bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Fracture Enhances Trauma Brain Injury
Authors: Yang L. , Guo Y. , Wen D. , Yang L. , Chen Y. , Zhang G. , Fan Z.
Published: October 2015

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity in young individuals worldwide. However, the understanding of TBI at secondary phase remained obscure, and more knowledge of the pathophysiology of TBI is necessary. In this study, we examined the influence of bone fracture (BF) on TBI and investigated whether blocking high mobility group 1 (HMGB1) protein, an inflammatory mediator, could be effective to alleviate TBI. We found neurological severity was significantly increased by BF at 4 days post‐TBI with longer removal time of adhesive tape and higher percentage of left turn in the corner test compared to TBI treatment alone. Additionally, higher brain lesion volume and severer brain oedema in TBI + BF mice supports the negative effect of BF on TBI. HMGB1 level was significantly stimulated by BF, suggesting the important role of HMGB1 in the development of secondary TBI. Notably, ablation of HMGB1 significantly reduced this negative influence of BF on TBI. These results suggest that HMGB1 can be massively induced by the systemic immune activation triggered by BF, which in turn aggravates inflammation. Blocking HMGB1 reduced the inflammatory effect of BF and therefore helps lessen the severity of secondary TBI. In conclusion, these results provided the evidence that anti‐HMGB1 may be an effective and feasible method to alleviate TBI.
Governing emergencies: the politics of delay and the logic of response
Authors: Anderson Ben
Published: October 2015

The paper focuses on the problematisation of delay in state response to the event of 7/7 in the UK in 2005 as a way of understanding how emergencies are governed. It argues that the widespread political, public and organisational concern in the UK with the delayed state is one expression of a distinct logic of governing emergencies: response. Focusing on the declaration of a ‘major incident’ by the UK emergency services, the paper argues that the logic of response is expressed in the tension between acting in an ‘interval’ as a space‐time of emergence and the generation of ‘intervals’ for action. As well as following how the logic of response operates in UK emergency management, the paper offers a conceptual vocabulary designed to understand the multiplicity of ways in which emergencies are governed. Emergency is conceptualised as a ‘mode of eventfulness’ (Berlant L 2011 Cruel optimism Duke University Press, London) characterised by the hope that action will make a difference as harms, damages or losses emerge. The government of emergency involves situations ‘becoming‐emergency’ through particular combinations of apparatuses of emergency and logics. The concern in the UK with delay in response to 7/7 is one example of the intersection of the logic of response with a particular apparatus based on a biopolitics of survival and the promise that lives can be saved by treating emergencies as logistical challenges.
ABO blood group incompatibility as an adverse risk factor for outcomes in patients with myelodysplastic syndromes and acute myeloid leukemia undergoing HLA‐matched peripheral blood hematopoietic cell transplantation after reduced‐intensity conditioning
Authors: Hefazi Mehrdad , Litzow Mark , Hogan William , Gastineau Dennis , Jacob Eapen , Damlaj Moussab , Hashmi Shahrukh , Al‐Kali Aref , Patnaik Mrinal M.
Published: October 2015

BACKGROUND

ABO incompatibility is not a contraindication to hematopoietic cell transplantation (HCT), but it has been associated with additional risks including delayed engraftment, pure red cell aplasia (PRCA), and higher transfusion needs. Data on these events and on patient survival after reduced‐intensity conditioning (RIC) HCT are limited.

STUDY DESIGN AND METHODS

A total of 127 consecutive patients, 86 with acute myeloid leukemia and 41 with myelodysplastic syndromes, who underwent HLA‐matched peripheral blood RIC allogenic HCT between 2005 and 2014 were retrospectively analyzed.

RESULTS

Eighty ABO‐compatible, 26 major/bidirectional, and 21 minor‐ABO‐mismatch HCT were identified. Compared to the ABO‐compatible group, major/bidirectional mismatches had increased red blood cell (RBC) transfusion requirement during the first 100 days (p = 0.009), delayed RBC and PLT engraftment (p = 0.0011 and p = 0.005, respectively), and higher incidence of grade II to IV acute graft‐versus‐host disease (aGVHD; p = 0.037). In multivariable analysis, major/bidirectional mismatches had significantly higher non‐relapse mortality (NRM) and inferior disease‐free survival (DFS) and overall survival (OS) compared with ABO‐compatible patients (p = 0.01, p = 0.04, and p = 0.035, respectively). Minor ABO mismatch had no impact on survival (p = 0.99). Four (15%) of 26 major/bidirectional mismatches developed PRCA. There was a significant association between fludarabine plus busulfan conditioning and PRCA (p = 0.0046).

