bluuebunny/crossref_metadata_2025 huggingface dataset:
Fracture epidemiology in male elite football players from 2001 to 2013: ‘How long will this fracture keep me out?’
Authors: Larsson David , Ekstrand Jan , Karlsson Magnus K
Published: March 2016

Background

Determining fracture risk and rehabilitation periods after specific fractures in professional football is essential for team planning.

Aim

To identify fracture epidemiology and absences after different types of fractures in male professional football players.

Methods

2439 players from 41 professional male teams in 10 countries were followed prospectively from 2001 to 2013. Team medical staff registered fractures, absences after fractures and player exposure.

Results

364 fractures were recorded, with an incidence of 0.27/1000 h of exposure (95% CI 0.25 to 0.30). The incidence of traumatic fractures was 0.25 (0.22 to 0.27) and that of stress fractures was 0.03 (0.02 to 0.04). 45% of traumatic fractures and 86% of stress fractures affected the lower extremities. Absence after a fracture was 32 days (1–278) (median (range)), compared to that after a traumatic fracture of 30 days (1–278) and a stress fracture of 65 days (6–168) (p<0.001). Annual fracture incidence was stable during the study period (R2=0.051, b=−0.011 (95% CI −0.043 to 0.021)). Young players had a relative risk of 10.9 (3.3 to 35.6) of sustaining stress fractures compared to old players (p<0.01). The fracture incidence did not differ between individuals in different playing positions (p=0.10).

A male professional football team can expect 1 to 2 fractures per season. There are more traumatic fractures than stress fractures; while most fractures affect the lower extremities, stress fractures yield longer absences than traumatic fractures and young players have more stress fractures than old players. There is no difference in risk among players at different playing positions.
In vitro assessment of bacterial colonisation rates of goat umbilical cord segments using three embodiments of a novel neonatal umbilical catheter protection device
Authors: Dambkowski Carl L , Chehab Eric F , Shih Joseph D , Venook Ross , Wall James K
Published: March 2016

Introduction

Central line-associated bloodstream infections (CLABSIs) in neonates with umbilical catheters occur at a rate that is 5 times higher than CLABSIs in adults with central catheters. No device currently exists tailored to the unique constraints umbilical catheters pose. The current study examined the natural progression of bacterial colonisation in goat umbilical cords and the relationship between embodiments of a novel neonatal umbilical catheter protection device and bacterial colonisation rates. The authors hypothesise that device venting is required to minimise bacterial colonisation in the unique umbilical stump environment.

Methods

The natural progression of bacterial colonisation in goat umbilical cord segments was studied by examining bacterial colonisation rates each day over 7 days. To understand the relationship between protection and bacterial colonisation, umbilical catheters were placed in goat umbilical cord segments and secured with 1 of 3 embodiments of a novel umbilical catheter protection device, which offered varying degrees of venting. After a 7-day period of incubation, colony counts were compared.

Results

Bacterial load was largest when umbilical cord segments were fresh and subsequently decreased over time. Further, bacterial colonisation rates showed a statistically significant difference between device embodiments (F(2,9)=4.26, p<0.05), with the non-vented embodiment showing the highest bacterial colonisation rate.

Conclusions

A device to better stabilise and protect umbilical catheters in order to reduce bloodstream infections in neonates is greatly needed. The current experiments confirm the hypothesis that completely enclosed, or non-vented, protection device will have increased bacterial growth.
Could a disruptive out patient healthcare delivery model reduce escalating in-hospital healthcare costs in knee osteoarthritis
Authors: Doss Arockia
Published: March 2016

Background

Healthcare costs from in-hospital joint surgery for degenerative joint diseases are predicted to significantly increase to potentially unsustainable levels in the next several decades.

Aim

As an index model, this paper presents cost-effectiveness predictions for an innovative combination treatment of image-guided percutaneous autologous blood-derived growth factors and exercises (IPGFE) for painful knee osteoarthritis managed in an out of hospital interventional radiology (IR) clinic through a disruptive healthcare delivery model.

Materials and methods

Non-randomised retrospective case registry data were analysed. Patients suitable for TKR who underwent IPGFE were included. Knee function outcome scores were converted to quality of life years (QALY) gained. Median percentage improvement after IPGFE in knee function was converted to cost per QALYs by input of direct costs.

Results

Median cost per QALY for IPGFE was AU$ 208.33 for 7.2 QALY gained. In comparison, the median cost per QALY for TKR was AU$2739 for 4.5 QALY gained. Incremental cost-effectiveness ratio for IPGFE was AU$4827.77 not spent per QALY gained in comparison to TKR.

Conclusions

An out of hospital care model may be a less expensive option to gain better quality of life in comparison to knee joint replacement surgery for some patients. Out of hospital IR techniques should be studied further for their efficacy and potential to offer considerable healthcare cost savings in comparison to joint replacement surgery.
Unemployment in the teens and trajectories of alcohol consumption in adulthood
Authors: Virtanen Pekka , Lintonen Tomi , Westerlund Hugo , Nummi Tapio , Janlert Urban , Hammarström Anne
Published: March 2016

Objectives

The unemployed are assumed to adopt unhealthy behaviours, including harmful use of alcohol. This study sought to elucidate the relations between unemployment before age 21 years and consumption of alcohol from 21 to 42 years. The design was based on the conception of youth as a sensitive period for obtaining ‘drinking scars’ that are visible up to middle age.

