bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of data sources and approaches for estimation of influenza‐associated mortality in India
Authors: Narayan Venkatesh Vinayak , Iuliano Angela Danielle , Roguski Katherine , Haldar Partha , Saha Siddhartha , Sreenivas Vishnubhatla , Kant Shashi , Zodpey Sanjay , Pandav Chandrakant S. , Jain Seema , Krishnan Anand
Published: December 2017

Background

No estimates of influenza‐associated mortality exist for India.

Objective

To evaluate national mortality and viral surveillance data from India for assessing their appropriateness in estimating influenza‐associated mortality using varied analytic approaches.

Methods

We reviewed influenza virus surveillance data from a national influenza surveillance network. We also reviewed national mortality data from Civil Registration System (CRS), Medical Certification of Cause of Death (MCCD) and the Sample Registration System (SRS). We compared and scored the different sources of mortality data using specific criteria, including the process of cause of death assignment, sample size, proportion of ill‐defined deaths, representativeness and availability of time series data. Each of these 5 parameters was scored on a scale from 1 to 5. To evaluate how to generate an influenza‐associated mortality estimate for India, we also reviewed 4 methodologic approaches to assess the appropriateness of their assumptions and requirements for these data sets.

Results

The influenza virus surveillance data included year‐round sample testing for influenza virus and was found to be suitable for influenza mortality estimation modelling. Based on scoring for the 5 mortality data criteria, the SRS data had the highest score with 20 of 25 possible score, whereas MCCD and CRS scored 16 and 12, respectively. The SRS which used verbal autopsy survey methods was determined to be nationally representative and thus adequate for estimating influenza‐associated mortality. Evaluation of the modelling methods demonstrated that Poisson regression, risk difference and mortality multiplier methods could be applied to the Indian setting.

Conclusion

Despite significant challenges, it is possible to estimate influenza‐associated mortality in India.
Influenza‐associated mortality in South Africa, 2009‐2013: The importance of choices related to influenza infection proxies
Authors: Gul Desmond , Cohen Cheryl , Tempia Stefano , Newall Anthony T. , Muscatello David J.
Published: December 2017

Background

Regression modeling methods are commonly used to estimate influenza‐associated mortality using covariates such as laboratory‐confirmed influenza activity in the population as a proxy of influenza incidence.

Objective

We examined the choices of influenza proxies that can be used from influenza laboratory surveillance data and their impact on influenza‐associated mortality estimates.

Method

Semiparametric generalized additive models with a smoothing spline were applied on national mortality data from South Africa and influenza surveillance data as covariates to obtain influenza‐associated mortality estimates from respiratory causes from 2009 to 2013. Proxies examined included alternative ways of expressing influenza laboratory surveillance data such as weekly or yearly proportion or rate of positive samples, using influenza subtypes, or total influenza data and expressing the data as influenza season‐specific or across all seasons.

Result

Based on model fit, weekly proportion and influenza subtype‐specific proxy formulation provided the best fit. The choice of proxies used gave large differences to mortality estimates, but the 95% confidence interval of these estimates overlaps.

Conclusion

Regardless of proxy chosen, mortality estimates produced may be broadly consistent and not statistically significant for public health practice.
Risk factors for serious outcomes associated with influenza illness in high‐ versus low‐ and middle‐income countries: Systematic literature review and meta‐analysis
Authors: Coleman Brenda L. , Fadel Shaza A. , Fitzpatrick Tiffany , Thomas Sera‐Melisa
Published: December 2017

Aim

To determine factors associated with a serious outcome (hospital admission or severe outcome: critical care or death) and associated with illness caused by laboratory‐confirmed influenza, with a specific interest in low‐ and middle‐income countries (LMIC).

Method

Databases were searched on 11 March 2016 for reports of influenza and factors associated with mortality or morbidity in humans, with no language restrictions. Pooled risks were estimated using random‐effects models.

Results

Despite the heterogeneity of results across studies, known risk factors for serious disease were associated with both hospital admission and severe outcomes (critical care and/or death). InLMIC, but not in high income countries (HIC), pregnant women, people withHIV/AIDSand children < 5 years old (compared with older children) were at increased risk of a severe outcome. Also, although all patients with neurological conditions were at higher risk of severe outcomes than those without, children were at higher risk than adults and children who lived in aLMICwere at significantly higher risk than those living inHIC. Adults were more likely than children to suffer a severe outcome if they had diabetes or a hematologic condition, were obese or had liver disease. Asthma is a risk factor for hospital admission but not for severe outcomes.

