees, and to the CCMG membership. Following incorporation of feedback, the document was approved by the CCMG Board of Directors.

Disclaimer

The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. The current CCMG Practice Guidelines were developed as a resource for clinical laboratories in Canada and should not be considered to be inclusive of all information laboratories should consider in the validation and use of NGS for a clinical laboratory service.
Comparison of endoscopic evacuation, stereotactic aspiration, and craniotomy for treatment of basal ganglia hemorrhage
Authors: Guo Wei , Liu Haixiao , Tan Zhijun , Zhang Xiaoyang , Gao Junmei , Zhang Lei , Guo Hao , Bai Hao , Cui Wenxing , Liu Xunyuan , Wu Xun , Luo Jianing , Qu Yan
Published: July 2019

Background

The main surgical techniques for spontaneous basal ganglia hemorrhage include stereotactic aspiration, endoscopic aspiration, and craniotomy. However, credible evidence is still needed to validate the effect of these techniques.

Objective

To explore the long-term outcomes of the three surgical techniques in the treatment of spontaneous basal ganglia hemorrhage.

Methods

Five hundred and sixteen patients with spontaneous basal ganglia hemorrhage who received stereotactic aspiration, endoscopic aspiration, or craniotomy were reviewed retrospectively. Six-month mortality and the modified Rankin Scale score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of different surgical techniques on patient outcomes.

Results

For the entire cohort, the 6-month mortality in the endoscopic aspiration group was significantly lower than that in the stereotactic aspiration group (odds ratio (OR) 4.280, 95% CI 2.186 to 8.380); the 6-month mortality in the endoscopic aspiration group was lower than that in the craniotomy group, but the difference was not significant (OR=1.930, 95% CI 0.835 to 4.465). A further subgroup analysis was stratified by hematoma volume. The mortality in the endoscopic aspiration group was significantly lower than in the stereotactic aspiration group in the medium (≥40–<80 mL) (OR=2.438, 95% CI 1.101 to 5.402) and large hematoma subgroup (≥80 mL) (OR=66.532, 95% CI 6.345 to 697.675). Compared with the endoscopic aspiration group, a trend towards increased mortality was observed in the large hematoma subgroup of the craniotomy group (OR=8.721, 95% CI 0.933 to 81.551).

Conclusion

Endoscopic aspiration can decrease the 6-month mortality of spontaneous basal ganglia hemorrhage, especially in patients with a hematoma volume ≥40 mL.
Does stress echocardiography add incremental value to baseline ejection fraction for the early identification of candidates for implantable defibrillators?
Authors: Muhrbeck Josephine , Gunyeli Elif , Andersson Eva , Alam Mahbubul , Frykman Viveka , Sjoblom Johanna
Published: July 2019

Objective

A reduction in left ventricular ejection fraction (EF) remains the strongest indicator of increased risk of sudden cardiac death after an acute myocardial infarction (AMI). Guidelines recommend that patients with an EF ≤35%, 6–12 weeks after AMI should be considered for implantable cardioverter defibrillator (ICD) therapy. Stress echocardiography is a safe method to detect viability in a stunned myocardium. The purpose of this study was to investigate if stress echocardiography early after AMI could identify ICD candidates before discharge.

Methods

Ninety-six patients with EF ≤40% early after AMI were prospectively included in a cohort study, and investigated by baseline and stress echocardiography before discharge. Follow-up echocardiography was performed after 3 months. EF, mitral annular plane systolic excursion (MAPSE) and peak systolic velocity (PSV) were determined for each examination.

Results

There were 80 (83%) patients who completed the baseline, stress and follow-up echocardiography. Among them there were 32 (40%) patients who met the ICD criteria of EF ≤35% at 3 months. For these patients, EF, MAPSE and PSV were significantly lower than for those patients who recovered. The area under the receiver operating characteristic curve (AUC) was 85% (95% CI 0.74 to 0.94) for baseline EF to predict non-recovery. None of the other variables had a higher AUC.

Conclusion

Patients who met the ICD criteria of EF ≤35% at 3 months after myocardial infarction had lower EF, MAPSE and PSV on baseline and stress echocardiograph before discharge. Stress echocardiography did not add additional value in predicting non-recovery.
Acute effect of multiple sets of fatiguing resistance exercise on muscle thickness, echo intensity, and extracellular-to-intracellular water ratio
Authors: Taniguchi Masashi , Yamada Yosuke , Ichihashi Noriaki
Published: July 2019

