bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Plakins in Human Genetic Disease
Authors: Favre Bertrand , Borradori Luca
Published: May 2016

The mammalian plakins comprise a small family of seven large proteins: bullous pemphigoid antigen 1, desmoplakin, envoplakin, epiplakin, microtubule‐actin crosslinking factor 1, periplakin and plectin. Their main functions consist of organising the different components of the cytoskeleton, crosslinking them to each other and anchoring them to various cell–matrix and cell–cell adhesion complexes. Thereby, these cytolinkers regulate cell stiffness, adhesion, migration and polarisation in a dynamic way. They can also interact with signal transducers, serve as scaffolds for signalling complexes and modulate vesicle trafficking. Congenital or engineered mutations in human and mouse plakin genes, respectively, reveal their essential functions in tissues either subjected to mechanical stress, such as the skin, skeletal and cardiac muscle, or highly sensitive to cytoskeletal and vesicle transport disorganisation, the nervous system. The pleiotropic diseases caused by plakin mutations reflect their multiple functions that have not yet been fully elucidated.

Key Concepts

The plakins are a family of cytolinker proteins that connect the three components of the cytoskeleton, intermediate filaments (IFs), microfilaments and microtubules (MTs), to each other and to junctional complexes at the cell membrane.

The plakin family can be subdivided into three classes: (1) the canonical IF‐anchoring plakins: BPAG1e, desmoplakin, envoplakin, periplakin and plectin, (2) the atypical IF‐interacting plakin: epiplakin and (3) the MT‐binding spectraplakins: BPAG1a/b and MACF1a/b.

The plakins often have a dynamic function on the cytoskeleton organisation, can modulate cell signalling and serve as scaffolds for signal transducers.

The plakins also play a role in the positioning and function of organelles and regulate vesicular trafficking.

Mutations in plakin genes can cause pleiotropic diseases, such as skin blistering, muscular dystrophy, cardiomyopathy and autonomic neuropathy.

Despite the delimitation of plakin subdomains and the present knowledge of plakin functions, there is no obvious genotype–phenotype relationship.
Use of Citizens' Juries to Address Complex Bioethical Challenges
Authors: Iredale Rachel
Published: May 2016

The ethical and social principles that guide decision making in relation to the human genome are well known. However, new bioethical challenges are emerging, such as gene editing, which require wider public discussion. One way of involving the public is by a Citizens' Jury. Originating almost 50 years ago, Citizens' Juries involve ordinary members of the public in policy discussions, not in their capacity as service users or consumers, but as citizens. The first Citizens' Jury in the United Kingdom on the topic of genetics took place in Wales in 1997. Whilst the method may vary, the fundamental premise remains the same; that given enough time and support, any person is capable of arriving at an informed decision about a complex policy matter. The defining characteristics of Citizens' Juries are that they are deliberative and inclusive and have an important role to play in addressing the new bioethical challenges that society faces.

Key Concepts

Complex bioethical challenges require public participation in policy making.

A Citizens' Jury involves the public in their capacity as citizens and not as users of services, or consumers, or members of specific interest groups.

The fundamental premise upon which every Citizens' Jury is based is that ordinary members of the public, given enough time, support and resources, are capable of arriving at decisions about complex policy matters.

The defining characteristics of Citizens' Juries are that they are deliberative and inclusive and have the aim of delivering high‐quality citizen input into any decision‐making process.

The complex bioethical challenges that society will face this century, such as human gene editing, are too important not to involve the public.
Disruption of the gene C12orf35 leads to increased productivities in recombinant CHO cell lines
Authors: Ritter Anett , Rauschert Tatjana , Oertli Mevion , Piehlmaier Daniel , Mantas Panagiotis , Kuntzelmann Genevieve , Lageyre Nadine , Brannetti Barbara , Voedisch Bernd , Geisse Sabine , Jostock Thomas , Laux Holger
Published: May 2016

Recently, we reported that the loss of a telomeric region of chromosome 8 in Chinese Hamster Ovary (CHO) cells correlates with higher recombinant productivities. New cell lines lacking this region, called CHO‐C8DEL, showed several advantages during cell line generation and for the production of recombinant proteins (Ritter et al., 2016, Biotechnol Bioeng). Here, we performed knock‐down and knock‐out experiments of genes located within this telomeric region of chromosome 8 to identify the genes causing the observed phenotypes of CHO‐C8DEL cell lines. We present evidence that loss or reduced expression of the gene C12orf35 is responsible for higher productivities and shorter recovery times during selection pressure. These effects are mediated by increased levels of mRNA of the exogenes heavy chain (HC) and light chain (LC) as well as dihydrofolate reductase (DHFR) and neomycin phosphotransferase (Neo) during the stable expression of antibodies. Biotechnol. Bioeng. 2016;113: 2433–2442. © 2016 Wiley Periodicals, Inc.
Outcomes of patients with chronic lymphocytic leukemia treated with first‐line idelalisib plus rituximab after cessation of treatment for toxicity
Authors: Thompson Philip A. , Stingo Francesco , Keating Michael J. , Ferrajoli Alessandra , Burger Jan A. , Wierda William G. , Kadia Tapan M. , O'Brien Susan M.
Published: May 2016

BACKGROUND

More active therapies are needed for older and unfit patients with chronic lymphocytic leukemia (CLL) who are not eligible for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The phosphyotidylinositol‐3‐kinase δ inhibitor idelalisib is effective in patients with treatment‐naive and relapsed/refractory CLL as monotherapy and in combination with rituximab, but it can be associated with treatment‐limiting adverse events, particularly diarrhea/colitis. The outcomes for patients who cease treatment for adverse events have not been previously described.

