bluuebunny/crossref_metadata_2025 huggingface dataset:
Videofluoroscopy, CT angiography, and ultrasonography of congenital esophageal stenosis in a Labrador retriever
Authors: Kopke Matthew A. , Gal Arnon , Ruaux Craig G. , Gans Leah C. , Aberdein Danielle , Owen Mark C. , Burchell Richard K.
Published: December 2018

A 7‐week‐old Labrador retriever presented for further investigation into acute onset regurgitation, following weaning from liquid to solid food. A videofluoroscopic swallow study demonstrated a severe, focal esophageal dilation in the mid‐cervical region, with marked luminal narrowing distally. Computed tomography with angiography revealed esophageal stenosis, extending from C4–T2, secondary to circumferential esophageal wall thickening. With the concern for development of secondary aspiration pneumonia, the owners elected to euthanize the dog and consented to postmortem examination. A diagnosis of segmental, cervical esophageal muscular hypertrophy was made on necropsy, consistent with the fibromuscular thickening type of congenital esophageal stenosis reported in humans.
Modeling and Identification of the Mechanical Properties of Achilles Tendon With Application in Health Monitoring
Authors: Kohut Piotr , Holak Krzysztof , Obuchowicz Rafal , Ekiert Martyna , Mlyniec Andrzej , Ambrozinski Lukasz , Tomaszewski Krzysztof A. , Uhl Tadeusz
Published: December 2018

In this study, we develop a modeling and experimental framework for multiscale identification of the biomechanical properties of the human Achilles tendon (AT). For this purpose, we extend our coarse-grained model of collagen fibrous materials with a chemomechanical model of collagen type I decomposition. High-temperature degradation of molecular chains of collagen in a water environment was simulated using a reactive molecular dynamics (MD) method. The results from MDs simulations allowed us to define the Arrhenius equation for collagen degradation kinetics and calculate the energy of activation together with the frequency factor. Kinetic coefficients obtained from a MD simulations were further used to provide better calibration of the a coarse grained (CG) model of collagen denaturation. For the experimental part of our framework, we performed a uniaxial tensile test of the human AT with additional use of digital image correlation (DIC) for ex vivo strain tracking. Using a different path of strain tracking, we were able to include the inhomogeneity of deformation and, therefore, regional variations in tissue stiffness. Our results, both in modeling and the experimental part of the study, are in line with already existing reports and thus provide an improved approach for multiscale biomechanical and chemomechanical studies of the human AT.
Chapter 2: The Teacher Pipeline for PETE: Context, Pressure Points, and Responses
Authors: Ward Phillip
Published: December 2018

Recruiting, teacher preparation, and acquiring teaching jobs can be viewed as a pipeline. The function of the pipeline is to provide competent and qualified physical education teachers to teach in our nation’s schools. On the exit end of the pipeline, jobs for physical education teachers are plentiful. At the entry level to the pipeline, the situation is problematic because there is a decline in the number of students entering many physical education teacher education programs. This decline, documented in some cases and reported anecdotally in others, has occurred across the United States, with the exception of some states such as Texas and Alabama. The personal, practical, and policy implications of declining admissions have yet to be played out in their entirety. In this paper, the author discusses the pipeline, its policy pressure points, and responses to the pressure points designed to address declining admission.
Non-alcoholic Wernicke encephalopathy: great masquerader
Authors: Okafor Chukwudumebi , Nimmagadda Manojna , Soin Sarthak , Lanka Lavanya
Published: December 2018

Thiamine is an important coenzyme, which is essential for metabolism and maintaining cellular osmotic gradient. Thiamine deficiency can cause focal lactic acidosis, alteration of the blood–brain barrier and the production of free radicals through cell death by necrosis and apoptosis. Wernicke encephalopathy (WE) is a clinical diagnosis. Cytotoxic and vasogenic oedema are the most typical neuroimaging findings of WE, presenting as bilateral symmetrical hyperintense signals on T2-weighted MR images. MRI is not necessary for the diagnosis of WE, but it can be helpful in ruling out alternative diagnosis. We present the case of an 61-year-old man with the history of class II obesity presenting with diplopia, dysarthria and vertigo, confirmed to be non-alcoholic WE. We aim to highlight the occurrence of WE in patients with large bowel resection though. Delay in diagnosis, particularly in obese individuals due to lack of suspicion, can lead to grim prognosis.
European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (EPAD LCS): study protocol
Authors: Solomon Alina , Kivipelto Miia , Molinuevo José Luis , Tom Brian , Ritchie Craig W
Published: December 2018

Introduction

The European Prevention of Alzheimer’s Dementia (EPAD) project is funded initially by the Innovative Medicines Initiative and has been established to overcome the major hurdles hampering drug development for secondary prevention of Alzheimer’s dementia, by conducting the EPAD Longitudinal Cohort Study (LCS) in alignment with the Bayesian adaptive designed EPAD Proof-of-Concept (PoC) trial.