Setting

The Northern Swedish Cohort Study has followed up a population sample from 1981 to 2007 with five surveys.

Participants

All pupils (n=1083) attending the last year of compulsory school in Luleå participated in the baseline survey in classrooms, and 1010 of them (522 men and 488 women) participated in the last follow-up survey that was conducted at classmate reunions or by post or by phone.

Outcome measure

The trajectory of alcohol consumption from 21 to 43 years, obtained with latent class growth analyses, was scaled.

Results

Men were assigned to five and women to three consumption trajectories. The trajectory membership was regressed on accumulation of unemployment from 16 to 21 years, with multinomial logistic regression analyses. The trajectory of moderate consumption was preceded by lowest exposure to unemployment in men and in women. With reference to this, the relative risk ratios for high-level trajectory groups were 3.49 (1.25 to 9.79) in men and 1.41 (0.74 to 2.72) in women, but also the trajectories of low-level consumption were more probable (relative risk ratio 3.18 (1.12 to 9.02) in men and 2.41 (1.24 to 4.67) in women).

Conclusions

High-level alcohol consumption throughout adulthood is, particularly among men, partly due to ‘scars’ from youth unemployment, particularly in men, but there are also groups of men and women where unemployment in the teens predicts a trajectory of low consumption.
Association between sexually transmitted disease and church membership. A retrospective cohort study of two Danish religious minorities
Authors: Kørup Alex Kappel , Thygesen Lau Caspar , Christensen René dePont , Johansen Christoffer , Søndergaard Jens , Hvidt Niels Christian
Published: March 2016

Objectives

Studies comprising Danish Seventh-day Adventists (SDAs) and Danish Baptists found that members have a lower risk of chronic diseases including cancer. Explanations have pointed to differences in lifestyle, but detailed aetiology has only been sparsely examined. Our objective was to investigate the incidence of sexually transmitted diseases (STDs) among Danish SDAs and Baptists as a proxy for cancers related to sexual behaviour.

Methods

We followed the Danish Cohort of Religious Societies from 1977 to 2009, and linked it with national registers of all inpatient and outpatient care contacts using the National Patient Register. We compared the incidence of syphilis, gonorrhoea and chlamydia among members of the cohort with the general population.

Results

The cohort comprised 3119 SDA females, 1856 SDA males, 2056 Baptist females and 1467 Baptist males. For the entire cohort, we expected a total of 32.4 events of STD, and observed only 9. Female SDAs and Baptists aged 20–39 years had significant lower incidence of chlamydia (both p<0.001). Male SDAs and Baptists aged 20–39 years also had significant lower incidence of chlamydia (p<0.01 and p<0.05, respectively). No SDA members were diagnosed with gonorrhoea, when 3.4 events were expected, which, according to Hanley's ‘rule of three’, is a significant difference. No SDA or Baptist was diagnosed with syphilis.

Conclusions

The cohort shows significant lower incidence of STD, most likely including human papillomavirus, which may partly explain the lower incidence of cancers of the cervix, rectum, anus, head and neck.
Chinese herbal medicine for patients with vascular cognitive impairment no dementia: protocol for a systematic review
Authors: Feng Mei , Lu Jingmin , May Brian H , Liu Shaonan , Guo Xinfeng , Zhang Anthony Lin , Xue Charlie Changli , Lu Chuanjian
Published: March 2016

Introduction

The aim of this systematic review is to assess the efficacy and safety of Chinese herbal medicine for the treatment of patients with vascular cognitive impairment but no dementia.

Methods and analysis

We will perform a comprehensive retrieval in the following electronic databases: PubMed, Cochrane Library, EMBASE, CINAHL, Chinese Biomedical Literature Service System (SinoMed), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database and other sources. After screening the studies, the methodological quality of all included trials will be assessed according to the risk of bias instrument provided by the Cochrane Collaboration. A meta-analysis of randomised controlled trials will be conducted using RevMan V.5.3 software. Funnel plot analysis and Egger's test will be used to assess publication bias, if possible. The quality of evidence will be assessed by the GRADE system.

Dissemination

This systematic review will be disseminated in a peer-reviewed journal and a relevant conference presentation.

Trial registration number

PROSPERO CRD 42015023682.
Clinical impact of neoadjuvant treatment in resectable pancreatic cancer: a systematic review and meta-analysis protocol
Authors: Lee Jong-chan , Ahn Soyeon , Paik Kyu-hyun , Kim Hyoung Woo , Kang Jingu , Kim Jaihwan , Hwang Jin-Hyeok
Published: March 2016

Introduction

Although the only curative strategy for pancreatic cancer is surgical resection, up to 85% of patients relapse after surgery. The efficacy of neoadjuvant treatment in resectable pancreatic cancer (RPC) remains unclear and there is no systematic review focusing fully on this issue. Recently, two prospective trials of neoadjuvant treatment in RPC were terminated early because of slow recruiting and existing randomised controlled trials (RCTs) have too small sample sizes. Therefore, to overcome probable biases, it would be more reasonable to include both RCTs and non-randomised studies (NRSs) with selected criteria. This review aims to investigate the effect of neoadjuvant chemotherapy (CTx) and chemoradiation therapy (CRT) in RPC using RCTs and specific NRSs.

