bluuebunny/crossref_metadata_2025 huggingface dataset:
Spaces of connectivity: The formation of medical travel destinations in Delhi National Capital Region (India)
Authors: Kaspar Heidi , Reddy Sunita
Published: June 2017

Existing research on the formation of Asian medical travel destinations has highlighted a variety of activities that attract and accommodate patients from abroad. This paper contributes to the literature by drawing insights from an Indian case study, a major transnational health‐care hub in Asia that has gained little scholarly attention thus far. Using connectivity as an analytical lens, we understand medical travel destinations as a contingent product of relating, connecting and assembling. We study how connectivity is embodied and how it unfolds in care encounters at corporate hospitals in the capital of New Delhi and surrounding urban areas. The following entities are the most effectual in the networks that constitute medical travel destinations in the National Capital Region: (i) circulating narrations of personal experiences; (ii) language interpreters; and (iii) commission fees. We further elaborate on how these connectors work to link foreign patients with Indian hospitals and how they affect itineraries as well as patients and other involved actors. Finally, we suggest that the approach deployed provides a suitable framework for future research aimed at gaining a better understanding of the wider impacts of medical travel by following these connections and examining their workings at places both close and distant.
Romiplostim monotherapy in thrombocytopenic patients with myelodysplastic syndromes: long‐term safety and efficacy
Authors: Fenaux Pierre , Muus Petra , Kantarjian Hagop , Lyons Roger M. , Larson Richard A. , Sekeres Mikkael A. , Becker Pamela S. , Orejudos Amelia , Franklin Janet
Published: June 2017

Romiplostim can improve platelet counts in about 50% of patients with low‐ or intermediate 1‐risk (lower risk) myelodysplastic syndromes (MDS) and thrombocytopenia, but its long‐term toxicity and efficacy are not known. This open‐label extension study evaluated the long‐term safety and efficacy of romiplostim in 60 patients with lower risk MDS and platelet counts ≤50 × 109/l. The primary endpoint was adverse event (AE) incidence. Secondary endpoints were efficacy parameters, including bleeding events and platelet response. Median (range) treatment time in the extension study and the median observation times thereafter were 25 (2–181) and 57 (11–209) weeks, respectively. Treatment‐related AEs and serious AEs were reported in 14/60 (23%) and 4/60 (7%) patients, respectively. Progression to acute myeloid leukaemia (AML) occurred in two patients after 44 and 46 weeks. Patients (n = 34, 57%) with a platelet response were further evaluated for length of response. Median (range) response duration was 33 (7–174) weeks; 28/34 (82%) patients had a continuous response. Five of 34 patients (15%) had grade ≥3 bleeding events; three when the platelet count was >50 × 109/l. There were no new safety concerns and the rate of progression to AML was low; response to romiplostim was maintained for most patients.
Cemetery Modernisation and the Common Good in Bogotá
Authors: KLAUFUS CHRISTIEN
Published: June 2017

Cemetery planning in high‐density urban areas is essential for more equitable societies in Latin America. This paper addresses the implementation of a cemetery master plan in Bogotá to explore the effects of public policies. I argue that tensions between the ‘city of the dead’ and the ‘city of the living’ demonstrate how politicians and planners increasingly envision public cemeteries as urban infrastructure rather than public space, making it more difficult to manage cemeteries as a public good. This paper engages with debates about urban planning in contemporary Latin America.
Changes in the inflow of saline water into the Bornholm Basin (SW Baltic Sea) during the past 7100 years – evidence from benthic foraminifera record
Authors: Binczewska Anna , Moros Matthias , Polovodova Asteman Irina , Sławińska Joanna , Bąk Małgorzata
Published: June 2017

The Baltic Sea (~393 000 km2) is the largest brackish sea in the world and its hydrographic and environmental conditions are strongly dependent on the frequency of saline water inflows from the North Sea. To improve our understanding of the natural variability of the Baltic Sea ecosystem detailed reconstructions of past saline water inflow changes based on palaeoecological archives are needed. Here we present a high‐resolution study of benthic foraminiferal assemblages accompanied by sediment geochemistry (loss on ignition, total organic carbon) and other microfossil data (ostracods and cladocerans) from a well‐dated 8‐m‐long gravity core taken in the Bornholm Basin. The foraminiferal diversity in the core is low and dominated by species of Elphidium. The benthic foraminiferal faunas in the central Baltic require oxic bottom water conditions and salinities >11–12 PSU. Consequently, shell abundance peaks in the record reflect frequent saline water inflow phases. The first appearance of foraminiferal tests and ostracods in the investigated sediment core is dated to c. 6.9 cal. ka BP and attributed to the first inflows of saline and oxygenated bottom waters into the Bornholm Basin during the Littorina Sea transgression. The transgression terminated the Ancylus Lake phase, reflected in the studied record by abundant cladocerans. High absolute foraminiferal abundances are found within two time intervals: (i) c. 5.5–4.0 cal. ka BP (Holocene Thermal Maximum) and (ii) c. 1.3–0.75 cal. ka BP (Medieval Climate Anomaly). Our data also show three intervals of absent or low saline water inflows: (i) c. 6.5–6.0 cal. ka BP, (ii) c. 3.0–2.3 cal. ka BP and (iii) c. 0.5–0.1 cal. ka BP (Little Ice Age). Our study demonstrates a strong effect of saline and well‐oxygenated water inflows from the Atlantic Ocean on the Baltic Sea ecosystem over millennial time scales, which is linked to the major climate transitions over the last 7 ka.
Pythons, parasites, and pests: anthropogenic impacts on Sarcocystis (Sarcocystidae) transmission in a multi‐host system
Authors: Devan‐Song Anne , Luz Sonja , Mathew Abraham , Low Mary‐Ruth , Bickford David P.
Published: June 2017