METHODS

The authors analyzed long‐term follow‐up data from 40 treatment‐naïve patients aged ≥65 years who received treatment at The University of Texas MD Anderson Cancer Center on a phase 2 study of idelalisib plus rituximab for CLL.

RESULTS

In patients who permanently ceased treatment because of toxicity, the time to subsequent disease progression was analyzed according to baseline characteristics. Fifteen patients permanently ceased therapy (PCT) because of toxicity (PCTTOX), most commonly diarrhea/colitis (n = 7), at a median of 11 months after commencing treatment. PCTTOX was associated with a higher risk of subsequent disease progression (hazard ratio, 6.61; 95% confidence interval, 1.77‐16.15) relative to that observed in patients who remained on therapy. Ten patients subsequently progressed, and 7 required salvage therapy; 5 patients remained progression‐free at a median of 23.3 months (range, 8.5‐28.6 months). Patients who were positive for ζ‐associated protein‐70 had more rapid disease progression after treatment cessation (P = .048). There were no CLL‐related deaths.

CONCLUSIONS

PCTTOX is the major determinant of PFS in patients who receive first‐line idelalisib‐based treatment. However, a subgroup of patients with favorable biologic characteristics has prolonged PFS, even after PCTTOX. The absence of CLL‐related deaths indicates that salvage treatment is generally successful after PCTTOX. Cancer 2016;122:2505–11. © 2016 American Cancer Society.
A Review of Evidence Presented in Support of Three Key Claims in the Validity Argument for the TextEvaluator® Text Analysis Tool
Authors: Sheehan Kathleen M.
Published: May 2016

The TextEvaluator® text analysis tool is a fully automated text complexity evaluation tool designed to help teachers and other educators select texts that are consistent with the text complexity guidelines specified in the Common Core State Standards (CCSS). This paper provides an overview of the TextEvaluator measurement approach and summarizes evidence related to three key claims in the TextEvaluator validity argument: (a) TextEvaluator has succeeded in expanding construct coverage beyond the two dimensions of text variation that are traditionally assessed by readability metrics; (b) the TextEvaluator strategy of estimating distinct prediction models for informational, literary, and mixed texts has succeeded in generating text complexity predictions that exhibit little, if any, genre bias; and (c) TextEvaluator scores are highly correlated with text complexity judgments provided by human experts, including judgments generated via the inheritance method and judgments generated via the exemplar method. Implications with respect to the goal of helping teachers and other educators select texts that are closely aligned with the accelerated text complexity exposure trajectory outlined in the CCSS are discussed.
Development of the Mission Skills Assessment and Evidence of Its Reliability and Internal Structure
Authors: Petway Kevin T. , Rikoon Samuel H. , Brenneman Meghan W. , Burrus Jeremy , Roberts Richard D.
Published: May 2016

The Mission Skills Assessment (MSA) is an online assessment that targets 6 noncognitive constructs: creativity, curiosity, ethics, resilience, teamwork, and time management. Each construct is measured by means of a student self‐report scale, a student alternative scale (e.g., situational judgment test), and a teacher report scale. Use of the MSA provides schools with the opportunity to examine and monitor development of noncognitive skills in their students from Grade 6 to Grade 8. The use of the MSA has facilitated changes to curricula and more targeted instruction. The MSA scales exhibited meaningful relationships with standardized test scores and absenteeism, suggesting that these constructs play an important role in student behaviors and academic performance. This report presents reliability and factor analysis evidence for the student self‐report and teacher report scales of the MSA to highlight its ability to measure the 6 constructs.
Genetic diversity of hepatitis B virus (HBV) in Madagascar
Authors: Andriamandimby Soa Fy , Lo Presti Alessandra , Lai Alessia , Olive Marie‐Marie , Angeletti Silvia , De Florio Lucia , Cella Eleonora , Razafindramparany Minoharimbola , Ravalohery Jean‐Piere , Andriamamonjy Seta , Gioffrè Sonia , Zehender Gianguglielmo , Mottini Giovanni , Ciccozzi Massimo , Heraud Jean‐Michel
Published: May 2016