Conclusion

Known risk factors for serious disease remain important predictors of hospital admission and severe outcomes with few differences betweenHICandLMICcountries. These differences likely reflect differences in health‐seeking behaviours and health services, but high heterogeneity between studies limits conclusions about the effect size.
Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents
Authors: Ruggeri Barbara , Macare Christine , Stopponi Serena , Jia Tianye , Carvalho Fabiana M. , Robert Gabriel , Banaschewski Tobias , Bokde Arun L.W. , Bromberg Uli , Büchel Christian , Cattrell Anna , Conrod Patricia J. , Desrivières Sylvane , Flor Herta , Frouin Vincent , Gallinat Jürgen , Garavan Hugh , Gowland Penny , Heinz Andreas , Ittermann Bernd , Martinot Jean Luc , Martinot Marie‐Laure Paillère , Nees Frauke , Papadopoulos‐Orfanos Dimitri , Paus Tomáš , Poustka Luise , Smolka Michael N. , Vetter Nora C. , Walter Henrik , Whelan Robert , Sommer Wolfgang H. , Bakalkin Georgy , Ciccocioppo Roberto , Schumann Gunter ,   the IMAGEN consortium
Published: December 2017

Background

Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome‐wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol‐use disorders.

Methods

Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen‐year‐old adolescents of the IMAGEN study. We validate our findings in marchigian sardinian (msP) alcohol‐preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity.

Results

We found that low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation. In individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of OPRL1 in the nucleus accumbens.

Conclusions

Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse.
Practitioner Review: School refusal: developments in conceptualisation and treatment since 2000
Authors: Elliott Julian G. , Place Maurice
Published: December 2017

Background

A generation has passed since the literature on the conceptualisation, assessment and treatment of school refusal was reviewed in this journal (Elliott, ). In the light of considerable gaps in the literature, identified at that time, and growing international interest, the current paper sought to identify progress subsequently made this century.

Methods

We open with discussion of continuing conceptual uncertainty as to whether school refusal should incorporate both truancy and absenteeism marked by anxiety and distress. We then consider progress in treatment, and conclude by examining prognosis and subsequent adult functioning. In selecting intervention studies for review, our primary focus has been upon RCTS, systematic reviews and meta‐analyses.

Results

The literature review indicates that, since the turn of the century, there has been little substantial advance in knowledge that can guide practitioners. Many of the issues raised in the 1999 paper, in particular, conceptual confusion over this heterogeneous condition, a dearth of rigorous RCT designs, limited knowledge of underlying mechanisms and uncertainty as to the long‐term effects of specific forms of intervention, are little clearer than before.

Conclusions

While several sound publications are available to guide intervention for school refusal, there is a continuing need for rigorous studies that can provide evidence to support individualised and tailored responses to an incapacitating problem with many causes and manifestations. While a multisystemic response to intervention approach is considered attractive, the practicalities of operating this across disparate professional borders are likely to present a long‐term challenge.
Developmental stability of general and specific factors of psychopathology from early childhood to adolescence: dynamic mutualism or p‐differentiation?
Authors: McElroy Eoin , Belsky Jay , Carragher Natacha , Fearon Pasco , Patalay Praveetha
Published: December 2017

Background

Recent research indicates that the best‐fitting structural model of psychopathology includes a general factor capturing comorbidity (p) and several more specific, orthogonal factors. Little is known about the stability of these factors, although two opposing developmental processes have been proposed: dynamic mutualism suggests that symptom‐level interaction and reinforcement may lead to a strengthening of comorbidity (p) over time, whereas p‐differentiation suggests a general vulnerability to psychopathology that gives way to increasingly distinct patterns of symptoms over time. In order to test both processes, we examine two forms of developmental stability from ages 2 to 14 years: strength (i.e., consistency in the amount of variance explained by general and specific factors) and phenotypic stability (i.e., homotypic and heterotypic continuity).

Methods

Data are from the NICHD Study of Early Child Care and Youth Development. Psychopathology symptoms were assessed nine times between ages 2 and 14 years (n = 1,253) using the Child Behavior Checklist completed by mothers. Confirmatory bifactor modeling was used to test structural models of psychopathology at each age. Consistency in strength was examined by calculating the Explained Common Variance (ECV) and phenotypic stability was investigated with cross‐lagged modeling of the general and specific factors.

Results

Bifactor models fit the data well across this developmental period. ECV values were reasonably consistent across development, with the general factor accounting for the majority of shared variance (61%–71%). Evidence of both homotypic and heterotypic continuity emerged, with most heterotypic continuity involving the general factor, as it both predicted and was predicted by specific factors.