Parasites are essential components of ecosystems and can be instrumental in maintaining host diversity and populations; however, their role in trophic interactions has often been overlooked. Three apicomplexan parasite species of Sarcocystis (S. singaporensis, S. zamani, and S. villivillosi) use the reticulated python as their definitive hosts and several species within the Rattus genus as intermediate hosts, and they form a system useful for studying interactions between host–parasite and predator–prey relationships, as well as anthropogenic impacts on parasite transmission. Based on predictions from a 1998 survey, which detected an inverse relationship between urban development and Sarcocystis infection in Rattus, we tested the hypothesis that Sarcocystis transmission in Singapore will decrease over time due to anthropogenic activities. Despite a large proportion of the reticulated python diet consisting of Rattus species at all sizes of pythons, Sarcocystis infection rates decreased from 1998 to 2010. Pythons found in industrial areas had lower Sarcocystis infection rates, particularly in the western industrial area of Singapore Island. Average python size also decreased, with implications that we predict may disrupt host–parasite relationships. Anthropogenic activities such as habitat modification, fragmentation, and systematic removal and translocation of pythons have negative impacts on Sarcocystis transmission in Singapore, which in turn may augment pest rat populations. Trends observed may ultimately have negative impacts on human health and biodiversity in the region.
piR‐823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1
Authors: Yin Jie , Jiang Xiao‐Yu , Qi Wei , Ji Chen‐Guang , Xie Xiao‐Li , Zhang Dong‐Xuan , Cui Zi‐Jin , Wang Cun‐Kai , Bai Yun , Wang Jia , Jiang Hui‐Qing
Published: June 2017

Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.
Impact of binding mechanism on selective inhibition of histone deacetylase isoforms
Authors: Meyners Christian , Meyer‐Almes Franz‐Josef
Published: June 2017

Industrialized drug screening campaigns usually deliver hundreds of compounds that are active on a particular pharmaceutical target. In light of high failure rates of drug candidates due to unforeseeable off‐target toxicity, the early identification of the most promising compounds with high potential for target selectivity is an urgent need to improve the quality of lead compounds and lower attrition rates in the drug development process. The reliable prediction of the selectivity of active substances for a target protein is a challenging task. A comprehensive study of the binding kinetics, thermodynamics, and selectivity of chemically related ligands of histone deacetylase (HDAC) like amidohydrolase from Pseudomonas aeruginosa (HDAHpa) reveals one general binding mechanism for all analyzed compounds consisting of a preceding conformational selection step followed by an optional subsequent induced fit. Depending on the chemical structure, the ligands bind to one or two of at least three protein conformations with different rate constants. Although these kinetic and mechanistic differences hamper the predictability of selectivity for the HDAC inhibitors, we demonstrate that the enthalpy‐weighted binding constant is a useful metric to predict isoform selectivity of inhibitors against HDAC enzymes and relatively robust toward different but related binding mechanisms.
Withasteroid B from D. metel L. regulates immune responses by modulating the JAK/STAT pathway and the IL-17+RORγt+/IL-10+FoxP3+ ratio
Authors: Su Y , Wang Q , Yang B , Wu L , Cheng G , Kuang H
Published: June 2017

Datura metel L. is a medicinal herb that contains withasteroids and has a wide range of biological activities. We isolated seven withasteroids from the flowers of D. metel L and examined their ability to inhibit immune responses in vitro and in vivo. Among the withasteroids, withasteroid B2 exhibited the strongest inhibitory effect on immune responses comparing B2 with other isolated compounds from D. metel L., including suppressing the differentiation of CD4+ T cells by inhibiting the expression and production of T cell lineage-specific master regulators and cytokines and directly suppressing the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathways. In the interleukin (IL)-23-induced mouse ear model of skin disease, B2 repressed disease development by inhibiting the expression of proinflammatory mediators in murine ear skin. Moreover, B2 affected the maturation of dendritic cells (DCs) in vitro which, in turn, induced T cell differentiation with an increased regulatory T cell (Treg) phenotype and decreased T helper type 17 (Th17) phenotype. This study provides new evidence that B2 might ameliorate chronic inflammatory skin diseases by suppressing pathogenic CD4+ T cell differentiation and the IL-17+retinoic-acid-receptor-related orphan receptor gamma t (RORγt)+/IL-10+forkhead box protein 3 (FoxP3)+ ratio. These findings suggest that B2 might mediate the therapeutic effects observed in psoriasis patients following treatment with D. metel L.
The Turner syndrome life course project: Karyotype‐phenotype analyses across the lifespan
Authors: Cameron‐ Pimblett Antoinette , La Rosa Clementina , King Thomas F. J. , Davies Melanie C. , Conway Gerard S.
Published: June 2017