Hepatitis B virus (HBV) is a DNA virus belonging to Hepadnaviridae family. Chronic infection with HBV is one major risk factor of hepatic disease. In Madagascar, former studies classified the country as part of high endemic area, as HBV prevalence can reach 23% in general population. However, this prevalence differs largely between urban and rural areas and is estimated to be, respectively, 5% and 26%. The aims of the present study were to describe the genetic diversity of HBV strains from different regions of Madagascar, and to describe the viral gene flow throughout the country by using phylogenetic analysis. This is the first large‐scale molecular and phylogenetic study analyzing HBV sequences from 28 different Malagasy areas, never sampled in the past. In this study, the most prevalent genotype/sub‐genotypes was E. Migration analysis showed a gene flow from zone 3 (rural) to zone 2 (suburban), and a greater gene flow from the middle part of Madagascar to the north than to the south. It is important to study the HBV infections in Madagascar and to monitor the potential spread of this viral strain inside this country. J. Med. Virol. 88:2138–2144, 2016. © 2016 Wiley Periodicals, Inc.
Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism
Authors: Wilkinson Daniel James
Published: May 2016

Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13C), nitrogen (15N), oxygen (18O), and hydrogen (2H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to “trace” the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC‐MS to LC‐MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level. Importantly, it will detail how this development has been closely aligned to the technological development within the area of mass spectrometry. Without the dedicated development provided by these mass spectrometrists over the past century, the use of stable isotope tracers within the field of protein metabolism would not be as widely applied as it is today, this relationship will no doubt continue to flourish in the future and stable isotope tracers will maintain their importance as a tool within the biological sciences for many years to come. © 2016 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Mass Spec Rev
KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients
Authors: Gao Weimin , Jin Jide , Yin Jinling , Land Stephanie , Gaither‐Davis Autumn , Christie Neil , Luketich James D. , Siegfried Jill M. , Keohavong Phouthone
Published: May 2016

Mutations in the KRAS and TP53 genes have been found frequently in lung tumors and specimens from individuals at high risk for lung cancer and have been suggested as predictive markers for lung cancer. In order to assess the prognostic value of these two genes’ mutations in lung cancer recurrence, we analyzed mutations in codon 12 of the KRAS gene and in hotspot codons of the TP53 gene in 176 bronchial biopsies obtained from 77 former lung cancer patients. Forty‐seven patients (61.0%) showed mutations, including 35/77 (45.5%) in the KRAS gene and 25/77 (32.5%) in the TP53 gene, among them 13/77 (16.9%) had mutations in both genes. When grouped according to past or current smoking status, a higher proportion of current smokers showed mutations, in particular those in the TP53 gene (P = 0.07), compared with ex‐smokers. These mutations were found in both abnormal lesions (8/20 or 40%) and histologically normal tissues (70/156 or 44.9%) (P = 0.812). They consisted primarily of G to A transition and G to T transversion in both the KRAS (41/56 or 73.2%) and TP53 (24/34 or 70.6%) genes, consistent with mutations found in lung tumors of smoking lung cancer patients. Overall, recurrence‐free survival (RFS) among all subjects could be explained by age at diagnosis, tumor stage, tumor subtype, and smoking (P < 0.05, Cox proportional hazard). Therefore, KRAS and TP53 mutations were frequently detected in bronchial tissues of former lung cancer patients. However, the presence of mutation of bronchial biopsies was not significantly associated with a shorter RFS time. © 2016 Wiley Periodicals, Inc.
Abrus Agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy‐dependent cell death
Authors: Panda Prashanta Kumar , Behera Birendra , Meher Biswa Ranjan , Das Durgesh Nandini , Mukhopadhyay Subhadip , Sinha Niharika , Naik Prajna Paramita , Roy Bibhas , Das Joyjyoti , Paul Subhankar , Maiti Tapas K. , Agarwal Rajesh , Bhutia Sujit K.
Published: May 2016

Abrus agglutinin (AGG), a type II ribosome‐inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG‐mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy‐dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3‐methyladenine (3‐MA) and siRNA of Beclin‐1 and ATG5 increased AGG‐induced apoptosis. Further, inhibiting apoptosis by Z‐DEVD‐FMK and N‐acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells. Additionally, it observed that AGG‐induced autophagic cell death in Bax knock down (Bax‐KD) and 5‐FU resistant HeLa cells, confirming as an alternate cell killing pathway to apoptosis. At the molecular level, AGG‐induced ER stress in PERK dependent pathway and inhibition of ER stress by salubrinal, eIF2α phosphatase inhibitor as well as siPERK reduced autophagic death in the presence of AGG. Further, our in silico and colocalization study showed that AGG interacted with pleckstrin homology (PH) domain of Akt to suppress its phosphorylation and consequent downstream mTOR dephosphorylation in HeLa cells. We showed that Akt overexpression could not augment GRP78 expression and reduced autophagic cell death by AGG as compared to pcDNA control, indicating Akt modulation was the upstream signal during AGG's ER stress mediated autophagic cell death. In conclusion, we established that AGG stimulated cell death by autophagy might be used as an alternative tumor suppressor mechanism in human cervical cancer. © 2016 Wiley Periodicals, Inc.
Pronghorn and mule deer use of underpasses and overpasses along U.S. Highway 191
Authors: Sawyer Hall , Rodgers Patrick A. , Hart Thomas
Published: May 2016

