bluuebunny/crossref_metadata_2025 huggingface dataset:
New clinical decision rule to exclude subarachnoid haemorrhage for acute headache: a prospective multicentre observational study
Authors: Kimura Akio , Kobayashi Kentaro , Yamaguchi Hitoshi , Takahashi Takeshi , Harada Masahiro , Honda Hideki , Mori Yoshio , Hirose Keika , Tanaka Noriko
Published: September 2016

Objective

To ensure good outcomes in the management of subarachnoid haemorrhage (SAH), accurate prediction is crucial for initial assessment of patients presenting with acute headache. We conducted this study to develop a new clinical decision rule using only objectively measurable predictors to exclude SAH, offering higher specificity than the previous Ottawa SAH Rule while maintaining comparable sensitivity.

Design

Multicentre prospective cohort study.

Setting

Tertiary-care emergency departments of five general hospitals in Japan from April 2011 to March 2014.

Participants

Eligible patients comprised 1781 patients aged >15 years with acute headache, excluding trauma or toxic causes and patients who presented in an unconscious state.

Main outcome measures

Definitive diagnosis of SAH was based on confirmation of SAH on head CT or lumbar puncture findings of non-traumatic red blood cells or xanthochromia.

Results

A total of 1561 patients were enrolled in this study, of whom 277 showed SAH. Using these enrolled patients, we reached a rule with mainly categorical predictors used in previous reports, called the ‘Ottawa-like rule’, offering 100% sensitivity when using any of age ≥40 years, neck pain or stiffness, altered level of consciousness or onset during exertion. Using the 1317 patients from whom blood samples were obtained, a new rule using any of systolic blood pressure >150 mm Hg, diastolic blood pressure >90 mm Hg, blood sugar >115 mg/dL or serum potassium <3.9 mEq/L offered 100% sensitivity (95% CI 98.6% to 100%) and 14.5% specificity (12.5% to 16.9%), while the Ottawa-like rule showed the same sensitivity with a lower specificity of 8.8% (7.2% to 10.7%).

Conclusions

While maintaining equal sensitivity, our new rule seemed to offer higher specificity than the previous rules proposed by the Ottawa group. Despite the need for blood sampling, this method can reduce unnecessary head CT in patients with acute headache.

Trial registration number

UMIN 00004871.
Relationship between mobility, violence and major depression among female sex workers: a cross-sectional study in southern India
Authors: Patel Sangram Kishor , Ganju Deepika , Prabhakar Parimi , Adhikary Rajatashuvra
Published: September 2016

Background

The relationship between mobility, violence and mental health has largely been unexplored in developing countries. This study screens for signs of major depression, and assesses its association with mobility and violence among female sex workers (FSWs) in southern India.

Methods

Data (N=2400) for this study were used from a cross-sectional Behavioral Tracking Survey (BTS-2014) conducted among FSWs from a southern state of India as part of the Avahan programme. Major depression of FSWs was assessed using the Patient Health Questionnaire-2 depression scale. Descriptive statistics, frequency, bivariate, interaction effect and multivariate logistic regression techniques were used for the analysis.

Results

More than one-fourth of FSWs (29%) screened positive for major depression. The likelihood of screening positive for major depression was 6 times higher among FSWs who were both mobile for sex work outside their district of residence and had experienced any violence (combined association) during the past 1 year (62% vs 19%, adjusted OR 6.1, 95% CI 4.4 to 8.6) compared with those who reported neither. The individual association results show that FSWs who reported being mobile outside the district, and FSWs who were beaten or raped in the past 1 year, were 3 times more likely to screen positive for major depression.

Conclusions

The findings indicate that violence and mobility are independently associated with major depression among FSWs. The combined association of mobility and violence poses a greater risk to the mental health of FSWs than their independent association. These results point to the need for creating an enabling environment for FSWs to enhance existing efforts to reduce the spread of HIV and mental health problems. The study highlights that HIV prevention efforts among FSWs in India require evidence-based research and integrated programme approaches to address mental health issues.
Measurement of the severity of disability in community-dwelling adults and older adults: interval-level measures for accurate comparisons in large survey data sets
Authors: Buz José , Cortés-Rodríguez María
Published: September 2016

Objectives

To (1) create a single metric of disability using Rasch modelling to be used for comparing disability severity levels across groups and countries, (2) test whether the interval-level measures were invariant across countries, sociodemographic and health variables and (3) examine the gains in precision using interval-level measures relative to ordinal scores when discriminating between groups known to differ in disability.

Design

Cross-sectional, population-based study.

Setting/participants

Data were drawn from the Survey of Health, Ageing and Retirement in Europe (SHARE), including comparable data across 16 countries and involving 58 489 community-dwelling adults aged 50+.

Main outcome measures

A single metric of disability composed of self-care and instrumental activities of daily living (IADLs) and functional limitations. We examined the construct validity through the fit to the Rasch model and the know-groups method. Reliability was examined using person separation reliability.

Results

The single metric fulfilled the requirements of a strong hierarchical scale; was able to separate persons with different levels of disability; demonstrated invariance of the item hierarchy across countries; and was unbiased by age, gender and different health conditions. However, we found a blurred hierarchy of ADL and IADL tasks. Rasch-based measures yielded gains in relative precision (11–116%) in discriminating between groups with different medical conditions.

