bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of the anti‐glutamic acid decarboxylase antibody in type 1 diabetes mellitus: Comparison between radioimmunoassay and enzyme‐linked immunosorbent assay
Authors: Murata Takashi , Tsuzaki Kokoro , Nirengi Shinsuke , Watanabe Tomokazu , Mizutani Yukako , Okada Hayami , Tsukamoto Masami , Odori Shinji , Nakagawachi Reiko , Kawaguchi Yaeko , Yoshioka Fumi , Yamada Kazunori , Shimatsu Akira , Kotani Kazuhiko , Satoh‐Asahara Noriko , Sakane Naoki
Published: November 2016

Aims/Introduction

The distributer of the anti‐glutamic acid decarboxylase antibody assay kit using radioimmunoassay (RIA) recently announced its discontinuation, and proposed an alternative kit using enzyme‐linked immunosorbent assay (ELISA). The aim of the present study was to investigate the diagnostic values of the anti‐glutamic acid decarboxylase antibody by RIA and ELISA among type 1 diabetes mellitus patients and control participants.

Materials and Methods

A total of 79 type 1 diabetes mellitus patients and 79 age‐matched controls were enrolled and assessed using RIA and ELISA. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for cut‐off values (RIA = 1.5 U/mL and ELISA = 5.0 U/mL, respectively). Kappa coefficients were used to test for agreements between the RIA and ELISA methods regarding the diagnosis of type 1 diabetes mellitus.

Results

The sensitivity, specificity, positive predictive values, and negative predictive values for diagnosing type 1 diabetes mellitus were 57.0, 97.5, 95.7, and 69.4% by RIA, and 60.8, 100.0, 100.0 and 71.8% by ELISA, respectively. The diagnosis of type 1 diabetes mellitus using the RIA and ELISA methods showed substantial agreement with the kappa values of 0.74 for all participants, and of 0.64 for the acute type; however, there was moderate agreement with the kappa value of 0.56 for the slowly progressive type.

Conclusions

The present study suggests that both anti‐glutamic acid decarboxylase antibody by RIA and ELISA was useful for diagnosing type 1 diabetes mellitus. However, in the slowly progressive type, the degree of agreement of these two kits was poorer compared with those in all participants or in the acute type.
Insulin resistance and the risk of hepatocellular carcinoma in chronic hepatitis B patients
Authors: Kim Jung Hee , Sinn Dong Hyun , Gwak Geum‐Youn , Kang Wonseok , Paik Yong‐Han , Choi Moon Seok , Lee Joon Hyeok , Koh Kwang Cheol , Paik Seung Woon
Published: November 2016

Background and Aim

We analyzed whether insulin resistance (IR) assessed by homeostasis model assessment (HOMA2‐IR) index can stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B virus (HBV) infection.

Methods

A retrospective cohort of 1696 chronic HBV‐infected patients (age: 50.0 ± 7.8 years, men = 964 [56.8%]) who underwent detailed health checkup program including C‐peptide and fasting blood glucose measurement and followed up for more than a year were analyzed.

Results

During a median follow‐up of 5.0 years (range, 1.0–10.5 years), 24 patients (1.4%) developed HCC. The HCC incidence rate was higher for patients with higher HOMA2‐IR value than those with lower HOMA2‐IR value (1.7% vs 0.5% for HOMA2‐IR >1.200 vs ≤1.200, P = 0.009). HOMA2‐IR was a significant factor associated with HCC development in multivariable‐adjusted model (HR [95% CI]: 3.25 [1.13–9.31], adjusted for age, sex, cirrhosis, and HBV DNA levels). The association between HOMA2‐IR and HCC was markedly attenuated and became no longer statistically significant (HR [95% CI]: 1.93 [0.57–6.51]) when further adjusted for obesity, hypertension, and diabetes. In subgroup analysis, HOMA2‐IR value was an independent factor associated with HCC in patients without overt metabolic abnormalities (hypertension, diabetes, and metabolic syndrome) but not for those with overt metabolic abnormalities.

Conclusion

Insulin resistance assessed by HOMA2 was associated with the risk of HCC, indicating that HOMA2‐IR can be a useful tool for stratifying the risk of HCC in chronic HBV‐infected patients, particularly in patients without overt metabolic abnormalities.
OPA1 haploinsufficiency induces a BNIP3‐dependent decrease in mitophagy in neurons: relevance to Dominant Optic Atrophy
Authors: Moulis Manon F , Millet Aurélie M , Daloyau Marlène , Miquel Marie‐Christine , Ronsin Brice , Wissinger Bernd , Arnauné‐Pelloquin Laetitia , Belenguer Pascale
Published: November 2016

Dominant optic atrophy (DOA) is because of mutations in the mitochondrial protein OPA1. The disease principally affects retinal ganglion cells, whose axons degenerate leading to vision impairments, and sometimes other neuronal phenotypes. The exact mechanisms underlying DOA pathogenesis are not known. We previously demonstrated that the main role of OPA1, as a mitochondrial fusogenic and anti‐apoptotic protein, are inhibited by interaction with the stress inducible pro‐apoptotic BNIP3 protein. Because BNIP3 was recently reported to participate in autophagy and mitophagy, we tested the involvement of these processes in DOA pathogenesis. Using an in vitro neuronal model of DOA, we identified a BNIP3 down‐regulation that reduced autophagy and mitophagy. Restoring BNIP3 had a biphasic effect, first rescuing autophagy and mitophagy levels but later leading to cell death. Similarly, in an in vivo mouse model of DOA, we showed that BNIP3 levels are decreased in young adult mice and increase to normal levels upon aging, paralleling disease progression. Altogether, our results indicate that the relationship between OPA1 and BNIP3 may have important bearings on DOA pathogenesis.