The seasonal migrations of ungulates are increasingly threatened by various forms of anthropogenic disturbance, including roads, fences, and other infrastructure. Although roadway impacts (e.g., wildlife–vehicle collisions and landscape permeability) to species such as mule deer (Odocoileus hemionus) can largely be mitigated with underpasses and continuous fencing, similar mitigation may not be effective for pronghorn (Antilocapra americana) or other ungulate species that are reluctant to move through confined areas. The Wyoming Department of Transportation recently installed 6 underpasses and 2 overpasses along 20 km of U.S. Highway 191 in western Wyoming, USA, where we evaluated species‐specific preferences by documenting the number of migratory mule deer and pronghorn that used adjacent overpasses and underpasses for 3 years (autumn 2012 to spring 2015) following construction. We also measured the amount of back‐and‐forth movement across the highway for each species through time. We documented 40,251 crossings of the highway by mule deer and 19,290 crossings by pronghorn. Of those highway crossings, 79% of mule deer moved under, whereas 93% of pronghorn moved over the highway. These strong species‐specific differences were evident at both sites and support the notion that overpasses are more amenable to pronghorn than underpasses. Concurrently, we documented a 64–306% increase in the amount of back‐and‐forth movement of mule deer and pronghorn across the highway during migration periods. Such movement flexibility is presumed to improve their ability to respond to changing environmental conditions by easily accessing habitats on either side of the highway. Our results highlight that species‐specific preferences are an important consideration when mitigating roadway impacts with wildlife crossing structures. © 2016 The Wildlife Society.
Blood Transfusion is an Independent Risk Factor for Postoperative Serious Infectious Complications After Pancreaticoduodenectomy
Authors: Zhang Liyang , Liao Quan , Zhang Taiping , Dai Menghua , Zhao Yupei
Published: May 2016

Background/purpose

Blood transfusionhas been considered as a risk factor for postoperative infection after major surgery. However, the relationship between perioperative blood transfusion and the development of serious infections after pancreaticoduodenectomy remains controversial. The purpose of this study was to analyze risk factors associated with postoperative serious infections following pancreaticoduodenectomy.

Methods

We conducted a retrospective study of 212 patients who underwent pancreaticoduodenectomy during past 2 years and assessed the risk factors for serious infectious complications.

Results

Serious infections developed in 61 patients (29 %) including 47 cases of surgical site infection (SSI), 19 cases of bacteremia, and 13 cases of pneumonia. One patient died of severe septic shock. A multivariate logistic regression analysis of perioperative factors identified that pancreatic fistula (P < 0.01, OR = 9.763) and blood transfusion (P < 0.01, OR = 3.216) were significant risk factors for serious infections. After excluding 46 patients with pancreatic fistula, blood transfusion continued to be an independent risk factor for serious infections (P < 0.01, OR = 5.831).

Conclusion

Blood transfusion was the strongest independent factor for serious infections after pancreaticoduodenectomy, which should be considered a quality indicator for the performance of pancreaticoduodenectomy.
The Effect of Reference Groups on Purchase Intention: Evidence in Distinct Types of Shoppers and Product Involvement
Authors: Hoonsopon Danupol , Puriwat Wilert
Published: May 2016

The extant research has investigated the impact of purchase intention by reference groups in different situations. Nonetheless, a few studies have examined the roles of reference groups (private and public) in the purchase intention of distinctive types of shoppers (utilitarian, social value, and hedonic) and the degree of product involvement (high and low). Drawing from social influence theory, using experimental research, and analysing data with ANOVA, the author reveals in Study 1 that private groups may have greater impact on motivation for both high and low product involvement compared to public groups. Studies 2 and 3 reveal that utilitarian shoppers tend to have higher purchase intention when private groups are used for information cues. On the other hand, reference groups do not affect the purchase intention of social value and hedonic shoppers. This research contributes to social influence theory by revealing that reference groups have a diverse impact on purchase intention under different stimuli.
Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT
Authors: Fang Fang , Peng Ting , Yang Shiming , Wang Weixi , Zhang Yinong , Li He
Published: May 2016

Huntington's disease (HD) is an inherited neurodegenerative disease that is caused by the abnormal expansion of CAG repeats in the gene encoding huntingtin (Htt). Reduced AKT phosphorylation and inhibited AKT activity have been shown to be involved in mutant Htt (mHtt)‐induced cell death. Lycium barbarum polysaccharide (LBP), the main bioactive component of Lycium barbarum, reportedly has neuroprotective roles in neural injuries, including neurodegenerative diseases. Here, we report that treatment with LBP can increased the viability of HEK293 cells that stably expressed mHtt containing 160 glutamine repeats and significantly improved motor behavior and life span in HD‐transgenic mice. Furthermore, we found that in LBP‐treated HEK293 cells expressing mHtt, mHtt levels were reduced and the phosphorylation of AKT at Ser473 (p‐AKT‐Ser473) was significantly increased. We also found that treatment with LBP increased p‐AKT‐Ser473 and decreased mHtt in the cortex, hippocampus and striatum in HD‐transgenic mice. The level of phosphorylation of p‐GSK3β‐Ser9 remained unchanged in both cultured cells and HD‐transgenic mice. Our findings suggest that LBP alleviates the cytotoxicity of mHtt by activating AKT and reducing mHtt levels, indicating that LBP may be potentially useful for treating HD.
Comparison of stillbirth rates by cause among Haitians and non‐Haitians in Canada
Authors: Auger Nathalie , Costopoulos André , Naimi Ashley I. , Bellingeri Fulvia , Vecchiato Léa , Fraser William D.
Published: May 2016

Objective

To compare rates of stillbirth among Haitians and non‐Haitians in Canada.