Method and analysis

This systematic review will include conventional RCTs as group I, and quasi-randomised controlled trials, non-randomised controlled trials and prospective cohort studies as group II. Two groups will be assessed and analysed separately. Comprehensive literature search will use Medline, Embase, Cochrane library and Scopus databases. Additionally, we will search references from relevant studies and abstracts from major conferences. Two authors will independently identify, screen, include studies, extract data and assess the risk of bias. Discrepancies will be resolved by consensus with another author. An independent methodologist will categorise and assess NRSs to minimise heterogeneity. In each study group, meta-analysis will be conducted using a random-effect model and statistical heterogeneity will be evaluated using I2-statistics. Publication bias will be visualised with contour-enhanced funnel plots and analysed with Egger's test. In group I, cumulative meta-analysis will be considered because the CTx regimen and CRT protocol have changed. The quality of evidence will be summarised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

Ethics and dissemination

This review does not use primary data, and formal ethical approval is not required. Findings will be disseminated through peer-reviewed journals and committee conferences.

Trial registration number

CRD42015023820.
Relationship between percentage of mean arterial pressure at the ankle and mortality in participants with normal ankle-brachial index: an observational study
Authors: Li Yu-Hsuan , Lin Shih-Yi , Sheu Wayne Huey-Herng , Lee I-Te
Published: March 2016

Objectives

Peripheral arterial disease (PAD) is associated with all-cause mortality. Ankle-brachial index (ABI) is the most widely used tool for detecting PAD, but can yield false-negative results in patients with non-compressible vessels. Pulse volume recording may be an alternative tool for assessing PAD in such patients. However, the association between pulse volume recording and all-cause mortality has seldom been reported. We hypothesised that the percentage of mean arterial pressure (%MAP) and upstroke time (UT), which are indexes of the arterial wave obtained on pulse volume recording, can predict mortality.

Design

We conducted this as a retrospective cohort study.

Setting

Data were collected from the Taichung Veterans General Hospital.

Participants

We included 314 participants with complete data on ABI and pulse volume recording performed between June 2007 and November 2011.

Primary outcome measure

Mortality data served as the follow-up outcome. Mortality data were obtained from the Collaboration Center of Health Information Application, Ministry of Health and Welfare, Executive Yuan, Taiwan.

Results

Participants with ABI ≤0.9 showed a highest mortality rate (p<0.001 in the log-rank test), but the mortality rate was not significantly different between participants with 0.9<ABI≤1.1 and those with 1.1<ABI≤1.3 (p=0.553). Among the participants with 0.945%) group showed a higher risk of all-cause mortality than the low %MAP (≤45%) group (HR=5.389, p=0.004) after adjustment for ABI, pulse wave velocity, UT, age, sex, blood pressure, serum cholesterol, and history of cardiovascular disease and diabetes.

Conclusions

We thus demonstrated that a high %MAP based on pulse volume recording in participants with 0.9<ABI≤1.3 could predict all-cause mortality during 20.3 months of follow-up.
Validity of ICD-9-CM codes for breast, lung and colorectal cancers in three Italian administrative healthcare databases: a diagnostic accuracy study protocol
Authors: Abraha Iosief , Serraino Diego , Giovannini Gianni , Stracci Fabrizio , Casucci Paola , Alessandrini Giuliana , Bidoli Ettore , Chiari Rita , Cirocchi Roberto , De Giorgi Marcello , Franchini David , Vitale Maria Francesca , Fusco Mario , Montedori Alessandro
Published: March 2016

Introduction

Administrative healthcare databases are useful tools to study healthcare outcomes and to monitor the health status of a population. Patients with cancer can be identified through disease-specific codes, prescriptions and physician claims, but prior validation is required to achieve an accurate case definition. The objective of this protocol is to assess the accuracy of International Classification of Diseases Ninth Revision—Clinical Modification (ICD-9-CM) codes for breast, lung and colorectal cancers in identifying patients diagnosed with the relative disease in three Italian administrative databases.

Methods and analysis

Data from the administrative databases of Umbria Region (910 000 residents), Local Health Unit 3 of Napoli (1 170 000 residents) and Friuli-Venezia Giulia Region (1 227 000 residents) will be considered. In each administrative database, patients with the first occurrence of diagnosis of breast, lung or colorectal cancer between 2012 and 2014 will be identified using the following groups of ICD-9-CM codes in primary position: (1) 233.0 and (2) 174.x for breast cancer; (3) 162.x for lung cancer; (4) 153.x for colon cancer and (5) 154.0–154.1 and 154.8 for rectal cancer. Only incident cases will be considered, that is, excluding cases that have the same diagnosis in the 5 years (2007–2011) before the period of interest. A random sample of cases and non-cases will be selected from each administrative database and the corresponding medical charts will be assessed for validation by pairs of trained, independent reviewers. Case ascertainment within the medical charts will be based on (1) the presence of a primary nodular lesion in the breast, lung or colon–rectum, documented with imaging or endoscopy and (2) a cytological or histological documentation of cancer from a primary or metastatic site. Sensitivity and specificity with 95% CIs will be calculated.