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Structural and functional characteristics of the thoracolumbar multifidus muscle in horses
Authors: García Liñeiro J. A. , Graziotti G. H. , Rodríguez Menéndez J. M. , Ríos C. M. , Affricano N. O. , Victorica C. L.
Published: November 2016

The multifidus muscle fascicles of horses attach to vertebral spinous processes after crossing between one to six metameres. The fascicles within one or two metameres are difficult to distinguish in horses. A vertebral motion segment is anatomically formed by two adjacent vertebrae and the interposed soft tissue structures, and excessive mobility of a vertebral motion segment frequently causes osteoarthropathies in sport horses. The importance of the equine multifidus muscle as a vertebral motion segment stabilizer has been demonstrated; however, there is scant documentation of the structure and function of this muscle. By studying six sport horses postmortem, the normalized muscle fibre lengths of the the multifidus muscle attached to the thoracic (T)4, T9, T12, T17 and lumbar (L)3 vertebral motion segments were determined and the relative areas occupied by fibre types I, IIA and IIX were measured in the same muscles after immunohistochemical typying. The values for the normalized muscle fibre lengths and the relative areas were analysed as completely randomized blocks using an anova (P ≤ 0.05). The vertebral motion segments of the T4 vertebra include multifidus bundles extending between two and eight metameres; the vertebral motion segments of the T9, T12, T17 and L3 vertebrae contain fascicles extending between two and four metameres The muscle fibres with high normalized lengths that insert into the T4 (three and eight metameres) vertebral motion segment tend to have smaller physiological cross‐sectional areas, indicating their diminished capacity to generate isometric force. In contrast, the significantly decreased normalized muscle fibre lengths and the increased physiological cross‐sectional areas of the fascicles of three metameres with insertions on T9, T17, T12, L3 and the fascicles of four metameres with insertions on L3 increase their capacities to generate isometric muscle force and neutralize excessive movements of the vertebral segments with great mobility. There were no significant differences in the values of relative areas occupied by fibre types I, IIA and IIX. In considering the relative areas occupied by the fibre types in the multifidus muscle fascicles attached to each vertebral motion segment examined, the relative area occupied by the type I fibres was found to be significantly higher in the T4 vertebral motion segment than in the other segments. It can be concluded that the equine multifidus muscle in horses is an immunohistochemically homogeneous muscle with various architectural designs that have functional significance according to the vertebral motion segments considered. The results obtained in this study can serve as a basis for future research aimed at understanding the posture and dynamics of the equine spine.
Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer
Authors: Lee Seungho , Choi Seowon , Lee Yookyung , Chung Donghae , Hong Suntaek , Park Nohhyun
Published: November 2016

Aim

Human epididymis protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer. This study was designed to evaluate the role of HE4 in chemo‐response against anti‐cancer drugs and prognosis of epithelial ovarian cancer.

Methods

HE4‐depleted cells and HE4‐overexpressing cells were generated. The effect of HE4 gene silencing and overexpression was examined using a cell viability assay after exposure to chemotherapeutic agents and the signaling pathway. We studied the expression of HE4 in ovarian cancer tissue and the prognostic significance. Cytoplasmic staining was graded for intensity and percentage of positive cells. The grades were multiplied to determine an H‐score.

Results

Knockdown of HE4 in OVCAR‐3 cells resulted in reduction in cell growth and increased sensitivity to paclitaxel and cisplatin compared to control cells. This effect originated from the decreased activation of cell‐growth‐related signaling, such as AKT and Erk mediated by epidermal growth factor (EGF), while overexpression of HE4 resulted in enhanced cell growth and suppressed the anti‐tumorigenic activity of paclitaxel. Activation of AKT and Erk pathways was enhanced in HE4‐overexpressing cells compared to control cells. Based on the results of multivariate analysis, the risk of death was significantly higher in patients with an H‐score > 4.

Conclusion

HE4 induces chemoresistance against anti‐cancer drugs and activates the AKT and Erk pathways to enhance tumor survival. HE4 expression in ovarian cancer tissue is associated with a worse prognosis for epithelial ovarian cancer patients.
Volatility Modeling with a Generalized t Distribution
Authors: Harvey Andrew , Lange Rutger‐Jan
Published: November 2016

Exponential generalized autoregressive conditional heteroscedasticity models in which the dynamics of the logarithm of scale are driven by the conditional score are known to exhibit attractive theoretical properties for the t distribution and general error distribution. A model based on the generalized t includes both as special cases. We derive the information matrix for the generalized t and show that, when parameterized with the inverse of the tail index, it remains positive definite in the limit as the distribution goes to a general error distribution. We generalize further by allowing the distribution of the observations to be skewed and asymmetric. Our method for introducing asymmetry ensures that the information matrix reverts to the usual case under symmetry. We are able to derive analytic expressions for the conditional moments of our exponential generalized autoregressive conditional heteroscedasticity model as well as the information matrix of the dynamic parameters. The practical value of the model is illustrated with commodity and stock return data. Overall, the approach offers a unified, flexible, robust, and effective treatment of volatility.
Prevalence of Enteropathogens in Dogs Attending 3 Regional Dog Parks in Northern California
Authors: Hascall K.L. , Kass P.H. , Saksen J. , Ahlmann A. , Scorza A.V. , Lappin M.R. , Marks S.L.
Published: November 2016

Background

The prevalence and risk factors for infection with enteropathogens in dogs frequenting dog parks have been poorly documented, and infected dogs can pose a potential zoonotic risk for owners.