Conclusions

A bifactor model effectively captures psychopathological comorbidity from early childhood through adolescence. The longitudinal associations between the general and specific factors provide evidence for both the hypothesized processes (dynamic mutualism and p‐differentiation) occurring through development.
Long‐term variability of sleep bruxism and psychological stress in patients with jaw‐muscle pain: Report of two longitudinal clinical cases
Authors: Muzalev K. , Visscher C. M. , Koutris M. , Lobbezoo F.
Published: December 2017

Sleep bruxism (SB) and psychological stress are commonly considered as contributing factors in the aetiology of temporomandibular disorder (TMD) pain. However, the lack of longitudinal studies and fluctuating nature of SB, psychological stress and TMD pain have led to contradictory results regarding the association between the possible aetiological factors and TMD pain. In the present study we investigated the contribution of SB and psychological stress to TMD pain in a longitudinal study of 2 clinical TMD pain cases during a 6‐week study protocol. Two female volunteers with clinically diagnosed myalgia based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) participated in the study. Questionnaires were used to record jaw‐muscle pain and psychological stress experience, and an ambulatory polysomnography technique was used to record SB intensity. Visual analysis of the data revealed that the intensity of TMD pain was not hardwired, neither with psychological stress experience nor with increased SB activity. Within the limitations of single‐patient clinical cases design, our study suggested that the presence of TMD pain cannot be explained by a simple linear model which takes psychological stress or SB into account. It also seems that psychological stress was a more important predictor factor for TMD pain than SB.
Non‐cultivated grass hosts of yellow dwarf viruses in Ethiopia and their epidemiological consequences on cultivated cereals
Authors: Bekele Berhanu , Kumari Safaa , Ahmed Seid , Fininsa Chemeda , Yusuf Abdurazak , Abraham Adane
Published: December 2017

The yellow dwarf (YD) disease complex epidemics in cultivated cereals grown in a specific period of the year mainly depend on the presence of potential reservoir alternative hosts harbouring both the viruses and the vectors over the off‐season and serve as a source of inoculum in subsequent cropping season, further spread being supported by efficient aphid vectors. As such, an extensive and intensive exploration to generate base line information on the identity and prevalence of YD viruses [barley yellow dwarf virus (BYDV)‐PAV, BYDV‐MAV and BYDV‐SGV; cereal yellow dwarf virus (CYDV)‐RPV; and maize yellow dwarf virus (MYDV)‐RMV] on wild annual and perennial grasses and forage cereals alternative hosts was conducted consecutively during 2013–2015 main‐ and short‐rainy seasons in cereals growing belts of Ethiopia. Random sampling was employed to collect the samples that were tested by the tissue blot immunoassay (TBIA) to identify the YDVs associated with the hosts using a battery of virus‐specific polyclonal antibodies. Of 13,604 samples analysed, YDVs were detected in 392 (2.9%) samples, which consisted of various wild grasses, forage cereals and three cultivated crops. YDVs were identified from at least 26 grass species and forage cereals, some of them are new records, and some are previously documented hosts. To our knowledge, this is the first report of YDV infection of Andropogon abyssinicus (FresenR.Br. ex Fresen.) (BYDV‐PAV), Avena abyssinica Hochst (BYDV‐PAV), Bromus pectinatus Thunb. (BYDV‐PAV and BYDV‐MAV), Eragrostis tef (Zuccagni) Trotter (BYDV‐PAV), Eragrostis sp. (BYDV‐PAV), Hyparrhenia anthistrioides Stapf. (BYDV‐PAV), Panicum coloratum L. (BYDV‐PAV), Polypogon monspeliensis (L.) Desf. (BYDV‐PAV), Setaria pumila (Poir.) Roem & Schult (BYDV‐PAV, BYDV‐SGV and MYDV‐RMV), Setaria australiensis (Scribn. & Merrill) Vickery (BYDV‐PAV, BYDV‐MAV and CYDV‐RPV) and Snowdenia polystachya (Fresen.) Pilg (BYDV‐PAV, BYDV‐MAV, BYDV‐SGV, CYDV‐RPV and MYDV‐RMV).
Metagenomic Investigation of Idiopathic Meningoencephalomyelitis in Dogs
Authors: Hoon‐Hanks L.L. , McGrath S. , Tyler K.L. , Owen C. , Stenglein M.D.
Published: December 2017

Background

Meningoencephalomyelitis of unknown origin (MUO) is a common and life‐threatening neuroinflammatory disease in dogs. Features of the disease are suggestive of an underlying immune‐mediated process, but the association of this disease with a pathogen is still unknown.

Hypothesis/Objectives

To search for candidate etiologic agent associated with cases if MUO using next generation metagenomic sequencing.

Animals

Twenty‐two dogs diagnosed with either MUO (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with MUO (11/22; 11 CSF and 2 brain) that served as negative controls.

Methods

A case control study was performed by identifying MUO and non‐MUO cases. Samples were blindly processed and then unblinded for comparative analyses. Inclusion criteria for MUO cases included consistent MRI lesions and inflammatory CSF with a negative PCR panel for infectious agents or histopathologic diagnosis. Dogs with glucocorticoid therapy within 2 weeks of sample collection were excluded. Fresh‐frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA and DNA were extracted separately for shotgun metagenomic sequencing. Known positive samples were used as controls to validate our sequencing and analysis pipelines and to establish limits of detection. Sequencing results were analyzed at a nucleotide and protein level for broad comparison to known infectious organisms.