Methods

A retrospective cohort study was performed using data on all stillborn and live‐born singletons weighing at least 500 g in the province of Quebec, Canada, from 1981 to 2010. Stillbirth rates were computed, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for Haitians relative to non‐Haitians. The main outcome measure was stillbirth by cause of death.

Results

Data for 9657 stillbirths (124 Haitian) and 2 414 751 live births (17 165 Haitian) were included. Stillbirth rates were higher for Haitians than non‐Haitians (7.17 [95% CI 5.91–8.43] vs 3.96 [95% CI 3.88–4.04] per 1000 births), particularly for cord prolapse (adjusted HR 1.87, 95% CI 1.10–3.18) and placental abruption (adjusted HR 2.84, 95% CI 1.95–4.15). Haitians had higher risks of stillbirth due to cord prolapse and abruption at every week of pregnancy. Risks were not elevated for stillbirth due to congenital anomaly, a cause less responsive to urgent intervention.

Conclusion

Stillbirth rates among Haitians are disproportionately high in Canada, particularly fetal death due to cord prolapse and placental abruption. The potential to reduce stillbirth rates through optimal emergency care in vulnerable minorities requires further investigation.
Supply chain risk management and hospital inventory: Effects of system affiliation
Authors: Zepeda E. David , Nyaga Gilbert N. , Young Gary J.
Published: May 2016

In this study we examine the effects of horizontal inter‐organizational arrangements on inventory costs for hospitals facing two key environmental conditions, namely the logistics services infrastructure where the hospital is located and the demand uncertainty for clinical requirements that a hospital experiences. Utilizing detailed data from hospitals in the State of California, we investigated the potential mitigating effects of affiliation with multi‐hospital systems while controlling for service performance. We argue that these arrangements potentially influence managers' confidence in their supply chains, which in turn impacts inventory accumulation. Results suggest that while affiliation with local, regional, and national systems has mitigating effects under weak logistics services infrastructure, the mitigating effect is greatest for affiliation in local systems. The results also point to potential for improved operating efficiency with system affiliation, a factor that is often not considered in policy discussions regarding hospital system formation. Theoretical and managerial implications are discussed.
Glacier naled evolution and relation to the subglacial drainage system based on water chemistry and GPR surveys (Werenskioldbreen, SW Svalbard)
Authors: Stachnik Łukasz , Yde Jacob C. , Kondracka Marta , Ignatiuk Dariusz , Grzesik Magdalena
Published: May 2016

Glacier naledi are extrusive ice masses that appear in front of glaciers as a consequence of refreezing of meltwater seepage during the accumulation season. These structures provide a unique opportunity to understand subglacial drainage activity during the accumulation season; however, only few detailed studies have previously focused on their characteristics. Here, we investigated glacier-derived naled assemblages in the proglacial zone of the polythermal glacier Werenskioldbreen (27.4 km2) in SW Svalbard. We determined the spatial distribution of naledi using ground penetrating radar surveys. The main subglacial drainage pattern was related to a channel under the medial moraine, and three sources are linked to a distributed subglacial drainage network. The relation between atmospherically-corrected (Ca2+ + Mg2+) and (SO42−) in sub-naled waters was closely related to sulphide oxidation coupled with carbonate dissolution (r = 0.99; slope = 1.6). This is consistent with the local lithology, which is dominated by schist containing carbonates. We also found high carbonate saturation indices in pale white ice layers within the naled. We conclude that sulphide oxidation coupled with carbonate dissolution is the dominant chemical weathering process in the subglacial drainage system of Werenskioldbreen during the accumulation season.
Assessing the Public Administration’s Intention in EU Economic Law: Chasing Ghosts or Dressing Windows?
Authors: SANCHEZ-GRAELLS Albert
Published: May 2016

Here I reflect on the role of subjective or intentional elements in EU economic law prohibitions, particularly in relation to rules concerning public administration. From a normative perspective, it is desirable to suppress the need for an assessment of subjective intent and to proceed with an objectified enforcement of such prohibitions. With this in view, I consider public procurement and Member State aid rules as two examples of areas of EU economic law subjected to interpretative and enforcement difficulties due to the introduction – sometimes veiled – of subjective elements in their main prohibitions. I establish parallels with other areas of EU economic law – such as antitrust, non-discrimination law and the common agricultural policy – and seek benchmarks to support the main thesis that such intentional elements need to be ‘objectified’, so that EU economic law can be enforced against the public administration to an adequate standard of legal certainty. This mirrors the development of the doctrine of abuse of EU law, where a similar ‘objectification’ in the assessment of subjective elements has taken place.