Resistance exercise (RE) causes an acute increase of the muscle thickness (MT) considered to relate to an increase in tissue water content. Segmental bioelectrical impedance spectroscopy (S-BIS) is a tool used to noninvasively assess intra- and extra-cellular water (ICW and ECW, respectively) of a given limb segment. The purpose of the present study was to examine the change of MT, ultrasound echo intensity (EI), ICW, and ECW after 3 sets of exhaustive RE. Eighteen untrained young males (age, 25.4 ± 4.1 years) performed RE consisting of 3 sets of knee extension concentric and eccentric contractions with 80% of 1-repetition maximum to failure. The MT and EI of the quadriceps measured by ultrasonography, and ECW/ICW ratio of the thigh assessed by S-BIS before (baseline) and after each set of RE (PostEx1, 2, and 3). The changes (Δ) in MT, EI, and ECW/ICW ratio were calculated as values of PostEx minus baseline values. The values of MT, EI, and ECW/ICW ratio at PostEx3 were significantly higher than baseline (effect size: MT, 1.11; EI, 0.47; and ECW/ICW ratio, 0.45). In addition, ΔMT was significantly and moderately correlated with ΔECW/ICW ratio (r = 0.61). Integrated data showed weak but significant correlation between ΔEI and ΔECW/ICW ratio as well (r = 0.31). The present results suggest multiple sets of exhaustive knee extension RE induce the acute increase of EI and ECW/ICW ratio as well as MT. The acute increase of muscle size after exercise can be at least partly explained by relative ECW increase.
Aggregate size distribution and associated carbon and nitrogen in mulched winter wheat and spring corn
Authors: Fu Xin , Wang Jun , Sainju Upendra M. , Liu Wenzhao
Published: July 2019

The influence of surface mulching on soil aggregation and associated carbon (C) and nitrogen (N) varies by mulching materials and crop types. The 6 yr effect of straw mulching (SM), plastic film mulching (PM), and no mulching (CK) on soil aggregation and associated C and N concentrations at 0–20 and 20–40 cm soil layers were studied under dryland winter wheat (Triticum aestivum L.) and spring corn (Zea mays L.) in the Loess Plateau of China. Regardless of crop types, aggregate proportion was greater in macroaggregates (2.00–10.00 mm), but lower in microaggregates (<0.50 mm) with mulching than without in both soil layers. The mean weight diameter of aggregates was greater with SM and PM than CK. Compared with CK and PM, SM increased soil organic C (SOC) and total N (STN) concentrations in both macroaggregates and bulk soil at 0–20 cm. Aggregate proportion and soil C and N concentrations at both depths were more pronounced in winter wheat than spring corn. The recovery rates of bulk soil SOC and STN in aggregates varied from 94% to 107%. Straw and plastic film mulching enhanced soil aggregation compared with no mulching. Straw mulching was more effective in increasing SOC and STN concentrations at the surface layer in dryland winter wheat and spring corn.
Spectral Noncommutative Geometry Standard Model and all that
Authors: Devastato Agostino , Kurkov Maxim , Lizzi Fedele
Published: July 2019

We review the approach to the Standard Model of particle interactions based on spectral noncommutative geometry. The paper is (nearly) self-contained and presents both the mathematical and phenomenological aspects. In particular, the bosonic spectral action and the fermionic action are discussed in detail, and how they lead to phenomenology. We also discuss the Euclidean versus Lorentz issues and how to go beyond the Standard Model in this framework.
Quantum confinement effects of formation energies and vibrational properties of CdS clusters: A DFT study
Authors: Kadhim Bahjat B. , Abdulsattar Mudar Ahmed , Ali Ali Mohammed
Published: July 2019

Formation energies of cadmium sulfide clusters are calculated with the help of density functional theory. The investigated structures include clusters that represent the CdS three main phases, wurtzite, zincblende and rock-salt. The investigation includes electronic, vibrational and thermal properties. CdS clusters are represented by wurtzoids, diamondoids and cuboids for the three phases, wurtzite, zincblende and rock-salt, respectively. The energy gap of the largest investigated molecules approaches that of bulk experimental 2.42 eV. The calculated longitudinal optical (LO) vibrational mode is 304.2 cm[Formula: see text] which is in good agreement with the experimental bulk value of 305 cm[Formula: see text]. To calculate Gibbs free energy, enthalpy and entropy of formation for the clusters, we redefined these quantities so that they represent the difference between the CdS formation energy and their constitutes Cd and S clusters energy. The calculated Gibbs free energy of formation, enthalpy and entropy of the investigated clusters approach that of bulk. Wurtzoids are more stable than diamondoids and cuboids with the release of more heat as deduced from their cluster Gibbs energy and enthalpy of formation. The entropy of clusters is dependent on the size of the cluster. The present method draws a relation between known solid state phases and small cluster calculations.
Molecular dynamics simulation of aggregation of monocrystal and polycrystal copper nanoparticles
Authors: Zhang Linxing , Hong Guang , Cai Shouyin
Published: July 2019

Molecular dynamics simulations were employed to investigate the aggregation of monocrystal and polycrystal nanoparticles. The lattice structure, displacement vector, potential energy, shrinkage ratio, relative gyration radius and mean square displacement of the two systems are compared. The results indicate that the aggregation of polycrystal nanoparticles is more drastic than that of monocrystal nanoparticles. Besides, the polycrystal nanoparticles are found contacted and melted at lower-temperature than that of monocrystal nanoparticles. The reason for all these phenomena is that there is additional surface energy in the grain boundary of polycrystal nanoparticles.