Results

No candidate etiologic agents were identified in dogs with MUO.

Conclusions and Clinical Importance

These results support but do not prove the hypothesis that MUO is not associated with infectious agents and might be an autoimmune disease.
Geographic variation in life‐history traits: factors shaping energy investment in reproduction in a highland dwelling rodent
Authors: Sassi P. L. , Menéndez J. , Cuevas M. F.
Published: December 2017

Variation in life‐history traits is shaped by intrinsic and extrinsic factors. Climate influences the availability of energy and nutrients in the environment, and thus animals’ energy balance, their allocation of resources to reproduction and ultimately, fitness. Temperature is reported as a prevailing influence on animals’ investment in reproduction, and diverse hypotheses propose mechanisms by which it occurs. Central and external limits to energy acquisition have been traditionally assumed. Hence, digestive limitations, periods of low food availability or demanding cold conditions would restrict this input. However, under warm conditions endotherms also face the need to dissipate heat from metabolic processes. From this perspective, a high metabolic rate process, such as lactation, would be restricted under increasing ambient temperatures (Ta). Our research addresses the variation in reproductive parameters in Phyllotis xanthopygus, a rodent species broadly distributed in the west highlands and southern parts of South America. Across a pronounced elevation gradient in the central Andes Mountains we found that litter size is comparatively smaller in pregnant females collected at lower elevations. This is congruent with expectations from the heat dissipation limit hypothesis. To disentangle the role of temperature on this pattern, we bred individuals under two thermal treatments. We recorded no changes in the litter size, but pups’ body mass was lower at higher Ta during lactation, also in agreement with decreased metabolism. Offspring size and number are relevant to a species’ fitness. The evidence suggests that in P. xanthopygus these traits vary geographically and are shaped by Ta in the laboratory. A species that evolved in high altitudes, inhabits cold and temperate areas and is sensitive to Ta increases in the laboratory, appears as an excellent candidate to further explore the ecophysiology‐thermal landscape interface, crucial to develop accurate predictive models of biodiversity dynamics.
Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft‐versus‐host disease: A pilot study
Authors: Motta ACF , Zhan Q , Larson A , Lerman M , Woo S‐B , Soiffer RJ , Murphy GF , Treister NS
Published: December 2017

Objective

To characterize the immunohistopathological features of oral chronic graft‐versus‐host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells.

Material and Methods

Paired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c‐kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5).

Results

Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+, CD4+, CD8+, CD103+, CD163+, and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells.

Conclusion

The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T‐cell‐driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.
Breastmilk cell trafficking induces microchimerism‐mediated immune system maturation in the infant
Authors: Molès Jean‐Pierre , Tuaillon Edouard , Kankasa Chipepo , Bedin Anne‐Sophie , Nagot Nicolas , Marchant Arnaud , McDermid Joann M. , Van de Perre Philippe
Published: December 2017

Initiating breastfeeding within the first hour of life confers an important benefit in terms of child mortality and severe morbidity. Intestinal permeability to ingested macromolecules and immunoglobulins is limited to the first days of human life. These exchanges cease in the very early post‐partum period but may increase beyond the neonatal period in response to local inflammation or introduction of a weaning food. From animal‐ and limited human‐based observations, compelling evidence points out to breastmilk cells also trafficking from mother to infant mucosal tissues and participating to the maternal microchimerism. The precise nature of breastmilk cells that are involved is presently not known but likely includes progenitor/stem cells—representing up to 6% of breastmilk cells—with possible contribution of mature immune cells. Stem cell microchimerism may induce tolerance to non‐inherited maternal antigens (NIMAs), breastfeeding generating regulatory T cells (Treg) that suppress antimaternal immunity. Therefore, in complement to pregnancy‐induced microchimerism, breastfeeding‐induced microchimerism may be pivotal in infant immune development, intestinal tissue repair/growth and protection against infectious diseases. As a continuum of the gestational period, the neonatal gut may be considered as a temporary, but important developmental extension of the role played by the placenta during intrauterine life; breastmilk playing the role of maternal blood by delivering maternal soluble factors (macromolecules, Ig, cytokines) and immunologically active milk cells. A better understanding of breastfeeding‐induced maternal microchimerism would provide further evidence in support of public health messages that reinforce the importance of early initiation of breastfeeding.
Patient self‐care of periodontal pocket infections
Authors: Arweiler Nicole Birgit , Auschill Thorsten M. , Sculean Anton
Published: December 2017