Introduction

Turner syndrome (TS) is associated with a variety of morbidities affecting nearly every body system, some of which increase in prevalence in adult life. The severity of clinical features in TS is roughly in parallel with the magnitude of the deficit of X‐chromosome material. The aim of this study was to extend the established karyotype‐phenotype relationships using data from a large adult cohort.

Materials and Methods

Karyotypes were available in 656 women with TS. 611 of whom could be classified into five major groups within the cohort: 45,X; 45,X mosaicism (45,X/46,XX); isochromosome X (isochromosome Xq); mosaicism 45,X/46,XY and ring X.

Continuous variables such as blood pressure and biochemical markers from clinic data were binarised allocating those in the upper quartile to represent at‐risk individuals. With the exception of bone mineral density T‐score for which the lower quartile was allocated as at risk. For comorbidities, initiation of formal treatment was recorded.

Results

45,X/46,XX had considerably lower frequency of comorbidities compared to 45,X. The isochromosome group experienced similar outcomes to 45,X. Novel associations were found between the XY mosaic karyotype group and a decreased prevalence of thyroid disease and severe hearing loss. A previously unreported increased incidence of metabolic syndrome was noted within the ring chromosome subgroup.

Conclusions

Karyotype may play an important factor against stratifying risk of comorbidity in TS and should be taken into consideration when managing adults with TS. Further investigations of the isochromosome (Xq) and ring groups are necessary to further clarify their associations with comorbidities.
Incidence of parathyroid disorders in Indian adult male population: A 25‐year follow‐up study
Authors: Hari Kumar K.V.S. , Patnaik S.K.
Published: June 2017

Context and objective

Detailed information on the epidemiology of parathyroid disorders in India is lacking. Most of the available data pertain to primary hyperparathyroidism (PHPT) rather than the overall burden of parathyroid disorders. We studied the incidence of parathyroid disorders in a cohort of service personnel followed for a long duration.

Design, setting and patients:

The data for this retrospective, descriptive epidemiological study were derived from the electronic medical records (EMR) of health care personnel enrolled between 1990 and 2015. Subjects were recruited between the ages of 17 and 20 years in good health, and the data pertaining to parathyroid disorders were derived from the EMR.

Main outcomes measures

We calculated the incidence rates per person‐years of parathyroid disorders using appropriate statistical methods.

Results

Our analysis includes 51 217 participants (median age 33, range 17‐54 years) with a mean follow‐up of 12.5 years. Yearly evaluation of the data gave cumulative follow‐up duration of 613 925 person‐years. PHPT was diagnosed in 37 patients and hypoparathyroidism in 16 patients, giving incidence rates of 6 and 2.6 per 100 000 person‐years, respectively. Only one patient was diagnosed with pseudohypoparathyroidism (0.16 per 100 000 person‐years). Of the 37 patients with PHPT, 16 (43%) developed postsurgical hypoparathyroidism.

Conclusions

Our cohort had a low incidence of PHPT when compared to Western populations. Long‐term epidemiological studies are essential to identify the demographic trends of metabolic bone disorders in India.
SAV1 represses the development of human colorectal cancer by regulating the Akt‐mTOR pathway in a YAP‐dependent manner
Authors: Jiang Jianwu , Chang Wei , Fu Yang , Gao Yongshun , Zhao Chunlin , Zhang Xiefu , Zhang Shuijun
Published: June 2017

Objectives

SAV1 is a human homologue of Salvador that contains two protein‐protein interaction modules known as WW domains and acts as a scaffolding protein. SAV1 participates in the development of diverse types of cancer. We aimed to investigate the role of SAV1 in human colorectal cancer.

Materials and methods

Human colorectal cancer samples were used to study the expression of SAV1 and YAP. Loss‐of‐function and gain‐of‐function strategies were used to study the effects of SAV1 on colorectal cancer cell growth. Rapamycin was used to treat cells and mice to investigate the effect of mTOR signalling.