Conclusions

Equal-interval measures, with person-invariance and item-invariance properties, provide epidemiologists and researchers with the opportunity to gain better insight into the hierarchical structure of functional disability, and yield more reliable and accurate estimates of disability across groups and countries. Interval-level measures of disability allow parametric statistical analysis to confidently examine the relationship between disability and continuous measures so frequent in health sciences (eg, cholesterol, blood pressure, C reactive protein).
Trustworthy patient decision aids: a qualitative analysis addressing the risk of competing interests
Authors: Elwyn Glyn , Dannenberg Michelle , Blaine Arianna , Poddar Urbashi , Durand Marie-Anne
Published: September 2016

Objective

Our aim in this study was to examine the competing interest policies and procedures of organisations who develop and maintain patient decision aids.

Design

Descriptive and thematic analysis of data collected from a cross-sectional survey of patient decision aid developer's competing interest policies and disclosure forms.

Results

We contacted 25 organisations likely to meet the inclusion criteria. 12 eligible organisations provided data. 11 organisations did not reply and 2 declined to participate. Most patient decision aid developers recognise the need to consider the issue of competing interests. Assessment processes vary widely and, for the most part, are insufficiently robust to minimise the risk of competing interests. Only half of the 12 organisations had competing interest policies. Some considered disclosure to be sufficient, while others imposed differing levels of exclusion.

Conclusions

Patient decision aid developers do not have a consistent approach to managing competing interests. Some have developed policies and procedures, while others pay no attention to the issue. As is the case for clinical practice guidelines, increasing attention will need to be given to how the competing interests of contributors of evidence-based publications may influence materials, especially if they are designed for patient use.
Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD
Authors: Carballal Sabela , Maisterra Sandra , López-Serrano Antonio , Gimeno-García Antonio Z , Vera María Isabel , Marín-Garbriel José Carlos , Díaz-Tasende José , Márquez Lucía , Álvarez Marco Antonio , Hernández Luis , De Castro Luisa , Gordillo Jordi , Puig Ignasi , Vega Pablo , Bustamante-Balén Marco , Acevedo Juan , Peñas Beatriz , López-Cerón María , Ricart Elena , Cuatrecasas Miriam , Jimeno Mireya , Pellisé María
Published: September 2016

Objective

Outside clinical trials, the effectiveness of chromoendoscopy (CE) for long-standing IBD surveillance is controversial. We aimed to assess the effectiveness of CE for neoplasia detection and characterisation, in real-life.

Design

From June 2012 to 2014, patients with IBD were prospectively included in a multicentre cohort study. Each colonic segment was evaluated with white light followed by 0.4% indigo carmine CE. Specific lesions' features were recorded. Optical diagnosis was assessed. Dysplasia detection rate between expert and non-expert endoscopists and learning curve were ascertained.

Results

Ninety-four (15.7%) dysplastic (1 cancer, 5 high-grade dysplasia, 88 low-grade dysplasia) and 503 (84.3%) non-dysplastic lesions were detected in 350 patients (47% female; mean disease duration: 17 years). Colonoscopies were performed with standard definition (41.5%) or high definition (58.5%). Dysplasia miss rate with white light was 40/94 (57.4% incremental yield for CE). CE-incremental detection yield for dysplasia was comparable between standard definition and high definition (51.5% vs 52.3%, p=0.30). Dysplasia detection rate was comparable between expert and non-expert (18.5% vs 13.1%, p=0.20). No significant learning curve was observed (8.2% vs 14.2%, p=0.46). Sensitivity, specificity, and positive and negative predictive values for dysplasia optical diagnosis were 70%, 90%, 58% and 94%, respectively. Endoscopic characteristics predictive of dysplasia were: proximal location, loss of innominate lines, polypoid morphology and Kudo pit pattern III–V.

Conclusions

CE presents a high diagnostic yield for neoplasia detection, irrespectively of the technology and experience available in any centre. In vivo, CE optical diagnosis is highly accurate for ruling out dysplasia, especially in expert hands. Lesion characteristics can aid the endoscopist for in situ therapeutic decisions.

Trial registration number

NCT02543762.
The cost-effectiveness of bike lanes in New York City
Authors: Gu Jing , Mohit Babak , Muennig Peter Alexander
Published: September 2016

Background

Our objective is to evaluate the cost-effectiveness of investments in bike lanes using New York City's (NYC) fiscal year 2015 investment as a case study. We also provide a generalizable model, so that localities can estimate their return on bike lane investments.

Methods and findings

We evaluate the cost-effectiveness of bike lane construction using a two-stage model. Our regression analysis, to estimate the marginal addition of lane miles on the expansion in bike ridership, reveals that the 45.5 miles of bike lanes NYC constructed in 2015 at a cost of $8 109 511.47 may increase the probability of riding bikes by 9.32%. In the second stage, we constructed a Markov model to estimate the cost-effectiveness of bike lane construction. This model compares the status quo with the 2015 investment. We consider the reduced risk of injury and increased probability of ridership, costs associated with bike lane implementation and maintenance, and effectiveness due to physical activity and reduced pollution. We use Monte Carlo simulation and one-way sensitivity analysis to test the reliability of the base-case result. This model reveals that over the lifetime of all people in NYC, bike lane construction produces additional costs of $2.79 and gain of 0.0022 quality-adjusted life years (QALYs) per person. This results in an incremental cost-effectiveness ratio of $1297/QALY gained (95% CI −$544/QALY gained to $5038/QALY gained).