I draw on the case law of the Court of Justice of the European Union to support such ‘objectification’ and highlight how the Court has been engaging in such interpretative strategy for some time. The paper explores the interplay between this approach and more general protections against behaviour of the public administration in breach of EU law: the right to good administration in Article 41 of the Charter of Fundamental Rights of the European Union and the doctrine of State liability for infringement of EU law. I conclude with the normative recommendation that the main prohibitions of EU economic law should be free from subjective elements focused on the intention of the public administration.
Emergency Department Visits after Diagnosed Chronic Obstructive Pulmonary Disease in Aboriginal People in Alberta, Canada
Authors: Ospina Maria B. , Rowe Brian H. , Voaklander Donald , Senthilselvan Ambikaipakan , Stickland Michael K. , King Malcolm
Published: May 2016

Objectives

This retrospective cohort study compared rates of emergency department (ED) visits after a diagnosis of chronic obstructive pulmonary disease (COPD) in the three Aboriginal groups (Registered First Nations, Métis and Inuit) relative to a non-Aboriginal cohort.

Methods

We linked eight years of administrative health data from Alberta and calculated age- and sex-standardized ED visit rates in cohorts of Aboriginal and non-Aboriginal individuals diagnosed with COPD. Rate ratios (RR) with 95% confidence intervals (CIs) were calculated in a Poisson regression model that adjusted for important sociodemographic factors and comorbidities. Differences in ED length of stay (LOS) and disposition status were also evaluated.

Results

A total of 2,274 Aboriginal people and 1,611 non-Aboriginals were newly diagnosed with COPD during the study period. After adjusting for important sociodemographic and clinical factors, the rate of all-cause ED visits in all Aboriginal people (RR=1.72, 95% CI: 1.67, 1.77), particularly among Registered First Nations people (RR=2.02; 95% CI: 1.97, 2.08) and Inuit (RR=1.28; 95% CI: 1.22, 1.35), were significantly higher than that in non-Aboriginals, while ED visit rates were significantly lower in the Métis (RR=0.94; 95% CI: 0.90, 0.98). The ED LOS in all Aboriginal groups were significantly lower than that of the non-Aboriginal group.

Conclusions

Aboriginal people with COPD use almost twice the amount of ED services compared to their non-Aboriginal counterparts. There are also important variations in patterns of ED services use among different Aboriginal groups with COPD in Alberta.
Development and Evaluation of a Simulation-based Curriculum for Ultrasound-guided Central Venous Catheterization
Authors: McGraw Robert , Chaplin Tim , McKaigney Conor , Rang Louise , Jaeger Melanie , Redfearn Damian , Davison Colleen , Ungi Tamas , Holden Matthew , Yeo Caitlin , Keri Zsuzsanna , Fichtinger Gabor
Published: May 2016

Objective

To develop a simulation-based curriculum for residents to learn ultrasound-guided (USG) central venous catheter (CVC) insertion, and to study the volume and type of practice that leads to technical proficiency.

Methods

Ten post-graduate year two residents from the Departments of Emergency Medicine and Anesthesiology completed four training sessions of two hours each, at two week intervals, where they engaged in a structured program of deliberate practice of the fundamental skills of USG CVC insertion on a simulator. Progress during training was monitored using regular hand motion analysis (HMA) and performance benchmarks were determined by HMA of local experts. Blinded assessment of video recordings was done at the end of training to assess technical competence using a global rating scale.

Results

None of the residents met any of the expert benchmarks at baseline. Over the course of training, the HMA metrics of the residents revealed steady and significant improvement in technical proficiency. By the end of the fourth session six of 10 residents had faster procedure times than the mean expert benchmark, and nine of 10 residents had more efficient left and right hand motions than the mean expert benchmarks. Nine residents achieved mean GRS scores rating them competent to perform independently.

Conclusion

We successfully developed a simulation-based curriculum for residents learning the skills of USG CVC insertion. Our results suggest that engaging residents in three to four distributed sessions of deliberate practice of the fundamental skills of USG CVC insertion leads to steady and marked improvement in technical proficiency with individuals approaching or exceeding expert level benchmarks.
Effect of Hurricane Sandy on Health Care Services Utilization Under Medicaid
Authors: Sharp Mark J. , Sun Mingzeng , Ledneva Tatiana , Lauper Ursula , Pantea Cristian , Lin Shao
Published: May 2016

Objective

This investigation assessed changes in utilization of inpatient, outpatient, emergency department, and pharmacy services in the aftermath of Hurricane Sandy in 8 counties in New York affected by the storm.

Methods

Medicaid data for enrollees residing in 8 counties in New York were used to obtain aggregated daily counts of claims for 4 service types over immediate, 3-month, and 1-year periods following the storm. Negative binomial regression was used to compare service utilization in the storm year with the 2 prior years, within areas differentially affected by the storm.

Results

Changes in service utilization within areas inside or outside the storm zone were most pronounced over the 1-year effect period. Differences in service utilization by year were the same by storm zone designation over the immediate effect period for all services.

