bluuebunny/crossref_metadata_2025 huggingface dataset:
Cómo se construyen las versiones de la memoria en estos tiempos: el ejemplo de la Segunda Guerra Mundial
Authors: Sarnacki, S.J. Andrzej
Published: August 2017

El artículo presenta una mirada crítica frente a los procesos de memoria en Europa y a los relatos de aquellos acontecimientos, en tanto ello puede quedar como un punto referencial y una pauta de la reflexión historiográfica crítica sobre los eventos violentos del pasado y por ende de cómo son preservados y transmitidos. El texto afirma que en el mundo académico se usa constantemente una repetición del esquema de la Guerra, que es demasiado limitada e injusta, y casi no se refiere a hechos históricos. Creer que la investigación sobre la memoria no es un enfoque estrictamente histórico, y reflexionar sobre las representaciones de los acontecimientos descartando su origen, no tiene ninguna herramienta de valoración y puede llevar a las conclusiones equivocadas. El artículo examina especialmente el caso de los campos de concentración, el papel de Alemania y Rusia, el problema de la culpabilidad conectado con las políticas de la memoria, la epidemia de las repeticiones mecánicas en los textos académicos o la idea del «reemplazo de un modelo histórico por un modelo memorial» (Rabotnikof).
Effects of Dry Sliding Conditions on Wear Properties of Al-Matrix Composites Produced by Selective Laser Melting Additive Manufacturing
Authors: Gu Dongdong , Jue Jiubin , Dai Donghua , Lin Kaijie , Chen Wenhua
Published: August 2017

The friction and wear properties of in situ Al-matrix composites prepared by selective laser melting (SLM) were evaluated on a ball-on-disk tribometer by sliding against GCr15 steel at room temperature. The influence of the applied load, sliding speed, and long-time continuous friction on the friction and wear properties of Al-matrix composites was systematically investigated. It showed that the wear rate and coefficient of friction (COF) increased when the applied load increased, due to the higher contact stress and larger extent of particle fracturing. As the sliding speed increased, the elevated rate of the formation of Al-oxide layer and the transfer of Fe-oxide layer from the counterface to the worn surface led to a significant reduction in wear rate and COF. As the sliding distance prolonged, the worn surface successively experienced the adhesive wear, the abrasive wear, the particle fracturing and crack nucleation, and the delaminated wear. The above processes were repeated on each exposed fresh surface, resulting in the fluctuation of COF. In the later stage of wear process, a large amount of oxides were produced on the worn surface, caused by the long-time accumulated frictional heat, which reduced the fluctuation of COF. The wear mechanisms of SLM-processed Al-matrix composite parts under various loads were dominated by abrasive wear and oxidation wear, whereas the predominant wear mechanisms were oxidation wear and delamination wear at different sliding speeds. For the long-time friction, all of these wear mechanisms were operational.
Nonlinear Dynamics of Flexible Rotors Supported on Journal Bearings—Part I: Analytical Bearing Model
Authors: Miraskari Mohammad , Hemmati Farzad , Gadala Mohamed S.
Published: August 2017

To determine the bifurcation types in a rotor-bearing system, it is required to find higher order derivatives of the bearing forces with respect to journal velocity and position. As closed-form expressions for journal bearing force are not generally available, Hopf bifurcation studies of rotor-bearing systems have been limited to simple geometries and cavitation models. To solve this problem, an alternative nonlinear coefficient-based method for representing the bearing force is presented in this study. A flexible rotor-bearing system is presented for which bearing force is modeled with linear and nonlinear dynamic coefficients. The proposed nonlinear coefficient-based model was found to be successful in predicting the bifurcation types of the system as well as predicting the system dynamics and trajectories at spin speeds below and above the threshold speed of instability.
Comparison-Based Optical Assessment of Hyperboloid and Ellipsoid Reflectors in a Beam-Down Solar Tower System With Linear Fresnel Heliostats
Authors: Li Xian , Lin Meng , Dai Yanjun , Wang Chi-Hwa
Published: August 2017

Beam-down concentrating solar tower (BCST) is known for its merits in easy installation and maintenance as well as lower convection heat loss of the central receiver (CR) when comparing to a traditional concentrated solar tower system. A point-line-coupling-focus (PLCF) BCST system using linear Fresnel heliostat (LFH) as the first stage concentrator (heliostat) and hyperboloid/ellipsoid reflector as the tower reflector (TR) is proposed and theoretically analyzed and compared in this paper. Theoretical investigation on the ray concentrating mechanism with two commonly used reflector structures, namely, hyperboloid and ellipsoid, is conducted utilizing Monte Carlo ray-tracing (MCRT) method. The objective of this study is to reveal the achievable optical performance of these types of TRs in the PLCF system considering the effect of LFH tracking errors on TR astigmatism as well as the differences of optical efficiency factors and power transmission in a large-scale biomimetic layout. Results indicate that the ellipsoid system is superior in terms of interception efficiency over the hyperboloid system due to smaller astigmatism at the CR aperture, especially at larger facet tracking error. However, the ellipsoid reflector shows significantly lower TR shading efficiency resulting from the larger TR surface area compared to that of the hyperboloid reflector. The total optical efficiency of the hyperboloid system is always better than that of the ellipsoid system, and this efficiency gap decreases as the ratio ε increases. The hyperboloid TR is proved to be more promising and practical for the PLCF system.
Teaching About Racial Equity in Introductory Physics Courses
Authors: Daane Abigail R. , Decker Sierra R. , Sawtelle Vashti
Published: August 2017