Conclusions

We conclude that investments in bicycle lanes come with an exceptionally good value because they simultaneously address multiple public health problems. Investments in bike lanes are more cost-effective than the majority of preventive approaches used today.
Motor vehicle-related deaths around two major holidays in South Korea
Authors: Sohn Kitae
Published: September 2016

South Korea has consistently exhibited high rates of motor vehicle-related deaths (MVDs) since the late 1980s. This study investigated the number of MVDs around two major public holidays in South Korea—Lunar New Year's Day and Thanksgiving Day. MVDs from records of all individual deaths in 1997–2014 were extracted; then, MVDs per day from 14 days before and after each holiday (ie, 29 days in total) were summed across the years. Eventually, the 3-day mean values of MVDs before and after the holiday were compared, when holiday-related traffic peaks. The 3-day mean before Lunar New Year's Day was 385 fatalities, but dropped to 324 after the holiday; the corresponding figures for Thanksgiving Day were 494 and 413. These results are contrary to those of other countries. It appears that the severe congestion of highway traffic around the holidays resulted in a decrease in MVDs.
Clinicopathological characteristics of oestrogen receptor negative, progesterone receptor positive breast cancers: re-evaluating subsets within this group
Authors: Ahmed Syed Salahuddin , Thike Aye Aye , Zhang Kathryn , Lim Jeffrey Chun Tatt , Tan Puay Hoon
Published: September 2016

Aims

The presence of oestrogen and progesterone receptors (ER, PR) in breast carcinoma is an important prognostic indicator as well as a predictor of likely response to hormonal treatment. Current ambiguity surrounds ER-negative (–)/PR-positive (+) breast cancer (BC) as to whether this phenotype exists as a distinct entity. The independent predictive value of PR for treatment considerations is also in question, as some investigators believe ER status to be the single most important therapeutic predictive factor in BC. We undertook this study to determine the existence of ER(–)/PR(+) BC and the prognostic effect, if any, of this phenotype.

Methods

We investigated 267 archival documented ER(–)/PR(+) BCs diagnosed between January 1994 and July 2009. Histological slides were retrieved and reviewed. Tissue microarrays were constructed by selecting two 1 mm cores of tumour per case. Repeat immunohistochemistry was performed for confirmation of the ER(–)/PR(+) status. Clinicopathological parameters including age, ethnicity, tumour size, histological grade, histological subtype, associated ductal carcinoma in situ, lymphovascular invasion and lymph node status were evaluated.

Results

On repeat immunohistochemistry, 92 tumours were confirmed as ER(–)/PR(+) BCs. This phenotype accounted for 1.1% of all BC phenotypes and exhibited different clinicopathological features and survival outcome when compared with other phenotypes. ER(–)/PR(+) tumours showed a trend for an early recurrence and poorer overall survival as compared with the patients with ER(+)/PR(+) tumours and similar to ER(–)/PR(–) tumours.

Conclusions

Our findings suggest that ER(–)/PR(+) BCs exist, although rare, with distinct pathological and clinical characteristics from patients with ER(+)/PR(+) BCs.
Tumour cell invasion into blood vessels is significantly related to breast cancer subtypes and decreased survival
Authors: Klingen Tor A , Chen Ying , Stefansson Ingunn M , Knutsvik Gøril , Collett Karin , Abrahamsen Anne L , Aase Hildegunn , Aas Hans , Aas Turid , Wik Elisabeth , Akslen Lars A
Published: September 2016

Aims

Vascular invasion in breast cancer is associated with increased risk of recurrence, metastases and death from disease. However, there are few studies discriminating between blood vessel invasion (BVI) and lymphatic vessel involvement (LVI).

Methods

A population-based series of 282 breast cancers was examined (200 screen-detected and 82 interval patients) with respect to BVI and LVI in addition to basic features and molecular subtypes, using CD31 and D2-40 antibodies. This series is part of the prospective Norwegian Breast Cancer Screening Program.

Results

The frequency of LVI and BVI was 25% and 15%, respectively. BVI was associated with HER2-positive and basal-like tumours, and several features of aggressive breast cancer, whereas LVI showed weaker associations. BVI was the strongest factor to predict interval cancer presentation. BVI showed significant associations with recurrence-free survival and disease-specific survival in univariate and multivariate analyses, whereas LVI was not significant.

Conclusions

Our findings indicate that BVI by tumour cells is strongly associated with aggressive tumour features including a basal-like phenotype, and BVI was an independent prognostic factor in contrast to what was found for LVI.
Epidemiology of positive mental health in a national census of children at school entry
Authors: Goldfeld Sharon , Kvalsvig Amanda , Incledon Emily , O'Connor Meredith
Published: September 2016

Background

Until now, child mental health promotion efforts have focused primarily on reducing the prevalence and severity of problems; yet the absence of mental health problems does not necessarily imply the presence of healthy psychosocial functioning. We aimed to investigate the epidemiology of child mental health competence in a full national population of school entrants.

Methods

The data source was the 2012 Australian Early Development Index, a national census of early childhood development completed for school entrants by teachers across Australia (n=275 800). The mental health competence outcome measure was derived from constructs that focused on children's social and emotional strengths. Children with mental health competence scores in the top quintile were compared with the standard population across individual and community characteristics.