Treatment of periodontitis aims to control the infection caused by the periodontal pathogenic flora and includes mechanical debridement of root surfaces to disrupt the supragingival and subgingival biofilm. As periodontal pockets of ≤ 5 mm can be perform in a stable condition and may not need additional therapy, the ability and the willingness of the patient to perform good oral hygiene on a long‐term basis are of utmost importance for ensuring long‐term success of periodontal treatment. In this context, the aim of all home‐care measures must be the optimal control of plaque biofilm in order to prevent or treat gingival inflammation as a primary stage of periodontitis. Despite the fact that toothbrushing and other mechanical cleaning practices are the most important elements for preventing periodontal diseases or their progression, other factors, including education, motivation, manual dexterity and compliance with professional recommendation, provision of time and socio‐economic status, as well as risk factors, play a role. The present article provides an overview on the various possibilities for self‐care of residual pockets in patients with periodontitis.
Symmetry-breaking inelastic wave-mixing atomic magnetometry
Authors: Zhou Feng , Zhu Chengjie J. , Hagley Edward W. , Deng Lu
Published: December 2017

Novel atomic magnetometry technology may lead to high sensitivity, room temperature chip-size magnetic probes.
Metal-organic frameworks and their derived materials for electrochemical energy storage and conversion: Promises and challenges
Authors: Wu Hao Bin , Lou Xiong Wen (David)
Published: December 2017

Metal-organic frameworks and their derived materials are highly interesting for electrochemical energy storage and conversion.
Bilateral ocular surface squamous neoplasia with bilateral periocular basal cell carcinoma in a case of xeroderma pigmentosum
Authors: Agarwal Rohit , Chawla Bhavna , Asif Mohamed Ibrahime , Pujari Amar
Published: December 2017

Xeroderma pigmentosum (XP) is an autosomal recessive disorder associated with multiple oculocutaneous manifestations.We discuss a unique case of XP having bilateral ocular surface squamous neoplasia (OSSN) and periocular basal cell carcinoma. In the right eye, a large OSSN mass involving the ocular surface extensively along with intraocular invasion was noted, whereas in the left eye, the tumour mass was involving the limbus, and extending up to three clock hours. Because of extensive disease in the right eye, orbital exenteration was performed, and for the left eye, a wide excision of the mass with triple freeze thaw cryo application to the margins followed by amniotic membrane grafting was done. Basal cell carcinoma was noted around the medial canthus on both sides. The right-sided basal cell carcinoma was treated by wide excision followed by a forehead rotation flap and the left-sided lesion was managed with topical 5% imiquimod cream.
Choriocapillaris flow deficit in Bietti crystalline dystrophy detected using optical coherence tomography angiography
Authors: Miyata Manabu , Oishi Akio , Hasegawa Tomoko , Ishihara Kenji , Oishi Maho , Ogino Ken , Sugahara Masako , Hirashima Takako , Hata Masayuki , Yoshikawa Munemitsu , Tsujikawa Akitaka
Published: December 2017

Background/Aims

This study aimed to evaluate blood flow in the choriocapillaris in patients with Bietti crystalline dystrophy (BCD) with CYP4V2 mutations using optical coherence tomography angiography (OCTA), and to explore the parameters associated with visual function.

Methods

This prospective case-series study included 13 eyes of 13 consecutive patients with BCD with CYP4V2 mutations and 20 healthy eyes. Using OCTA, we obtained en face images of blood flow in the choriocapillaris. The residual choriocapillaris area on en face images in a 10°×10° macular cube was manually measured and graded according to whether the choriocapillaris remained at the subfovea. We also investigated factors associated with visual acuity (VA) and the mean deviation (MD) value using a Humphrey field analyser with a 10–2 Swedish Interactive Threshold Algorithm standard program among OCTA-derived parameters.

Results

Choriocapillaris blood flow deficit was observed in 12 eyes (92%), whereas this was observed in none of healthy eyes. The adjusted residual choriocapillaris area was 2.47±1.79 mm2. The presence of the choriocapillaris at the subfovea was significantly correlated with VA and the MD value (P=0.006, r=0.71; P=0.04, r=−0.59, respectively).

Conclusions

Using OCTA, choriocapillaris blood flow deficit could be observed in most patients with BCD with CYP4V2 mutations. The presence of the choriocapillaris at the subfovea was significantly correlated with visual function in these patients. Analysis of choriocapillaris blood flow using OCTA allows non-invasive assessment of the patient’s state.
Prehospital intravenous access for survival from out-of-hospital cardiac arrest: propensity score matched analyses from a population-based cohort study in Osaka, Japan
Authors: Fujii Tomoko , Kitamura Tetsuhisa , Kajino Kentaro , Kiyohara Kosuke , Nishiyama Chika , Nishiuchi Tatsuya , Hayashi Yasuyuki , Kawamura Takashi , Iwami Taku
Published: December 2017

Objectives

Prehospital intravenous access is a common intervention for patients with out-of-hospital cardiac arrest (OHCA). We aimed to assess the effectiveness of prehospital intravenous access and subsequent epinephrine administration on outcomes among OHCA patients.