Even after you have decided to tackle a problem like racial equity, it may seem daunting to broach the subject in a physics classroom. After all, the idea of a (typically White) instructor in power tackling a sensitive topic such as social justice can be scary in any (mostly White) classroom. Not only that, but physics is typically viewed as a “culture with no culture.” The physicist’s quest for objectivity, along with a general focus on a fixed set of laws and formulae, support the treatment of this subject as untouched by people. Sometimes it is easier to ignore the problem and just focus on the Conservation of Energy Principle. However, ignoring the striking underrepresentation of ethnic/racial minorities and women in both the physics classroom and the field at large is a great disservice to all our students. We take the position that the persistence of representation disparities in physics is evidence that culture plays a role in who and what is involved in physics. Instructors have an opportunity to explicitly address the absence of equitable circumstances in classrooms and highlight the obstacles that contribute to the disparity (e.g., varied access to learning opportunities and support structures, dominant cultural norms, stereotype threat, implicit bias, hidden curricula, etc.). We acknowledge that incorporating these discussions in a physics classroom is fraught with difficulty, but we also believe that trying to lead these discussions is better than ignoring the problem. Furthermore, a set of resources for teachers interested in leading these discussions has been developing in the physics teacher community. Rifkin offers resources for leading a two-week unit on equity designed for secondary science classrooms. Here we describe another possible pathway for integrating a shorter equity unit into the traditional content of a (predominantly White) university physics classroom, addressing racial inequity and sharing common student responses that may arise.
Using Stellarium to cyber-observe the Great American Eclipse
Authors: Prim Ellie R. , Sitar David J.
Published: August 2017

The Great American Eclipse is over. Somewhat sad, is it not? Individuals who were unable to experience the event on August 21, 2017, can now cyber-observe the eclipse with Stellarium (http://www.stellarium.org). In the authors’ opinion, it is fun and has many great applications in the classroom. In addition it is open source and available for Android, iOS, and Linux users. We here at Appalachian use it in our introductory astronomy labs for specific activities such as investigating coordinate systems, discovering differences between solar and sidereal days, as well as determining why your “astrological sign” is most often not your “astronomical sign.”
Localization of weak objects in reverberant fields using waveform inversion
Authors: Firouzi Kamyar , Khuri-Yakub Butrus T.
Published: August 2017

This paper presents an application of the Waveform inversion approach to localization of objects in reverberant fields and with limited spatial measurements. Reverberant fields in enclosures can potentially carry useful information, however, in an incoherent way. Incoherency comes from the consecutive reflections of the wave energy several times in the domain. This, along with diffraction and dispersion effects, can ultimately lead to mixing of the wave energy in a seemingly random way. However, spreading of the wave energy can lead to multiple interrogations of each point in the enclosure. Hence, any substructural changes in the enclosure can be sensed with sufficient information carried by the wave energy flow. Furthermore, the temporal information buried in the data makes it feasible to conduct only a few spatial measurements. The authors present a localization scheme that benefits from the reverberant field and can reduce the required number of spatial measurements.
The role of short-time intensity and envelope power for speech intelligibility and psychoacoustic masking
Authors: Biberger Thomas , Ewert Stephan D.
Published: August 2017

The generalized power spectrum model [GPSM; Biberger and Ewert (2016). J. Acoust. Soc. Am. 140, 1023–1038], combining the “classical” concept of the power-spectrum model (PSM) and the envelope power spectrum-model (EPSM), was demonstrated to account for several psychoacoustic and speech intelligibility (SI) experiments. The PSM path of the model uses long-time power signal-to-noise ratios (SNRs), while the EPSM path uses short-time envelope power SNRs. A systematic comparison of existing SI models for several spectro-temporal manipulations of speech maskers and gender combinations of target and masker speakers [Schubotz et al. (2016). J. Acoust. Soc. Am. 140, 524–540] showed the importance of short-time power features. Conversely, Jørgensen et al. [(2013). J. Acoust. Soc. Am. 134, 436–446] demonstrated a higher predictive power of short-time envelope power SNRs than power SNRs using reverberation and spectral subtraction. Here the GPSM was extended to utilize short-time power SNRs and was shown to account for all psychoacoustic and SI data of the three mentioned studies. The best processing strategy was to exclusively use either power or envelope-power SNRs, depending on the experimental task. By analyzing both domains, the suggested model might provide a useful tool for clarifying the contribution of amplitude modulation masking and energetic masking.
Exploring the Conceptualization and Persistence of Disordered Eating in Retired Swimmers
Authors: Cooper Hannah , Winter Stacy
Published: August 2017

