bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-treatment with Mycobacterium avium-derived lipids reduces the macrophage response to interferon γ in BCG-vaccinated mice
Authors: Yang Daqing , Liu Beiyi , Hou Xiaoriu , Jiao Delong , Li Xueli , Wen Liyan , Zhu Ping , Fu Ning
Published: April 2013

Mycobacterium bovisBacille Calmette–Guérin (BCG) is the current vaccine used againstMycobacterium tuberculosis(MTB) infection. However, exposure to environmental pathogens, such asMycobacterium avium, interferes with the immune response induced by BCG vaccination. HowM. aviumaffects the efficiency of BCG is unclear. In this study, BCG-vaccinated mice pre-treated withM. avium-derived lipids (MALs) showed a higher mycobacterial load and increased infiltration of inflammatory cells compared to control mice treated withEscherichia coli-derived lipids (ELs). Unexpectedly, there were no changes in cell proliferation or IFN-γ levels in spleen cells stimulated with protein purified derivatives (PPD) or heat-inactivated BCG in MALs-treated mice. However, pre-treatment with MALs decreased the bactericidal effect as well as the production of TNF-α and nitric oxide (NO) in murine macrophages from BCG-vaccinated mice stimulated with IFN-γ. These results suggest that MAL pre-treatment dampens the immune response against MTB and that this dampening is associated with a decreased response to IFN-γ stimulation in murine macrophages. T-lymphocyte responses, however, were unaffected.
Structural, optical and thermal properties of Zr–Fe co-doped congruent LiNbO3single crystals
Authors: Riscob B. , Bhatt R. , Vijayan N. , Bhaumik Indranil , Ganesamoorthy S. , Wahab M. A. , Rashmi  , Bhagavannarayana G.
Published: April 2013

Zr–Fe-doped congruent lithium niobate single crystals were grown by the Czochralski technique. The crystal structure and lattice parameter of the grown crystals were assessed by powder X-ray diffraction and the strain developed as a result of doping has been calculated (−1.19 × 10−3) by using the Williamson–Hall relation. The incorporated dopant concentration along with the dopant distribution in the specimen crystal was estimated by X-ray florescence spectrometry. A multi-crystal X-ray diffraction analysis was carried out to identify the crystalline perfection of the sample and revealed that the investigated crystal does not contain any structural grain boundaries but does contain point defects and micrometre size mosaic blocks. Birefringence measurements were carried out using a prism coupler spectrometer and found that the optical birefringence is 0.0822 for 532 nm and 0.705 for 1064 nm. A thermal conductivity (κ) study reveals that the doped sample has a lower κ value than the undoped equivalent.
A cautionary tale on the use of GE-7031 varnish: low-temperature thermal expansion studies of ScF3
Authors: Morelock Cody R. , Suchomel Matthew R. , Wilkinson Angus P.
Published: April 2013

GE-7031 varnish, a commonly used low-temperature adhesive and electrical insulator owing to its high thermal conductivity and mechanical strength at low temperatures, was used as a sample matrix for low-temperature powder X-ray diffraction measurements of the negative thermal expansion (NTE) material ScF3. When ScF3powder was mixed with GE-7031 varnish, an unexpected cubic to rhombohedral phase transition in the ScF3sample was observed at ∼50 K, and it exhibited smaller low-temperature unit-cell volumes than samples without the varnish matrix. Experimental observations and quantitative estimates suggest that these anomalies are the result of stress induced by a thermal expansion mismatch between the varnish matrix (large positive coefficient of thermal expansion, CTE) and ScF3(quite large negative CTE). The use of GE-7031 varnish as a sample matrix for low-temperature measurements should be approached with caution if a large thermal expansion mismatch is expected.
Health care access and barriers for the physically disabled in rural Punjab, Pakistan
Authors: Ahmad Mahtab
Published: April 2013

Purpose

The purpose of this paper is to assess disabled persons' access to health care, and highlight barriers.

Design/methodology/approach

A total of 245 rural men and women with physical disabilities were interviewed, to determine their level of access to healthcare services. A simple composite mean of the weighted average indices of responses on the effectiveness of healthcare provision, equity, and users' satisfaction was calculated, to assess the overall level of access of the respondents to healthcare. The qualitative component highlighted an array of barriers that prevented the disabled individuals from accessing healthcare services.