Methods and analysis

EPAD LCS is an ongoing prospective, multicentre, pan-European longitudinal cohort study. Participants are recruited mainly from existing parent cohorts across Europe to form a ‘probability-spectrum’ population covering the entire continuum of anticipated probability for Alzheimer’s dementia development. The primary objective of the EPAD LCS is to be a readiness cohort for the EPAD PoC trial though a second major objective is to generate a comprehensive and large data set for disease modelling of preclinical and prodromal Alzheimer’s disease. This characterisation of cognitive, biomarker and risk factor (genetic and environmental) status of research participants over time will provide the necessary well-phenotyped population for developing accurate longitudinal models for Alzheimer’s disease covering the entire disease course and concurrently create a pool of highly characterised individuals for the EPAD PoC trial.

Ethics and dissemination

The study has received the relevant approvals from numerous Institutional Review Boards across Europe. Findings will be disseminated to several target audiences, including the scientific community, research participants, patient community, general public, industry, regulatory authorities and policy-makers. Regular and coordinated releases of EPAD LCS data will be made available for analysis to help researchers improve their understanding of early Alzheimer’s disease stages and facilitate collaborations.

Trial registration number

NCT02804789.
Comparison of standardised mortality ratios for renal failure before and after the 2011 Great East Japan Earthquake and Tsunami: an analysis of national vital statistics
Authors: Tsukinoki Rumi , Murakami Yoshitaka , Kawado Miyuki , Hashimoto Shuji
Published: December 2018

Objective

The impact of the 2011 Great East Japan Earthquake on renal failure (RF) risk remains unclear. We examined the 1-year impact of this disaster on RF mortality.

Setting

This ecological study focused on the year before and after the earthquake. The data sources were national vital statistics (2010–2012), the national census (2010) and the Basic Resident Registration (2010–2012).

Participants

Our study included all residents in Iwate, Miyagi and Fukushima, 1 year before and after the earthquake.

Primary and secondary outcome measures

We calculated standardised mortality ratios (SMRs) for RF, chronic RF and acute RF. Postearthquake weekly SMRs were calculated using the number of RF deaths for the corresponding weeks in 2010 as a reference. The SMRs for RF were compared between the coastal and inland municipalities using kernel-weighted polynomial smoothing.

Results

There were 1290 RF deaths in the three prefectures during the year after the earthquake (chronic RF: 804 and acute RF: 236). The SMR for RF increased significantly in the first week after the earthquake in coastal areas (3.11; 95% CI: 1.84 to 4.37), but did not increase in inland areas (0.93; 95% CI: 0.47 to 1.38). A similar trend was observed for chronic RF (coastal: 4.0; 95% CI: 2.0 to 6.0; inland: 1.1; 95% CI: 0.4 to 1.7). SMRs for RF and chronic RF decreased over time and reached 1.0 approximately 20 weeks after the disaster. Changes in SMRs for acute RF were not apparent due to the low number of deaths.

Conclusions

Mortality due to RF and chronic RF, but not acute RF, increased in coastal areas after the earthquake. Chronic RF may have been exacerbated by disaster-induced sympathetic activation and poor management of renal dysfunction. Increased hypertension and damage to essential infrastructure and medical equipment may also have increased mortality in people with kidney disease.
Impact of genetic testing on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia (GenTLe-FH): a randomised waiting list controlled open-label study protocol
Authors: Nomura Akihiro , Tada Hayato , Okada Hirofumi , Nohara Atsushi , Ishikawa Hideki , Yoshimura Kenichi , Kawashiri Masa-aki
Published: December 2018

Introduction

Familial hypercholesterolemia (FH) is an autosomal-dominant inherited genetic disease. High-throughput sequencing quickly and comprehensively detects causative variants of FH-related genes (LDLR,PCSK9,APOBandLDLRAP1). Although the presence of causative variants in FH-related genes correlates with future cardiovascular events, it remains unclear whether detection of causative gene mutation and disclosure of its associated cardiovascular risk affects outcomes in patients with FH. Therefore, this study intends to evaluate the efficacy of counselling future cardiovascular risk based on genetic testing in addition to standard patients’ education programme in patients with FH.

Methods and analysis

A randomised, waiting-list controlled, open-label, single-centre trial will be conducted. We will recruit patients with clinically diagnosed FH without previous history of coronary heart disease from March 2018 to December 2019, and we plan to follow up participants until March 2021. For the intervention group, we will perform genetic counselling and will inform an estimated future cardiovascular risk based on individuals’ genetic testing results. The primary endpoint of this study is the plasma low-density lipoprotein cholesterol level at 24 weeks after randomisation. The secondary endpoints assessed at 24 and 48 weeks are as follows: blood test results; smoking status; changes of lipid-lowering agents’ regimen and Patients Satisfaction Questionnaire Short Form scores among the four groups divided by the presence of genetic counselling and genetic status of FH.