Disordered eating is a psychological ailment that befalls many athletes and can persist into retirement. Links have been established between disordered eating and societal and sport-specific pressures; however, little research has focused on the perspective of retired athletes in a time-based sport. The purpose of the current research was to explore the conceptualization of disordered eating in relation to swimming participation, how retirement affects eating patterns, and ways to mitigate disordered eating. Following IPA methodological guidelines, a homogeneous sample of retired swimmers (N = 6) was chosen for semistructured, participant-driven interviews determined by scores on a disordered-eating questionnaire. Three superordinate themes were revealed: (1) pressures unique to swimming, (2) transition to eating pattern awareness, and (3) maintaining ideal eating patterns in retirement. The results revealed a combination of novel findings and expansion of previous data on disordered eating. Suggestions for applications of current findings and for future research are also discussed.
Papers of note in
Science
357
(6352)
Authors: Ferrarelli Leslie K.
Published: August 2017

This week’s articles describe placental and intrinsic signals that direct development in embryos.
A lower-extremity exoskeleton improves knee extension in children with crouch gait from cerebral palsy
Authors: Lerner Zachary F. , Damiano Diane L. , Bulea Thomas C.
Published: August 2017

A powered exoskeleton alleviates knee extension deficiency while preserving volitional muscle activity during overground walking in children with cerebral palsy.
Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated
Salmonella enterica
Serovar Typhimurium Vaccine Strains
Authors: Łaniewski Paweł , Baek Chang-Ho , Roland Kenneth L. , Curtiss Roy
Published: August 2017

Salmonella enterica
serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized
in vivo
. We used an
in vivo
expression technology (IVET) strategy to identify four fimbrial operons,
agf
,
saf
,
sti
, and
stc
that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 × 10
5
 CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 × 10
9
 CFU of wild-type
S
. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a
Salmonella
vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, χ9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the
Streptococcus pneumoniae
antigen PspA. Strains that constitutively expressed
saf
or
stc
elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying
saf
or
stc
deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent
S. pneumoniae
. Our results indicate that these fimbriae play important roles, as yet not understood, in
Salmonella
virulence and immunogenicity.

IMPORTANCE
Salmonella enterica
is the leading cause of bacterial food-borne infection in the United States. S. Typhimurium is capable of producing up to 13 distinct surface structures called fimbriae that presumably mediate its adherence to surfaces. The roles of most of these fimbriae in disease are unknown. Identifying fimbriae produced during infection will provide important insights into how these bacterial structures contribute to disease and potentially induce protective immunity to
Salmonella
infection. We identified four fimbriae that are produced during infection. Deletion of all four of these fimbriae results in a significant reduction in virulence. We explored ways in which the expression of these fimbriae may be exploited for use in recombinant
Salmonella
vaccine strains and found that production of Saf and Stc fimbriae are important for generating a strong immune response against a vectored antigen. This work provides new insight into the role of fimbriae in disease and their potential for improving the efficacy of
Salmonella
-based vaccines.
TSH and PRL, side-effect markers in aripiprazole treatment: adjunctive aripiprazole-induced thyrotropin oversuppression in a young man with schizophrenia
Authors: Ohta Hidenobu , Inoue Satoru , Hara Koichiro , Watanabe Akihiko
Published: August 2017

A 26-year-old Japanese man was admitted to our unit with exacerbated paranoid schizophrenia. Prior to his admission, daily administration of olanzapine had been sufficient to maintain a partial remission of his schizophrenia, but due to an exacerbation of his delusions, he had then also been prescribed aripiprazole, which had been followed by no improvement in symptoms and a gradual further exacerbation of auditory delusions. Physical examinations, brain MRI and neurophysiological assessment were unremarkable. Blood analysis, however, revealed extremely low thyroid-stimulating hormone (TSH) and prolactin-releasing hormone (PRL) concentration. Interestingly, after aripiprazole discontinuation, he returned to partial remission with an increase in plasma TSH and PRL concentration.
Trends in diagnostic patterns and mortality in emergency ambulance service patients in 2007−2014: a population-based cohort study from the North Denmark Region
Authors: Christensen Erika Frischknecht , Bendtsen Mette Dahl , Larsen Thomas Mulvad , Jensen Flemming Bøgh , Lindskou Tim Alex , Holdgaard Hans Ole , Hansen Poul Anders , Johnsen Søren Paaske , Christiansen Christian Fynbo
Published: August 2017

Objective

Demand for ambulances is growing. Nevertheless, knowledge is limited regarding diagnoses and outcomes in patients receiving emergency ambulances. This study aims to examine time trends in diagnoses and mortality among patients transported with emergency ambulance to hospital.