Dissemination

Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences.
An investigation of general predictors for cognitive–behavioural therapy outcome for anxiety disorders in a routine clinical setting
Authors: Nielsen Sara Kerstine Kaya , Vangkilde Signe , Wolitzky-Taylor Kate B , Daniel Sarah Ingrid Franksdatter , Hageman Ida
Published: March 2016

Introduction

Cognitive–behavioural therapy (CBT) is effective for treating anxiety disorders and is offered in most mental health services around the world. However, a relatively large number of patients with anxiety disorders do not benefit from CBT, experience relapses or drop out. Reliable predictors of treatment effects are lacking. The aim of this study is to investigate the predictive value of emotion regulation and attentional control for CBT outcome in a routine setting.

Methods and analysis

In this prospective and practice-based study, 112 patients with anxiety disorders referred for manual-based group CBT at two psychiatric outpatient clinics will be recruited. Emotion regulation, severity of anxiety and attentional control will be assessed with self-report measures and with an experimental computer-based attentional control task at baseline, post-treatment and at a 6-month follow-up. Emotion regulation will be measured with Difficulties in Emotion Regulation Questionnaire, severity of anxiety will be assessed with Beck Anxiety Inventory and attentional control will be measured with the self-report questionnaire, Attention Control Scale, and with an experimental computer-based attentional control task based on theory of visual attention. Data will be analysed using multilevel mixed-effects modelling.

Ethics and dissemination

The study is approved by the Danish National Ethical Board, the Department of Psychology Ethical Board, University of Copenhagen and by the Danish Data Protection Agency. Study findings will be disseminated through peer-reviewed journal publications and conference presentations. The Danish Committee System on Health Research Ethics has been notified about the project.

Trial registration number

NCT02638363.
The evolution of multiagency partnerships for safety over the course of research engagement: experiences from the NoGAPS project
Authors: Finch Caroline F , Donaldson Alex , Gabbe Belinda J , Muhammad Akram , Shee Anna Wong , Lloyd David G , Cook Jill
Published: March 2016

Objective

Implementation of effective population-level injury prevention interventions requires broad multiagency partnerships. Different stakeholders address this from varying perspectives, and potential conflicts in priorities need to be addressed for such partnerships to be effective. The researcher-led National Guidance for Australian football Partnerships and Safety (NoGAPS) project involved the engagement and participation of seven non-academic partners, including government health promotion and safety agencies; peak sports professional and advocacy bodies and health insurance organisations.

Design

The partnership's ongoing development was assessed by each partner completing the Victorian Health Promotion Foundation Partnership Analysis Tool (VPAT) annually over 2011–2015. Changes in VPAT scores were compared through repeated measures analysis of variance.

Results

Overall, mean total VPAT scores increased significantly over the 5-year period (125.1–141.2; F5,30=4.61, p=0.003), showing a significant improvement in how the partnership was functioning over time. This was largely driven by significant increases in several VPAT domains: ‘determining the need for a partnership’ (F5,30=4.15, p=0.006), ‘making sure the partnership works’ (F5,30=2.59, p=0.046), ‘planning collaborative action’ (F5,30=5.13, p=0.002) and ‘minimising the barriers to the partnership’ (F5,30=6.66, p<0.001).

Conclusion

This is the first study to assess the functioning of a multiagency partnership to address sport injury prevention implementation. For NoGAPS, the engagement of stakeholders from the outset facilitated the development of new and/or stronger links between non-academic partners. Partners shared the common goal of ensuring the real-world uptake of interventions and research evidence-informed recommendations. Effective multiagency partnerships have the potential to influence the implementation of policies and practices beyond the life of a research project.
Quality of consumer-targeted internet guidance on home firearm and ammunition storage
Authors: Freundlich Katherine L , Skoczylas Maria Shakour , Schmidt John P , Keshavarzi Nahid R , Mohr Bethany Anne
Published: March 2016

Background and objectives

Four storage practices protect against unintentional and/or self-inflicted firearm injury among children and adolescents: keeping guns locked (1) and unloaded (2) and keeping ammunition locked up (3) and in a separate location from the guns (4). Our aim was to mimic common Google search strategies on firearm/ammunition storage and assess whether the resulting web pages provided recommendations consistent with those supported by the literature.

Methods

We identified 87 web pages by Google search of the 10 most commonly used search terms in the USA related to firearm/ammunition storage. Two non-blinded independent reviewers analysed web page technical quality according to a 17-item checklist derived from previous studies. A single reviewer analysed readability by US grade level assigned by Flesch–Kincaid Grade Level Index. Two separate, blinded, independent reviewers analysed deidentified web page content for accuracy and completeness describing the four accepted storage practices. Reviewers resolved disagreements by consensus.

Results

The web pages described, on average, less than one of four accepted storage practices (mean 0.2 (95% CL 0.1 to 0.4)). Only two web pages (2%) identified all four practices. Two web pages (2%) made assertions inconsistent with recommendations; both implied that loaded firearms could be stored safely. Flesch–Kincaid Grade Level Index averaged 8.0 (95% CL 7.3 to 8.7). The average technical quality score was 7.1 (95% CL 6.8 to 7.4) out of an available score of 17. There was a high degree of agreement between reviewers regarding completeness (weighted κ 0.78 (95% CL 0.61 to 0.97)).