CONCLUSION

Major/bidirectional ABO mismatch is associated with higher NRM and shortened DFS and OS in the setting of RIC HCT. Increased transfusion need, delayed RBC and platelet engraftment, PRCA, and increased severity of aGVHD are additional complications contributing to the morbidity.
Platelet components associated with adverse reactions: predictive value of mitochondrial DNA relative to biological response modifiers
Authors: Cognasse Fabrice , Aloui Chaker , Anh Nguyen Kim , Hamzeh‐Cognasse Hind , Fagan Jocelyne , Arthaud Charles‐Antoine , Eyraud Marie‐Ange , Sebban Marc , Fromont Elisa , Pozzetto Bruno , Laradi Sandrine , Garraud Olivier
Published: October 2015

BACKGROUND

Biological response modifiers (BRMs), secreted by platelets (PLTs) during storage, play a role in adverse events (AEs) associated with transfusion. Moreover, mitochondrial DNA (mtDNA) levels in PLT components (PCs) are associated with AEs. In this study we explore whether there is a correlation between pathogenic BRMs and mtDNA levels and whether these markers can be considered predictors of transfusion pathology.

STUDY DESIGN AND METHODS

We investigated a series of reported AEs after PC transfusion, combining clinical observations and mathematical modeling systems.

RESULTS

mtDNA was consistently released during the first days of PC storage; however, mtDNA release was earlier in “pathogenic” than in nonpathogenic PCs. PC supernatants with high levels of mtDNA along with soluble CD40 ligand (sCD40L) were significantly associated with occurrences of AEs. The fact that mtDNA did not associate with the 14 BRMs tested suggests the role of mtDNA in PC transfusion‐linked inflammation is independent of that of BRMs, known to be associated with AEs. We present evidence that PLTs generate distinct pathogenic secretion profiles of BRMs and mtDNA. The calculated area under the curve for mtDNA was significantly associated with AEs, although less stringently predictive than those of sCD40L or interleukin‐13, standard predictors of AE. The established model predicts that distinct subtypes of AEs can be distinguished, dependent on mtDNA levels and PC storage length.

CONCLUSIONS

Further work should be considered to test the propensity of mtDNA in PLT concentrates to generate inflammation and cause an AE.
Simply connected varieties in characteristic
Authors: Esnault Hélène , Srinivas Vasudevan , Bost Jean-Benoît
Published: October 2015

We show that there are no non-trivial stratified bundles over a smooth simply connected quasi-projective variety over an algebraic closure of a finite field if the variety admits a normal projective compactification with boundary locus of codimension greater than or equal to $2$.
Determining the consequences of maternal obesity for offspring health
Authors: Patel Nashita , Pasupathy Dharmintra , Poston Lucilla
Published: October 2015

New Findings

What is the topic of this review?

Observational studies have highlighted the association of increasing maternal body mass index with offspring adiposity and the subsequent risk of cardiometabolic disorders in adulthood. The in utero environment has become a target for intervention in order to reduce the burden of obesity, despite the mechanistic pathways of this association remaining unclear.

What advances does it highlight?

This short review provides a critical appraisal of the recent literature, including biological pathways and strategies to address causal relationships.

The global obesity epidemic has been causally linked to changes in diet and lifestyle. Observational data and animal studies have now highlighted associations between in utero environmental exposures and increased susceptibility to obesity and related cardiometabolic disorders in later life. Maternal body mass index has been reported to show an independent association with offspring adiposity from an early age and to play an important role in the predisposition to obesity and metabolic disease in later life. Thus, the in utero environment has been the focus of recent targeted interventions to improve public health. In this review, we summarize recent progress in this field, including the use of animal models to investigate mechanistic links between maternal obesity and offspring metabolic risk. We then assess the level of evidence and challenges in establishing causal inferences from present birth cohorts.
Numerical Prediction of Maximum Load-Carrying Capacity of Cracked Alloy 690TT Steam Generator Tubes
Authors: Jeon Jun-Young , Kim Yun-Jae , Kim Jin-Weon , Lee Kuk-Hee , Kim Jong-Sung
Published: October 2015

This paper presents a finite element (FE) simulation technique to predict maximum load-carrying capacity of cracked steam generator tubes and its application to Alloy 690TT tubes. The simulation method is based on a simplified version of the stress modified fracture strain model. The damage model is determined from tensile test and one cracked tube test data. Predicted maximum pressures are compared with 23 test data of axial through-wall and surface cracked Alloy 690TT steam generator tubes. Comparison with experimental data shows good agreement.
Creep Life Evaluations of ASME B31.1 Allowance for Variation From Normal Operation
Authors: Cohn Marvin J.
Published: October 2015