Hypothesis/Objectives

To determine the prevalence and risk factors of infection with enteropathogens and zoonotic Giardia strains in dogs attending dog parks in Northern California and to compare results of fecal flotation procedures performed at a commercial and university parasitology laboratory.

Animals

Three‐hundred dogs attending 3 regional dog parks in Northern California.

Methods

Prospective study. Fresh fecal specimens were collected from all dogs, scored for consistency, and owners completed a questionnaire. Specimens were analyzed by fecal centrifugation flotation, DFA, and PCR for detection of 11 enteropathogens. Giardia genotyping was performed for assemblage determination.

Results

Enteropathogens were detected in 114/300 dogs (38%), of which 62 (54%) did not have diarrhea. Frequency of dog park attendance correlated significantly with fecal consistency (P = .0039), but did not correlate with enteropathogen detection. Twenty‐seven dogs (9%) were infected with Giardia, and genotyping revealed nonzoonotic assemblages C and D. The frequency of Giardia detection on fecal flotation was significantly lower at the commercial laboratory versus the university laboratory (P = .013), and PCR for Giardia was negative in 11/27 dogs (41%) that were positive on fecal flotation or DFA.

Conclusions and Clinical Importance

Enteropathogens were commonly detected in dogs frequenting dog parks, and infection with Giardia correlated with fecal consistency. PCR detection of Giardia had limited diagnostic utility, and detection of Giardia cysts by microscopic technique can vary among laboratories.
Profiles of miRNAs in serum in severe acute drug induced liver injury and their prognostic significance
Authors: Russo Mark W. , Steuerwald Nury , Norton Harry J. , Anderson William E. , Foureau David , Chalasani Naga , Fontana Robert J. , Watkins Paul B. , Serrano Jose , Bonkovsky Herbert L.
Published: November 2016

Background & Aims

Drug induced liver injury (DILI) is challenging because of the lack of biomarkers to predict mortality. Our aim was to describe miRNA changes in sera of subjects with acute idiosyncratic DILI and determine if levels of miRNAs were associated with 6 month mortality.

Methods

Clinical data and sera were collected from subjects enrolled in the Drug Induced Liver Injury Network prospective study. miRNAs were isolated from serum obtained from 78 subjects within 2 weeks of acute DILI and followed up for 6 months or longer. miRNAs were compared to 40 normal controls and 6 month survivors vs non‐survivors.

Results

The mean age of the DILI cohort was 48 years, and 55% were female. Eleven (14.1%) subjects died, 10 within 6 months of DILI onset, 5 (45%) liver related. Lower levels of miRNAs‐122, ‐4463 and ‐4270 were associated with death within 6 months (P<.05). None of the subjects with miRNA‐122 greater than the median value died within 6 months for a sensitivity of 100% and specificity of 57%. In subjects with a serum albumin <2.8 g/dL and miR‐122<7.89 RFU the sensitivity, specificity, positive and negative predictive values for death within 6 months were 100%, 57%, 38% and 100% respectively.

Conclusions

Serum miRNA‐122 combined with albumin accurately identified subjects who died within 6 months of drug induced liver injury. If confirmed prospectively, miRNA‐122 and albumin may be useful in identifying patients at high risk for mortality or liver transplantation.
Liberalism, Post‐liberalism and the Fact‐Value Divide
Authors: Rashkover Randi
Published: November 2016

Jewish and Christian thought of the modern and contemporary period is frequently described as either liberal or post‐liberal. In lieu of this widely accepted categorization, this essay narrates developments in modern and contemporary Jewish and Christian thought in wake of the impact of the fact‐value dichotomy on theological and ethical discourse. This essay demonstrates the negative ramifications of this logical distinction on Jewish and Christian thought and shows how these negative repercussions can stimulate an immanent critique of this logic and a new paradigm in Jewish and Christian thinking.
Acotiamide improves stress‐induced impaired gastric accommodation
Authors: Ikeo K. , Oshima T. , Sei H. , Kondo T. , Fukui H. , Watari J. , Miwa H.
Published: November 2016

Background

Gastric accommodation is a reflex reaction related to gastric reservoir function. Psychological stress, such as anxiety, inhibits gastric accommodation in humans. Acotiamide enhances the effect of acetylcholine in the enteric nervous system, enhances gastric contractility, and accelerates delayed gastric emptying. However, the effect of acotiamide on stress‐induced impaired gastric accommodation remains unclear. Therefore, we examined the effect of acotiamide on gastric accommodation and stress‐induced impaired gastric accommodation using a conscious guinea pig model.

Methods

A polyethylene bag was inserted through the distal region of the gastric body into the proximal stomach of 5‐week‐old male Hartley guinea pigs. Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after oral administration of a liquid meal. In the stress model, animals were subjected to water‐avoidance stress. Acotiamide (Z‐338) or nizatidine was administered subcutaneously. Fecal output was determined as the number of fecal pellets.