Results

SAV1 represses the development of colorectal cancer by inhibiting the Akt‐mTOR signalling in a YAP‐dependent manner. The mRNA and protein levels of SAV1 are down‐regulated in human colorectal cancer tissues compared with adjacent non‐cancer tissues. SAV1 knockdown promotes the growth of colorectal cancer cells in vitro and in vivo, whereas SAV1 overexpression leads to opposing results. SAV1 represses the activation of the Akt‐mTOR signalling, and rapamycin treatment blunts the effects of SAV1 on in vitro and in vivo growth of colorectal cancer cells. Finally, we show that SAV1 promotes the phosphorylation and inactivation of YAP, which contributes to the effect of SAV1 on Akt‐mTOR signalling pathway.

Conclusions

SAV1 is a repressor during the development of human colorectal cancer by inhibiting the YAP‐Akt‐mTOR signalling pathway.
Tiger abundance and gene flow in Central India are driven by disparate combinations of topography and land cover
Authors: Reddy P. Anuradha , Cushman Samuel A. , Srivastava Ankita , Sarkar Mriganka Shekhar , Shivaji Sisinthy
Published: June 2017

Aim

Effective conservation of the endangered tiger depends upon reliable knowledge of factors driving genetic differentiation and population connectivity. Connectivity models frequently use resistance surfaces not optimized with actual movement or genetic data which limits reliability. Our aim is to use empirical data on genetic diversity of tiger populations to optimize landscape resistance to gene flow and identify factors that predict local population abundance across Central India.

Location

The study area covers 697,000 km2 across Madhya Pradesh and parts of Rajasthan, Jharkhand and Maharashtra.

Methods

We used genetic data of 309 tigers and restricted multivariate optimization of correlation between landscape variables and genetic distance in a reciprocal causal modelling framework to parameterize a resistance surface for gene flow. We further evaluated the association between effective population size and landscape connectivity using all‐subsets logistic regression with model averaging based on AICc.

Results

Gene flow is primarily related to topographic roughness and slope position and secondarily to human footprint and land cover. It is much higher in areas of rough topography and ridge tops and is facilitated by forest cover in areas with low human footprint. In contrast, effective population size in protected areas is primarily driven by extent of protected areas and surrounding forest cover, and is not significantly related to resistant kernel connectivity value.

Main Conclusions

This is the first study to use a rigorous multivariate optimization approach to identify factors which limit gene flow of tigers. Tiger movement is highly affected by landscape features, and dispersing tigers move through rough terrain along forested ridges, avoiding non‐forest areas with high human footprint, while local tiger population density is driven primarily by the extent of protected forested habitat. These results have important implications for tiger conservation and can be used to develop empirically supported prioritization of core areas and corridors.
Losing concentration? Lessons from a Swedish aid policy reform
Authors: Hagen Rune Jansen
Published: June 2017

Sweden is one of the donor countries that signed up for the Paris Agenda, which among other things advocated reducing aid dispersion. It also adopted its own geographical concentration policy in 2007. My empirical analysis shows that Sweden managed to achieve this goal only for two years following the reform and that this was followed by backsliding. Moreover, its current aid policy framework barely mentions the topic. I argue that a major reason was the failure to institutionalize the policy. This left it vulnerable to the regular politics of aid, which tend to generate both geographic and thematic spread. Reduced peer pressure, as the international community has moved away from the Paris Agenda, might also have contributed.
BCRP mRNA and FLT3‐ITD are independent poor risk factors in adult patients with acute myeloid leukemia and intermediate or normal karyotype
Authors: Nasiłowska‐Adamska Barbara , Warzocha Krzysztof , Solarska Iwona , Borg Katarzyna , Pieńkowska‐Grela Barbara , Czyż Anna
Published: June 2017

Purpose

FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) is aberration associated with poor prognosis in AML. We have analyzed the expression of MDR‐1, MRP‐1, and BCRP mRNA in relation to FLT3‐ITD in 100 AML adult patients with normal and intermediate karyotype.

Methods

The RQ‐PCR method was performed to assess the expression of MDR‐1, MRP‐1, and BCRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule.

Results

According to univariate analysis, the following pretreatment variables negatively influenced disease‐free survival (DFS): WBC count ≥25×109/L (P=.037), MRP‐1 mRNA ≥1.6818 (P=.028), BCRP mRNA ≥1.1892 (P=.004), FLT3‐ITD (P=.005) and overall survival (OS): WBC count ≥25×109/L (P=.031), MRP‐1 mRNA ≥1.6818 (P=.01), BCRP mRNA ≥1.1892 (P=.01), FLT3‐ITD (P=.001). When all prognostic variables were pooled into a multivariate model, we found that WBC count ≥25×109/L (P=.026) and BCRP mRNA ≥1.1892 (P=.011). We observed trend in negative influence of FLT3‐ITD on DFS (P=.057). BCRP mRNA ≥1.1892 (P=.035) and FLT3‐ITD (P=.006) negatively, independently influenced the OS.