The ASME B31.1-2012 Power Piping Code (Code) paras. 102.2.4, 102.3.3, and 104.8.2 provide an allowance regarding operating above the design temperature and internal pressure for short time periods. This study is a quantitative evaluation of the permitted increased life consumption associated with the 2012 Code operating allowances for piping materials operating in the creep range. Three base metal materials are considered in this paper—ASTM A335 Grades P11, P22, and P91. Results of this evaluation could be used to improve the ASME B31.1 Code, including a technical basis for a recommended revision. The para. 102.2.4 allowables were evaluated: (A) 15% stress increase for 10% of the operating hours and (B) 20% stress increase for 1% of the operating hours. It was determined that these allowances increased the base metal creep rupture life consumption of Grade P11 material up to 8%, Grade P22 material up to 14%, and Grade P91 material up to 25%. Allowance A results in permitting significantly more creep life consumption than Allowance B. An evaluation was performed to realign the increased creep life consumption of Allowance B to be approximately equivalent to the increased creep life consumption of Allowance A. If Allowance B event duration is increased from 80 hrs per year to 400 hrs per year (from 1% to 5% of the operating hours per year), Allowance B increased the creep life consumption which is slightly less than Allowance A life consumption for Grades P11, P22, and P91 materials. Main steam (MS) and hot reheat (HRH) piping system typical operating temperatures and stresses were evaluated for these variation allowances. This study revealed that Grade P22 base metal creep damage is slightly more sensitive to stress than Grade P11 material creep rupture damage, and Grade P91 base metal creep damage is substantially more sensitive to stress than Grade P22 material creep rupture damage.
Rounded Fin Edge and Step Position Effects on Discharge Coefficient in Rotating Labyrinth Seals
Authors: Rapisarda Andrea , Desando Alessio , Campagnoli Elena , Taurino Roberto
Published: October 2015

The design of modern aircrafts propulsion systems is strongly influenced by the important objective of environmental impact reduction. Through a great number of researches carried out in the last decades, significant improvements have been obtained in terms of lower fuel consumption and pollutant emission. Experimental tests are a necessary step to achieve new solutions that are more efficient than the current designs, even if during the preliminary design phase, a valid alternative to expensive experimental tests is the implementation of numerical models. The processing power of modern computers allows indeed the simulation of more complex and detailed phenomena than the past years. The present work focuses on the implementation of a numerical model for rotating stepped labyrinth seals installed in low-pressure turbines. These components are widely employed in sealing turbomachinery to reduce the leakage flow between rotating components. The numerical simulations were performed by using computational fluid dynamics (CFD) methodology, focusing on the leakage performances at different rotating speeds and inlet preswirl ratios. Investigations on velocity profiles into seal cavities were also carried out. To begin with, a smooth labyrinth seal model was validated by using the experimental data found in the literature. The numerical simulations were extended to the honeycomb labyrinth seals, with the validation performed on the velocity profiles. Then, the effects of two geometrical parameters, the rounded fin tip leading edge, and the step position were numerically investigated for both smooth and honeycomb labyrinth seals. The obtained results are generally in good agreement with the experimental data. The main effect found when the fin tip leading edge was rounded was a large increase in leakage flow, while the step position contribution to the flow path behavior is nonmonotone.
Numerical analysis of three-dimensional acoustic propagation in the Catoche Tongue
Authors: Ballard Megan S. , Sagers Jason D.
Published: October 2015

Analysis of modeled time series data is presented to provide insight into propagation physics of horizontally refracted sound in the Catoche Tongue region of the Gulf of Mexico. The analysis is motivated by the observation of out-of-plane arrivals in measured time series data. In particular, the extended duration of the refracted arrivals is shown to be caused by interaction with multiple locations along the steep sides of the Tongue. Comparison of the modeled time series is made to previous work by Sturm [J. Acoust. Soc. Am. 117(3), 1058–1079 (2005)], who examined the frequency dependence of out-of-plane modal arrivals for the wedge-shaped ocean.
Calculation of an axial temperature distribution using the reflection coefficient of an acoustic wave
Authors: Červenka Milan , Bednařík Michal
Published: October 2015

This work verifies the idea that in principle it is possible to reconstruct axial temperature distribution of fluid employing reflection or transmission of acoustic waves. It is assumed that the fluid is dissipationless and its density and speed of sound vary along the wave propagation direction because of the fluid temperature distribution. A numerical algorithm is proposed allowing for calculation of the temperature distribution on the basis of known frequency characteristics of reflection coefficient modulus. Functionality of the algorithm is illustrated on a few examples, its properties are discussed.
In Canada, science campaigns for attention from voters
Authors: Owens Brian
Published: October 2015

Opponents of Prime Minister Stephen Harper try to make his record on research an issue in election.
Erosion by an Alpine glacier
Authors: Herman Frédéric , Beyssac Olivier , Brughelli Mattia , Lane Stuart N. , Leprince Sébastien , Adatte Thierry , Lin Jiao Y. Y. , Avouac Jean-Philippe , Cox Simon C.
Published: October 2015

The glacial way of wearing away

The rate at which glaciers erode landscapes is an important but poorly constrained relationship. Herman
et al.
tackle this issue by considering the Franz Josef alpine glacier in New Zealand. The amount of sediment piling up at the edge of the glacier provided erosion rates, whereas remote sensing allowed for simultaneous tracking of glacial motion. The result was a nonlinear relationship, suggesting that fast glaciers are much more effective at gouging landscapes. This could explain the paradox of why long-term erosion rates are so much lower in polar regions with more permanent glaciers.

Science
, this issue p.
193
Math at home adds up to achievement in school
Authors: Berkowitz Talia , Schaeffer Marjorie W. , Maloney Erin A. , Peterson Lori , Gregor Courtney , Levine Susan C. , Beilock Sian L.
Published: October 2015

A little bit of math goes a long way

Children's emerging language skills are supported when their caregivers read to them at home. Math skills, however, are often relegated to the schools. Berkowitz
et al.
developed a mobile-device app designed to help caregivers bring a little bit of math into the home. Improved math skills were apparent within months for elementary school students. Improvements were most dramatic in families where the caregivers reported themselves to be anxious about math.