Key Results

Administration of the liquid meal significantly decreased intrabag pressure, indicating induction of gastric accommodation. Acotiamide treatment prolonged liquid meal‐induced gastric accommodation and significantly increased the number of fecal pellets compared to controls. Water‐avoidance stress significantly inhibited liquid meal‐induced gastric accommodation. Pretreatment with acotiamide significantly improved stress‐induced impaired gastric accommodation. The number of fecal pellets in the acotiamide group increased significantly compared to controls. Acotiamide, but not nizatidine, significantly decreased gastric emptying.

Conclusions & Inferences

Acotiamide prolongs gastric accommodation and improves stress‐induced impaired gastric accommodation, indicating a potential role for acotiamide in the treatment of functional dyspepsia through its effects on gastric accommodation reactions.
A single base change explains the independent origin of and selection for the nonshattering gene in African rice domestication
Authors: Win Khin Thanda , Yamagata Yoshiyuki , Doi Kazuyuki , Uyama Kazuhiro , Nagai Yasuko , Toda Yosuke , Kani Takahiro , Ashikari Motoyuki , Yasui Hideshi , Yoshimura Atsushi
Published: November 2016

Reduced seed shattering was a critical evolutionary step in crop domestication. Two cultivated rice species, Oryza sativa and Oryza glaberrima, were independently domesticated from the wild species Oryza rufipogon in Asia and Oryza barthii in Africa, respectively. A single nucleotide polymorphism (SNP) in the c gene, which encodes a trihelix transcription factor, causes nonshattering in O. sativa. However, the genetic mechanism of nonshattering in O. glaberrima is poorly understood.

We conducted an association analysis for the coding sequences of SH3/SH4 in AA‐ genome rice species and the mutation suggested to cause nonshattering was demonstrated to do so using a positional‐cloning approach in the O. sativa genetic background.

We found that the loss of seed shattering in O. glaberrima was caused by an SNP resulting in a truncated SH3/SH4 protein. This mutation appears to be endemic and to have spread in the African gene pool by hybridization with some O. barthii accessions. We showed that interaction between the O. sativa and O. glaberrima domestication alleles of SH3 in heterozygotes induces a ‘throwback’ seed‐shattering phenotype similar to that in the wild species.

Identification of the causative SNP provides new insights into the molecular basis of seed shattering in crops and may facilitate investigation of the history of African rice domestication.
New views on the selection acting on genetic polymorphism in central metabolic genes
Authors: Eanes Walter F.
Published: November 2016

Studies of the polymorphism of central metabolic genes as a source of fitness variation in natural populations date back to the discovery of allozymes in the 1960s. The unique features of these genes and their enzymes and our knowledge base greatly facilitates the systems‐level study of this group. The expectation that pathway flux control is central to understanding the molecular evolution of genes is discussed, as well as studies that attempt to place gene‐specific molecular evolution and polymorphism into a context of pathway and network architecture. There is an increasingly complex picture of the metabolic genes assuming additional roles beyond their textbook anabolic and catabolic reactions. In particular, this review emphasizes the potential role of these genes as part of the energy‐sensing machinery. It is underscored that the concentrations of key cellular metabolites are the reflections of cellular energy status and nutritional input. These metabolites are the top‐down signaling messengers that set signaling through signaling pathways that are involved in energy economy. I propose that the polymorphisms in central metabolic genes shift metabolite concentrations and in that fashion act as genetic modifiers of the energy‐state coupling to the transcriptional networks that affect physiological trade‐offs with significant fitness consequences.
Association of β1‐Adrenergic, M2‐Muscarinic Receptor Autoantibody with Occurrence and Development of Nonvalvular Atrial Fibrillation
Authors: HU BING , SUN YANXIANG , LI SHA , SUN JIE , LIU TONG , WU ZIDI , FENG LI
Published: November 2016

Background

Atrial fibrillation (AF) is the most common sustained arrhythmia and is independently associated with increased risk of stroke and death. Although the exact mechanisms of AF are not completely elucidated, a large number of evidences demonstrate that autoimmunity may play an important role in the initiation, the progression, and the maintenance of AF. In this study, we aimed to compare anti‐β1‐adrenergic receptor autoantibody (anti‐β1‐R) and anti‐M2‐muscarinic receptor autoantibody (anti‐M2‐R) levels between nonvalvular AF patients and healthy control subjects.

Methods

The levels of serum anti‐β1‐R, antinuclear antibodies, and anti‐M2‐R were measured in both groups by enzyme‐linked immunosorbent assay (ELISA). High‐sensitivity C‐reactive protein (hs‐CRP) and interleukin (IL)‐6 concentration were measured, respectively, by immunoturbidimetry and chemiluminescence.

Results

Anti‐β1‐R and anti‐M2‐R levels were significantly higher in patients with nonvalvular AF than in healthy controls (anti‐β1‐R 221.11 [132.38–291.69] ng/mL vs 198.14 [125.70–278.40] ng/mL, P < 0.01; anti‐M2‐R 271.81 [144.99–378.20] ng/mL vs 235.01 [121.53–358.99] ng/mL, P < 0.01). Compared with the control group, the serum levels of IL‐6 and hs‐CRP were higher in the nonvalvular AF group (IL‐6 19.65 ± 5.6 pg/mL vs 6.79 ± 1.09 pg/mL, hs‐CRP 6.03 ± 1.35 mg/L vs 2.73 ± 0.63 mg/L, P < 0.05). Antinuclear antibody (ANA) levels were similar between two groups (ANA 10.55 [1.86–271.8] U/mL vs 10.49 [1.303–161.7] U/mL, P > 0.05). The baseline value of serum anti‐β1‐R (odds ratio [OR]: 13.176, P < 0.001), anti‐M2‐R (OR: 4.41, P < 0.001), IL‐6 (OR: 6.126, P < 0.05) levels, and left atrial diameter (OR: 5.781, P < 0.05) were independent predictors of nonvalvular AF by multivariable analyses.