Conclusions

The internet currently provides incomplete information about safe firearm storage. Understanding existing deficiencies may inform future strategies for improvement.
Validation of an ‘endovascular-first’ approach to spinal dural arteriovenous fistulas: an intention-to-treat analysis
Authors: Gross Bradley A , Albuquerque Felipe C , Moon Karam , McDougall Cameron G
Published: March 2016

Background/objective

Spinal dural arteriovenous fistulas (SDAVFs) require pretreatment angiography; embolization can be performed in the same session. To validate this approach, obliteration and morbidity rates of ‘endovascular-first’ (embolization and microsurgery in the case of embolization failures) must be compared with rates for ‘microsurgery-first’ (microsurgical ligation without attempted embolization) approaches.

Methods

We reviewed our institutional database (January 1998–October 2015) for SDAVFs, performing an intention-to-treat analysis comparing endovascular-first and microsurgery-first approaches.

Results

A total of 71 patients underwent surgical and/or endovascular treatment for SDAVFs. All SDAVFs were ultimately occluded. Of 35 patients under consideration for an endovascular-first approach, radicular artery anatomy or anterior spinal artery embolization risk precluded attempting embolization in seven cases (20%). Among 28 patients undergoing embolization, angiographic non-opacification of the fistula was noted in 18 (64%). Fourteen patients had obliteration with excellent casting of the draining vein (50%) and did not undergo surgery. There were no significant differences in total complications (9% vs 11%; p=1.0) or permanent complications (3% vs 4%; p=1.0) after attempted endovascular and surgical treatment. Based on an intention-to-treat analysis, there were no significant differences in total complications (11% vs 14%; p=1.0), permanent complications (6% vs 3%; p=0.61), or the symptomatic resolution/improvement rate (80% vs 78%; p=1.0) between endovascular-first and microsurgery-first groups.

Conclusions

Our results support attempted embolization of SDAVFs prior to consideration of microsurgery, allowing for a less invasive treatment option in the same session as diagnostic angiography.
Long-term survival after surgical aortic valve replacement among patients over 65 years of age
Authors: Sharabiani Mansour T A , Fiorentino Francesca , Angelini Gianni D , Patel Nishith N
Published: March 2016

Objective

Surgical aortic valve replacement (AVR) remains the gold standard therapy for severe aortic stenosis. Long-term survival data following AVR is required. Our objective was to provide a detailed contemporary benchmark of long-term survival following AVR among elderly patients (≥65 years) in the UK.

Methods

We conducted a retrospective cohort study of 1815 adult patients undergoing surgical AVR± coronary artery bypass graft (CABG) surgery at a single UK centre between 1996 and 2011. Our main outcome was patient survival, which was assessed by linkage to census records at the Office for National Statistics.

Results

The mean age of the cohort was 75 (±5.6) years. Patients in the AVR alone group had a slightly higher median survival of 10.9 (95% CI 10.5 to 11.8) years than the AVR+CABG group which had a median survival of 9.6 (95% CI 8.7 to 10.1) years (p=0.001 of log-rank test (LRT) for equality of survivor functions). The presence of chronic kidney disease, severely impaired left ventricular function or being a current smoker were each associated with a ≥50% increased risk of long-term mortality. Comparison of our study cohort patients and the reference (operation year, age and gender matched) UK population suggested no difference in survival probability up to 8 years (p=0.55). However, for longer periods of follow-up, the difference became increasingly significant (p<0.0001).

Conclusions

Long-term survival following surgical AVR in patients over 65 years of age is excellent and up to 8 years is comparable to the matched general population.
Graphic warning labels and the demand for cigarettes
Authors: Starr Martha A , Drake Keith
Published: March 2016

Background

In 2010, the US Food and Drug Administration (FDA) proposed requiring tobacco companies to add graphic warning labels (GWLs) to cigarette packs. GWLs are large prominently placed warnings that use both text and photographic images to depict health risks of smoking. The companies challenged FDA's authority on First Amendment grounds; the courts accepted that FDA could compel companies to add GWLs, but argued that FDA had not established that GWLs would significantly reduce smoking.

Objective

This paper adds new evidence on the question of whether GWLs would have reduced cigarette demand, by examining whether tobacco companies’ share prices fell unusually after news indicating a higher likelihood of having GWLs, and rose on the opposite news. Such findings would be expected if investors viewed GWLs as likely to reduce cigarette demand.

Methods

An event-study approach is used to determine whether the stock prices of US tobacco companies rose or fell unusually after news events in the period when GWLs were proposed, finalised, challenged and withdrawn.

Findings

Tobacco companies’ stock prices indeed realised significant abnormal returns after GWL news, consistent with expected negative effects on cigarette demand. Our estimates suggest investors expected GWLs to reduce the number of smokers by an extra 2.4–6.9 million in the 10 years after the rule took effect.