Science
, this issue p.
196
The martian lake chronicles
Authors: Chan Marjorie A.
Published: October 2015

Curiosity reveals evidence for ancient lakes on Mars

[Also see Research Article by

Grotzinger
et al.

]
Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes
Authors: Lee Andrew C. Y. , Zhu Houshun , Zhang Anna J. X. , Li Can , Wang Pui , Li Chuangen , Chen Honglin , Hung Ivan F. N. , To Kelvin K. W. , Yuen Kwok-Yung
Published: October 2015

Influenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus.
Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague
Authors: Tiner Bethany L. , Sha Jian , Ponnusamy Duraisamy , Baze Wallace B. , Fitts Eric C. , Popov Vsevolod L. , van Lier Christina J. , Erova Tatiana E. , Chopra Ashok K.
Published: October 2015

Earlier, we showed that the ΔlppΔmsbBΔailtriple mutant ofYersinia pestisCO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the ΔlppΔmsbBΔailtriple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 106CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD50) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modifiedailreplaced the nativeailgene on the chromosome of the ΔlppΔmsbBdouble mutant, creating a ΔlppΔmsbB::ailL2vaccine strain. This newly generated mutant was attenuated similarly to the ΔlppΔmsbBΔailtriple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the ΔlppΔmsbBΔailand ΔlppΔmsbB::ailL2mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but with a much diminished virulence potential.
Commentary: Individualized Quality Control Plan (IQCP): Is It Value-Added for Clinical Microbiology?
Authors: Sharp Susan E. , Miller Melissa B. , Hindler Janet
Published: October 2015

The Center for Medicaid and Medicare Services (CMS) recently published their Individualized Quality Control Plan (IQCP [
https://www.cms.gov/regulations-and-guidance/legislation/CLIA/Individualized_Quality_Control_Plan_IQCP.html
]), which will be the only option for quality control (QC) starting in January 2016 if laboratories choose not to perform Clinical Laboratory Improvement Act (CLIA) [U.S. Statutes at Large 81(1967):533] default QC. Laboratories will no longer be able to use “equivalent QC” (EQC) or the Clinical and Laboratory Standards Institute (CLSI) standards alone for quality control of their microbiology systems. The implementation of IQCP in clinical microbiology laboratories will most certainly be an added burden, the benefits of which are currently unknown.
Genetic Pathway of HIV-1 Resistance to Novel Fusion Inhibitors Targeting the Gp41 Pocket
Authors: Su Yang , Chong Huihiui , Xiong Shengwen , Qiao Yuanyuan , Qiu Zonglin , He Yuxian
Published: October 2015

The peptide drug enfuvirtide (T20) is the only HIV-1 fusion inhibitor in clinical use, but it easily induces drug resistance, calling for new strategies for developing effective drugs. On the basis of the M-T hook structure, we recently developed highly potent short-peptide HIV-1 fusion inhibitors (MTSC22 and HP23), which mainly target the conserved gp41 pocket and possess high genetic barriers to resistance. Here, we focused on the selection and characterization of HIV-1 escape mutants of MTSC22, which revealed new resistance pathways and mechanisms. Two mutations (E49K and L57R) located at the inhibitor-binding site and two mutations (N126K and E136G) located at the C-terminal heptad repeat region of gp41 were identified as conferring high resistance either singly or in combination. While E49K reduced the C-terminal binding of inhibitors via an electrostatic repulsion, L57R dramatically disrupted the N-terminal binding of M-T hook structure and pocket-binding domain. Unlike E49K and N126K, which enhanced the stability of the endogenous viral six-helical bundle core (6-HB), L57R and E136G conversely destabilized the 6-HB structure. We also demonstrated that both primary and secondary mutations caused the structural changes in 6-HB and severely impaired the capability for HIV-1 entry. Collectively, our data provide novel insights into the mechanisms of short-peptide fusion inhibitors targeting the gp41 pocket site and help increase our understanding of the structure and function of gp41 and HIV-1 evolution.

IMPORTANCE
The deep pocket on the N-trimer of HIV-1 gp41 has been considered an ideal drug target because of its high degree of conservation and essential role in viral entry. Short-peptide fusion inhibitors, which contain an M-T hook structure and mainly target the pocket site, show extremely high binding and inhibitory activities as well as high genetic barriers to resistance. In this study, the HIV-1 mutants resistant to MTSC22 were selected and characterized, which revealed that the E49K and L57R substitutions at the inhibitor-binding site and the N126K and E136G substitutions at the C-terminal heptad repeat region of gp41 critically determine the resistance phenotype. The data provide novel insights into the mechanisms of action of the M-T hook structure-based fusion inhibitors which will help further our understanding of the structure-function relationship of gp41 and molecular pathways of HIV-1 evolution and eventually facilitate the development of new anti-HIV drugs.
Infections Acquired in the Garden
Authors: Cunha Cheston B. , Cunha Burke A.
Published: October 2015

Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one’s vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis.
Prevalence and outcomes of multimorbidity in South Asia: a systematic review
Authors: Pati Sanghamitra , Swain Subhashisa , Hussain Mohammad Akhtar , van den Akker Marjan , Metsemakers Job , Knottnerus J André , Salisbury Chris
Published: October 2015

Objective

To systematically review the studies of prevalence, patterns and consequences of multimorbidity reported from South Asia.