Findings

The results indicated that access to the so‐called “inclusive” public healthcare for both males and females with physical disabilities was poor. The barriers identified were related to the built environments, healthcare delivery processes, and ceiling of health subsidies. The findings suggest that the absence of advocacy of disability rights and failure to adopt circumstantial equities at dispensing levels have resulted in the collapse of the promotion of disability rights at grassroots levels.

Research limitations/implications

The study is location specific (rural), and it mainly focuses on individuals with physical disabilities in working‐age (15‐35 years) to assess their access to the rural healthcare.

Originality/value

Having an effective healthcare provision in an area and its equal access to both males and females is crucially important for their social and economic development. In this paper, the assessment of access to healthcare provides both an aggregated and a disaggregated picture by gender, which is poor for individuals with physical disabilities.
Unobserved investment, endogenous quality, and trade
Authors: Hermalin Benjamin E.
Published: April 2013

A seller can make investments that affect a tradable asset’s future returns. The potential buyer of the asset cannot observe the seller’s investment prior to trade, nor does he receive any signal of it, nor can he verify it in any way after trade. Despite this severe moral‐hazard problem, this article shows the seller will invest with positive probability in equilibrium and that trade will occur with positive probability. The outcome of the game is sensitive to the distribution of bargaining power between the parties, with a holdup problem existing if the buyer has the bargaining power. A consequence of the holdup problem is surplus‐reducing distortions in investment level. Perhaps counterintuitively, in many situations, this distortion involves an increase in the expected amount invested vis‐à‐vis the situation without holdup.
Trophy hunting inAfrica: long‐term trends in antelope horn size
Authors: Crosmary W.‐G. , Loveridge A. J. , Ndaimani H. , Lebel S. , Booth V. , Côté S. D. , Fritz H.
Published: April 2013

Trophy hunting in ungulates may favour individuals with smaller horns. A decrease in horn/antler size may jeopardize the conservation potential of hunting areas, which would be a major concern inAfrica where hunting zones represent over half of the total area of protected lands. We investigated horn length trends of harvested male impalasAepyceros melampus, greater kudusTragelaphus strepsicerosand sable antelopesHippotragus niger, from 1974 to 2008 inMatetsiSafariArea,Zimbabwe. Horn length declined by 4% in impalas, partly because male harvest age decreased. In greater kudus, surprisingly, horn length increased by 14%, while mean age of harvested male greater kudus increased during the study period. Reduced hunting pressure on this species during the study may have allowed males to live longer and to grow longer horns before being harvested. Horn length declined by 6% in sable antelopes, independent of age, suggesting that trophy hunting selected male sable antelopes with smaller horns through time, provided that horn length is heritable. Hunting pressure and trophy value were higher for sable antelopes than for impalas and greater kudus. Accordingly, the decline of horn length in this species was more pronounced. More valuable trophy species, such as sable antelopes, require special attention because they may be exposed to higher hunting pressure, and are therefore more likely to experience a decrease in horn size.
Demand for meat and dairy products by Turkish households: a Bayesian censored system approach
Authors: Bilgic Abdulbaki , Yen Steven T.
Published: April 2013

We extend the Tobit (censored) linear equation system procedure to utility‐theoretic demand functions, along with a mapping mechanism to impose the adding‐up restriction implied by consumer utility maximization theory—a theoretical restriction very often ignored in previous empirical studies with censored demand systems. In this context, the Bayesian Markov Chain Monte Carlo (MCMC) procedure is applied to the censored linear approximate almost ideal demand system (LAIDS) for 12 food products, using data from the Turkish Household Expenditure Survey. All own‐price elasticities are negative and expenditure elasticities positive. Uncompensated own‐price elasticities for rural households are generally much higher than those for their urban peers, though demand for most food products are own‐price elastic for both types of households. The differential patterns in demand elasticities between urban and rural households become even more evident (almost twice) as relatively more expensive foodstuffs are consumed, showing that accessibilities to alternative products have made rural Turkish households more cognizant toward price changes in foods. Household characteristics play a key role in food expenditures, notably so in urban areas, and regional and seasonal differences are also present.
‘A problem shared is a problem halved’: success of a statewide collaborative approach to fetal therapy. Outcomes of fetoscopic laser photocoagulation for twin–twin transfusion syndrome in Victoria
Authors: Teoh Mark , Walker Sue , Cole Stephen , Edwards Andrew
Published: April 2013

Aims

To evaluate the performance of a collaborative fetal therapy service for treatment for twin–twin transfusion syndrome (TTTS).