Design

Population-based cohort study with linkage of Danish national registries.

Setting

The North Denmark Region in 2007–2014.

Participants

Cohort of 148 757 patients transported to hospital by ambulance after calling emergency services.

Main outcome measures

The number of emergency ambulance service patients, distribution of their age, sex, hospital diagnoses, comorbidity, and 1-day and 30-day mortality were assessed by calendar year. Poisson regression with robust variance estimation was used to estimate both age-and sex-adjusted relative risk of death and prevalence ratios for Charlson Comorbidity Index (CCI) to allow comparison by year, with 2007 as reference year.

Results

The annual number of emergency ambulance service patients increased from 24.3 in 2007 to 40.2 in 2014 per 1000 inhabitants. The proportions of women increased from 43.1% to 46.4% and of patients aged 60+ years from 39.9% to 48.6%, respectively. The proportion of injuries gradually declined, non-specific diagnoses increased, especially the last year. Proportion of patients with high comorbidity (CCI≥3) increased from 6.4% in 2007 to 9.4% in 2014, corresponding to an age- and sex-adjusted prevalence ratio of 1.27 (95% CI 1.16 to 1.39). The 1-day and 30 day mortality decreased from 2.40% to 1.21% and from 5.01% to 4.36%, respectively, from 2007 to 2014, corresponding to age-adjusted and sex-adjusted relative risk of 0.43 (95% CI 0.37 to 0.50) and 0.72 (95% CI 0.66 to 0.79), respectively.

Conclusion

During the 8-year period, the incidence of emergency ambulance service patients, the proportion of women, elderly, and non-specific diagnoses increased. The level of comorbidity increased substantially, whereas the 1-day and 30-day mortality decreased.
Longitudinal and secular trends in total cholesterol levels and impact of lipid-lowering drug use among Norwegian women and men born in 1905–1977 in the population-based Tromsø Study 1979–2016
Authors: Hopstock Laila Arnesdatter , Bønaa Kaare Harald , Eggen Anne Elise , Grimsgaard Sameline , Jacobsen Bjarne K , Løchen Maja-Lisa , Mathiesen Ellisiv B , Njølstad Inger , Wilsgaard Tom
Published: August 2017

Objectives

Elevated blood cholesterol is a modifiable risk factor for cardiovascular disease. Cholesterol level surveillance is necessary to study population disease burden, consider priorities for prevention and intervention and understand the effect of diet, lifestyle and treatment. Previous studies show a cholesterol decline in recent decades but lack data to follow individuals born in different decades throughout life.

Methods

We investigated changes in age-specific and birth cohort-specific total cholesterol (TC) levels in 43 710 women and men born in 1905–1977 (aged 20–95 years at screening) in the population-based Tromsø Study. Fifty-nine per cent of the participants had more than one and up to six repeated TC measurements during 1979–2016. Linear mixed models were used to test for time trends.

Results

Mean TC decreased during 1979–2016 in both women and men and in all age groups. The decrease in TC in age group 40–49 years was 1.2 mmol/L in women and 1.0 mmol/L in men. Both the 80th and the 20th percentile of the population TC distribution decreased in both sexes and all age groups. Longitudinal analysis showed that TC increased with age to a peak around middle age followed by a decrease. At any given age, TC significantly decreased with increase in year born. Lipid-lowering drug use was rare in 1994, increased thereafter, but was low (<3% in women and <5% in men) among those younger than 50 years in all surveys. Between 1994 and 2016, lipid-lowering drug treatment in individuals 50 years and older explained 21% and 28% of the decrease in TC levels in women and men, respectively.

Conclusions

We found a substantial decrease in mean TC levels in the general population between 1979 and 2016 in all age groups. In birth cohorts, TC increased with age to a peak around middle age followed by a decrease.
Do hospitalisations for ambulatory care sensitive conditions reflect low access to primary care? An observational cohort study of primary care usage prior to hospitalisation
Authors: Vuik Sabine I , Fontana Gianluca , Mayer Erik , Darzi Ara
Published: August 2017

Objectives

To explore whether hospitalisations for ambulatory care sensitive conditions (ACSCs) are associated with low access to primary care.

Design

Observational cohort study over 2008 to 2012 using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases.

Setting

English primary and secondary care.

Participants

A random sample of 300 000 patients.

Main outcome measures

Emergency hospitalisation for an ACSC.

Results

Over the long term, patients with ACSC hospitalisations had on average 2.33 (2.17 to 2.49) more general practice contacts per 6 months than patients with similar conditions who did not require hospitalisation. When accounting for the number of diagnosed ACSCs, age, gender and GP practice through a nested case–control method, the difference was smaller (0.64 contacts), but still significant (p<0.001).