Design

Systematic review.

Setting

South Asia.

Data sources

Articles were retrieved from two electronic databases (PubMed and Embase) and from the relevant references lists. Methodical data extraction according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was followed. English-language studies published between 2000 and March 2015 were included.

Eligibility criteria

Studies addressing prevalence, consequences and patterns of multimorbidity in South Asia. Articles documenting presence of two or more chronic conditions were included in the review. The quality and risk of bias were assessed using STROBE criteria.

Data selection

Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Due to heterogeneity in methodologies among reported studies, only narrative synthesis of the results was carried out.

Results

Of 11 132, 61 abstracts were selected and 13 were included for final data synthesis. The number of health conditions analysed per study varied from 7 to 22, with prevalence of multimorbidity from 4.5% to 83%. The leading chronic conditions were hypertension, arthritis, diabetes, cardiac problems and skin diseases. The most frequently reported outcomes were increased healthcare utilisation, lowered physical functioning and quality of life, and psychological distress.

Conclusions

Our study, a comprehensive mapping of multimorbidity research in South Asia, reveals the insufficient volume of work carried out in this domain. The published studies are inadequate to provide an indication of the magnitude of multimorbidity in these countries. Research into clinical and epidemiological aspects of multimorbidity is warranted to build up scientific evidence in this geographic region. The wide heterogeneity observed in the present review calls for greater methodological rigour while conducting these epidemiological studies.

Trial registration number

CRD42013005456.
A protocol for engaging unlicensed private drug shops in Rural Eastern Uganda for Integrated Community Case Management (ICCM) of malaria, pneumonia and diarrhoea in children under 5 years of age
Authors: Buchner Denise L , Awor Phyllis
Published: October 2015

Introduction

Malaria, pneumonia and diarrhoea are leading causes of death in young children in Uganda. In 2010, Integrated Community Case Management (ICCM) was adopted in Uganda for community level diagnosis and treatment of these diseases through community health workers. However, 50–60% of sick children will receive treatment from the private sector, especially drug shops. Only about half of drug shops are licensed and the quality of care is poor. There is an urgent need to improve quality of care and regulation of drug shops in Uganda.

Methods

This is a pre–post cross-sectional study with before and after measurement in an intervention area in Kamujli district. A snowball mapping exercise, exit interviews, focus group discussions and interviews will be used. 25 randomly selected drug shops will be selected for an intervention that will assist drug shops to become licensed, and provide five days of ICCM training, subsidised prepackaged medicines (artemisinin-based combination therapies for malaria, amoxicillin for pneumonia, Oral Rehydration Salts/zinc for diarrhoea) and free diagnostic tools (rapid diagnostic tests, respiratory timers, thermometers, algorithms). We anticipate a sample size of 1200 (600 at baseline and 600 at the end of the study).

Analysis

Quantitative data will be analysed using SPSS for proportions and CIs. Bivariate and multiple logistic regression analysis with adjustment for clustering of data will be performed to adjust for confounding and determine intervention effect. Qualitative data will be entered into NVivo 10 and analysed using content analysis.

Ethics and Dissemination

Research ethics approval is received from the University of Calgary (REB 14–0269), and Makerere University (IRB00011353). Findings from this study will be disseminated through journal articles and conference presentations, and will illustrate the feasibility of introducing ICCM for drug shops.
Sedimentology of the lower Serpukhovian (upper Mississippian) Mabou Group in the Cumberland Basin of eastern Canada: tectonic, halokinetic, and climatic implications
Authors: Jutras Pierre , McLeod Jason R. , Utting John
Published: October 2015

The Visean–Serpukhovian transition in Atlantic Canada was marked by a general humidification of the climate as the region drifted towards equatorial latitudes. It also corresponds to a time when ice volume was increasing on Gondwana, which marked the end of Mississippian marine incursions in the region. Glacioeustatic fluctuations of greater magnitude are thought to have increased the response of the regional climate to third-order cyclicity from orbital forcing. In the Cumberland Basin, fluvial grey beds of the lower Serpukhovian Shepody Formation were deposited in sub-humid conditions during highstands, whereas red playa deposits of the same unit were deposited under semi-arid conditions during lowstands. Basin reconstruction suggests that this unit was sourced from the fault-bounded Cobequid and Caledonia highlands and deposited in two separate salt-withdrawal minibasins. This fluvial system was seemingly discharging to the north into the broad lake that deposited the contemporaneous Hastings Formation. A disconformity separates the Shepody Formation from mid-Serpukhovian red beds of the Claremont Formation and is tentatively associated with another increase in ice volume on Gondwana followed by a recrudescence of fault activity and basin subsidence. A prolonged time of aridity, floral crisis, non-deposition, deep weathering and karstification in late Serpukhovian to early Bashkirian times is contemporaneous with abundant glacial deposits in higher latitudes, suggesting that globally low sea levels may have been at play in creating a situation of greater continentality in the study area.
Hawking radiation of massive vector particles from a warped AdS3 black hole
Authors: Gursel H. , Sakalli I.
Published: October 2015