Conclusions

These findings support the view that the GWLs proposed by FDA would have curbed cigarette consumption in the USA in an appreciable way.
Geomorphic and geological constraints on the active normal faulting of the Gediz (Alaşehir) Graben, Western Turkey
Authors: Kent E. , Boulton S. J. , Stewart I. S. , Whittaker A. C. , Alçiçek M. C.
Published: March 2016

The Gediz (Alaşehir) Graben is located in the highly tectonically active region of Western Turkey. Extension owing to regional geodynamic controls has resulted in a broadly two-phase evolution of the graben; first, low-angle normal faulting relating to the exhumation of the Menderes Massif metamorphic core complex took place between 16 and 2.6 Ma; second, high-angle normal faulting initiated
c.
2 Ma forming the Gediz and other east–west-trending graben in the region. Here we quantify the throw rate along the fault array over the last 2.6, 2 and 0.7 myr using structural and geological constraints, along with analysis of topographic relief as a proxy for footwall uplift. We derive, for the first time, time-averaged rates of fault motion from 0.4 to 1.3 mm a
−1
along the strike of the Gediz Graben, with variation in throw rate associated with the geometry of single fault strands. Patterns in throw rate along-strike of the graben-bounding fault array also suggest that the fault segments have become linked during the last 2.6–2 myr, possibly at 0.8–0.7 Ma. Furthermore, these data suggest that an earthquake occurring along the graben-bounding fault could have a maximum predicted M
w
of 6.3–7.6.
The use of chemostratigraphy to refine ambiguous sequence stratigraphic correlations in marine mudrocks. An example from the Woodford Shale, Oklahoma, USA
Authors: Turner B. W. , Tréanton J. A. , Slatt R. M.
Published: March 2016

Application of sequence stratigraphy to fine-grained lithologies has previously been hindered by the difficulty of identifying distinct facies shifts within mudrocks. Three cores from Lincoln, Pottawatomie and Pontotoc Counties in Oklahoma and two outcrops at the Hunton Anticline Quarry in Murray County, OK record both proximal and distal regions of the Arkoma Basin. Handheld X-ray fluorescence data and gamma-ray profiles together with lithological descriptions can be used to develop sequence-stratigraphic interpretations.

Stratigraphic successions that are challenging to correlate based on gamma-ray (GR) profiles alone can be correlated accurately by utilizing surfaces that are recognized within chemostratigraphic profiles. Within the Arkoma Basin, Oklahoma, the chemostratigraphic profile of the Woodford Shale is interpreted within a sequence-stratigraphic framework using the following general criteria. The Lowstand Systems Tract (LST) is defined by increasing concentrations of Ti, Zr, Al and K as well as high levels of Mo and V. The Transgressive Systems Tract (TST) is defined by declining concentrations of Ti and Zr, although Al and K may remain elevated; Mo and V also show general declines. The Highstand Systems Tract (HST) is defined by increasing concentrations of Ti, Zr, Al and K, but is distinguished from the LST by low levels of Mo and V.

Supplementary material:
Chemofacies profiles are available at
http://doi.org/10.6084/m9.figshare.c.2849599
.
Towards a sequence stratigraphic solution set for autogenic processes and allogenic controls: Upper Cretaceous strata, Book Cliffs, Utah, USA
Authors: Hampson Gary J.
Published: March 2016

Upper Cretaceous strata exposed in the Book Cliffs of east–central Utah are widely used as an archetype for the sequence stratigraphy of marginal-marine and shallow-marine deposits. Their stratal architectures are classically interpreted in terms of accommodation controls that were external to the sediment routing system (allogenic), and that forced the formation of flooding surfaces, sequence boundaries, and parasequence and parasequence-set stacking patterns. Processes internal to the sediment routing system (autogenic) and allogenic sediment supply controls provide alternatives that can plausibly explain aspects of the stratal architecture, including the following: (1) switching of wave-dominated delta lobes, expressed by the internal architecture of parasequences; (2) river avulsion, expressed by the internal architecture of multistorey fluvial sandbodies and related deposits; (3) avulsion-generated clustering of fluvial sandbodies in delta plain strata; (4) ‘autoretreat’ owing to increasing sediment storage on the delta plain as it lengthened during progradation, expressed by progradational-to-aggradational stacking of parasequences; (5) sediment supply control on the stacking of, and sediment grain-size fractionation within, parasequence sets. The various potential allogenic controls and autogenic processes are combined to form a sequence stratigraphic solution set. This approach avoids anchoring of sequence stratigraphic interpretations on a specific control and acknowledges the non-unique origin of stratal architectures.
Uranium distribution as a proxy for basin-scale fluid flow in distributive fluvial systems
Authors: Owen A. , Hartley A. J. , Weissmann G. S. , Nichols G. J.
Published: March 2016

We infer system-scale fluid flow in the Late Jurassic Salt Wash fluvial succession (SW USA) by plotting uranium deposit distribution against sedimentological data, using uranium distribution as a proxy for subsurface fluid flow. More than 90% of uranium deposits in the Salt Wash occur where sandstone forms 40–55% and sand-rich channel-belts form 20–50% of the succession, which coincides with changes in channel-belt connectivity and gross-scale architecture. The paucity of uranium below these cut-off values suggests that fluid flow is related directly to predictable downstream fining and facies variations in distributive fluvial systems.