Methods

We conducted a prospective cohort study of patients with OHCA from non-traumatic causes aged ≥18 years in Osaka, Japan from January 2005 through December 2012. The primary outcome was 1-month survival with favourable neurological outcome defined as a cerebral performance category of 1 or 2. The association between intravenous line placement and survival with favourable neurological outcome was evaluated by logistic regression, after propensity score matching for the intravenous access attempt stratified by initial documented rhythm of ventricular fibrillation (VF) or non-VF. The contribution of epinephrine administration to the outcome was also explored.

Results

Among OHCA patients during the study period, 3208 VF patients and 38 175 non-VF patients were included in our analysis. Intravenous access attempt was negatively associated with 1-month survival with a favourable neurological outcome in VF group (OR 0.76, 95% CI 0.59 to 0.98), while no association was observed in the non-VF group (OR 1.06, 95% CI 0.84 to 1.34). Epinephrine administration had no positive association in the VF patients (OR 0.75, 95% CI 0.51 to 1.07) and positively associated in the non-VF patients (OR 1.52, 95% CI 1.08 to 2.08) with the favourable neurological outcome.

Conclusions

Intravenous access attempt could be negatively associated with survival with a favourable neurological outcome after OHCA. Subsequent epinephrine administration might be effective for non-VF OHCAs.
Measurement of harms in community care: a qualitative study of use of the NHS Safety Thermometer
Authors: Brewster Liz , Tarrant Carolyn , Willars Janet , Armstrong Natalie
Published: December 2017

Objectives

Measurement is a vital part of improvement work. While it is known that the context of improvement work influences its success, less is known about how context affects measurement of underlying harms. We sought to explore the use of a harm measurement tool, the NHS Safety Thermometer (NHS-ST), designed for use across diverse healthcare settings in the particular context of community care.

Methods

This is a qualitative study of 19 National Health Service (NHS) organisations, 7 of which had community service provision. We conducted ethnographic observations of practice and interviews with front-line nursing and senior staff. Analysis was based on the constant comparison method.

Results

Measurement in community settings presents distinct challenges, calling into question the extent to which measures can be easily transferred. The NHS-ST was seen as more appropriate for acute care, not least because community nurses did not have the same access to information. Data collection requirements were in tension with maintaining a relationship of trust with patients. The aim to collect data across care settings acted to undermine perceptions of the representativeness of community data. Although the tool was designed to measure preventable harms, care providers questioned their preventability within a community setting. Different harms were seen as priorities for measurement and improvement within community settings.

Conclusions

Measurement tools are experienced by healthcare staff as socially situated. In the community setting, there are distinct challenges to improving care quality not experienced in the acute sector. Strategies to measure harms, and use of any resulting data for improvement work, need to be cognisant of the complexity of an environment where healthcare staff often have little opportunity to monitor and influence patients.
Suramin increases cartilage proteoglycan accumulation in vitro and protects against joint damage triggered by papain injection in mouse knees in vivo
Authors: Guns Laura-An , Monteagudo Silvia , Kvasnytsia Maryna , Kerckhofs Greet , Vandooren Jennifer , Opdenakker Ghislain , Lories Rik J , Cailotto Frederic
Published: December 2017

Objectives

Suramin is an old drug used for the treatment of African sleeping sickness. We investigated therapeutic repositioning of suramin to protect against cartilage damage, as suramin may interact with tissue inhibitor of metalloproteinase-3 (TIMP3).

Methods

In vitro extracellular matrix (ECM) accumulation and turnover in the presence or absence of suramin were studied in the ATDC5 micromass model of chondrogenesis and in pellet cultures of human articular chondrocytes from osteoarthritis and control patients, by gene expression, protein analysis, colorimetric staining, immunoprecipitation, fluorimetric analysis and immunohistochemistry. To study suramin in vivo, the drug was injected intra-articularly in the papain model of joint damage. Disease severity was analysed by histology, immunohistochemistry and contrast-enhanced nanofocus CT.

Results

In ATDC5 micromasses, suramin increased TIMP3 levels and decreased the activity of matrix metalloproteinases (MMPs) and aggrecanases. Suramin treatment resulted in increased glycosaminoglycans. This effect on the ECM was blocked by an anti-TIMP3 antibody. Direct interaction between suramin and endogenous TIMP3 was demonstrated in immunoprecipitates. Mice treated intra-articularly with suramin injections showed reduced cartilage damage compared with controls, with increased TIMP3 and decreased MMP and aggrecanase activity. Translational validation in human chondrocytes confirmed increased TIMP3 function and reduced cartilage breakdown after suramin treatment.