Ethics and dissemination

This study will be conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects and all other applicable laws and guidelines in Japan. This study protocol was approved by the IRB at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.

Trial registration number

UMIN000029375.
What do European women know about their female cancer risks and cancer screening? A cross-sectional online intervention survey in five European countries
Authors: Wegwarth Odette , Widschwendter Martin , Cibula David , Sundström Karin , Portuesi Rosalba , Lein Ines , Rebitschek Felix G
Published: December 2018

Objectives

Informed decisions about cancer screening require accurate knowledge regarding cancer risks and screening. This study investigates: (1) European women’s knowledge of their risk of developing breast, ovarian, cervical or endometrial cancer, (2) their knowledge about mammography screening and (3) whether an evidence-based leaflet improves their knowledge.

Design

Cross-sectional online intervention survey.

Setting

National samples from five European countries (Czech Republic, Germany, UK, Italy and Sweden)—drawn from the Harris Interactive and the Toluna panel, respectively, in January 2017—were queried on their knowledge of age-specific risks of developing breast, cervical, ovarian or endometrial cancer within the next 10 years and of mammography screening before and after intervention.

Participants

Of 3629 women (inclusion criteria: age 40–75 years) invited, 2092 responded and 1675 completed the survey (response rate: 61.4%).

Intervention

Evidence-based leaflet summarising information on age-adjusted female cancer risks, mammography and aspects of cancer prevention.

Primary outcome measures

Proportion of women (1) accurately estimating their risk of four female cancers, (2) holding correct assumptions of mammography screening and (3) changing their estimations and assumptions after exposure to leaflet.

Findings

Across countries, 59.2% (95% CI 56.8% to 61.6%) to 91.8% (95% CI 90.3% to 93.0%) overestimated their female cancer risks 7–33 fold (mediansacross tumours: 50.0 to 200.0). 26.5% (95% CI 24.4% to 28.7%) were aware that mammography screening has both benefits and harms. Women who accurately estimated their breast cancer risk were less likely to believe that mammography prevents cancer (p<0.001). After leaflet intervention, knowledge of cancer risks improved by 27.0 (95% CI 24.9 to 29.2) to 37.1 (95% CI 34.8 to 39.4) percentage points and of mammography by 23.0 (95% CI 21.0 to 25.1) percentage points.

Conclusion

A considerable number of women in five European countries may not possess the prerequisites for an informed choice on cancer screening. Evidence-based information in patient leaflets can improve this situation.
Validity and reliability of maternal recall of pregnancy history and service use among signing Deaf women: a cross-sectional descriptive study from South Africa
Authors: Fontes Marx Mayara , Heap Marion , Gichane Margaret W , London Leslie
Published: December 2018

Introduction

There is little credible quantitative data on pregnancy histories and outcomes for disabled women in low-income and middle-income countries. The purpose of this study, based in Cape Town, South Africa, was to test the reliability and validity of maternal recall of pregnancy history and service use among a sample of Deaf women who use South African Sign Language (SASL).

Methods

We interviewed 42 signing Deaf women of childbearing age (18–49 years) in SASL using a structured questionnaire in July 2016. To assess reliability, seven participants (16% of the sample) were reinterviewed by different interviewers under the same conditions after 10–30 min. For the analysis we used (1) Cohen’s kappa, an inter-rater statistical method, and (2) overall percentage agreement. Validity was explored by comparing the participants’ pregnancy history to the Western Cape Provincial Health Data Centre (PHDC) database.

Results

The reliability results showed that out of 19 questions 14 demonstrated substantial to perfect agreement kappa scores (kappa between 0.61 and 1) and 5 had the lowest kappa agreement scores (kappa <0.61). With respect to percentage agreement, participants provided identical responses in 87% cases. Overall, women provided more reliable responses to pregnancy outcomes compared with demographic information. Validity results showed that 29 out of 35 Deaf women provided survey responses that matched or nearly matched (83% agreement) the PHDC database for birth history and delivery location.

Conclusion

This study suggests that for this sample of signing Deaf women recall of pregnancy history and service use is reliable and valid. Extending this approach to other similar populations will require further research, but it is important that methods to access hard-to-reach disabled populations are developed so that health system responsiveness to marginal populations can be based on robust evidence.
Patient-centred care for addiction treatment: a scoping review protocol
Authors: Marchand Kirsten , Beaumont Scott , Westfall Jordan , MacDonald Scott , Harrison Scott , Marsh David C , Schechter Martin T , Oviedo-Joekes Eugenia
Published: December 2018

Introduction

Substance use disorders are chronic conditions that require a multidimensional treatment approach. Despite ongoing efforts to diversify such treatments, evidence continues to illuminate modest rates of treatment engagement and perceived barriers to treatment. Patient-centred care (PCC) is one approach that may strengthen the responsiveness of treatments for people with problematic substance use. The aim of this scoping review is to explore how the principles of PCC have been implemented and operationalised in healthcare settings for people with problematic substance use.