Supplementary material:
A summary table of location data, key trends and the amalgamation ratio method is available at
https://doi.org/10.6084/m9.figshare.c.2849581
.
The role of perfusion in the oxygen extraction capability of skin and skeletal muscle
Authors: Thorn Clare E. , Shore Angela C.
Published: March 2016

Oxygen extraction (OE) by all cells is dependent on an adequate supply of oxygen in proximal blood vessels and the cell's need and ability to uptake that oxygen. Here the role of blood flow in regulating OE in skin and skeletal muscle was investigated in lean and obese men. OE was derived by two optical reflectance spectroscopy techniques: 1) from the rate of fall in mean blood saturation during a 4 min below knee arterial occlusion, and thus no blood flow, in calf skin and skeletal muscle and 2) in perfused, unperturbed skin, using the spontaneous falls in mean blood saturation induced by vasomotion in calf and forearm skin of 24 subjects, 12 lean and 12 obese. OE in perfused skin was significantly higher in lean compared with obese subjects in forearm (Mann-Whitney, P < 0.004) and calf ( P < 0.001) and did not correlate with OE in unperfused skin (ρ = −0.01, P = 0.48). With arterial occlusion and thus no blood flow, skin OE in lean and obese subjects no longer differed ( P = 0.23, not significant). In contrast in skeletal muscle with arterial occlusion and no blood flow, the difference in OE between lean and obese subjects occurred, with obese subjects exhibiting significantly higher OE ( P < 0.012). The classic model of metabolic blood flow regulation to support oxygen extraction is evident in perfused skin; OE is perturbed without blood flow and reduced in obesity. In resting skeletal muscle other mechanism(s), independent of blood flow, are implicated in oxygen extraction.
A technical review of optical mapping of intracellular calcium within myocardial tissue
Authors: Jaimes Rafael , Walton Richard D. , Pasdois Philippe , Bernus Olivier , Efimov Igor R. , Kay Matthew W.
Published: March 2016

Optical mapping of Ca2+-sensitive fluorescence probes has become an extremely useful approach and adopted by many cardiovascular research laboratories to study a spectrum of myocardial physiology and disease conditions. Optical mapping data are often displayed as detailed pseudocolor images, providing unique insight for interpreting mechanisms of ectopic activity, action potential and Ca2+transient alternans, tachycardia, and fibrillation. Ca2+-sensitive fluorescent probes and optical mapping systems continue to evolve in the ongoing effort to improve therapies that ease the growing worldwide burden of cardiovascular disease. In this technical review we provide an updated overview of conventional approaches for optical mapping of Cai2+within intact myocardium. In doing so, a brief history of Cai2+probes is provided, and nonratiometric and ratiometric Ca2+probes are discussed, including probes for imaging sarcoplasmic reticulum Ca2+and probes compatible with potentiometric dyes for dual optical mapping. Typical measurements derived from optical Cai2+signals are explained, and the analytics used to compute them are presented. Last, recent studies using Cai2+optical mapping to study arrhythmias, heart failure, and metabolic perturbations are summarized.
Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats
Authors: Jameson Heather , Bateman Ryan , Byrne Peter , Dyavanapalli Jhansi , Wang Xin , Jain Vivek , Mendelowitz David
Published: March 2016

Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H. To assess OXT release from PVN fibers, Chinese hamster ovarian (CHO) cells were engineered to be highly sensitive to OXT by stable expression of the human recombinant OXT receptor and the calcium indicator R-GECO1. PVN fibers in the DMNX were selectively photoactivated in vitro by expression of channelrhodopsin. The release of OXT onto CHO cells in the DMNX was blunted in rats exposed to 21 days of CIH/H. Chronic activation of PVN OXT neurons in vivo, using designer receptors exclusively activated by designer drugs, restored the release of OXT onto CHO cells in the DMNX. Chronic PVN OXT neuron activation in vivo also prevented the hypertension that occurred in conscious unrestrained telemetry-equipped sham rats exposed to 3 wk of CIH/H. These results demonstrate that chronic activation of OXT neurons restores the release of OXT from PVN fibers in the DMNX and prevents the hypertension that occurs with 3 wk of CIH/H exposure.
A coupled chemo-fluidic computational model for thrombogenesis in infarcted left ventricles
Authors: Seo Jung Hee , Abd Thura , George Richard T. , Mittal Rajat
Published: March 2016

A coupled chemo-fluidic computational model for investigating flow-mediated thrombogenesis in infarcted left ventricles (LVs) is proposed. LV thrombus (LVT) formation after the acute myocardial infarction (AMI) may lead to thromboembolic events that are associated with high mortality and morbidity, and reliable stratification of LVT risk is the key to managing the treatment of AMI patients. There have been several studies emphasizing the importance of LV blood flow patterns on thrombus formation; however, given the complex interplay between ventricular flow dynamics and biochemistry of thrombogenesis, current understanding is mostly empirical. In the present model, blood flow in the LV is obtained by solving the incompressible Navier-Stokes equations, and this is coupled to the biochemical modeling of the coagulation cascade, platelet activation, and fibrinogen polymerization. The coupled model is used to examine the effect of ventricular flow patterns on thrombogenesis in modeled ventricles. It is expected that the method developed here will enable in-depth studies of thrombogenesis in patient-derived infarcted LV models.
Cardiac activation heat remains inversely dependent on temperature over the range 27–37°C
Authors: Johnston Callum M. , Han June-Chiew , Loiselle Denis S. , Nielsen Poul M. F. , Taberner Andrew J.
Published: March 2016