Methods

The Victorian Fetal Therapy Service (VFTS) was developed in 2006. It is a state‐based three‐centre collaborative service comprising a surgical team and clinical leadership group, designed to optimise access to, and performance of, fetoscopic procedures in Victoria. This is a prospective cohort study of VFTS patients referred for fetoscopic laser photocoagulation (FLP) for TTTS since 2006.

Results

Forty‐nine consecutive women with advanced (stage 2–4) TTTS between 2006 and 2011 were included in this study. Overall survival was 67 of 98 (68%), and survival of ≥1 twin was seen in 42 of 49 pregnancies (86%). There was no difference in survival by disease stage at diagnosis (≥1 survivor: 66% (stage 2 or 3 TTTS) vs 77% (stage 4 TTTS), P = 0.44), nor by surgical era (≥1 survivor: 60% (2006–2008) vs 74% of cases (2009–2011), P = 0.21). The median gestation gained post‐FLP was 10.5 weeks.

Conclusion

These results are consistent with published series and confirm the success of a novel service delivery model for fetal therapy in Victoria. We suggest that collaborative models such as ours should be considered for fetal conditions where treatment is complex and the total number of cases is small to ensure a consistent approach to assessment, management and follow‐up of patients and to optimise training and research opportunities.
First Level Prevention Instead of Third Level Intervention—Review of Research to Improve Biocompatibility and Performance of Capillary Membrane Apheresis in Critically Ill Patients
Authors: Russ Martin , Bedarf Janis R. , Grosch‐Ott Sascha , Haltern Claudia , Rossaint Rolf , Unger Juliane K.
Published: April 2013

In intensive care medicine, convection‐based apheresis is of growing interest. Applying extracorporeal systems in the critically ill patient can cause severe complications like nosocomial infections and bleeding, which can be worsened or even initialized by the anticoagulation protocol used. Furthermore, the filter modules (hemo‐ and plasmafilters) often tend to a fast blockage. A decrease in sieving performance due to membrane fouling may be tolerable for some time, but the complete blockage of high percentages of hollow fibers, which is named “clotting,” often requires the immediate exchange of the filter. Extracorporeal detoxification and high clearance renal replacement regimes both require high blood flow and filtration rates. As a consequence, filter clotting and anticoagulation‐associated bleeding are the most sensitive aspects in these applications. We were interested in the paradox phenomenon of the parallel occurrence of intra vitam bleeding and filter clotting in critically ill patients. Through stepwise investigations based on in vitro and animal experiments, we identified a stasis of blood flow followed by blood cell sedimentation and aggregation (“clogging”) as the main factor of hollow fiber blockage in hemo‐ and plasma filters. As a result, various aspects which increase the risk of stasis inside the hollow fibers were investigated, for example, patient's hemorheology, configuration of an extracorporeal treatment system including interaction of catheter features with the filtration procedure, and basic therapeutic approaches such as colloidal volume substitutes and tolerated acidosis. Finally, an etiological triad for the blockage of hollow fibers due to filter clogging and consecutive filter failure was formed.
GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations
Authors: Green Claire L. , Tawana Kiran , Hills Robert K. , Bödör Csaba , Fitzgibbon Jude , Inglott Sarah , Ancliff Phil , Burnett Alan K. , Linch David C. , Gale Rosemary E.
Published: April 2013

GATA2 mutations have recently been reported in acute myeloid leukaemia (AML) patients with CEBPA‐double mutations. To explore their impact on this favourable‐risk disease, we determined GATA2 status in 153 sporadic AML patients and three members of a germ‐line CEBPA‐mutant family at AML presentation. Overall, 27% (15/55) CEBPA‐double, 16% (7/43) CEBPA‐single and 0% (0/55) normal karyotype/CEBPA‐wild‐type patients were GATA2‐mutant. All familial AML patients acquired both a second CEBPA and a GATA2 mutation. CEBPA and GATA2 mutant levels indicated that both mutations were likely to be early events in leukaemogenesis. GATA2 status did not impact on the favourable outcome of CEBPA‐double/FLT3‐inernal tandem duplication‐negative patients.
High‐resolution ERG‐expression profiling on GeneChip exon 1.0 ST arrays in primary and castration‐resistant prostate cancer
Authors: Smit Frank P. , Salagierski Maciej , Jannink Sander , Schalken Jack A.
Published: April 2013

Objective

To assess whether oestrogen‐regulated gene (ERG) expression analysis using GeneChip arrays can predict transmembrane protease, serine 2 (TMPRSS2)‐ERG fusion. The expression level of the TMPRSS2‐ERG gene was studied in various histological grades of prostate cancer and castration‐resistant prostate cancer (CPRC).