In the short-term analysis, measured over the 6 months prior to hospitalisation, patients used more GP services than on average over the 5 years. Cases had significantly (p<0.001) more primary care contacts in the 6 months before ACSC hospitalisations (7.12, 95% CI 6.95 to 7.30) than their controls during the same 6 months (5.57, 95% CI 5.43 to 5.72). The use of GP services increased closer to the time of hospitalisation, with a peak of 1.79 (1.74 to 1.83) contacts in the last 30 days before hospitalisation.

Conclusions

This study found no evidence to support the hypothesis that low access to primary care is the main driver of ACSC hospitalisations. Other causes should also be explored to understand how to use ACSC admission rates as quality metrics, and to develop the appropriate interventions.
Usage of ambulance transport and influencing factors in acute coronary syndrome: a cross-sectional study at a tertiary centre in China
Authors: Ma Jingjing , Wang Jiali , Zheng Wen , Zheng Jiaqi , Wang Hao , Wang Guangmei , Zhang He , Xu Feng , Chen Yuguo
Published: August 2017

Objectives

The aim of this study was to explore the choice of transportation mode to hospital in patients with acute coronary syndrome (ACS) and to determine the factors influencing the use of ambulance.

Design, setting and participants

This cross-sectional study was conducted in a tertiary and teaching hospital in China. The study was carried out between 24 August 2015 and 24 July 2016. A total of 828 patients with ACS presented at the emergency department (ED) were included. The study population was dichotomised according to their primary mode of transport (ambulance or self-transport) to hospital. Social demographics, cardiovascular history, risk factors, prehospital medications, clinical characteristics and symptom characteristics were collected. Multivariable logistic regression was used to examine the factors associated with ambulance use.

Results

We found that only 179 (21.6%) patients with ACS chose taking ambulance to hospital. Factors associated with ambulance use were single (OR 1.66, 95% CI 1.07 to 2.57), taking Suxiaojiuxin pills (OR 1.91, 1.31 to 2.80) or nitrates (OR 2.91, 1.70 to 4.99) before going to hospital, diagnosed as ST-elevation myocardial infarction (STEMI) (OR 2.43, 1.45 to 4.05), with persistent symptoms (OR 1.95, 1.33 to 2.86) and symptoms accompanied with vomiting (OR 2.35, 1.19 to 4.62). The patients who had symptoms precipitated or aggravated by exercise (OR 0.37, 0.14 to 0.98) tended to choose self-transport.

Conclusion

The usage of ambulance in patients with ACS presenting to the ED was low in China. Factors like single, taking Suxiaojiuxin pills or nitrates before going to hospital, diagnosed as STEMI, accompanied with vomiting and persistent symptoms were independently associated with ambulance use. Future education programmes should focus on these factors and increase people’s knowledge on ACS and the benefits of ambulance use.
Involving clinical experts in prioritising topics for health technology assessment: a randomised controlled trial
Authors: Cook Andrew , Streit Elke , Davage Gill
Published: August 2017

Objectives

The objective of this study was to explore whether reducing the material supplied to external experts during peer review and decreasing the burden of response would maintain review quality into prioritising research questions for a major research funder.

Methods and analysis

Clinical experts who agreed to review documents outlining research for potential commissioning were screened for eligibility and randomised in a factorial design to two types of review materials (long document versus short document) and response modes (structured review form versus free text email response). Previous and current members of the funder’s programme groups were excluded. Response quality was assessed by use of a four-point scoring tool and analysed by intention to treat.

Results

554 consecutive experts were screened for eligibility and 460 were randomised (232 and 228 to long document or short document, respectively; 230 each to structured response or free text). 356 participants provided reviews, 90 did not respond and 14 were excluded after randomisation as not eligible.

The pooled mean quality score was 2.4 (SD=0.95). The short document scored 0.037 (Cohen’s d=0.039) extra quality points over the long document arm, and the structured response scored 0.335 (Cohen’s d=0.353) over free text. The allocation did not appear to have any effect on the experts' willingness to engage with the task.

Conclusions

Neither providing a short or a long document outlining suggested research was shown to be superior. However, providing a structured form to guide the expert response provided more useful information than allowing free text. The funder should continue to use a structured form to gather responses. It would be acceptable to provide shorter documents to reviewers, if there were reasons to do so.

Trial registration number

ANZCTR12614000167662.
Self-reported health status, treatment decision and survival in asymptomatic and symptomatic patients with aortic stenosis in a Western Norway population undergoing conservative treatment: a cross-sectional study with 18 months follow-up
Authors: Oterhals Kjersti , Haaverstad Rune , Nordrehaug Jan Erik , Eide Geir Egil , Norekvål Tone M
Published: August 2017

Objectives

To investigate symptoms and self-reported health of patients conservatively treated for aortic stenosis (AS) and to identify factors associated with treatment decision and patient outcomes.

Design

A cross-sectional survey with an 18-month follow-up.

Setting

One tertiary university hospital in Western Norway.