Results

Average age at assessment was 5 years 7 months. Higher odds of mental health competence were observed for children who lived in more advantaged areas (OR 1.62; 99% CI 1.49 to 1.75), had attended preschool (1.38; 1.25 to 1.51) and demonstrated effective oral communication skills in the classroom (19.01; 15.62 to 23.13). Indigenous children had lower odds compared with non-Indigenous children (0.59; 0.54 to 0.64). Children in disadvantaged areas who attended preschool did not ‘catch up’ with their more advantaged peers.

Conclusions

Mental health competence is unequally distributed across the Australian child population at school entry and is strongly predicted by measures and correlates of disadvantage. Effective oral communication and attendance at preschool warrant further investigation as potentially modifiable factors that may support mental health competence in new school entrants.
IVF, same-sex couples and the value of biological ties
Authors: Di Nucci Ezio
Published: September 2016

Ought parents, in general, to value being biologically tied to their children? Is it important, in particular, that both parents be biologically tied to their children? I will address these fundamental questions by looking at a fairly new practice within IVF treatments, so-called IVF-with-ROPA (Reception of Oocytes from Partner), which allows lesbian couples to ‘share motherhood’, with one partner providing the eggs while the other becomes pregnant. I believe that IVF-with-ROPA is, just like other IVF treatments, morally permissible, but here I argue that the increased biological ties which IVF-with-ROPA allows for do not have any particular value beside the satisfaction of a legitimate wish, because there is no intrinsic value in a biological tie between parents and children; further, I argue that equality within parental projects cannot be achieved by redistributing biological ties.
Suicide voices: testimonies of trauma in the French workplace
Authors: Waters Sarah
Published: September 2016

Workplace suicide has become an urgent social concern internationally with rising numbers of employees choosing to kill themselves in the face of extreme pressures at work. Yet, research on this phenomenon is hampered by fragmentary statistical data and the sheer contentiousness of this issue. This paper presents the preliminary findings of a research project on workplace suicides in France, where there has been a ‘suicide epidemic’ across a wide range of companies. I draw on an analysis of suicide letters linked to 23 suicide cases across three French companies during the period 2005–2015. My methodological approach is informed by the work of suicide sociologist, Jack D Douglas, who emphasised the importance of narrative, testimony and voice to our understanding of the causes of suicide. Douglas argued that an analysis of the ‘social meanings’ of suicide should start with a consideration of the motivations attributed to self-killing by suicidal individuals themselves and those close to them. Why does work or conditions of work push some individuals to take their own lives? What can the ‘suicide voices’ articulated in recent testimonies tell us about the causes of workplace suicide? In this paper, I treat suicide letters as a unique mode of testimony that can reveal some of the profound effects of workplace transformations on subjective, intimate and lived experiences of work. By examining French suicide testimonies, my aim is to deepen our understanding of the nature and causes of suicide in today's globalised workplaces.
Is reproduction of male eastern rock sengis (Elephantulus myurus) from southern Africa affected by photoperiod?
Authors: Medger K. , Chimimba C.T. , Bennett N.C.
Published: September 2016

Many mammals use the change in day length to time physiological and behavioural activities on a seasonal basis. Particularly, mammals from temperate regions use photoperiod to regulate reproductive functions; however, information on the role of photoperiod in small mammals from the tropics and subtropics is scarce. We studied the response of the reproductive system of male eastern rock sengis (Elephantulus myurus Thomas and Schwann, 1906) from southern Africa to photoperiods of differing length. Elephantulus myurus breeds seasonally during the spring and summer months of the southern hemisphere despite its subtropical distribution. It is one of only three sengi species known to breed seasonally. Fourteen male E. myurus were subjected to either long-day (LD; 16 h light (L) : 8 h dark (D)) or short-day (SD; 8 h L : 16 h D) photoperiods and the photoperiodic effects on the testes, testosterone concentration, and body mass were examined. Testicular volume and mass, seminiferous tubule diameter, and body mass were not significantly different between LD and SD conditions. However, plasma testosterone concentration was significantly lower in males on LD photoperiods compared with SD photoperiods. Male E. myurus may not use photoperiod as a cue to control seasonal reproductive changes. Other environmental factors such as temperature, rainfall, food abundance, or social factors are possibly influencing seasonal reproduction in this species.
A new Lagerstätte from the Late Ordovician Big Hill Formation, Upper Peninsula, Michigan
Authors: Lamsdell James C. , LoDuca Steven T. , Gunderson Gerald O. , Meyer Ronald C. , Briggs Derek E. G.
Published: September 2016

A new exceptionally preserved marginal marine biota is reported from the Late Ordovician Big Hill Formation of Stonington Peninsula in Michigan's Upper Peninsula. The new Lagerstätte hosts a moderately diverse fauna of medusae, linguloid brachiopods, non-mineralized arthropods and orthocone nautiloids, alongside dasycladalean green algae. The biota is similar to those of Lagerstätten from the Late Ordovician of Canada, revealing an extensive distribution of a distinctive marginal marine palaeocommunity in Laurentia at this time. The Big Hill biota extends the geographical range of exceptionally preserved Late Ordovician faunas in Laurentia and indicates that further examples remain to be discovered.
Mesozoic orogens of the Arctic from Novaya Zemlya to Alaska
Authors: Toro J. , Miller E. L. , Prokopiev A. V. , Zhang Xiaojing , Veselovskiy R.
Published: September 2016