Patients and methods

GeneChip Affymetrix exon 1.0 ST arrays were used for expression profiling of ERG, erythroblast transformation‐specific (ETS) variant gene 1 (ETV1), ETV4 and ETV5 genes in 67 prostate cancer tissue specimens.

Real‐time quantitative polymerase chain reaction analysis and in some cases DNA sequencing was used to validate the presence and the expression levels of TMPRSS2‐ERG gene fusions.

Results

In our series of patients with prostate cancer over expression of the ERG gene predicted the presence of TMPRSS2‐ERG rearrangements in almost all cases.

ETS expression by itself outmatched the diagnostic performance of the ERG exons ratioing allowing equal detection of the less frequent ETS gene fusion transcripts.

The gene fusions were expressed at significantly lower levels in CPRC but occurred more frequently than in primary prostate cancer.

Conclusions

ERG expression analysis using GeneChip arrays appears to be an excellent diagnostic tool for identifying gene rearrangements.

In coming years, measuring expression of the ETS gene family by itself might become a clinically relevant surrogate test to identify patients with fusion‐positive prostate cancer.

The variation of gene fusion expression levels, particularly in CPRC, needs to be taken into account when using quantitative molecular diagnosis of prostate cancer.
Reactive astrocytes express the potassium channel Kir4.1 in active multiple sclerosis lesions
Authors: Satoh Jun‐ichi , Tabunoki Hiroko , Ishida Tsuyoshi , Saito Yuko , Konno Hidehiko , Arima Kunimasa
Published: April 2013

Objectives

Kir4.1, an inwardly rectifying potassium channel expressed on perivascular and perisynaptic end‐feet of astrocytes, plays a pivotal role in the spatial buffering of the potassium in the brain. A recent study showed that autoantibodies directed to Kir4.1 are detectable in the serum derived from approximately half of the patients with multiple sclerosis (MS) and clinically isolated syndrome, although their pathogenic roles should be elucidated.

Methods

We studied Kir4.1 expression in MS and control brains by immunohistochemistry.

Results

We found that reactive astrocytes expressed an intense immunoreactivity for Kir4.1 in active demyelinating lesions of MS, active lesion edges of neuromyelitis optica, ischemic lesion edges of cerebral infarction and neurodegenerative lesions of Alzheimer's disease. Reactive astrocytes accumulated in active MS lesions coexpressed Kir4.1 and AQP4. A subset of amyloid plaques in Alzheimer's disease brains also expressed Kir4.1. In contrast, infiltrating macrophages, activated microglia and surviving oligodendrocytes in active MS lesions did not express Kir4.1. Furthermore, cultured human astrocytes expressed Kir4.1, and the expression levels were not altered by exposure to tumor necrosis factor‐α or interleukin‐1β, but were elevated by transforming growth factor‐β1.

Conclusions

These results show that reactive astrocytes abundantly express Kir4.1, and Kir4.1 immunoreactivity is not lost in active demyelinating lesions of MS.
Clinical and microbiological characteristics of community‐acquired pneumonia in human immunodeficiency virus‐infected patients: a retrospective analysis of 79 HIV/AIDS patients
Authors: Bao Zhiyao , Rong Xiajun , Cheng Qijian , Zhou Min , Gong Qiming , Shi Guochao , Wan Huanying
Published: April 2013

Introduction

HIV infections are prevalent; however, the clinical characteristics of these patients are atypical.

Objectives

In the present study, we analysed 79 patients who were newly diagnosed with HIV/acquired immunodeficiency syndrome (AIDS) at Ruijin Hospital between January 1998 and August 2011 to improve awareness of the physicians' diagnoses and to elucidate the risk factors for community‐acquired pneumonia (CAP) and the progression to severe pneumonia or respiratory failure in AIDS patients.

Methods

The patients were divided into a CAP group (A) and a non‐CAP group (B). Furthermore, group A was divided into a severe pneumonia group (A1) and a non‐severe pneumonia group (A2).