Conclusion

Suramin prevented loss of articular cartilage in a mouse model of cartilage damage. The effects appear to be mediated by a functional increase of TIMP3 and a subsequent decrease in the activity of catabolic enzymes. Thus, suramin repositioning could be considered to prevent progressive cartilage damage and avoid evolution toward osteoarthritis.
Whey protein concentrate supplementation protects rat brain against aging-induced oxidative stress and neurodegeneration
Authors: Garg Geetika , Singh Sandeep , Singh Abhishek Kumar , Rizvi Syed Ibrahim
Published: December 2017

Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids and is consumed as a functional food, incorporating a wide range of nutritional attributes. The purpose of this study is to evaluate the neuroprotective effect of WPC on rat brain during aging. Young (4 months) and old (24 months) male Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days. Biomarkers of oxidative stress and antioxidant capacity in terms of ferric reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T-SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and acetylcholinesterase (AChE) activity were measured in brain of control and experimental (WPC supplemented) groups. In addition, gene expression and histopathological studies were also performed. The results indicate that WPC augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old control. Furthermore, WPC-treated groups exhibited significant reduction in LHP, PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)-1β, IL-6), and upregulated the expression of marker genes associated with autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase, Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional nutritional food supplement that prevents the progression of age-related oxidative damage in Wistar rats.
Assessing the sensitivity of data-limited methods (DLMs) to the estimation of life-history parameters from length–frequency data
Authors: Sun Ming , Zhang Chongliang , Chen Yong , Xu Binduo , Xue Ying , Ren Yiping
Published: December 2017

Data-limited methods (DLMs) in stock assessment may provide potential critical information for data-limited stock management. However, the sensitivity of those methods to life-history parameters is largely unknown, resulting in extra uncertainty and consequent risks. In the present study, we designed six parallel workflows (WFs) to incorporate classic and state-of-the-art methods of estimating life-history parameters and examined their influences on the assessment of small yellow croaker (Larimichthys polyactis) in Haizhou Bay, China. The sensitivity was evaluated with three objectives: (i) the evaluation of stock status with the spawning potential ratio following different assumptions; (ii) the length-based harvest control rules derived from three management procedures; and (iii) the management performance of these harvest control rules with simulation of management strategy evaluation. The results showed considerable sensitivity regarding the three objectives to the estimations with different WFs, indicating the previous practice of credulously accepting empirical values and indiscriminately selecting references are inadvisable. We also identified the most appropriate WFs used for different purposes with limited data, aiming to provide more reliable inputs for effective fisheries management.
The energetics of mosquito feeding by insectivorous bats
Authors: Wetzler Gabrielle C. , Boyles Justin G.
Published: December 2017

Dietary studies have long shown that insectivorous bats do not often consume mosquitoes, despite cosmopolitan distribution and occasional ubiquity of mosquitoes (Culicidae). The apparent avoidance of mosquitoes relative to availability may relate to their small size, as bats may have difficulties detecting and capturing mosquitoes or they may not return sufficient energy per unit effort of capture. We used bomb calorimetry to determine the energetic content of mosquitoes from Alaska and Illinois, USA, and compared resulting estimates to daily energy expenditure of several bat species. On a per gram basis, mosquitoes were energetically comparable with other insects (26.82 ± 2.40 kJ/g dry mass); however, an individual mosquito contains little energy. Some small insectivorous bats could theoretically meet daily energy needs by foraging exclusively on mosquitoes for <2 h, assuming maximal estimates of the rate of successful capture of mosquitoes. Larger, omnivorous bats may require >25 h of foraging on mosquitoes to meet daily energy needs. Wet mass of the mosquitoes required to balance energy budgets represent 18%–92% of body mass of bats and tends to be higher for smaller species. Thus, it appears that a mosquito-based diet may be constrained by different factors in small and large bat species.
Geological and geophysical evidence for a mafic igneous origin of the Porcupine Arch, offshore Ireland
Authors: Gagnevin Damien , Haughton Peter D. W. , Whiting Lewis , Saqab Muhammad Mudasar
Published: December 2017