Mesozoic orogenic belts fringe the Alaska and eastern Russia portion of the Arctic Basin. From west to east, these include the fold belts of Novaya Zemlya, Taimyr Peninsula, northern Verkhoyansk–Kolyma, Chukotka and the Brooks Range, as well as their continuations onto the continental shelves. The Taimyr and Novaya Zemlya structures were traditionally interpreted as the continuation of the late Palaeozoic Uralian orogenic belt. This is probably correct for Taimyr, but not for Novaya Zemlya, where shortening post-dates Uralian deformation. The Mesozoic tectonic evolution of the Verkhoyansk–Kolyma, Chukotka and Brooks Range orogens relates to the accretion of numerous continental and arc terranes to the Siberian and North American margins starting in the Late Jurassic and driven by palaeo-Pacific dynamics. This history is complicated by the opening of the Amerasia Basin of the Arctic, which displaced the Arctic Alaska–Chukotka microplate from a position adjacent to Arctic Canada towards the palaeo-Pacific. Although the Chukotka fold belt and the Brooks Range both formed along the southern edge of Arctic Alaska–Chukotka, most shortening took place prior to Amerasia Basin opening. The remoteness of this region and the complexity of its geology has left numerous questions regarding its tectonic evolution unresolved, providing rich avenues for future research.
Review of velocity models in the Faroe–Shetland Channel
Authors: Petersen Uni K. , Funck Thomas
Published: September 2016

Over the last few decades, a number of wide-angle seismic experiments have been conducted in the Faroe–Shetland Channel area with the objective of mapping the crustal structure. However, the volcanic rocks covering most of the area present a challenge for the imaging of sub-basalt structures. The results of the seismic studies are consistent in describing the Faroe–Shetland Channel as thinned continental crust and in establishing the presence of sub-basalt sediments. However, the various datasets often show differences in depth to crystalline basement and to the Moho. This paper presents a review of the velocity models in the Faroe–Shetland Channel and analyses the differences at line intersections. Down to top basalt the models are fairly consistent, while there are deviations of up to 1 km s
−1
in basalt velocities and sub-basalt sediment velocities, 2 km in basalt thickness, 3.2 km in depth to crystalline basement, and 11.7 km in depth to the Moho.
Interaction between the muscle metaboreflex and the arterial baroreflex in control of arterial pressure and skeletal muscle blood flow
Authors: Kaur Jasdeep , Alvarez Alberto , Hanna Hanna W. , Krishnan Abhinav C. , Senador Danielle , Machado Tiago M. , Altamimi Yasir H. , Lovelace Abe T. , Dombrowski Maryetta D. , Spranger Marty D. , O'Leary Donal S.
Published: September 2016

The muscle metaboreflex and arterial baroreflex regulate arterial pressure through distinct mechanisms. During submaximal exercise muscle metaboreflex activation (MMA) elicits a pressor response virtually solely by increasing cardiac output (CO) while baroreceptor unloading increases mean arterial pressure (MAP) primarily through peripheral vasoconstriction. The interaction between the two reflexes when activated simultaneously has not been well established. We activated the muscle metaboreflex in chronically instrumented canines during dynamic exercise (via graded reductions in hindlimb blood flow; HLBF) followed by simultaneous baroreceptor unloading (via bilateral carotid occlusion; BCO). We hypothesized that simultaneous activation of both reflexes would result in an exacerbated pressor response owing to both an increase in CO and vasoconstriction. We observed that coactivation of muscle metaboreflex and arterial baroreflex resulted in additive interaction although the mechanisms for the pressor response were different. MMA increased MAP via increases in CO, heart rate (HR), and ventricular contractility whereas baroreflex unloading during MMA caused further increases in MAP via a large decrease in nonischemic vascular conductance (NIVC; conductance of all vascular beds except the hindlimb vasculature), indicating substantial peripheral vasoconstriction. Moreover, there was significant vasoconstriction within the ischemic muscle itself during coactivation of the two reflexes but the remaining vasculature vasoconstricted to a greater extent, thereby redirecting blood flow to the ischemic muscle. We conclude that baroreceptor unloading during MMA induces preferential peripheral vasoconstriction to improve blood flow to the ischemic active skeletal muscle.
Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling
Authors: Galan Diogo T. , Bito Virginie , Claus Piet , Holemans Patricia , Abi-Char Joëlle , Nagaraju Chandan K. , Dries Eef , Vermeulen Kristel , Ventura-Clapier Renée , Sipido Karin R. , Driesen Ronald B.
Published: September 2016

Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MIadjacent) and less so in the remote, nonischemic myocardium (MIremote). We used a pig model of chronic coronary stenosis and MI ( n = 13). Functional and perfusion MR imaging 6 wk after intervention showed reduced ejection fraction and increased global wall stress compared with sham-operated animals (Sham; n = 14). Regional strain in MIadjacent was reduced with reduced contractile reserve; in MIremote strain was also reduced but responsive to dobutamine and perfusion was normal compared with Sham. Capillary density was unchanged. Cardiac myocytes isolated from both regions had reduced basal and maximal oxygen consumption rate, as well as through complex I and II, but complex IV activity was unchanged. Reduced respiration was not associated with detectable reduction of mitochondrial density. There was no significant change in AMPK or glucose transporter expression levels, but glycogen content was significantly increased in both MIadjacent and MIremote. Glycogen accumulation was predominantly perinuclear; mitochondria in this area were smaller but only in MIadjacent where also subsarcolemmal mitochondria were smaller. In conclusion, after MI reduction of mitochondrial respiration and glycogen accumulation occur in all LV regions suggesting that reduced perfusion does not lead to additional specific changes and that increased hemodynamic load is the major driver for changes in mitochondrial function.
Human lung fibroblasts produce proresolving peroxisome proliferator-activated receptor-γ ligands in a cyclooxygenase-2-dependent manner
Authors: Lacy Shannon H. , Woeller Collynn F. , Thatcher Thomas H. , Maddipati Krishna Rao , Honn Kenneth V. , Sime Patricia J. , Phipps Richard P.
Published: September 2016