Conclusions

The high expressions of BCRP mRNA calculated with Pfaffl's rule and FLT3‐ITD are independent poor risk factors in adult patients with AML and intermediate or normal karyotype.
ABCG2 and CD200 define patients at high risk of relapse in ELN favorable subgroup of AML
Authors: Tiribelli Mario , Geromin Antonella , Cavallin Margherita , Di Giusto Sara , Simeone Erica , Fanin Renato , Damiani Daniela
Published: June 2017

Objective

Overexpression of ABCG2 and CD200 has been independently associated with poor outcome in acute myeloid leukemia (AML). However, no data are available on the role of these two factors in patients with core‐binding factor (CBF)‐positive or FLT3‐negative/NPM1‐mutated cytogenetically normal (CN) AML.

Methods

We analyzed 65 adult AML patients with CBF+ (n=16) or FLT3−/NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia‐free survival (LFS) and overall survival (OS).

Results

ABCG2 was expressed in 36 (55%) cases, and CD200 was positive in 33 (51%) cases, six at high levels. Both ABCG2 and CD200 positivity have a negative impact on relapse risk: 3‐year LFS was 51% vs 82% in ABCG2+ cases (RR 3.3), 49% vs 82% in CD200+ patients (RR=4.4), and 25% in CD200− high cases (RR=17.1). ABCG2 and CD200 affected also OS with 3‐year OS of 39% in ABCG2+ (compared to 71% in ABCG2−; RR=2.6) and CD200+ (compared to 68% in CD200−; RR=2.5) patients.

Conclusions

Our data confirm a negative impact of ABCG2 and CD200 overexpression also in AML patients considered at favorable risk according to ELN cytogenetic/molecular classification.
Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open‐label clinical study with cannabidiol
Authors: Rosenberg Evan C. , Louik Jay , Conway Erin , Devinsky Orrin , Friedman Daniel
Published: June 2017

Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment‐resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver‐reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open‐label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9‐point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure‐reducing effects; however, further studies in placebo‐controlled, double‐blind trials are necessary to confirm this finding.
Liver microsomal lipid enhances the activity and redox coupling of colocalized cytochrome P450 reductase‐cytochrome P450 3A4 in nanodiscs
Authors: Liu Kang‐Cheng , Hughes John M. X. , Hay Sam , Scrutton Nigel S.
Published: June 2017

The haem‐containing mono‐oxygenase cytochrome P450 3A4 (CYP3A4) and its redox partner NADPH‐dependent cytochrome P450 oxidoreductase (CPR) are among the most important enzymes in human liver for metabolizing drugs and xenobiotic compounds. They are membrane‐bound in the endoplasmic reticulum (ER). How ER colocalization and the complex ER phospholipid composition influence enzyme activity are not well understood. CPR and CYP3A4 were incorporated into phospholipid bilayer nanodiscs, both singly, and together in a 1 : 1 ratio, to investigate the significance of membrane insertion and the influence of varying membrane composition on steady‐state reaction kinetics. Reaction kinetics were analysed using a fluorimetric assay with 7‐benzyloxyquinoline as substrate for CYP3A4. Full activity of the mono‐oxygenase system, with electron transfer from NADPH via CPR, could only be reconstituted when CPR and CYP3A4 were colocalized within the same nanodiscs. No activity was observed when CPR and CYP3A4 were each incorporated separately into nanodiscs then mixed together, or when soluble forms of CPR were mixed with preassembled CYP3A4‐nanodiscs. Membrane integration and colocalization are therefore essential for electron transfer. Liver microsomal lipid had an enhancing effect compared with phosphatidylcholine on the activity of CPR alone in nanodiscs, and a greater enhancing effect on the activity of CPR‐CYP3A4 nanodisc complexes, which was not matched by a phospholipid mixture designed to mimic the ER composition. Furthermore, liver lipid enhanced redox coupling within the system. Thus, natural ER lipids possess properties or include components important for enhanced catalysis by CPR‐CYP3A4 nanodisc complexes. Our findings demonstrate the importance of using natural lipid preparations for the detailed analysis of membrane protein activity.
Lipid interactions modulate the structural and antigenic properties of the C‐terminal domain of the malaria antigen merozoite surface protein 2
Authors: Das Sreedam C. , Morales Rodrigo A.V. , Seow Jeffrey , Krishnarjuna Bankala , Dissanayake Ravindu , Anders Robin F. , MacRaild Christopher A. , Norton Raymond S.
Published: June 2017

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI‐anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full‐length MSP2 with lipid surfaces induces a conformational change in the conserved N‐terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C‐terminal region of MSP2, a construct corresponding to this domain, MSP2172–221, was designed. NMR studies indicate that many residues in MSP2172–221 interact with DPC micelles, including some in epitopes recognised by C‐terminal‐specific monoclonal antibodies, but, in contrast to the MSP2 N‐terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172–221 is antigenically similar to full‐length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172–221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates.