Conclusions

Results are consistent with previous investigations demonstrating that some of the greatest effects of a disaster on health services utilization occur well beyond the initial event. One-year effects, combined with some 3-month effects, suggests that storm recovery, with its effect on health care services utilization, may have followed different paths in areas designated as inside or outside the storm zone. (Disaster Med Public Health Preparedness. 2016;10:472–484)
Food and Waterborne Disease in the Greater New York City Area Following Hurricane Sandy in 2012
Authors: Bloom Michael S. , Palumbo Jillian , Saiyed Nazia , Lauper Ursula , Lin Shao
Published: May 2016

Objective

We aimed to evaluate residence in evacuation areas (storm areas) as a risk factor for food and waterborne disease (FWBD) associated with Hurricane Sandy flooding.

Methods

We captured 9601 incident outpatient and inpatient FWBD hospital discharge diagnoses for residents of the greater New York City area. We used Poisson or negative binomial regression models to compare the covariate-adjusted risk for a FWBD diagnosis, pre-Sandy (10/28-11/09, 2001-2011) vs. post-Sandy (10/28-11/09, 2012), for residents of “storm” and “non-storm” areas.

Results

Outpatient FWBD risk was lower for storm area residents after Hurricane Sandy (risk ratio [RR]=0.58, 95% confidence interval [CI]: 0.46-0.74), and varied by age, sex, and county. However, storm area residents 65 years of age or older experienced higher risk after Hurricane Sandy (RR=2.16, 95% CI: 1.11-4.19), albeit based on few cases. Inpatient FWBD risk was lower for non-storm area residents after Hurricane Sandy (RR=0.79, 95% CI: 0.66-0.95), and varied by age, race, and county, although there was no significant change for storm area residents (RR=0.86, 95% CI: 0.69-1.08). Those ≥65 years of age were also at lower risk for inpatient FWBD diagnosis, yet the effect was weaker for storm area (RR=0.89, 95% CI: 0.67-1.18) than for non-storm area residents (RR=0.68, 95% CI: 0.52-0.89).

Conclusions

Hurricane preparation, mitigation, and response activities in the greater New York City area may have led to “protective” effects for FWBD. (Disaster Med Public Health Preparedness. 2016;10:503–511)
A continuum approach for predicting segregation in flowing polydisperse granular materials
Authors: Schlick Conor P. , Isner Austin B. , Freireich Ben J. , Fan Yi , Umbanhowar Paul B. , Ottino Julio M. , Lueptow Richard M.
Published: May 2016

Segregation of polydisperse granular materials occurs in many natural and industrial settings, but general theoretical modelling approaches with predictive power have been lacking. Here we describe a model capable of accurately predicting segregation for both discrete and continuous particle size distributions based on a generalized expression for the percolation velocity. The predictions of the model depend on the kinematics of the flow and other physical parameters such as the diffusion coefficient and the percolation length scale, quantities that can be determined directly from experiment, simulation or theory and that are not arbitrarily adjustable. The model is applied to heap and chute flow, and the resulting predictions are consistent with experimentally validated discrete element method (DEM) simulations. Several different continuous particle size distributions are considered to demonstrate the broad applicability of the approach.
Self-destabilising loop of a low-speed water jet emanating from an orifice in microgravity
Authors: Umemura Akira
Published: May 2016

A one-dimensional global mode analysis is conducted for low-speed water jets emanating from a circular orifice in microgravity, in which the observed spontaneous convective instability causes almost periodic jet disintegrations at a fixed location for each jet-issue speed that exceeds a certain threshold. The inviscid spatial linear stability analysis identifies four wave modes excitable at the frequency: the Plateau–Rayleigh (PR) unstable wave, its complex conjugate and two neutral waves which may transfer energy upstream. Their linear combination satisfying the orifice exit condition may describe the synchronised reproduction of a PR unstable wave from each neutral wave at the orifice exit. On the other hand, a weakly nonlinear analysis shows that the growth of the nonlinear PR unstable wave produces the two neutral waves near the orifice. Thus, the same PR unstable wave can be reproduced on a newly issued liquid surface owing to the neutral waves produced by its own nonlinear growth. This self-destabilising loop, dominantly operating for the most unstable PR wave, determines the initial PR unstable wave amplitude and, consequently, the breakup length as a function of jet-issue speed. The predicted initial amplitude of the PR unstable wave is in reasonably good agreement with the value calculated from the average breakup length measured in our microgravity experiments. It is found that that the loop consists mainly of the downstream- and upstream-moving neutral waves at relatively high and low jet speeds, respectively. The stability of the self-destabilising loop is also discussed.
Turbulent/non-turbulent interfaces in wakes in stably stratified fluids
Authors: Watanabe Tomoaki , Riley James J. , de Bruyn Kops Stephen M. , Diamessis Peter J. , Zhou Qi
Published: May 2016

We report on a study, employing direct numerical simulations, of the turbulent/non-turbulent interface of a wake in a stably stratified fluid. It is found that thresholds for both enstrophy and potential enstrophy are needed to identify the interface. Using conditional averaging relative to the location of the interface, various quantities of interest are examined. The thickness of the interface is found to scale with the Kolmogorov scale. From an examination of the Ozmidov and Kolmogorov length scales as well as the buoyancy Reynolds number, it is found that the buoyancy Reynolds number decreases and becomes of order 1 near the interface, indicating the suppression of the turbulence there by the stable stratification. Finally the overall rate of loss of energy due to internal wave radiation is found to be comparable to the overall rate of loss due to turbulent kinetic energy dissipation.
Effects of ice deformation on Röthlisberger channels and implications for transitions in subglacial hydrology
Authors: MEYER COLIN R. , FERNANDES MATHEUS C. , CREYTS TIMOTHY T. , RICE JAMES R.
Published: May 2016