Methods and analysis

This scoping review follows the iterative stages of the Arksey and O’Malley framework. Both empirical (from Medline, Embase, PsycINFO, CINAHL and ISI Web of Science) and grey literature references will be considered if they focused on populations with problematic substance use and described or measured PCC or one of its principles in a health-oriented context. Two reviewers will independently screen references in two successive stages of title/abstract screening and then full-text screening for references meeting title/abstract criteria. A descriptive overview, tabular and/or graphical summaries, and a directed content analysis will be carried out on extracted data. This scoping review has been registered with Open Science Framework (https://osf.io/5swvd/).

Ethics and dissemination

This review will systematically examine the extent and nature of existing evidence of PCC in addiction research and clinical practice. Such evidence will contribute to the operationalisation of PCC for people with problematic substance use. A multidisciplinary team has been gathered to represent the needs of people with problematic substance use, healthcare providers and decision-makers. The team’s knowledge users will be engaged throughout this review and will participate in dissemination activities (eg, workshops, presentations, publications, reports).
Evaluating associations between metabolic health, obesity and depressive symptoms: a prospective analysis of data from the English Longitudinal Study of Ageing (ELSA) with a 2‑year follow‑up
Authors: Slater Natasha , Rowley Charlotte , Venables Rebecca Hayley , White Simon , Frisher Martin
Published: December 2018

Objectives

Conflicting results have been reported when the associations between metabolic health, obesity and depression were examined previously. The primary aim of this study was to determine whether metabolic health or obesity are independently associated with depressive symptoms, among a representative sample of older people living in England. Independent associations between covariates and depression were also examined.

Design

Prospective study with a 2-year follow-up.

Setting

The English Longitudinal Study of Ageing Wave 6 (2012–2013) and Wave 7 (2014–2015).

Participants

6804 participants aged older than 50 years.

Data Analysis

Multivariate models were used to determine whether metabolic health or obesity are independently associated with depressive symptoms at 2-year follow-up. Unadjusted and adjusted ORs with corresponding 95% CI were calculated; the adjusted ORs took account of baseline depression, gender, age, wealth, obesity and poor metabolic health.

Results

Before adjusting for covariates, poor metabolic health was associated with depressive symptoms at 2-year follow-up (OR 1.24; 95% CI, 1.07 to 1.44, p<0.01). After adjusting for covariates, the association was no longer statistically significant (OR 1.17; 95% CI, 0.99 to 1.38, p=0.07). Similarly, obesity was associated with depressive symptoms at 2-year follow-up before adjusting for covariates (OR 1.54; 95% CI, 1.33 to 1.79, p<0.01). However, after adjusting for covariates the association between obesity and depressive symptoms at 2-year follow-up became statistically insignificant (OR 1.19; 95% CI, 1.00 to 1.41, p=0.06). The strongest predictors for future depression were baseline depression (OR 10.59; 95% CI, 8.90 to 12.53, p<0.01) and lower wealth (OR 3.23; 95% CI, 2.44 to 4.35, p<0.01).

Conclusion

Neither poor metabolic health nor obesity were associated with a risk of depressive symptoms at 2-year follow-up, after adjusting for covariates. As wealth inequalities continue to rise across England, the risk of depressive symptoms at 2-year follow-up is likely to be elevated in individuals living in the lower wealth quintiles.
Exploring the precision of femtosecond laser-assisted descemetorhexis in Descemet membrane endothelial keratoplasty
Authors: Pilger Daniel , von Sonnleithner Christoph , Bertelmann Eckart , Maier Anna-Karina B , Joussen Antonia M , Torun Necip
Published: December 2018

Objective

Descemet membrane endothelial keratoplasty (DMEK) remains a challenging technique. We compare the precision of femtosecond laser-assisted DMEK to manual DMEK.

Methods and Analysis

A manual descemetorhexis (DR) of 8 mm diameter was compared with a femtosecond laser-assisted DR of the same diameter (femto-DR) in 22 pseudophakic patients requiring DMEK. We used OCT images with a centred xy-diagram to measure the postoperative precision of the DR and the amount of endothelial denuded area. Endothelial cell loss (ECL) and best corrected visual acuity were measured 3 months after surgery.