Conclusion

We found a significant association between circulating serum anti‐β1‐R, anti‐M2‐R, IL‐6 levels, and nonvalvular AF. We presume that the autoimmunity and inflammation might take part in electrical remodeling and structural remodeling of left atrium.
A Critical Caring Theory of Protection for Migrants and Seasonal Farmworkers
Authors: Shearer Jennifer E.
Published: November 2016

Pesticide exposures represent inequities among a vulnerable population of migrant and seasonal farmworkers. A social justice theory synthesized from an environmental health research framework, a middle range theory of critical caring, and literature on pesticide exposure is presented as a situation‐specific public health practice theory. Concepts from the physiological, epistemological, vulnerability, and health protection domains are related to concepts of critical caring revealing protective strategies for vulnerable populations exposed to pesticides. The key concepts are risk exposure, community assessment, transpersonal health promotion, community competence, and controllability. Protection from exposure involves raising awareness, critically assessing communities, educating for empowerment, building capacity, and advocating to ensure social justice. Critical caring protection is provided in a mutually respectful relationship that promotes responsibility at the individual and population levels.
Acute exercise has a general facilitative effect on cognitive function: A combined ERP temporal dynamics and BDNF study
Authors: Chang Yu‐Kai , Alderman Brandon L. , Chu Chien‐Heng , Wang Chun‐Chih , Song Tai‐Fen , Chen Feng‐Tzu
Published: November 2016

This study examined whether acute moderate intensity exercise results in a general or selective improvement in cognitive function. In addition, multiple stimulus‐locked ERP components and serum BDNF levels were assessed to investigate potential neurobiological mechanisms underlying acute exercise effects on select aspects of cognitive performance. Thirty young adults were recruited and participated in exercise and reading control sessions in a counterbalanced order. Following treatments, the Stroop task was administrated, and N1, N2, P3, and N450 components of the ERP waveform were recorded and analyzed. Additionally, blood samples were withdrawn immediately following exercise or rest conditions prior to administration of the Stroop task. Acute exercise facilitated response times for both Stroop congruent and incongruent task conditions, with a similar magnitude of improvement. Larger P3 and reduced N450 amplitudes as well as decreased N450 latency were observed following exercise, but no effects on N1 and N2 components were found. This dose of exercise also did not influence serum BDNF levels. These findings suggest that moderate intensity acute exercise results in a generalized rather than selective improvement in cognition. The facilitation may be related to an increase in attentional or neural resource allocation and conflict detection processes reflected by longer latency endogenous components (P3, N450), but is not influenced by earlier sensory and monitoring processes revealed by earlier ERP components or by serum levels of BDNF.
ECONOMIC CHANGE AND SPECIALIZATION IN INDIA'S CITIES
Authors: Sridhar Kala Seetharam
Published: November 2016

Urban areas contribute to nearly two‐thirds of India's gross domestic product, but only constitute 31% of the country's population. In this paper, I address the following questions: What are the specializations of Indian cities and towns, and how have these changed over time; and what part of the specialization identified is a result of local advantages versus industry or national economic growth? Answers to these questions are basic to sustaining the competitiveness of India's cities. I used standard Census of India data at city level to compute location quotients for India's cities and towns, and examined changes in their economic base over time. Further, I performed shift‐share analyses for selected large cities to disaggregate their employment growth. On average, over 1991–2001, specialization in all sectors, with the exception of trade, decreased. I found evidence of persistence in the sectoral specialization of Indian cities during 1991–2001. Further, in all non‐agricultural economic sectors, cities in states know to be backward and lagging are specialized in most sectors. Based on location quotient analyses, I find that Mumbai is the financial capital of the country, Delhi is the seat of public administration, and Bengaluru specializes in transport, storage, and communications.
The role of ICU nurses in the spiritual aspects of end‐of‐life care in the ICU: an explorative study
Authors: Noome Marijke , Beneken Genaamd Kolmer Deirdre M. , van Leeuwen Evert , Dijkstra Boukje M. , Vloet Lilian C. M.
Published: November 2016

Aim

The aim of this study was to examine the role and responsibilities of intensive care unit (ICU) nurses regarding the spiritual aspects of end‐of‐life care in the ICU, from the chaplains’ perspectives.

Method

An explorative study including inductive thematic analysis was used. Two focus group interviews with in total eleven chaplains working in several Dutch ICUs were performed.

Results

The focus group interviews resulted in five themes: (i) awareness of ICU nurses, (ii) communication, (iii) nursing interventions, (iv) multidisciplinary care and (v) education. In total, twenty recommendations were formulated.