Databases

Resonance assignments are available in the BioMagResBank (BMRB) database under the accession number 27134.
Towards improved ODS steels: A comparative high‐temperature low‐cycle fatigue study
Authors: Chauhan A. , Walter M. , Aktaa J.
Published: June 2017

Within the frame of this work, the mechanical behaviour of a bimodal ferritic 12Cr‐ODS steel as well as of a ferritic‐martensitic 9Cr‐ODS steel under alternating load conditions was investigated. In general, strain‐controlled low‐cycle fatigue tests at 550°C and 650°C revealed similar cyclic stress response. At elevated temperatures, the two steels manifest transitional stages, ie, cyclic softening and/or hardening corresponding to the small fraction of the cyclic life, which is followed by a linear cyclic softening stage that occupies the major fraction of the cyclic life until failure. However, it is clearly seen that the presence of the nano‐sized oxide particles is certainly beneficial, as the degree of cyclic softening is significantly reduced compared with non‐ODS steels. Besides, it is found that both applied strain amplitude and testing temperature show a strong influence on the cyclic stress response. It is observed that the degree of linear cyclic softening in both steels increases with increasing strain amplitude and decreasing test temperature. The effect of temperature on inelastic strain and hence lifetime becomes more pronounced with decreasing applied strain amplitude. When analysing the lifetime behaviour of both ODS steels in terms of inelastic strain energy calculations, it is found that comparable inelastic strain energies lead to similar lifetimes at 550°C. At 650°C, however, the higher inelastic strain energies of 12Cr‐ODS steel result in significant lower lifetimes compared with those of the 9Cr‐ODS steel. The strong degradation of the cyclic properties of the 12Cr‐ODS steel is obviously linked to the fact that the initial hardening response appears significantly more pronounced at 650°C than at 550°C. Finally, the obtained results depict that the 9Cr‐ODS steel offers higher number of cycles to failure at 650°C, compared with other novel ODS steels described in literature.
Crack incubation in shot peened AA7050 and mechanism for fatigue enhancement
Authors: Chadwick Daniel J. , Ghanbari Siavash , Bahr David F. , Sangid Michael D.
Published: June 2017

Shot peening is a dynamic cold‐working process involving the impingement of peening media onto a substrate surface. Shot peening is commonly used as a surface treatment technique within the aerospace industry during manufacturing to improve fatigue performance of structural components. The compressive residual stress induced during shot peening results in fatigue crack growth retardation, improving the performance of shot‐peened components. However, shot peening is a compromise between the benefit of inducing a compressive residual stress and causing detrimental surface damage. Because of the relatively soft nature of AA7050‐T7451, shot peening can result in cracking of the constituent precipitate particles, creating an initial damage state. The aim of this paper is to understand the balance and fundamentals of these competing phenomena through a comparative study throughout the fatigue lifecycle of baseline versus shot‐peened AA7050‐T7451. Microstructure and surface topology characterization and comparison of the baseline and shot‐peened AA7050‐T7451 has been performed using scanning electron microscopy, electron backscatter diffraction, energy dispersive spectroscopy, and optical profilometry techniques. A residual stress analysis through interrupted fatigue of the baseline and shot‐peened AA7050‐T7451 was completed using a combination of X‐ray diffraction and nanoindentation. The fatigue life performance of the baseline versus shot‐peened material has been evaluated, including crack initiation and propagation. Subsurface particles crack upon shot peening but did not incubate into the matrix during fatigue loading, presumably due to the compressive residual stress field. In the baseline samples, the particles were initially intact, but upon fatigue loading, crack nucleation was observed in the particles, and these cracks incubated into the matrix. In damage tolerant analysis, an initial defect size is needed for lifetime assessment, which is often difficult to determine, leading to overly conservative evaluations. This work provides a critical assessment of the mechanism for shot peening enhancement for fatigue performance and quantifies how incubation of a short crack is inhibited from an initially cracked particle into the matrix within a residual stress field.
Direct and indirect effects of predatory young‐of‐year fishes in a dryland river food web
Authors: Krabbenhoft Corey A. , Burdett Ayesha S. , Turner Thomas F.
Published: June 2017

Young‐of‐year (YOY) fishes are sometimes numerically dominant vertebrate consumers in many large river systems, but their effects as predators are not as well understood as those of adult fishes. We predicted that YOY fishes influence community composition and abundance of invertebrate prey. Predation effects could be especially important in recruitment‐driven dryland river systems, where YOY fishes seasonally comprise a large portion of overall fish biomass.

We conducted a mesocosm experiment to quantify effects of YOY fishes on trophic dynamics and interactions with environmental factors in a dryland river food web. We manipulated presence of YOY fishes (an assemblage of cypriniform species) and supplemental allochthonous carbon (LEAF treatments) in 24 mesocosms, and measured invertebrate abundance and diversity over 6 weeks. Experimental conditions mimicked a seasonal river drying regime that occurs during YOY fish growth. Seasonal drying in the Rio Grande frequently results in isolated pools with altered habitat complexity and riparian connectivity.