Participants

In all, 1436 patients were diagnosed with AS between 2000 and 2012, and those 245 still under conservative treatment in 2013 were included in this study.

Primary and secondary outcome measures

Primary outcome measures were symptoms and self-reported health status. Secondary outcomes were treatment decision and patient survival after 18 months.

Results

A total of 136 patients with mean (SD) age 79 (12) years, 52% men responded. Among conservatively treated patients 77% were symptomatic. The symptom most frequently experienced was dyspnoea. Symptomatic patients reported worse physical and mental health compared with asymptomatic patients (effect size 1.24 and 0.74, respectively). In addition, symptomatic patients reported significantly higher levels of anxiety and depression compared with asymptomatic patients. However, symptom status did not correlate with haemodynamic severity of AS. After 18 months, 117 (86%) were still alive, 20% had undergone surgical aortic valve replacement (AVR) and 7% transcatheter aortic valve implantation (TAVI). When adjusting for age, gender, symptomatic status, severity of AS and European system for cardiac operative risk evaluation (EuroSCORE), patients with severe AS had more than sixfold chance of being scheduled for AVR or TAVI compared with those with moderate AS (HR 6.3, 95% CI 1.9 to 21.2, p=0.003). Patients with EuroSCORE ≥11 had less chance for undergoing AVR or TAVI compared with those with EuroSCORE ≤5 (HR 0.06, 95% CI 0.01 to 0.46, p=0.007).

Conclusions

Symptoms affected both physical and mental health in conservatively treated patients with AS. Many patients with symptomatic severe AS are not scheduled for surgery, despite the recommendations in current guidelines. The referral practice for AVR is a path for further investigation.
A systematic review and meta-analysis of trials of social network interventions in type 2 diabetes
Authors: Spencer-Bonilla Gabriela , Ponce Oscar J , Rodriguez-Gutierrez Rene , Alvarez-Villalobos Neri , Erwin Patricia J , Larrea-Mantilla Laura , Rogers Anne , Montori Victor M
Published: August 2017

Objectives

In the care of patients with type 2 diabetes, self-management is emphasised and studied while theory and observations suggest that patients also benefit from social support. We sought to assess the effect of social network interventions on social support, glycaemic control and quality of life in patients with type 2 diabetes.

Research design and methods

We searched Ovid MEDLINE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO and CINAHL through April 2017 for randomised clinical trials (RCTs) of social network interventions in patients with type 2 diabetes. Reviewers working independently and in duplicate assessed eligibility and risk of bias, and extracted data from eligible RCTs. We pooled estimates using inverse variance random effects meta-analysis.

Results

We found 19 eligible RCTs enrolling 2319 participants. Social network interventions were commonly based on individual behaviour change rather than social or interpersonal theories of self-management, were educational, and sought to engage social network members for their knowledge and experience. Interventions improved social support (0.74 SD (95% CI 0.32 to 1.15), I2=89%, 8 RCTs) and haemoglobin A1c at 3 months (−0.25 percentage points (95% CI −0.40 to -0.11), I2=12%, 9 RCTs), but not quality of life.

Conclusions

Despite a compelling theoretical base, researchers have only minimally studied the value of interventions targeting patients’ social networks on diabetes care. Although the body of evidence to date is limited, and based on individual behaviour change theories, the results are promising. This review challenges the scientific community to design and test theory-based interventions that go beyond self-management approaches to focus on the largely untapped potential of social networks to improve diabetes care.

PROSPERO registration

CRD42016036117.
Polymorphisms of the stem cell marker geneCD133are associated the clinical outcome in a cohort of Chinese non-small cell lung cancer patients
Authors: Liu Qing-Feng , Zhang Zhi-Fei , Hou Guang-Jie , Yang Guang-Yu , He Yi
Published: August 2017

Objectives

To evaluate the prognostic relevance of four functional single nucleotide polymorphisms (SNPs) inCD133(rs2240688A>C,rs10022537T>A,rs7686732C>G, andrs3130C>T) on overall survival (OS) of non-small cell lung cancer (NSCLC) patients.

Design

Retrospective cohort study.

Setting

Department of General Surgery, in a general hospital, Henan Province, China.

Participants

NSCLC patients aged ≥18 years, who were not receiving preoperative neoadjuvant therapies and had a blood sample available for genotyping, were eligible for inclusion. Those participants who were pregnant or breastfeeding, had a previous history of cancer, had other primary tumours, or who had had primary tumours of the skin and nasopharynx, were excluded from the study.

Outcome measures

The primary endpoint was OS, which was calculated from the date of enrolment until the date of death or date of last follow-up.