Conclusions

This explorative study provides an overview of the perspectives of chaplains about the role of ICU nurses during end‐of‐life care, specified to spiritual care. Chaplains mentioned different roles, responsibilities and competences which are needed for ICU nurses to give spiritual care. These roles, responsibilities and competences included giving spiritual care to patients and families as standard care. Chaplains agreed that ICU nurses should start and maintain a dialogue with patient and families, but that it is also important to be aware of one's own spiritual background. However, education about spiritual care is needed to establish this. It could be recommended to educate ICU nurses during their ICU training or retraining about spiritual care and reflection.
Between Occupation and Politics: Legislative Professionalization in the Swiss Cantons
Authors: Bundi Pirmin , Eberli Daniela , Bütikofer Sarah
Published: November 2016

In this article, we consider the question of how professionalized the cantonal parliamentarians are and which factors are related to this professionalization. By definition, Swiss parliamentarians exert an occupation in parallel to their mandate. We argue that parliamentarians who spend more time for their mandate have more resources to do so and, more importantly, intend to pursue a political career. In doing so, we analyze data gathered from a survey that was conducted among all Swiss cantonal parliaments in 2014. Our multi‐level analysis shows that parliamentarians who run for office at the national level spend significantly more time for their parliamentary mandate than their colleagues. This effect decreases with the parliamentarians’ age. This finding could be relevant in order to understand the career paths of Swiss parliamentarians. In addition, the study contributes to the discussion of the future development of the militia system in Switzerland.
Systems genetics reveals a transcriptional network associated with susceptibility in the maize–grey leaf spot pathosystem
Authors: Christie Nanette , Myburg Alexander A. , Joubert Fourie , Murray Shane L. , Carstens Maryke , Lin Yao‐Cheng , Meyer Jacqueline , Crampton Bridget G. , Christensen Shawn A. , Ntuli Jean F. , Wighard Sara S. , Van de Peer Yves , Berger Dave K.
Published: November 2016

We used a systems genetics approach to elucidate the molecular mechanisms of the responses of maize to grey leaf spot (GLS) disease caused by Cercospora zeina, a threat to maize production globally. Expression analysis of earleaf samples in a subtropical maize recombinant inbred line population (CML444 × SC Malawi) subjected in the field to C. zeina infection allowed detection of 20 206 expression quantitative trait loci (eQTLs). Four trans‐eQTL hotspots coincided with GLS disease QTLs mapped in the same field experiment. Co‐expression network analysis identified three expression modules correlated with GLS disease scores. The module (GY‐s) most highly correlated with susceptibility (r = 0.71; 179 genes) was enriched for the glyoxylate pathway, lipid metabolism, diterpenoid biosynthesis and responses to pathogen molecules such as chitin. The GY‐s module was enriched for genes with trans‐eQTLs in hotspots on chromosomes 9 and 10, which also coincided with phenotypic QTLs for susceptibility to GLS. This transcriptional network has significant overlap with the GLS susceptibility response of maize line B73, and may reflect pathogen manipulation for nutrient acquisition and/or unsuccessful defence responses, such as kauralexin production by the diterpenoid biosynthesis pathway. The co‐expression module that correlated best with resistance (TQ‐r; 1498 genes) was enriched for genes with trans‐eQTLs in hotspots coinciding with GLS resistance QTLs on chromosome 9. Jasmonate responses were implicated in resistance to GLS through co‐expression of COI1 and enrichment of genes with the Gene Ontology term ‘cullin‐RING ubiquitin ligase complex’ in the TQ‐r module. Consistent with this, JAZ repressor expression was highly correlated with the severity of GLS disease in the GY‐s susceptibility network.
Granulocytapheresis with modified fluid gelatin versus high‐molecular‐weight hydroxyethyl starch: a matched‐pair analysis
Authors: Dullinger Katharina , Pamler Irene , Brosig Andreas , Mohrez Morad , Hähnel Viola , Offner Robert , Dormann Frauke , Becke Christine , Holler Ernst , Ahrens Norbert
Published: November 2016

BACKGROUND

Granulocyte apheresis requires a sedimentation agent. Usually, hydroxyethyl starch (HES) is administered to donors for this purpose and, as granulocyte concentrate (GC) ingredient, also to patients. Authorities recently recommended suspending market authorizations for starch‐containing products due to side effects. Therefore, we tested the efficacy of modified fluid gelatin (MFG, Gelafundin 4%) versus hetastarch (Hespan) for GC apheresis.

STUDY DESIGN AND METHODS

This retrospective matched‐pair analysis compared MFG‐ and hetastarch‐derived GCs. Each group consisted of 15 unrelated male donors mobilized with dexamethasone and granulocyte–colony‐stimulating factor for apheresis on 1 or 2 days with the COBE Spectra's PMN program.

RESULTS

In each group, 24 GCs were collected from 15 male donors and analyzed. None of the HES‐derived products, but two of the MFG‐derived products (8.3%), had aggregates and could not be used. The HES‐derived products had significantly higher neutrophil counts on the first day (7.7 × 1010/unit vs. 4.0 × 1010/unit; p = 0.00005) as well as second day of apheresis (4.0 × 1010/unit vs. 1.1 × 1010/unit; p = 0.0002). Median white blood cell collection efficacies were lower with MFG than with HES on Day 1 (24% vs. 43%) and Day 2 (15% vs. 37%). Twenty‐one percent of the MFG‐derived products had less than 1 × 1010 granulocytes.