Along the base of glaciers and ice sheets, the sliding of ice over till depends critically on water drainage. In locations where drainage occurs through Röthlisberger channels, the effective pressure along the base of the ice increases and can lead to a strengthening of the bed, which reduces glacier sliding. The formation of Röthlisberger channels depends on two competing effects: (1) melting from turbulent dissipation opens the channel walls and (2) creep flow driven by the weight of the overlying ice closes the channels radially inward. Variation in downstream ice velocity along the channel axis, referred to as an antiplane shear strain rate, decreases the effective viscosity. The softening of the ice increases creep closure velocities. In this way, even a modest addition of antiplane shear can double the size of the Röthlisberger channels for a fixed water pressure or allow channels of a fixed radius to operate at lower effective pressure, potentially decreasing the strength of the surrounding bed. Furthermore, we show that Röthlisberger channels can be deformed away from a circular cross section under applied antiplane shear. These results can have broad impacts on sliding velocities and potentially affect the total ice flux out of glaciers and ice streams.
Feasibility of a clinical trial to assess the effect of dietary calciumv.supplemental calcium on vascular and bone markers in healthy postmenopausal women
Authors: Ong Angel M. , Weiler Hope A. , Wall Michelle , Haddad Rouba , Gorgui Jessica , Daskalopoulou Stella S. , Goltzman David , Morin Suzanne N.
Published: May 2016

Whether supplemental Ca has similar effects to dietary Ca on vascular and bone markers is unknown. The present trial investigated the feasibility of applying dietary and supplemental interventions in a randomised-controlled trial (RCT) aiming to estimate the effect of supplemental Ca as compared with dietary Ca on vascular and bone markers in postmenopausal women. In total, thirteen participants were randomised to a Ca supplement group (CaSuppl) (750 mg Ca from CaCO3+450 mg Ca from food+20 µg vitamin D supplement) or a Ca diet group (CaDiet) (1200 mg Ca from food+10 µg vitamin D supplement). Participants were instructed on Ca consumption targets at baseline. Monthly telephone follow-ups were conducted to assess adherence to interventions (±20 % of target total Ca) using the multiple-pass 24-h recall method and reported pill count. Measurements of arterial stiffness, peripheral blood pressure and body composition were performed at baseline and after 6 and 12 months in all participants who completed the trial (n9). Blood and serum biomarkers were measured at baseline and at 12 months. Both groups were compliant to trial interventions (±20 % of target total Ca intake; pill count ≥80 %). CaSuppl participants maintained a significantly lower average dietary Ca intake compared with CaDiet participants throughout the trial (453 (sd187) mg/dv.1241 (sd319) mg/d;P<0·001). There were no significant differences in selected vascular outcomes between intervention groups over time. Our pilot trial demonstrated the feasibility of conducting a large-scale RCT to estimate the differential effects of supplemental and dietary Ca on vascular and bone health markers in healthy postmenopausal women.
The naturally occurringα-tocopherol stereoisomer RRR-α-tocopherol is predominant in the human infant brain
Authors: Kuchan Matthew J. , Jensen Søren K. , Johnson Elizabeth J. , Lieblein-Boff Jacqueline C.
Published: May 2016

α-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with syntheticα-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural stereoisomerRRR-α-tocopherol.α-Tocopherol stereoisomer profiles have not been previously reported in the human brain. In the present study, we analysed totalα-tocopherol andα-tocopherol stereoisomers in the frontal cortex (FC), hippocampus (HPC) and visual cortex (VC) of infants (n36) who died of sudden infant death syndrome or other conditions.RRR-α-tocopherol was the predominant stereoisomer in all brain regions (P<0·0001) and samples, despite a large intra-decedent range in totalα-tocopherol (5–17 μg/g). MeanRRR-α-tocopherol concentrations in FC, HPC and VC were 10·5, 6·8 and 5·5 μg/g, respectively. In contrast, mean levels of the synthetic stereoisomers wereRRS, 1–1·5;RSR, 0·8–1·0;RSS, 0·7–0·9; and Σ2S0·2–0·3 μg/g. Samples from all but two decedents contained measurable levels of the synthetic stereoisomers, but the intra-decedent variation was large. The ratio ofRRR:the sum of the synthetic 2Rstereoisomers (RRS+RSR+RSS) averaged 2·5, 2·3 and 2·4 in FC, HPC and VC, respectively, and ranged from 1 to at least 4·7, indicating that infant brain discriminates against synthetic 2Rstereoisomers in favour ofRRR. These findings reveal thatRRR-α-tocopherol is the predominant stereoisomer in infant brain. These data also indicate that the infant brain discriminates against the synthetic 2Rstereoisomers, but is unable to do so completely. On the basis of these findings, investigation into the impact ofα-tocopherol stereoisomers on neurodevelopment is warranted.