Fishes exerted direct top‐down control of invertebrate assemblage composition through differential prey selection, and indirect control mediated by non‐lethal responses of invertebrates to predatory fishes. We observed enhanced water clarity in LEAF treatments associated with greater prey selectivity in fishes, presumably through enhanced visual feeding. Stable isotope analysis (C and N) was used to measure indirect impacts of YOY fishes on invertebrate prey items. YOY fishes caused a significant decrease in “isotopic niche breadth” among invertebrate taxa, suggesting that fish predators limit foraging opportunities for these consumers. However, allochthonous carbon sources were predominant in invertebrate diets in all LEAF treatments, suggesting consumer access to more biologically available autochthonous production is limited by factors other than fish predation.

Although the roles of abiotic drivers and adult fishes in determining food web structure have received more attention, our results indicate that YOY fishes exert biologically relevant top‐down control of invertebrate assemblage composition and trophic complexity in dryland river ecosystems against a backdrop of substantial changes in carbon availability and abiotic conditions (e.g. water quality and habitat volume) over the growing season.
Framing bovine tuberculosis: a ‘political ecology of health’ approach to circulation of knowledge(s) about animal disease control
Authors: Robinson Philip A
Published: June 2017

Bovine tuberculosis (bTB) remains a significant animal health problem with a global distribution. In addition to the ecological complexities, socio‐economic and socio‐cultural factors also affect efforts to control and eliminate the disease. Interrogating bTB from the author's positionality of being both a veterinary epidemiologist and a human geographer, this interdisciplinary engagement in the political ecology of health investigates the experiences and opinions of the actors involved in disease control. The findings of this research in one part of the United Kingdom – Northern Ireland – demonstrate gaps between expert scientific discourse and circulating on‐the‐ground perceptions and lay knowledges of the disease. bTB is therefore known and framed in multiple, often antithetical, ways by those who meet and experience the disease on farms. The paper concludes that farmers, vets and state policy‐makers must accept the heterogeneity of the disease; make it visible again; and create new imaginaries for a future where bTB is no longer an everyday ubiquity.
“Hug‐an‐orphan vacations”: “Love” and emotion in orphanage tourism
Authors: Guiney Tess
Published: June 2017

Experiences involving vulnerable children are among the most popular volunteer tourism practices. Celebrity humanitarianism and aid campaigns promote images of vulnerable children receiving love and care from international celebrities and humanitarian actors (mainly women), normalising intimacy within popular humanitarianism, or “hug‐an‐orphan” vacations – vacations where tourists crave direct contact with children in global South countries (Schimmelpfennig, 2011, http://goodintents.org/orphanages/hug-an-orphan-vacations-3). Through accounts given by orphanage directors, volunteers, and commentaries on orphanage tourism, this paper describes the layered emotional entanglements within orphanage tourism. Volunteer tourism literature increasingly recognises the importance of affect in such experiences, principally concentrating on how it leads to its growing popularity. Indeed, many volunteer tourists are motivated from a distance to volunteer at orphanages, being drawn to the possibility of engaging with children. However, their emotions within these encounters are far less examined, and the reality of the lifestyle these children live in is often far more upsetting than expected. Regarding the orphans themselves, the argument I make within this paper is that the commodification of children through orphanage tourism experiences has resulted in an expectation that they will interact with tourists in particular forms. Children are expected to be “poor‐but‐happy” and to engage intimately with volunteers and visitors to engender tourist satisfaction and encourage sympathy and donations. The performance of this behaviour is mediated and controlled by their emotional supervisors, orphanage directors. Through volunteer tourism, children are now a tourist commodity, utilising their love and emotions and creating space for exploitation.
Groundwater Quality: Analysis of Its Temporal and Spatial Variability in a Karst Aquifer
Authors: Pacheco Castro Roger , Pacheco Ávila Julia , Ye Ming , Cabrera Sansores Armando
Published: June 2017

This study develops an approach based on hierarchical cluster analysis for investigating the spatial and temporal variation of water quality governing processes. The water quality data used in this study were collected in the karst aquifer of Yucatan, Mexico, the only source of drinking water for a population of nearly two million people. Hierarchical cluster analysis was applied to the quality data of all the sampling periods lumped together. This was motivated by the observation that, if water quality does not vary significantly in time, two samples from the same sampling site will belong to the same cluster. The resulting distribution maps of clusters and box‐plots of the major chemical components reveal the spatial and temporal variability of groundwater quality. Principal component analysis was used to verify the results of cluster analysis and to derive the variables that explained most of the variation of the groundwater quality data. Results of this work increase the knowledge about how precipitation and human contamination impact groundwater quality in Yucatan. Spatial variability of groundwater quality in the study area is caused by: a) seawater intrusion and groundwater rich in sulfates at the west and in the coast, b) water rock interactions and the average annual precipitation at the middle and east zones respectively, and c) human contamination present in two localized zones. Changes in the amount and distribution of precipitation cause temporal variation by diluting groundwater in the aquifer. This approach allows to analyze the variation of groundwater quality controlling processes efficiently and simultaneously.
Gamma‐Aminobutyric Acid (Gaba) Receptors Rho (Gabrr) Gene Polymorphisms and Risk for Migraine
Authors: García‐Martín Elena , Martínez Carmen , Serrador Mercedes , Alonso‐Navarro Hortensia , Navacerrada Francisco , Esguevillas Gara , García‐Albea Esteban , Agúndez José A. G. , Jiménez‐Jiménez Félix Javier
Published: June 2017