The relation between heat output and stress production (force per cross-sectional area) of isolated cardiac tissue is a key metric that provides insight into muscle energetic performance. The heat intercept of the relation, termed “activation heat,” reflects the metabolic cost of restoring transmembrane gradients of Na+and K+following electrical excitation, and myoplasmic Ca2+concentration following its release from the sarcoplasmic reticulum. At subphysiological temperatures, activation heat is inversely dependent on temperature. Thus one may presume that activation heat would decrease even further at body temperature. However, this assumption is prima facie inconsistent with a study, using intact hearts, which revealed no apparent change in the combination of activation and basal metabolism between 27 and 37°C. It is thus desired to directly determine the change in activation heat between 27 and 37°C. In this study, we use our recently constructed high-thermal resolution muscle calorimeter to determine the first heat-stress relation of isolated cardiac muscle at 37°C. We compare the relation at 37°C to that at 27°C to examine whether the inverse temperature dependence of activation heat, observed under hypothermic conditions, prevails at body temperature. Our results show that activation heat was reduced (from 3.5 ± 0.3 to 2.3 ± 0.3 kJ/m3) at the higher temperature. This leads us to conclude that activation metabolism continues to decline as temperature is increased from hypothermia to normothermia and allows us to comment on results obtained from the intact heart by previous investigators.
Caveolae are involved in mechanotransduction during pulmonary hypertension
Authors: Gilbert Guillaume , Ducret Thomas , Savineau Jean-Pierre , Marthan Roger , Quignard Jean-François
Published: March 2016

Caveolae are stiff plasma membrane microdomains implicated in various cell response mechanisms like Ca2+ signaling and mechanotransduction. Pulmonary arterial smooth muscle cells (PASMC) transduce mechanical stimuli into Ca2+ increase via plasma membrane stretch-activated channels (SAC). This mechanotransduction process is modified in pulmonary hypertension (PH) during which stretch forces are increased by the increase in arterial blood pressure. We propose to investigate how caveolae are involved in the pathophysiology of PH and particularly in mechanotransduction. PASMC were freshly isolated from control rats (Ctrl rats) and rats suffering from PH induced by 3 wk of chronic hypoxia (CH rats). Using a caveolae disrupter (methyl-β-cyclodextrin), we showed that SAC activity measured by patch-clamp, stretch-induced Ca2+ increase measured with indo-1 probe and pulmonary arterial ring contraction to osmotic shock are enhanced in Ctrl rats when caveolae are disrupted. In CH rats, SAC activity, Ca2+, and contraction responses to stretch are all higher compared with Ctrl rats. However, in contrast to Ctrl rats, caveolae disruption in CH-PASMC, reduces SAC activity, Ca2+ responses to stretch and arterial contractions. Furthermore, by means of immunostainings and transmission electron microscopy, we observed that caveolae and caveolin-1 are expressed in PASMC from both Ctrl and CH rats and localize close to subplasmalemmal sarcoplasmic reticulum (ryanodine receptors) and mitochondria, thus facilitating Ca2+ exchanges, particularly in CH. In conclusion, caveolae are implicated in mechanotransduction in Ctrl PASMC by buffering mechanical forces. In PH-PASMC, caveolae form a distinct Ca2+ store facilitating Ca2+ coupling between SAC and sarcoplasmic reticulum.
Isolation of individual cellular components from lung tissues of patients with lymphangioleiomyomatosis
Authors: Ando Katsutoshi , Fujino Naoya , Mitani Keiko , Ota Chiharu , Okada Yoshinori , Kondo Takashi , Mizobuchi Teruaki , Kurihara Masatoshi , Suzuki Kenji , Hoshika Yoshito , Ebana Hiroki , Kobayashi Etsuko , Takahashi Kazuhisa , Kubo Hiroshi , Seyama Kuniaki
Published: March 2016

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease entailing cystic destruction of the lungs and progressive respiratory failure. LAM lungs are histologically characterized by the proliferation of smooth muscle-like cells (LAM cells) and an abundance of lymphatic vessels. To elucidate the pathophysiological processes of LAM, cell-type-specific analyses are required. However, no method exists for isolating the individual types of cells in LAM lesions. Therefore, we established a fluorescence-activated cell sorting (FACS)-based method for the direct isolation of LAM cells and other various cellular components from LAM-affected lung tissue. We obtained LAM-affected lung tissue from resections or transplant recipients and prepared single-cell suspensions. FACS, immunohistochemical, and molecular analysis were used cooperatively to isolate HMB45-positive LAM cells with tuberous sclerosis complex ( TSC) 2 loss of heterozygosity (LOH). Using a combination of antibodies against an epithelial cell adhesion molecule (EpCAM) and podoplanin, we fractionated CD45-negative lung cells into three groups: lymphatic endothelial cells (LEC) (EpCAM−/podoplaninhi subset), alveolar type II cells (EpCAMhi/podoplanin− subset), and mesenchymal cells (EpCAM−/podoplanin−/low subset). During subsequent analysis of HMB45 expression, as a LAM-specific marker, we clearly identified LAM cells in the mesenchymal cell population. We then discovered that CD90+/CD34− cells in the mesenchymal cell population are not only positive for HBM45 but also had TSC2 LOH. These isolated cells were viable and subsequently amenable to cell culture. This method enables us to isolate LAM cells and other cellular components, including LAM-associated LEC, from LAM-affected lung tissues, providing new research opportunities in this field.