Hawking radiation of massive vector particles from a rotating warped anti-de Sitter black hole in 2+1 dimensions (WAdS3 BH) is studied in detail. The quantum tunneling approach with the Hamilton–Jacobi method is applied in the Proca equation, and we show that the radial function yields the tunneling rate of the outgoing particles. Comparing the result obtained with the Boltzmann factor, we satisfactorily reproduce the Hawking temperature of the WAdS3 BH.
Comparison of Cytotoxicity and the Anti-Adipogenic Effect of Green Tea Polyphenols with Epigallocatechin-3-Gallate in 3T3-L1 Preadipocytes
Authors: Lao Weiguo , Tan Yi , Jin Xingliang , Xiao Linda , Kim Jane J.Y. , Qu Xianqin
Published: October 2015

Recent studies have demonstrated the effects of green tea polyphenols (GTP) and epigallocatechin-3-gallate (EGCG) on obesity. However, high doses of EGCG have also exhibited cytotoxicity. The aim of this study was to compare total GTP with purified EGCG on cytotoxicity, and to investigate the effects and the molecular mechanism of total GTP and EGCG on adipogenesis. Cytotoxicity was determined by cell viability assay. For the adipogenesis study, 3T3-L1 preadipocytes were incubated with three doses of GTP (1, 10, and 100 μg/ml) and the effect of EGCG (6.8 μg/ml) was compared with 10 μg/ml GTP containing 68% EGCG. Oil Red O staining and triglyceride content assay were carried out 10 days after differentiation and treatment. Adipogenic regulators CCAAT element binding protein α (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein-1c (SREBP-1c) were determined by qRT-PCR and immunoblotting. GTP at 1000 μg/ml and EGCG (68 and 680 μg/ml) significantly affected cell viability. Purified EGCG had greater cytotoxicity than corresponding doses of GTP. About 10 μg/ml of GTP showed stronger reduction in triglyceride accumulation than EGCG treatment. Transcriptional factors of C/EBPα, SREBP-1c and PPARγ were markedly decreased in both GTP and EGCG-treated cells and GTP exhibited stronger inhibitory effects on C/EBPα and PPARγ protein expression than EGCG (p < 0.05). In conclusion, total GTP exerted greater inhibitory effects than purified EGCG on adipogenesis through down-regulating the adipogenic factor C/EBPα, SREBP-1c and PPARγ expression. These findings support that a polyphenol mixture is safer and more effective than EGCG alone for preventing obesity and obesity-related chronic diseases.
A study of fluctuations of voids in relativistic ion–ion collisions
Authors: Ahmad Shakeel , Khan M. M. , Khan Shaista , Khatun A. , Irfan M.
Published: October 2015

Event-by-event (ebe) fluctuations of hadronic patterns are investigated in terms of voids by analyzing the experimental data on 4.5, 14.5 and 60 A GeV/c 16 O - AgBr collisions. The findings are compared with the predictions of a multi-phase transport AMPT model. Dependence of voids on phase space bin width is examined in terms of two lowest moments of ebe fluctuations of voids, 〈Gq〉 and Sq. The findings reveal that scaling exponent estimated from the observed power-law behavior of the voids may be used to characterize the various properties of hadronic phase transition. The results also rule out occurrence of second-order quark–hadron phase transition at the projectile energies considered.
Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells
Authors: Singh Shatrunjai P. , Chhunchha Bhavana , Fatma Nigar , Kubo Eri , Singh Sanjay P. , Singh Dhirendra P.
Published: October 2015

Oxidative stress or reduced expression of naturally occurring antioxidants during aging has been identified as a major culprit in neuronal cell/tissue degeneration. Peroxiredoxin (Prdx) 6, a protective protein with GSH peroxidase and acidic calcium-independent phospholipase A2 activities, acts as a rheostat in regulating cellular physiology by clearing reactive oxygen species (ROS) and thereby optimizing gene regulation. We found that under stress, the neuronal cells displayed reduced expression of Prdx6 protein and mRNA with increased levels of ROS, and the cells subsequently underwent apoptosis. Using Prdx6 fused to TAT transduction domain, we showed evidence that Prdx6 was internalized in human brain cortical neuronal cells, HCN-2, and mouse hippocampal cells, HT22. The cells transduced with Prdx6 conferred resistance against the oxidative stress inducers paraquat, H2O2, and glutamate. Furthermore, Prdx6 delivery ameliorated damage to neuronal cells by optimizing ROS levels and overstimulation of NF-κB. Intriguingly, transduction of Prdx6 increased the expression of endogenous Prdx6, suggesting that protection against oxidative stress was mediated by both extrinsic and intrinsic Prdx6. The results demonstrate that Prdx6 expression is critical to protecting oxidative stress-evoked neuronal cell death. We propose that local or systemic application of Prdx6 can be an effective means of delaying/postponing neuronal degeneration.
Fluorescence dilution technique for measurement of albumin reflection coefficient in isolated glomeruli
Authors: Fan Fan , Chen Chun Cheng Andy , Zhang Jin , Schreck Carlos M. N. , Roman Eric A. , Williams Jan M. , Hirata Takashi , Sharma Mukut , Beard Daniel A. , Savin Virginia J. , Roman Richard J.
Published: October 2015