Results

In the manual group, the median error of the DR was 7% (range 3%–16%) in the x-diameter and 8% (range 2%–17%) in the y-diameter. In the femto group, the median error in the respective x and y-diameters was 1% (range 0.4%–3%) and 1% (range 0.006%–2.5%), smaller than in the manual group (p=0.001). Endothelial denuded areas were larger in the manual group (11.6 mm2, range 7.6–18 mm2) than in the femto group (2.5 mm2, range 1.2–5.9 mm2) (p<0.001). The ECL was 21% (range 5%–78%) in the manual DR and 17% (range 6%–38%) in the femto-DR group (p=0.351). The median visual acuity increased from 0.4 logMAR (range 0.6–0.4 logMAR) in both groups to 0.1 logMAR (range 0.4–0 logMAR) in the manual group and to 0.1 logMAR (range 0.3–0 logMAR) in the femto group (p=0.461). Three rebubblings were required in the manual group, whereas the femto group required only one.

Conclusion

The higher precision of the femto-DR bears the potential to improve DMEK surgery.
Role of corneal biomechanical properties in predicting of speed of myopic progression in children wearing orthokeratology lenses or single-vision spectacles
Authors: Wan Kin , Cheung Sin Wan , Wolffsohn James S , Orr Janis B , Cho Pauline
Published: December 2018

Objective

To determine the characteristics of children who were likely to progress rapidly and gain the greatest benefit from orthokeratology (ortho-k) treatment.

Methods and analysis

The files of 113 children who participated in two myopia control studies and wore either ortho-k lenses (n=62) or single-vision spectacles (SVS) (n=51) were reviewed. Baseline cycloplegic subjective refraction, central corneal thickness, axial length, keratometry, intraocular pressure, corneal biomechanical properties and 24-month axial length data were retrieved and analysed.

Results

Multivariate analysis showed that there was significant negative correlation between axial elongation and baseline age and corneal hysteresis (p<0.05) in the SVS group. In the ortho-k group, only baseline age was significantly and negatively associated with axial elongation (p<0.01).

Conclusion

Corneal biomechanical properties and baseline age can predict the rate of axial elongation in myopic children. It may be beneficial for younger myopic children with low corneal hysteresis to commence ortho-k treatment as early as possible.
British Thoracic Society guideline for bronchiectasis in adults
Authors: Hill Adam T , Sullivan Anita L , Chalmers James D , De Soyza Anthony , Elborn J Stuart , Floto R Andres , Grillo Lizzie , Gruffydd-Jones Kevin , Harvey Alex , Haworth Charles S , Hiscocks Edwin , Hurst John R , Johnson Christopher , Kelleher W Peter , Bedi Pallavi , Payne Karen , Saleh Hesham , Screaton NIcholas J , Smith Maeve , Tunney Michael , Whitters Deborah , Wilson Robert , Loebinger Michael R
Published: December 2018

The full British Thoracic Society Guideline for Bronchiectasis in Adults is published inThorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline.
Epidemiology of sports injuries in basketball: integrative systematic review
Authors: Andreoli Carlos Vicente , Chiaramonti Bárbara Camargo , Biruel Elisabeth , Pochini Alberto de Castro , Ejnisman Benno , Cohen Moises
Published: December 2018

Introduction

Basketball is a contact sport with complex movements that include jumps, turns and changes in direction, which cause frequent musculoskeletal injuries in all regions of the body.

Objective

This is an integrative systematic review of the epidemiology of musculoskeletal injuries in basketball.

Methods

This is an integrative review based on the following sources of information: PubMed/MEDLINE, Embase, LILACS, BBO-Biblioteca Brasileira de Odontologia, IBECS-Índice Bibliográfico Espanhol em Ciências da Saúde, nursing journals, dental journals and core clinical journals in the last 10 years with studies addressing the general epidemiology of sports injuries in basketball.

Results

In total, 268 articles were selected, of which 11 were eligible for the integrative review. A total of 12 960 injuries were observed, most of which occurred in the lower limbs (63.7%), with 2832 (21.9%) ankle injuries and 2305 (17.8%) knee injuries. Injuries in the upper limbs represented 12%–14% of the total injuries. Children and adolescents received head injuries more often compared with the other age and skill categories. In the adult category, there was an increased prevalence of injuries in the trunk and spine. In the upper limbs, hands, fingers and wrists were affected more frequently than the shoulders, arms and forearms. In the masters’ category, there was an increase in the incidence of thigh injuries.