Human lung fibroblasts (HLFs) act as innate immune sentinel cells that amplify the inflammatory response to injurious stimuli. Here, we use targeted lipidomics to explore the hypothesis that HLFs also play an active role in the resolution of inflammation. We detected cyclooxygenase-2 (COX-2)-dependent production of both proinflammatory and proresolving prostaglandins (PGs) in conditioned culture medium from HLFs treated with a proinflammatory stimulus, IL-1β. Among the proresolving PGs in the HLF lipidome were several known ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor whose activation in the lung yields potent anti-inflammatory, antifibrotic, and proresolving effects. Next, we used a cell-based luciferase reporter to confirm the ability of HLF supernatants to activate PPARγ, demonstrating, for the first time, that primary HLFs activated with proinflammatory IL-1β or cigarette smoke extract produce functional PPARγ ligands; this phenomenon is temporally regulated, COX-2- and lipocalin-type PGD synthase-dependent, and enhanced by arachidonic acid supplementation. Finally, we used luciferase reporter assays to show that several of the PGs in the lipidome of activated HLFs independently activate PPARγ and/or inhibit NFκB. These results indicate that HLFs, as immune sentinels, regulate both proinflammatory and proresolving responses to injurious stimuli. This novel endogenous resolution pathway represents a new therapeutic target for globally important inflammatory diseases such as chronic obstructive pulmonary disease.
Immune and inflammatory responses to freediving calculated from leukocyte gene expression profiles
Authors: Eftedal Ingrid , Flatberg Arnar , Drvis Ivan , Dujic Zeljko
Published: September 2016

Freedivers hold their breath while diving, causing blood oxygen levels to decrease (hypoxia) while carbon dioxide increases (hypercapnia). Whereas blood gas changes are presumably involved in the progression of respiratory diseases, less is known about their effect on healthy individuals. Here we have used gene expression profiling to analyze elite athletes' immune and inflammatory responses to freediving. Blood was collected before and 1 and 3 h after a series of maximal dynamic and static freediving apneas in a pool, and peripheral blood gene expression was mapped on genome-wide microarrays. Fractions of phenotypically distinct immune cells were computed by deconvolution of the gene expression data using Cibersort software. Changes in gene activity and associated biological pathways were determined using R and GeneGo software. The results indicated a temporary increase of neutrophil granulocytes, and a decrease of cytotoxic lymphocytes; i.e., CD8+ T cells and resting NK cells. Biological pathway associations indicated possible protective reactions: genes involved in anti-inflammatory responses to proresolving lipid mediators were upregulated, whereas central factors involved in granule-mediated lymphocyte cytotoxicity were downregulated. While it remains unresolved whether freediving alters the immune system's defensive function, these results provide new insight into leukocyte responses and the protection of homeostasis in healthy athletes.
Devolución de comisiones ¿Cuánto cuesta la equidad?
Authors: Lopez Fernando , Morgado Andrés
Published: September 2016

Este estudio analiza el impacto que tendría una reforma al sistema de pensiones que obligue a las AFP a devolver las comisiones cobradas en los periodos en que los fondos que administran tengan rentabilidades negativas. Los resultados muestran que esta medida inducirá a las administradoras a implementar estrategias de inversión más conservadoras y esto reducirá el valor esperado de las pensiones futuras. El análisis muestra que mientras mayor sea el periodo considerado para calcular la rentabilidad de referencia para la devolución, menor será el impacto de esta medida. Sin embargo, incluso considerando un periodo de 5 años, los Fondos A y B se verían afectados.
Infraestructura científica-tecnológica en Chile: propuestas y desafíos
Authors: Jimenez Alejandro
Published: September 2016

La infraestructura científica es clave para sostener las capacidades de I+D de los países. Es la base para adquirir nuevas ventajas competitivas y avanzar hacia una productividad basada en la innovación. Lamentablemente, en Chile hay un déficit en infraestructura y equipamiento para el desarrollo de las ciencias experimentales. El artículo plantea priorizar las inversiones en nuevos espacios para la I+D y propone una nueva infraestructura -separada de la institucionalidad universitaria-  orientada a atender las necesidades de la industria y la generación de empresas de base científica.
Protective Role for TWEAK/Fn14 in Regulating Acute Intestinal Inflammation and Colitis-Associated Tumorigenesis
Authors: Di Martino Luca , Dave Maneesh , Menghini Paola , Xin Wei , Arseneau Kristen O. , Pizarro Theresa T. , Cominelli Fabio
Published: September 2016