Background/objectives

The possible role of gammaaminobutyric acid (GABA) in the pathogenesis of migraine has been suggested by a number of biochemical, pharmacological, neurophysiological and experimental data. We investigated the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptor rho1, 2, and 3 genes (GABRR1, GABRR2, and GABRR3) and the risk of developing migraine.

Methods

The frequency of GABRR1 rs12200969, GABRR1 rs1186902, GABRR2 rs282129, and GABRR3 rs832032 genotypes and allelic variants were studied in a case‐control association study involving 197 patients with migraine and 278 healthy controls by means of a TaqMan‐based qPCR Assay. We also studied the possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes.

Results

The frequencies of the genotypes and allelic variants of the 4 SNPs were similar in migraine patients and controls. Gender, positive family history of migraine, presence or absence of aura, and triggering of migraine attacks by ethanol did not influence the frequency of these genotypes. Carriers of the minor allele of the rs1186902 SNP showed a trend towards later onset of migraine.

Conclusion

The most common polymorphisms in the GABRR genes seemed to be not associated with the risk for migraine in Caucasian Spanish people, although one of them (GABRR1 rs1186902) shows a statistically significant association with the age of onset of migraine.
Prevalence of Restless Legs Syndrome in Migraine Patients: A Case‐Control Study. Analysis of Risk Factors for Restless Legs Syndrome in Migraine Patients
Authors: Valente Mariarosaria , Janes Francesco , Russo Valentina , Fontana Augusto , Travanut Alessia , Sommaro Martina , Canal Giessica , Gentile Carolina , Luigi Gigli Gian
Published: June 2017

Background

Restless legs syndrome (RLS) is a sensorimotor disorder. It can be idiopathic, associated to other diseases or to pharmacologic treatments. RLS has been reported to occur more frequently in migraine patients, but a clear pathogenetic link seems still under debate. We aimed to evaluate RLS prevalence in migraine, impact on sleep quality and the main clinical determinants of this association.

Methods

Migraine patients and age‐ and sex‐matched controls were enrolled from 1st January 2011 to 30th December 2012. Migraine and RLS diagnosis complied with already published clinical criteria. Medical and pharmacological histories, as well as structured questionnaires were collected.

Results

RLS was found in 29/180 (16.1%) patients and 11/180 (6.1%) controls. The odds ratio (OR) for RLS was 2.95 (CI 95%, 1.42‐6.11). Among migraine patients, after adjustment for possible confounding factors, familial history (OR 3.863, CI 1.076‐13.873), and serotoninergic overload (OR 3.654, CI 1.347‐9.916) were significantly associated with RLS occurrence. Pittsburgh Sleep Quality Index score was higher in migraine patients with RLS than in subjects without RLS.

Conclusions

The confirmed association between migraine and RLS might be because of familial predisposition and to serotoninergic drugs effect, possibly interfering with the balance between dopaminergic and serotoninergic pathways.
A qualitative formative evaluation of a patient‐centred patient safety intervention delivered in collaboration with hospital volunteers
Authors: Louch Gemma , O'Hara Jane , Mohammed Mohammed A.
Published: June 2017

Background

Evidence suggests that patients can meaningfully feed back to healthcare providers about the safety of their care. The PRASE (Patient Reporting and Action for a Safe Environment) intervention provides a way to systematically collect feedback from patients to support service improvement. The intervention is being implemented in acute care settings with patient feedback collected by hospital volunteers for the first time.

Objective

To undertake a formative evaluation which explores the feasibility and acceptability of the PRASE intervention delivered in collaboration with hospital volunteers from the perspectives of key stakeholders.

Design

A qualitative evaluation design was adopted across two acute NHS trusts in the UK between July 2014 and November 2015. We conducted five focus groups with hospital volunteers (n=15), voluntary services and patient experience staff (n=3) and semi‐structured interviews with ward staff (n=5). Data were interpreted using framework analysis.

Results

All stakeholders were positive about the PRASE intervention as a way to support service improvement, and the benefits of involving volunteers. Volunteers felt adequate training and support would be essential for retention. Staff concentrated on the infrastructure needed for implementation and raised concerns around sustainability. Findings were fed back to the implementation team to support revisions to the intervention moving into the subsequent summative evaluation phase.

Conclusion

Although there are concerns regarding sustainability in practice, the PRASE intervention delivered in collaboration with hospital volunteers is a promising approach to collect patient feedback for service improvement.