Conclusion

The lower limbs were the most affected, with the ankle and knee joints having the highest prevalence of injuries regardless of gender and category. Further randomised studies, increased surveillance and epidemiological data collection are necessary to improve knowledge on sports injuries in basketball and to validate the effectiveness of preventive interventions.
Relative criticalness of common laboratory tests for critical value reporting
Authors: Yang Zhutian , Tan Eng Hooi , Li Yingda , Lim Brian , Metz Michael Patrick , Loh Tze Ping
Published: December 2018

We determined the relative strengths of association between 23 most commonly ordered laboratory tests and the adverse outcome as indicators of relative criticalness. The lowest and highest results for 23 most commonly ordered laboratory tests, 24 hours prior to death during critical care unit (CCU) stay or discharge from CCU were extracted from a publicly available CCU database (Medical Information Mart for Intensive Care-III). Following this, the Random Forest model was applied to assess the association between the laboratory results and the outcomes (death or discharge). The mean decrease in Gini coefficient for each laboratory test was then ranked as an indication of their relative importance to the outcome of a patient. In descending order, the 10 laboratory tests with the strongest association with death were: bicarbonate, phosphate, anion gap, white cell count (total), partial thromboplastin time, platelet, total calcium, chloride, glucose and INR; moreover, the strength of association was different for critically high versus low results.
Dark R2 at low energy
Authors: Brax Philippe , Valageas Patrick , Vanhove Pierre
Published: December 2018

We consider the consequences of the leading quartic corrections to the Einstein–Hilbert action of gravity at low energy. Using the equivalence between the scalar [Formula: see text] contribution and a scalar-tensor field theory, we analyze the possible ways of detecting the associated scalaron and suggest that short distance tests of gravity, and in particular future tests of Newton’s law aboard satellites, would provide the best environment to detect such a modification of gravity. We also analyze the regimes for which the [Formula: see text] theory would result as a low energy manifestation of putative high energy UV completions involving extra dimensions. In the four-dimensional [Formula: see text] supergravity limit of such extra-dimensional models, the [Formula: see text] models would emerge from the stabilization of a nearly no-scale superfield such as the ones associated to the Kähler modulus corresponding to the breathing mode of a six-dimensional compactification.
Double-beta decay and its potential to explore beyond standard model physics
Authors: Stoica Sabin
Published: December 2018

Double-beta decay (DBD) is a rare nuclear process of great interest due to its potential to provide information about physics beyond the Standard Model (BSM). For example, the discovery of the neutrinoless double-beta [Formula: see text] decay mode could give information about important issues such as possible violations of Lorentz symmetry and lepton number, nature of neutrinos (are they Dirac- or Majorana-like particles?), neutrino absolute masses, neutrino mass hierarchy, existence of heavy (sterile) neutrinos, etc. In the theoretical study of DBD, one needs a precise calculation of the nuclear matrix elements (NMEs) and phase space factors (PSFs) entering the half-lives formulas, for different decay modes, transitions and mechanisms of occurrence. Reliable computations of these quantities may result in reliable predictions of DBD half-lives and constrains of the BSM parameters related to the possible mechanisms that can contribute to the [Formula: see text] decay.

In this paper, I briefly review the theoretical challenges in the study of [Formula: see text] decay. I describe the computation of the NMEs and PSFs and present results for a number of selected nuclei. Then, I show the broader potential of this process to provide information about BSM physics and present new upper limits for parameters associated with light neutrino, heavy neutrino and SUSY exchange mechanisms. Finally, I suggest a more consistent approach to calculate the NMEs and PSFs, namely to compute directly their product and discuss some possibilities to reduce the errors related to the uncertain value of the axial-vector constant.
Covariant information theory and emergent gravity
Authors: Vanchurin Vitaly
Published: December 2018

Informational dependence between statistical or quantum subsystems can be described with Fisher information matrix or Fubini-Study metric obtained from variations/shifts of the sample/configuration space coordinates. Using these (noncovariant) objects as macroscopic constraints, we consider statistical ensembles over the space of classical probability distributions (i.e. in statistical space) or quantum wave functions (i.e. in Hilbert space). The ensembles are covariantized using dual field theories with either complex scalar field (identified with complex wave functions) or real scalar field (identified with square roots of probabilities). We construct space–time ensembles for which an approximate Schrodinger dynamics is satisfied by the dual field (which we call infoton due to its informational origin) and argue that a full space–time covariance on the field theory side is dual to local computations on the information theory side. We define a fully covariant information-computation tensor and show that it must satisfy certain conservation equations.

Then we switch to a thermodynamic description of the quantum/statistical systems and argue that the (inverse of) space–time metric tensor is a conjugate thermodynamic variable to the ensemble-averaged information-computation tensor. In (local) equilibrium, the entropy production vanishes, and the metric is not dynamical, but away from the equilibrium the entropy production gives rise to an emergent dynamics of the metric. This dynamics can be described approximately by expanding the entropy production into products of generalized forces (derivatives of metric) and conjugate fluxes. Near equilibrium, these fluxes are given by an Onsager tensor contracted with generalized forces and on the grounds of time-reversal symmetry, the Onsager tensor is expected to be symmetric. We show that a particularly simple and highly symmetric form of the Onsager tensor gives rise to the Einstein–Hilbert term. This proves that general relativity is equivalent to a theory of nonequilibrium (thermo)dynamics of the metric, but the theory is expected to break down far away from equilibrium where the symmetries of the Onsager tensor are to be broken.
The Role of Entrepreneurial Coaching in the Restarting Process After Business Failure
Authors: Anis Ben Salem , Lassaad Lakhal , Mbarek Rahmoun , Carrera-Jiménez Javier A.
Published: December 2018

The aim of this paper is to identify the adequate entrepreneurial support elements for business restarting after business failure. An exploratory study was conducted with fifteen SMEs within the interpretivist paradigm. The study reveals a matrix of factors that make for adequate entrepreneurial support to assist restarting business. In addition, this study shows that psychological coaching is an efficient remedy to reduce emotional shock after experiencing unplanned failure whereas social coaching is an efficient support of integrating successor following a planned failure in some social network. However, current thinking on incubation should be increased in order to help with business recovery especially as there is a high failure rate associated with startups.