Results

There was a total of 1383 participants, with a median age of 63 years; 726 (52.5%) were male. Compared with thers2240688AA genotype, the variant AC/CC genotypes were independently associated with OS (HR 1.27, 95% CI 1.12 to 1.45 for AC genotype; HR 2.32, 95% CI 1.91 to 2.80 for CC genotype). Higher hazard ratios for associations betweenCD133 rs2240688polymorphism and OS were observed in patients with adjuvant chemotherapy (HR 1.86, 95% CI 1.52 to 2.26) and radiotherapy for curative intent (HR 1.90, 95% CI 1.55 to 2.33).

Conclusions

The study confirmed the significant association between the SNPrs2240688 A>Cof CD133 and OS of NSCLC patients. Larger population-based studies in different ethnic groups are necessary to further validate the role and mechanisms ofCD133in NSCLC.
RADAR study: protocol for an observational cohort study to identify early warning signals on the pathways to alcohol use disorder
Authors: Slade Tim , Swift Wendy , Mewton Louise , Kypri Kypros , Lynskey Michael T , Butterworth Peter , Tibbetts Joel , McCraw Stacey , Upton Emily
Published: August 2017

Introduction

Harmful alcohol consumption, particularly alcohol use disorder (AUD), is a worldwide health priority, contributing substantially to global morbidity and mortality. The peak age of onset of AUD is 18–24, thus a deeper understanding of the young adult experience is vital if we are to identify modifiable risk factors and intervene early in the developmental course of this disabling disorder. Critical unanswered questions include: How soon after drinking initiation do AUD symptoms begin to emerge? Which symptoms come first? Do the symptoms unfold in a predictable pattern? In what ways do the emerging symptoms interact with individual, peer, family and environmental risk factors to impact on the transition to disorder?

Methods and analysis

The proposed RADAR study will examine the prospective development of AUD symptoms over the young adulthood (18–24) years. We will capitalise on an existing cohort of 1911 community-based adolescents who were recruited at age 13 and have completed a baseline and five annual follow-up assessments as part of an observational cohort study. We will interview these adolescents every 6 months between the ages of 19 and 23 to derive monthly histories of both alcohol use and AUD symptomatology, along with a comprehensive battery of risk and protective factor scales hypothesised to predict the emergence and course of AUD. The results of this study will inform the natural history of AUD and will be used to identify specific targets for prevention and early intervention of AUD.

Ethics and dissemination

Ethical approval has already been granted for the study (UNSW HREC 10144). We will disseminate the results of the study through published manuscripts, conferences and seminar presentations. Data used in published manuscripts will be made available through a suitable online repository (eg, Dryad–datadryad.org).
Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer
Authors: Chong Irene Yushing , Aronson Lauren , Bryant Hanna , Gulati Aditi , Campbell James , Elliott Richard , Pettitt Stephen , Wilkerson Paul , Lambros Maryou B , Reis-Filho Jorge S , Ramessur Anisha , Davidson Michael , Chau Ian , Cunningham David , Ashworth Alan , Lord Christopher J
Published: August 2017

Objective

Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited.

Design

To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations. We also interrogated recently described RNA interference screen data for these tumour cell lines to identify candidate genetic dependencies or vulnerabilities that could be exploited as therapeutic targets.

Results

By integrating the genomic features of oesophageal tumour cell lines with siRNA and drug screening data, we identified a series of candidate targets in oesophageal cancer, including a sensitivity to inhibition of the kinase BTK in
MYC
amplified oesophageal tumour cell lines. We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib. In both
MYC
and
ERBB2
amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G
1
cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer.

Conclusions

BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib. On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with
MYC
and/or
ERBB2
amplified advanced oesophageal cancer is currently underway (
NCT02884453
).

Trial registration number

NCT02884453; Pre-results
Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant
Authors: Ain Noor ul , Makitie Outi , Naz Sadaf
Published: August 2017

Background

Heterozygous mutations in COL10A1 underlie metaphyseal chondrodysplasia, Schmid type (MCDS), an autosomal dominant skeletal dysplasia.

Objective

To identify the causative variant in a large consanguineous Pakistani family with severe skeletal dysplasia and marked lower limb deformity.

Methods

Whole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. In silico variant pathogenicity predictions and amino acid conservation analyses were performed.

Results

A homozygous c.133 C>T (p.Pro45Ser) variant was identified in COL10A1 in all six severely affected individuals (adult heights 119–130 cm, mean ~−6.33 SD). The individuals heterozygous for the variant had mild phenotype of short stature (adult heights 140–162 cm, mean ~−2.15 SD) but no apparent skeletal deformities. The variant was predicted to be pathogenic by in silico prediction tools and was absent from public databases and hundred control chromosomes. Pro45 is conserved in orthologues and is located in the non-collagenous 2 domain of COL10A1, variants of which have never been associated with skeletal dysplasia.