This study describes a high-throughput fluorescence dilution technique to measure the albumin reflection coefficient (σAlb) of isolated glomeruli. Rats were injected with FITC-dextran 250 (75 mg/kg), and the glomeruli were isolated in a 6% BSA solution. Changes in the fluorescence of the glomerulus due to water influx in response to an imposed oncotic gradient was used to determine σAlb. Adjustment of the albumin concentration of the bath from 6 to 5, 4, 3, and 2% produced a 10, 25, 35, and 50% decrease in the fluorescence of the glomeruli. Pretreatment of glomeruli with protamine sulfate (2 mg/ml) or TGF-β1 (10 ng/ml) decreased σAlbfrom 1 to 0.54 and 0.48, respectively. Water and solute movement were modeled using Kedem-Katchalsky equations, and the measured responses closely fit the predicted behavior, indicating that loss of albumin by solvent drag or diffusion is negligible compared with the movement of water. We also found that σAlbwas reduced by 17% in fawn hooded hypertensive rats, 33% in hypertensive Dahl salt-sensitive (SS) rats, 26% in streptozotocin-treated diabetic Dahl SS rats, and 21% in 6-mo old type II diabetic nephropathy rats relative to control Sprague-Dawley rats. The changes in glomerular permeability to albumin were correlated with the degree of proteinuria in these strains. These findings indicate that the fluorescence dilution technique can be used to measure σAlbin populations of isolated glomeruli and provides a means to assess the development of glomerular injury in hypertensive and diabetic models.
Is It Possible to Differentiate Chronic Kidney Disease and Preeclampsia by means of New and Old Biomarkers? A Prospective Study
Authors: Rolfo Alessandro , Attini Rossella , Tavassoli Elisabetta , Vigotti Neve Federica , Nigra Marco , Cicilano Matteo , Nuzzo Anna Maria , Giuffrida Domenica , Biolcati Marilisa , Nichelatti Michele , Gaglioti Pietro , Todros Tullia , Piccoli Giorgina Barbara
Published: October 2015

Objective. Chronic kidney disease (CKD) and preeclampsia (PE) may both present with hypertension and proteinuria in pregnancy. Our objective is to test the possibility of distinguishing CKD from PE by means of uteroplacental flows and maternal circulating sFlt-1/PlGF ratio.Design. Prospective analysis.Population. Seventy-six patients (35 CKD, 24 PE, and 17 other hypertensive disorders), with at least one sFlt-1/PlGF and Doppler evaluation after the 20th gestational week.Methods. Maternal sFlt-1-PlGF were determined by immunoassays. Abnormal uterine artery Doppler was defined as resistance index ≥ 0.58. Umbilical Doppler was defined with gestational-age-adjusted Pulsatility Index. Clinical diagnosis was considered as reference. Performance of Doppler study was assessed by sensitivity analysis; sFlt-1/PlGF cut-off values were determined by ROC curves.Results. The lowest sFlt-1/PlGF ratio (8.29) was detected in CKD, the highest in PE (317.32) (P<0.001). Uteroplacental flows were mostly preserved in CKD patients in contrast to PE (P<0.001). ROC analysis suggested two cut-points: sFlt-1/PlGF ≥ 32.81 (sensitivity 82.93%; specificity 91.43%) and sFlt-1/PlGF ≥ 78.75 (sensitivity 62.89%, specificity 97.14%). Specificity reached 100% at sFlt-1/PlGF ≥ 142.21 (sensitivity: 48.8%). Early-preterm delivery was associated with higher sFlt-1/PlGF ratio and abnormal uteroplacental flows relative to late-preterm and term deliveries.Conclusions. sFlt-1/PlGF ratio and uteroplacental flows significantly correlated with PE or CKD and preterm delivery.
Role and Function of MicroRNAs in Extracellular Vesicles in Cardiovascular Biology
Authors: Pfeifer Philipp , Werner Nikos , Jansen Felix
Published: October 2015