This research attempts to ensure a possible relationship between entrepreneurial support practices and failing entrepreneurs’ needs.
ZEO, Inc.: Is the Market Ready for Wearables?
Authors: Marty Martin Wm. , Welsch Harold
Published: December 2018

Zeo, Inc. was one of the pioneer companies in the quantified self-industry offering a digital solution for individuals suffering from sleep problems. The company was founded by three undergraduate students who successfully raised capital, make strategic partnerships with major brands like the National Football League (NFL), and introduced their products in stores like Best Buy.

The collegiate founders recognized their lack of knowledge and skills from the beginning. To address this gap, they developed an advisory board to guide them on scientific matters. Later, they hired a seasoned executive with industry experience to run and grow the company. Zeo, Inc. also was getting favorable attention among leading sleep experts with publications in scientific journals about the promise of this innovative technology. Zeo, Inc. was positioned to potentially disrupt the technological and business model of the sleep industry at the time.

Suddenly, Zeo, Inc. announced it was shutting down the company. Technology pundits, the media and customers were surprised, “Why would a fast-rising company shut down?” Given the lack of board and senior leadership transparency, many speculated as to why Zeo, Inc. closed. The reasons ranged from a lack of a focus on the business model to not keeping up with new entrants into the digital health space such as FitBit. This case highlights for students the growth stages of startups with an emphasis of how a widely acclaimed startup can fail and the lessons to be learned from failure.
China, Europe and the G-Zero World
Authors: Banik Katja
Published: December 2018

What does it mean to live in a world without global leadership? Where is the European Union heading? What impact will Trump’s “America first” policy and China’s Belt and Road Initiative have on tomorrow’s world order? Geopolitical reflections on the G-Zero world.
Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis
Authors: Lillo Osuna Maria Angeles , Garcia-Lopez Jesus , El Ayachi Ikbale , Fatima Iram , Khalid Aysha B. , Kumpati Jerusha , Slayden Alexandria V. , Seagroves Tiffany N. , Miranda-Carboni Gustavo A. , Krum Susan A.
Published: December 2018

Osteosarcoma is a malignant tumor in the bone, which originates from normal osteoblasts or osteoblast precursors. Normal osteoblasts express estrogen receptor alpha (ERα); however, osteosarcomas do not express ERα due to promoter DNA methylation. Here we show that treatment of 143B osteosarcoma cells with decitabine (DAC, 5-Aza-2′-deoxycytidine) induces expression of ERα and leads to decreased proliferation and concurrent induction of osteoblast differentiation. DAC exposure reduced protein expression of metastasis-associated markers VIMENTIN, SLUG, ZEB1, and MMP9, with a concurrent decrease in mRNA expression of known stem cell markers SOX2, OCT4, and NANOG. Treatment with 17β-estradiol (E2) synergized with DAC to reduce proliferation. Overexpression of ERα inhibited proliferation and induced osteoblast differentiation, whereas knockout of ERα by CRISPR/Cas9 prevented the effects of DAC. In an orthotopic model of osteosarcoma, DAC inhibited tumor growth and metastasis of 143B cells injected into the tibia of NOD SCID gamma mice. Furthermore, ERα overexpression reduced tumor growth and metastasis, and ERα knockout prevented the effects of DAC in vivo. Together, these experiments provide preclinical evidence that the FDA-approved DNA methylation inhibitor DAC may be repurposed to treat patients with osteosarcoma based on its efficacy to decrease proliferation, to induce osteoblast differentiation, and to reduce metastasis to visceral organs.

Significance: These findings describe the effects of DNA methyltransferase inhibition on ERα and its potential role as a tumor suppressor in osteosarcoma.

See related commentary by Roberts, p. 1034

See related article by El Ayachi and colleagues; Cancer Res 79(5);982–93.
Urinary Cytokine Profile to Predict Response to Intravesical BCG with or without HS-410 Therapy in Patients with Non–muscle-invasive Bladder Cancer
Authors: Salmasi Amirali , Elashoff David A. , Guo Rong , Upfill-Brown Alexander , Rosser Charles J. , Rose Jason M. , Giffin Louise C. , Gonzalez Louis E. , Chamie Karim
Published: December 2018

Background:

Despite extensive research to identify biomarkers of response in patients with non–muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC.