Inflammatory bowel disease causes chronic, relapsing intestinal inflammation that can lead to the development of colorectal cancer. Members of the TNF superfamily are key regulators of intestinal inflammation. In particular, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, are involved in normal and pathologic intestinal tissue remodeling. In this study, we show that the TWEAK/Fn14 signaling complex plays a protective role during the acute stage of intestinal inflammation and contributes to the prevention of colitis-associated cancer during chronic inflammation through its proapoptotic effects. Colitis was induced in Fn14−/− and Fn14+/+ wild-type littermates by administering 3% dextran sodium sulfate (DSS) for 7 days followed by 2-week recovery; azoxymethane (AOM) administration followed by two cycles of DSS/recovery was used to induce tumors. Reciprocal bone marrow chimeric mice were generated to compare hematopoietic and nonhematopoietic-specific effector tissues. Fn14−/− mice had enhanced susceptibility to colitis compared with Fn14+/+ controls as assessed by endoscopic and histologic inflammatory scores, daily weight loss, and mortality rates during recovery after DSS administration. Bone marrow transfer experiments showed that both hematopoietic and nonhematopoietic components are involved in protection against colitis. Tumor lesions were found in the colons of most Fn14−/− mice, but not Fn14+/+ controls. AOM/DSS administration enhanced susceptibility to tumorigenesis in Fn14−/− mice. Overall, these findings show that Fn14 plays a protective role during the acute stages of intestinal inflammation, and its absence promotes the development of colitis-associated cancer. Cancer Res; 76(22); 6533–42. ©2016 AACR.
Agonistic CD40 mAb-Driven IL12 Reverses Resistance to Anti-PD1 in a T-cell–Rich Tumor
Authors: Ngiow Shin Foong , Young Arabella , Blake Stephen J. , Hill Geoffrey R. , Yagita Hideo , Teng Michele W. L. , Korman Alan J. , Smyth Mark J.
Published: September 2016

The durability and efficacy of anti-human PD1 monoclonal antibodies (PD1 mAb) vary across different malignancies. Although an absence of tumor-infiltrating cytotoxic T lymphocytes has been identified as a cause for resistance to PD1 mAb, the presence of intratumor exhausted PD1hi T cells also contributes to insensitivity to this immune checkpoint therapy. In this study, we used mouse tumor models of PD1 mAb resistance that harbored PD1hi T cells and flow cytometry analysis of tumor-infiltrating leukocytes immediately post-therapy as a screening platform to identify agents that could resensitize T cells to PD1 blockade. We showed that an agonistic anti-CD40 mAb converted PD1hi T cells into PD1lo T cells, reversing phenotypic T-cell exhaustion and allowing the anti-PD1 refractory tumors to respond to anti-PD1 therapy. PD1 downmodulation by anti-CD40 mAb relied upon IL12 but not IL23, CD80/CD86/CD28, or CD70/CD27. Consistent with a role for regulatory T cells (Treg) in promoting T-cell exhaustion, we also showed that intratumor Treg presented with a less activated and attenuated suppressive phenotype, marked by reductions in CTLA4 and PD1. Similar to anti-CD40 mAb, anti-CTLA4 mAb also lowered intratumor T-cell PD1 expression. Our study provides a proof-of-principle framework to systematically identify immune conditioning agents able to convert PD1hi T cells to PD1lo T cells, with clinical implications in the management of anti-PD1 refractory patients. Cancer Res; 76(21); 6266–77. ©2016 AACR.
Age‐Dependent Predictive Value of Endothelial Dysfunction for Arrhythmia Recurrence Following Pulmonary Vein Isolation
Authors: Matsuzawa Yasushi , Suleiman Mahmoud , Guddeti Raviteja R. , Kwon Taek‐Geun , Monahan Kristi H. , Lerman Lilach O. , Friedman Paul A. , Lerman Amir
Published: September 2016

Background

The mechanisms of atrial fibrillation (AF) are highly divergent. The prevalence of AF increases significantly with age, and underling mechanisms might vary with age. Endothelial dysfunction may be associated with AF and atrial arrhythmia recurrence after catheter ablation. We tested the hypothesis that the impact of endothelial dysfunction on arrhythmia recurrence following catheter ablation is age dependent.

Methods and Results

This study enrolled 92 participants with AF undergoing catheter ablation. Endothelial function was assessed by peripheral arterial tonometry before ablation, and the natural logarithmic transformation of reactive hyperemia index was calculated. Endothelial dysfunction was defined as a natural logarithmic transformation of reactive hyperemia index <0.618 (median). Participants were followed for atrial tachycardia, flutter, and fibrillation recurrence for a median of 14 months. The mean age was 57±10 years. There was significant interaction between age and endothelial dysfunction in association with recurrence of AF (
P
=0.029) and any atrial arrhythmia (
P
=0.015), and the risk associated with endothelial dysfunction for arrhythmia recurrence was higher in younger versus older participants. Participants were divided into 2 age groups at a threshold of 60 years. Among participants aged ≤60 years, multivariate Cox proportional hazards analysis revealed the independent association between endothelial dysfunction and increased risk of arrhythmia recurrence (hazard ratio for AF 4.18 [95% CI 1.33–15.82],
P
=0.014, and for any atrial arrhythmia 3.62 [95% CI 1.29–11.81],
P
=0.014). Kaplan–Meier analysis showed that participants with endothelial dysfunction had significantly higher rates of recurrence of AF (
P
=0.01) and any atrial arrhythmia (
P
=0.002).