Intercellular communication mediated by extracellular vesicles is crucial for preserving vascular integrity and in the development of cardiovascular disease. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes that can be found in almost every fluid compartment of the body like blood, saliva, and urine. In the recent years, a lot of reports came up suggesting that major cardiovascular and metabolic pathologies like atherogenesis, heart failure, or diabetes are highly influenced by transfer of microRNAs via extracellular vesicles leading to altered protein expression and phenotypes of recipient cells. The following review will summarize the fast developing field of intercellular signaling in cardiovascular biology by microRNA-containing extracellular vesicles.
Synthesis and Characterization of Chemically Cross-Linked Acrylic Acid/Gelatin Hydrogels: Effect of pH and Composition on Swelling and Drug Release
Authors: Bukhari Syed Majid Hanif , Khan Samiullah , Rehanullah Muhammad , Ranjha Nazar Mohammad
Published: October 2015

This present work was aimed at synthesizing pH-sensitive cross-linked AA/Gelatin hydrogels by free radical polymerization. Ammonium persulfate and ethylene glycol dimethacrylate (EGDMA) were used as initiator and as cross-linking agent, respectively. Different feed ratios of acrylic acid, gelatin, and EGDMA were used to investigate the effect of monomer, polymer, and degree of cross-linking on swelling and release pattern of the model drug. The swelling behavior of the hydrogel samples was studied in 0.05 M USP phosphate buffer solutions of various pH values pH 1.2, pH 5.5, pH 6.5, and pH 7.5. The prepared samples were evaluated for porosity and sol-gel fraction analysis. Pheniramine maleate used for allergy treatment was loaded as model drug in selected samples. The release study of the drug was investigated in 0.05 M USP phosphate buffer of varying pH values (1.2, 5.5, and 7.5) for 12 hrs. The release data was fitted to various kinetic models to study the release mechanism. Hydrogels were characterized by Fourier transformed infrared (FTIR) spectroscopy which confirmed formation of structure. Surface morphology of unloaded and loaded samples was studied by surface electron microscopy (SEM), which confirmed the distribution of model drug in the gel network.
Optimal Jamming Attack Scheduling in Networked Sensing and Control Systems
Authors: Zhang Lifu , Zhang Heng , Li Cunhua , Ni Buxi
Published: October 2015

This paper investigates the optimal jamming attack scheduling in Networked Sensing and Control Systems (NSCS). From viewpoint of the attacker, we formulate an optimization problem which maximizes the Linear Quadratic Gaussian (LQG) control cost with attacking energy constraint in a finite time horizon. For two special cases, we obtain that the optimal jamming attack schedule is to consecutively attack in the given time horizon. For the general case, we propose an algorithm to find the optimal schedules. Finally, we study the effectiveness of our proposed attack strategies on our established semiphysical testbed.
Rutherford Backscattering Spectrometry Analysis and Structural Properties of ZnxPb1-xS Thin Films Deposited by Chemical Spray Pyrolysis
Authors: Adeoye Abiodun E. , Ajenifuja Emmanuel , Taleatu Bidini A. , Fasasi A. Y.
Published: October 2015

Zinc lead sulphide ternary thin films were prepared by chemical spray pyrolysis on soda lime glass substrates using zinc acetate, lead acetate, and thiourea sources precursor. The films were characterized using Rutherford backscattering (RBS) spectrometry, energy dispersive X-ray (EDX) spectroscopy, scanning electron microscopy (SEM), and X-ray diffractometry (XRD). RBS studies revealed variation in thickness and stoichiometry of the films with respect to compositional substitution between Zn and Pb, thereby giving effective composition ZnxPb1-xS, where x=0, 0.035, 0.069, 0.109, 0.176, and 0.217. Film thickness obtained by length conversion ranged from 81.02 nm to 90.03 nm. Microstructural analyses also indicated that the growth and particle distribution of the films were uniform across substrate’s surface. Diffraction studies showed that the films possess FCC crystalline structure. Crystallite size reduced from 14.28 to 9.8 nm with increase in Zn2+ in the ZnxPb1-xS samples.
A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation
Authors: Park Young Gun , Kang Seungbum , Brinkmann Ralf , Roh Young-Jung
Published: October 2015

Purpose.This study evaluates functional changes in electroretinographic findings after selective retina therapy (SRT) compared to panretinal photocoagulation (PRP) in rabbits.Methods.The right eyes of 12 Chinchilla rabbits received 200 laser treatment spots. The right eyes of six rabbits received SRT (SRT group), whereas the other six animals were treated using PRP on the right eye (PRP group). The eyes were investigated using full-field ERG 1 hour and 3 weeks after treatment. Histologic exam to assess the tissue response of lasers was performed on 3 weeks.Results.No significant changes in the mean ROD or CR b-wave amplitudes of the SRT lesions were evident, compared to baseline, 1 h after laser treatment (p=0.372and 0.278, resp.). In addition, the OPs and 30 Hz flickers of the SRT lesions were not significantly altered (p=0.17and 0.243, resp.). At 3 weeks, similar results were found. Comparing the two groups, the ROD b-wave amplitude was reduced in the PRP and SRT groups to60.04±4.2% and92.32±6.43% of baseline (p<0.001). Histologically, there was no visible photoreceptor alterations on week 3.Conclusions.SRT in rabbit eyes induced less functional loss than PRP in both rod-mediated retinal function and cone-mediated retinal function. In addition, SRT irradiated eyes had no functional loss compared to its control.