Methods:

Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed.

Results:

Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14–0.99; P = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16–3.44; P = 0.01), IL23 (HR 1.12; 95% CI, 1.01–1.23; P = 0.03), IL8 (HR 0.27; 95% CI, 0.07–1.08; P = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91–0.99; P = 0.04) at week 13 from baseline best predicted time to event.

Conclusions:

Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC.

Impact:

This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.
Mutational Analysis of 472 Urothelial Carcinoma Across Grades and Anatomic Sites
Authors: Nassar Amin H. , Umeton Renato , Kim Jaegil , Lundgren Kevin , Harshman Lauren , Van Allen Eliezer M. , Preston Mark , Dong Fei , Bellmunt Joaquim , Mouw Kent W. , Choueiri Toni K. , Sonpavde Guru , Kwiatkowski David J.
Published: December 2018

Purpose:

The purpose of this study is to characterize the mutational landscape across the spectrum of urothelial carcinoma (UC) to identify mutational features and potential therapeutic targets.

Experimental Design:

Using targeted exome sequencing (n = 237 genes), we analyzed the mutation spectra of 82 low-grade nonmuscle-invasive bladder cancers (LG-NMIBC), 126 high-grade (HG) NMIBC, 199 muscle-invasive bladder cancers (MIBC), 10 LG-upper tract urothelial cancers (LG-UTUC), and 55 HG-UTUC.

Results:

FGFR3 and KDM6A mutations were significantly more common in LG-NMIBC (72% and 44%, respectively) versus other bladder subtypes. FGFR3 alterations were also enriched in LG-UTUC versus HG-UTUC tumors (80% vs. 16%). In contrast, TP53 and RB1 mutations were significantly more frequent in all 3 HG urothelial carcinoma subtypes than in LG-NIMBC (45%–58% vs. 4%; 9%–22% vs. 0; respectively). Among LG-NMIBC tumors, KDM6A mutations were more common in women than in men (71% vs. 38%). HG-NMIBC and MIBC had higher tumor mutational burden (TMB) than LG-NMIBC (P = 0.001 and P < 0.01, respectively). DNA-damage repair (DDR) alterations were associated with a higher TMB in HG-NMIBC and MIBC tumors, and these two tumor types were also enriched for an APOBEC mutational signature compared with LG-NMIBC and HG-UTUC. Alterations in FGFR3, PIK3CA, and EP300 correlated with worse overall survival in HG-UTUC and occurred concurrently.

Conclusions:

Our analysis suggests that a fraction of MIBCs likely arise from precursor lesions other than LG-NMIBC. KDM6A mutations are twice as common in women with LG-NIMBC than those in men. DDR gene mutations and APOBEC mutagenesis drive mutations in HG-NMIBC and MIBC. UTUC has a distinct mutation profile from bladder cancer.
One-Year Outcomes After MitraClip for Functional Mitral Regurgitation
Authors: Ailawadi Gorav , Lim D. Scott , Mack Michael J. , Trento Alfredo , Kar Saibal , Grayburn Paul A. , Glower Donald D. , Wang Andrew , Foster Elyse , Qasim Atif , Weissman Neil J. , Ellis Jeffrey , Crosson Lori , Fan Frank , Kron Irving L. , Pearson Paul J. , Feldman Ted ,   On behalf of the EVEREST II Investigators
Published: December 2018

Background:

Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System).

Methods:

Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality ≥12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated.

Results:

A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3±10.5 years; Society of Thoracic Surgeons risk, 10.2±6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR ≤2+. At 1 year, there were 139 deaths, and the Kaplan-Meier estimate of freedom from mortality was 76.8%. The majority of surviving patients (84.7%) remained with MR ≤2+ and New York Heart Association class I/II (83.0%). Kaplan-Meier survival at 1 year was 74.1% in HR patients and 86.4% in non-HR patients (
P
=0.0175). At 1 year, both groups achieved comparable MR reduction (MR ≤2+, 84.0% versus 87.0%) and improvement in left ventricular end-diastolic volume (−8.0 mL versus −12.7 mL), whereas New York Heart Association class I/II was found in 80.1% versus 91.8% (
P
=0.008) of HR and non-HR patients, respectively. In HR patients, the annualized rate of heart failure hospitalizations decreased from 0.68 to 0.46 in the 12 months before to 12 months after the procedure (
P
<0.0001).

Conclusions:

Transcatheter mitral valve repair with the MitraClip in patients with secondary MR is associated with acceptable safety, reduction of MR severity, symptom improvement, and positive ventricular remodeling.

Clinical Trial Registration:

https://www.clinicaltrials.gov
. Unique identifiers: NCT00209274, NCT01940120, and NCT01931956.