CONCLUSION

These results indicate that granulocyte apheresis is feasible with MFG as well as with hetastarch and that the latter is superior for GC production, if used in the same dosage. In addition, aggregates in GC from the COBE Spectra were observed in the MFG group but not in the hetastarch group.
Sludge settling and algal flocculating activity of extracellular polymeric substance (EPS) derived from bacillus cereus SK
Authors: Busi Siddhardha , Karuganti Sukumar , Rajkumari Jobina , Paramanandham Parasuraman , Pattnaik Subhaswaraj
Published: November 2016

Exopolysaccharides (EPS) of microbial origin is a promising alternative to chemical flocculants due to their sustainability and eco‐friendly nature. In the present study, EPS produced by Bacillus cereus SK was studied and their flocculating activity was investigated. On incubation for 48 h, B. cereus SK produced 0.919 ± 0.022 g/L of EPS from a cell mass of 3.59 ± 0.06 g/L. The isolated EPS was identified as glycoprotein and chemical characterization by FTIR spectroscopic analysis suggested the presence of hydroxyl, amino and carboxyl groups. The kaolin clay flocculating activity of 83.4% was obtained on treatment with 12 mg/L of EPS. At 30% (v/v) of EPS 31.22 ± 4.71 mL/g of Sludge volume index (SVI) and 34.44 ± 1.51 mL/g of algal flocculation was observed. The EPS produced by B. cereus SK was non‐toxic and did not exert any adverse effect on Danio rerio even at a concentration of 800 mg/mL.
A comprehensive microbiological safety approach for agarose encapsulated porcine islets intended for clinical trials
Authors: Gazda Lawrence S. , Collins James , Lovatt Archie , Holdcraft Robert W. , Morin Merribeth J. , Galbraith Daniel , Graham Melanie , Laramore Melissa A. , Maclean Christine , Black John , Milne Euan W. , Marthaler Douglas G. , Vinerean Horatiu V. , Michalak Michelle M. , Hoffer Deborah , Richter Steven , Hall Richard D. , Smith Barry H.
Published: November 2016

Background

The use of porcine islets to replace insulin‐producing islet β‐cells, destroyed during the diabetogenic disease process, presents distinct challenges if this option is to become a therapeutic reality for the treatment of type 1 diabetes. These challenges include a thorough evaluation of the microbiological safety of the islets. In this study, we describe a robust porcine islet‐screening program that provides a high level of confidence in the microbiological safety of porcine islets suitable for clinical trials.

Methods

A four‐checkpoint program systematically screens the donor herd (Large White – Yorkshire × Landrace F1 hybrid animals), individual sentinel and pancreas donor animals and, critically, the islet macrobeads themselves. Molecular assays screen for more than 30 known viruses, while electron microscopy and in vitro studies are employed to screen for potential new or divergent (emergent) viruses.

Results

Of 1207 monthly samples taken from random animals over a 2‐year period, only a single positive result for Transmissible gastroenteritis virus was observed, demonstrating the high level of biosecurity maintained in the source herd. Given the lack of clinical signs, positive antibody titers for Porcine reproductive and respiratory syndrome virus, Porcine parvovirus, and Influenza A confirm the efficacy of the herd vaccination program. Porcine respiratory coronavirus was found to be present in the herd, as expected for domestic swine. Tissue homogenate samples from six sentinel and 11 donor animals, over the same 2‐year period, were negative for the presence of viruses when co‐cultured with six different cell lines from four species. The absence of adventitious viruses in separate islet macrobead preparations produced from 12 individual pancreas donor animals was confirmed using validated molecular (n = 32 viruses), in vitro culture (cells from four species), and transmission electron microscopy assays (200 cell profiles per donor animal) over the same 2‐year period. There has been no evidence of viral transmission following the implantation of these same encapsulated and functional porcine islets into non‐immunosuppressed diabetic cynomolgus macaques for up to 4 years. Isolated peripheral blood mononuclear cells from all time points were negative for PCV (Type 2), PLHV, PRRSV, PCMV, and PERV‐A, PERV‐B, and PERV‐C by PCR analysis in all six recipient animals.

Conclusion

The four‐checkpoint program is a robust and reliable method for characterization of the microbiological safety of encapsulated porcine islets intended for clinical trials.
Magnitude and scope of non-communicable disease-related disability: a systematic review protocol
Authors: Lisy Karolina , Aromataris Edoardo , Moola Sandeep , Tufanaru Catalin , Lockwood Craig
Published: November 2016

Review question/objective:

The objective of the review will be to identify, assess and synthesize the evidence that examines the magnitude and scope of disability including impairments, activity limitations and participation restrictions associated with four main non-communicable diseases (NCDs): cardiovascular diseases (CVDs), cancers, diabetes and chronic respiratory diseases.

To systematically examine the magnitude of disability associated with CVDs, cancers, diabetes and chronic lung diseases, the questions that this review will specifically address are:

What is the prevalence of disability related to each of the four NCDs (presented by country and NCD where possible)?

What is the prevalence of co-existing diseases/conditions (comorbidity) in persons with disabilities related to the four NCDs?

To systematically examine the scope of disability associated with CVDs, cancers, diabetes and chronic respiratory diseases, the questions that this review will address are:

What is the impact of disability on a person's life (measured using patient reported outcomes including quality of life measures)?

What are the unmet needs in persons with disabilities related to the four NCDs?
Tattoos and administration of regional anesthesia: a comprehensive systematic review protocol
Authors: Houhoulis Kathryn , Lewis Kevin , Fasone Rachel , Benham Brian E.
Published: November 2016

Review question/objective:

The review question is what is the impact of tattoos on the administration of regional anesthesia?