Sedimentary basins west of Ireland contain a number of deep seismic structures that have been variously interpreted as fault blocks, serpentinite extrusions or igneous complexes. The Porcupine Arch (PA) is a deep-level (>11 km) domal 50 km wide seismic feature associated with a prominent free-air gravity anomaly high and high P-wave velocities. Detailed seismic mapping of igneous sill complexes in the Porcupine Basin suggests a possible connection with the PA. The sills form a thick (>5 km) interconnected network extending from the PA into the flanking post-rift Cretaceous stratigraphy, suggesting that the PA may be the top of a large (ultra)mafic intrusion that fed the sills. An intrusive origin for the PA is in agreement with geophysical modelling (gravity and
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), the seismic character of the Porcupine Arch structure and the primitive bulk composition of the Porcupine sills, and is consistent with documented regional Cenozoic uplift in the basin with the development of shallow water and the occurrence of Paleocene–Eocene deltaic depositional systems. Similar mafic–ultramafic intrusive complexes have been documented elsewhere on the northeastern Atlantic margin, including the Rockall Trough. These findings emphasize that higher heat flow in the early Cenozoic may have prevailed over the northern part of the Porcupine Basin.
Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer
Authors: Strickler John H. , Loree Jonathan M. , Ahronian Leanne G. , Parikh Aparna R. , Niedzwiecki Donna , Pereira Allan Andresson Lima , McKinney Matthew , Korn W. Michael , Atreya Chloe E. , Banks Kimberly C. , Nagy Rebecca J. , Meric-Bernstam Funda , Lanman Richard B. , Talasaz AmirAli , Tsigelny Igor F. , Corcoran Ryan B. , Kopetz Scott
Published: December 2017

“Liquid biopsy” approaches analyzing cell-free DNA (cfDNA) from the blood of patients with cancer are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cohorts of patients with cancer can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based colorectal cancer sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range, 1–13; median, 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biological insights.

Significance: This study provides one of the first examples of how large-scale genomic profiling of cfDNA from patients with colorectal cancer can detect genomic alterations at frequencies comparable to those observed by direct tumor sequencing. Sequencing of cfDNA also generated insights into tumor heterogeneity and therapeutic resistance and identified novel EGFR ectodomain mutations. Cancer Discov; 8(2); 164–73. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 127
Issues Hindering the Development of Jamaica’s Publishing Industry
Authors: Haley Alexandra
Published: December 2017

This article is an overview of the issues affecting the publishing industry in Jamaica. It examines broad concepts such as the state of the economy, national literacy, and reading culture, as well as specific issues hindering the development of Jamaican publishing and literary culture. Using a wide range of sources from UNICEF analyses to newspaper interviews, I have assembled a market picture of a slowly developing industry in a slowly developing nation.
How Do You Choose a Book for a Pre-arrival Shared Reading Scheme in a University?
Authors: Baverstock Alison , Steinitz Jackie , Bryars Laura , Sheehan Kimberley , Butler Charlotte , Williams Allison , Dalba Angelika , Brixey Dan , Conor Adam , Higgins Ciara , Waddington Elle
Published: December 2017

This paper continues the exploration of Kingston University’s pre-arrival shared reading scheme, the Kingston University Big Read (KUBR), this time considering action research into how best to choose a common book. After a review of methods used to choose books both specifically in American universities and generally within large shared reading groups, the method used for the KUBR is described. A key objective of the KUBR is to promote inclusion, so the longlist of titles considered was produced by inviting the entire community to submit suggestions. Since the list was extensive, time to make a choice was short, and there was a strong desire for the methodology to be as objective as possible, it was decided to identify the key criteria relevant to choosing a suitable book and then use a simple algorithm—essentially a weighted scoring system—to score each book using readily available data in order to make a shortlist of six books. These were then read by a panel of students and administrative and academic staff. The book finally chosen was Matt Haig’s The Humans. This paper details each step of the method and finishes with an appraisal and lessons learnt for next time.
Exemptions for Religion or Conscience under the Canopy of the Rule of Law
Authors: Ahdar Rex
Published: December 2017

This essay endeavours to restate the case for the right to freedom of conscience and religion. Specifically, it seeks to make the case for exemptions from the law of the land for religious believers and similarly-situated citizens who hold sincere conscientious beliefs. The rule of law is not something to be ignored, and carving out exemptions for conscience has been criticized as unfair, anomalous, potentially open-ended in scope, and difficult to administer. I attempt to assuage these legitimate concerns by underscoring the importance of the dignity of the individual and the virtue of protecting religious minorities (and dissenters of all stripes), who challenge the conventions of the day. If the default position is the rule of law, believers face an uphill task. Ultimately, only a truly liberal polity can offer protection to what, in every age, is a fragile liberty.
Rule of Law, Religious Liberty, and Harmony
Authors: Thio Li-ann
Published: December 2017

This article examines the state of regulation of religion within Singapore, which is the world’s most religiously diverse country. It considers how fundamental principles of the rule of law, religious liberty and legal pluralism operate within the constitutional order predicated on communitarianism and accommodative secularism. While the rule of law seeks to vindicate a range of values which requires sameness and satisfies claims for inclusion, limits to it through exemptions and accommodative measures that multiculturalism and pluralism may prescribe can protect differences and satisfy claims to be left alone, outside the sphere of state govenance. Drawing from Singapore case law, legislation and executive policy, it interrogates the question of whether a policy of multicultural and legal pluralism protective of religious freedom can be reconciled with the rule of law, which in this context is closely associated with the quasi constitutional objective of preserving racial and religious harmony.