Conclusions

This first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of MCDS and idiopathic short stature.
Cell-bound complement activation products in SLE
Authors: Ramsey-Goldman Rosalind , Li Jian , Dervieux Thierry , Alexander Roberta Vezza
Published: August 2017

Diagnosis of SLE is based on clinical manifestations and laboratory findings. Timely diagnosis and treatment are important to control disease activity and prevent organ damage. However, diagnosis is challenging because of the heterogeneity in clinical signs and symptoms, and also because the disease presents with alternating periods of flare and quiescence. As SLE is an autoimmune disease characterised by the formation of autoantibodies, diagnostic immunology laboratory tests for detecting and quantifying autoantibodies are commonly used for the diagnosis and classification of SLE. These include ANA, anti-double-stranded DNA antibodies and anti-Smith antibodies, together with other antibodies such as antiphospholipid or anti-Cq1. Complement proteins C3 and C4 are commonly measured in patients with SLE, but their serum levels do not necessarily reflect complement activation. Cell-bound complement activation products (CB-CAPs) are fragments formed upon complement activation that bind covalently to haematopoietic cells. This review focuses on the complement system and, in particular, on CB-CAPs as biomarkers for the diagnosis and monitoring of SLE, vis-à-vis complement proteins and other biomarkers of complement activation.
Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder
Authors: Popova Svetlana , Lange Shannon , Probst Charlotte , Gmel Gerrit , Rehm Jürgen
Published: August 2017

Alcohol use during pregnancy is an established cause of fetal alcohol spectrum disorder (FASD), with heavy drinking during pregnancy being explicitly linked to fetal alcohol syndrome (FAS). This paper presents recent estimates of the prevalence of: (i) any amount of alcohol use during pregnancy; (ii) one or more binge drinking episode(s) (4 or more standard drinks on a single occasion) during pregnancy; (iii) FAS; and (iv) FASD among the general population globally and by World Health Organization region. It is apparent, based on the presented estimates, that alcohol use and binge drinking occur frequently among pregnant women in many countries and as a result, FASD is a prevalent alcohol-related developmental disability. Urgent action is required around the globe to eliminate prenatal alcohol exposure and prevent future children, adolescents, and adults from having FASD.
Analysis of the interaction between the cocaine-binding aptamer and its ligands using fluorescence spectroscopy
Authors: Shoara Aron A. , Slavkovic Sladjana , Donaldson Logan W. , Johnson Philip E.
Published: August 2017

We used fluorescence spectroscopy to measure the binding affinity and provide new insights into the binding mechanism of cocaine and quinine with the cocaine-binding DNA aptamer. Using the intrinsic fluorescence of quinine and cocaine, we have observed quenching of ligand fluorescence upon binding of the aptamer. Quantification of this quenching provides an easy method to measure the binding constant using small amounts of sample. The observed quenching coupled with a red shift of the Stokes shift in the emission spectrum indicates that quinine and cocaine interact with the aptamer through stacking interactions.
Escape behavior of Side-blotched Lizards (Utastansburiana) in response to model predators
Authors: Wagner E.A. , Zani P.A.
Published: August 2017

Few field studies have tested for geographic variation in escape behavior and even fewer have examined responses of prey to multiple predators despite most prey occurring in multipredator environments. We performed 458 escape trials on Side-blotched Lizards (Uta stansburiana Baird and Girard, 1852) from 10 populations that differed in predator abundances. We quantified escape behavior of Side-blotched Lizards when approached with one of two model predators: a lizard (Great Basin Collared Lizard (Crotaphytus bicinctores N.M. Smith and Tanner, 1972)) or a snake (Western Yellow-bellied Racer (Coluber mormon Baird and Girard, 1852)). Our results suggest that the escape responses of Side-blotched Lizards (flight initiation distance, distance fled, refuge entry) do not differ when approached by either a model predatory lizard or a model predatory snake. Nor do the escape responses of individual Side-blotched Lizards differ in relation to the abundances of predatory lizards or snakes in the local environment. Rather, only the directness of fleeing toward a refuge differed based on model predator type with Side-blotched Lizards fleeing more directly toward a refuge in response to a model lizard. These findings suggest that Side-blotched Lizards tend to use a more generalized escape response to approaching predators.
Puerarin Improves Vascular Insulin Resistance and Cardiovascular Remodeling in Salt-Sensitive Hypertension
Authors: Tan Chunxiang , Wang Aimei , Liu Chan , Li Yao , Shi Yuepin , Zhou Ming-Sheng
Published: August 2017

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NF[Formula: see text]B/TNF[Formula: see text]/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NF[Formula: see text]B inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NF[Formula: see text]B/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases.
Elementary particles with continuous spin
Authors: Bekaert Xavier , Skvortsov Evgeny D.
Published: August 2017

Classical results and recent developments on the theoretical description of elementary particles with “continuous” spin are reviewed. At free level, these fields are described by unitary irreducible representations of the isometry group (either Poincaré or anti-de Sitter group) with an infinite number of physical degrees of freedom per space–time point. Their basic group-theoretical and field-theoretical descriptions are reviewed in some details. We mention a list of open issues which are crucial to address for assessing their physical status and potential relevance.