The quantitative objective is to identify and quantify the risks to a patient when advancing a needle through tattooed skin for the purpose of administering a regional anesthetic.

The qualitative objective is to investigate anesthesia providers’ perceptions and experiences when presented with a patient and/or a surgeon requests for a regional anesthetic that would require needle trespass through tattooed skin. An additional qualitative objective is to identify the thoughts, opinions and biases related to the administration of a regional anesthetic through tattooed skin from the perspective of the patient, anesthesia provider, surgeon or other affected parties (e.g. patient families, hospital or clinic administrators or insurance providers).
Effectiveness of intrathecal dexmedetomidine as an adjuvant to bupivacaine spinal anesthesia in adult patients undergoing elective surgery: a systematic review protocol
Authors: Pierce Stephanie , Bonanno Laura , Sanvi Stephanie
Published: November 2016

Review question

The current review aims to identify the effects of intrathecal dexmedetomidine as an adjuvant to bupivacaine spinal anesthesia compared to the sole use of bupivacaine spinal anesthesia alone in adult patients undergoing elective surgical procedures.
Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol
Authors: Bennett Marsha , Bonanno Laura , Kuhn William
Published: November 2016

Review question/objective:

The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.

The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?
A unifying hypothesis for M1 muscarinic receptor signalling in pyramidal neurons
Authors: Dasari Sameera , Hill Corey , Gulledge Allan T.
Published: November 2016

Key points

Phasic release of acetylcholine (ACh) in the neocortex facilitates attentional processes.

Acting at a single metabotropic receptor subtype, ACh exerts two opposing actions in cortical pyramidal neurons: transient inhibition and longer‐lasting excitation.

Cholinergic inhibitory responses depend on calcium release from intracellular calcium stores, and run down rapidly at resting membrane potentials when calcium stores become depleted.

We demonstrate that cholinergic excitation promotes calcium entry at subthreshold membrane potentials to rapidly refill calcium stores, thereby maintaining the fidelity of inhibitory cholinergic signalling.

We propose a ‘unifying hypothesis’ for M1 receptor signalling whereby inhibitory and excitatory responses to ACh in pyramidal neurons represent complementary mechanisms governing rapid calcium cycling between the endoplasmic reticulum, the cytosol and the extracellular space.

Gq‐coupled M1‐type muscarinic acetylcholine (ACh) receptors (mAChRs) mediate two distinct electrophysiological responses in cortical pyramidal neurons: transient inhibition driven by calcium‐dependent small conductance potassium (‘SK’) channels, and longer‐lasting and voltage‐dependent excitation involving non‐specific cation channels. Here we examine the interaction of these two cholinergic responses with respect to their contributions to intracellular calcium dynamics, testing the ‘unifying hypothesis’ that rundown of inhibitory SK responses at resting membrane potentials (RMPs) reflects depletion of intracellular calcium stores, while mAChR‐driven excitation acts to refill those stores by promoting voltage‐dependent entry of extracellular calcium. We report that fidelity of cholinergic SK responses requires the continued presence of extracellular calcium. Inhibitory responses that diminished after repetitive ACh application at RMPs were immediately rescued by pairing mAChR stimulation with subthreshold depolarization (∼10 mV from RMPs) initiated with variable delay (up to 500 ms) after ACh application, but not by subthreshold depolarization preceding mAChR stimulation. Further, rescued SK responses were time‐locked to ACh application, rather than to the timing of subsequent depolarizing steps, suggesting that cholinergic signal transduction itself is not voltage‐sensitive, but that depolarization facilitates rapid cycling of extracellular calcium through the endoplasmic reticulum to activate SK channels. Consistent with this prediction, rescue of SK responses by subthreshold depolarization required the presence of extracellular calcium. Our results demonstrate that, in addition to gating calcium release from intracellular stores, mAChR activation facilitates voltage‐dependent refilling of calcium stores, thereby maintaining the ongoing fidelity of SK‐mediated inhibition in response to phasic release of ACh.
Impact of Heat Release Distribution on the Spinning Modes of an Annular Combustor With Multiple Matrix Burners
Authors: Laera Davide , Prieur Kevin , Durox Daniel , Schuller Thierry , Camporeale Sergio M. , Candel Sébastien
Published: November 2016

The present article reports a numerical analysis of instability coupled by a spinning mode in an annular combustor. This corresponds to experiments carried out on the MICCA test facility equipped with 16 matrix burners. Each burner response is represented by means of a global experimental flame describing function (FDF). A harmonic balance nonlinear stability analysis is carried out by combining the FDF with a Helmholtz solver to determine the system dynamics trajectories in a frequency-growth rate plane. The influence of the distribution of the volumetric heat release corresponding to each burner is investigated in a first stage. Even though each of the 16 burners is compact with respect to the transverse mode wavelength, and the 16 flames occupy the same volume, this distribution of heat release is not compact in the azimuthal direction and simulations reveal an influence of this volumetric distribution on frequencies and growth rates. This study emphasizes the importance of providing a suitable description of the flame zone geometrical extension and correspondingly an adequate representation of the level of heat release rate fluctuation per unit volume. It is found that these two items can be deduced from a knowledge of the heat release distribution under steady-state operating conditions. Once the distribution of the heat release fluctuations is unequivocally defined, limit cycle simulations are performed. For the conditions explored, simulations retrieve the spinning nature of the self-sustained mode that was identified in the experiments both in the plenum and in the combustion chamber.