Conclusions

The risk associated with endothelial dysfunction for arrhythmia recurrence following catheter ablation was age dependent and was higher in younger participants.
Relation of Body Mass Index With Adverse Outcomes Among Patients With Atrial Fibrillation: A Meta‐Analysis and Systematic Review
Authors: Zhu Wengen , Wan Rong , Liu Fuwei , Hu Jinzhu , Huang Lin , Li Juxiang , Hong Kui
Published: September 2016

Background

Several studies have investigated the impact of body mass index (BMI) on the prognosis of atrial fibrillation, but the results remain controversial. We sought to estimate the association of
BMI
with atrial fibrillation–related outcomes.

Methods and Results

We systematically searched the Cochrane Library, PubMed, and Elsevier databases for all studies reporting associations between
BMI
and atrial fibrillation–related outcomes. Relative risks (
RR
s) and 95% CIs were extracted and pooled. Nine studies with 49 364 participants were included. Underweight BMI was associated with an increased risk of stroke or systemic embolism (
RR
1.67, 95% CI 1.12–2.49), all‐cause mortaliity (
RR
2.61, 95% CI 2.21–3.09), and cardiovascular death (
RR
2.49, 95% CI 1.38–4.50). Nevertheless, the pooled
RR
s of overweight and obese patients were lower than those of normal‐weight patients for stroke or systemic embolism (overweight:
RR
0.91, 95% CI 0.80–1.04; obese: RR 0.84, 95% CI 0.72–0.98; grade 1 obesity: RR 0.89, 95% CI 0.71–1.11; grade 2 obesity: RR 0.64, 95% CI 0.45–0.91; grade 3 obesity: RR 0.82, 95% CI 0.54–1.25), all‐cause death (overweight:
RR
0.78, 95% CI 0.62–0.96; obese: RR 0.84, 95% CI 0.64–1.10; grade 1 obesity: RR 0.64, 95% CI 0.57–0.73; grade 2 obesity: RR 0.70, 95% CI 0.47–1.03; grade 3 obesity: RR 0.72, 95% CI 0.59–0.88), and cardiovascular death (overweight:
RR
0.79, 95% CI 0.58–1.08; obese: RR 0.99, 95% CI 0.79–1.24).

Conclusions

Underweight BMI is associated with an increased risk of stroke or systemic embolism, cardiovascular death, and all‐cause death in Asian patients with atrial fibrillation, whereas in all atrial fibrillation patients, overweight and obese BMI was not associated with increased risks of these outcomes.
A New Join of Two Fragments of 4QcryptA Serekh haEdah and Its Implications
Authors: Gayer Asaf , Stökl Ben Ezra Daniel , Ben-Dov Jonathan
Published: September 2016

Two cryptic A fragments of Serekh haEdah from cave 4 are hereby physically joined, and a third one constitutes a distant join. The composite text parallels 1QSa 1: 8–12 albeit with significant variants. The join is proven here in terms of the continuity of papyrus fibers and partial letters, as well as by the coherent composite text. The join requires separating a fragment that had been assembled by Milik. Substantially, although the joined fragments had been assigned in djd 36 to different copies, they evidently constitute one and the same fragment. This join thus calls into question the classification of 8–9 different copies of the Serekh in cryptic script.
Stray Remarks on the Tobit Fragments
Authors: Stadel Christian
Published: September 2016

This paper discusses the rhetorical functions of quotative frames in the dialogue between Tobiah and Edna (4Q197 4 iii 3–8, Tob 7:1–5) and of Hebrew loan words in the Aramaic Tobit fragments and suggests a new explanation for the puzzling קשיטא in 4Q197 4 iii 2 (Tob 7:1), which might be a mistranslation of a Hebrew original.
ואל תמחולהי ביד שחפא: ‪4Q541, Frag. 24 Again
Authors: Yuditsky Alexey (Eliyahu) , Ariel Chanan
Published: September 2016

This article deals with the puzzling fragment 24 in scroll 4Q541 for which many explanations have been proposed. A fresh examination of the text itself and a comparison to fragment 2ii+3+4i in the same scroll suggests that the topic of the fragment is a dove which seeks asylum from birds of prey. This examination also contributes to understanding some linguistic issues. In light of the semantic field of the verbs meaning ‘physical departure’, ‘forgiveness’ and ‘relinquishing a debt’ we learn about the development of the root מח״ל to the sense ‘to give over into the hands of’. In addition, the morphological form תמחולהי and the masculine form יון (a dove) are accounted for.
Strangers Come to Devour the Land: Changing Views of Foreign Migrants in Early Eighteenth-Century England
Authors: O’Reilly William
Published: September 2016

This article investigates the debates surrounding immigration to England some three hundred years ago and considers why it was that between the 1680s and the 1710s a discernible change occurred in how migrants were treated. Work on the emergence of a “British” Protestant identity and its relationship with continental Europe, on changing ideas of Englishness and on the campaign for a relaxation in rights of access to the English and colonial labor market are considered. The shift in popular and political responses to the arrival of refugees in England in 1709 provides a contrast to the charitable welcome extended to migrants a generation before and offers an opportunity to see that views of foreign migrants changed for a combination of reasons. True vocalization of “England’s first nationalist revolution” of 1688-89 came one generation later in 1709. Then, the first full pronouncement of a rhetoric of “suitability” for English society and of economic utility meant that a refugee community was denied Protestant charity, denied employment, and was directed away from England’s shores.