Results and Conclusion

The serum albumin (25.60 ± 5.31 vs 34.00 ± 6.90; P < 0.05) and CD4 cell count (28.5 ± 30.5 vs 229.50 ± 229.45; P < 0.05) of group A were much lower than those of group B. The serum albumin and CD4 cell count negatively correlated with the incidence of CAP. The CD4 cell count (24.15 ± 25.1 vs 47.85 ± 132.5; P < 0.05) and partial pressure of oxygen (7.86 ± 1.43 vs 9.41 ± 2.15; P < 0.05) of group A1 were significantly lower than those of group A2. Low serum albumin levels and high blood urea nitrogen levels were the risk factors of hypoxaemia in group A. Early screening and diagnosis of AIDS, as well as nutritional support, would prevent AIDS patients from developing CAP or progressing to severe pneumonia or respiratory failure.
Visitor Comments as Dialogue
Authors: Coffee Kevin
Published: April 2013

Museum use is a process of ideological negotiation, and thus museum users are active agents, not empty vessels waiting to be filled with curatorial narrative. Ensuing dialogues argue over trivia as well as important ethical issues. Discussants take up topics that range over specific public programs, the object maker's motivations and intentions, the choice of a subject, the phrasing of a caption, or the selection of objects on display. These discussions are held in hushed conversations in crowded galleries, in casual conversations within museum hallways, or with animated gestures on the front steps. In the course of this dialogic social practice, each participant's cultural repertoire is enhanced and grows. Every dialogic event is part of a socio‐cultural continuum that will engender other events, with other participants. The comments made by visitors in a visitor comment book are therefore instances of the specificities and the universality of that discussion.
The Natural History Museum: Taking on a Learning Agenda
Authors: Steiner Mary Ann , Crowley Kevin
Published: April 2013

Carnegie Museum of Natural History and the University of Pittsburgh are engaged in a research and practice partnership to bring new learning sciences findings and theories into contact with the design and deployment of innovative natural history learning experiences. In this article, we describe four strands of work: 1) connecting people to nature; 2) engaging people of all ages in complex and current scientific debates of regional consequence; 3) partnerships to build a strong regional learning ecology for nature and science; and 4) iterative professional development to support staff as they work with new definitions of learning and engagement in the museum.
A review of artificial pancreas technologies with an emphasis on bi‐hormonal therapy
Authors: Bakhtiani P. A. , Zhao L. M. , El Youssef J. , Castle J. R. , Ward W. K.
Published: April 2013

Since the discovery of insulin, great progress has been made to improve the accuracy and safety of automated insulin delivery systems to help patients with type 1 diabetes achieve their treatment goals without causing hypoglycaemia. In recent years, bioengineering technology has greatly advanced diabetes management, with the development of blood glucose meters, continuous glucose monitors, insulin pumps and control systems for automatic delivery of one or more hormones. New insulin analogues have improved subcutaneous absorption characteristics, but do not completely eliminate the risk of hypoglycaemia. Insulin effect is counteracted by glucagon in non‐diabetic individuals, while glucagon secretion in those with type 1 diabetes is impaired. The use of glucagon in the artificial pancreas is therefore a logical and feasible option for preventing and treating hypoglycaemia. However, commercially available glucagon is not stable in aqueous solution for long periods, forming potentially cytotoxic fibrils that aggregate quickly. Therefore, a more stable formulation of glucagon is needed for long‐term use and storage in a bi‐hormonal pump. In addition, a model of glucagon action in type 1 diabetes is lacking, further limiting the inclusion of glucagon into systems employing model‐assisted control. As a result, although several investigators have been working to help develop bi‐hormonal systems for patients with type 1 diabetes, most continue to utilize single hormone systems employing only insulin. This article seeks to focus on the attributes of glucagon and its use in bi‐hormonal systems.
Testing creative destruction in an opening economy
Authors: Aghion Philippe , Fedderke Johannes , Howitt Peter , Viegi Nicola
Published: April 2013

This paper analyses the relationship between trade liberalization and economic growth using a Schumpeterian framework of technological innovation and applies it to sector‐level South African data. The framework examines direct and indirect effects of trade liberalization on productivity growth. Indirect impacts operate through a differential impact of trade liberalization on firms conditional on their distance from the international technological frontier. Results confirm positive direct impacts of trade liberalization. Results confirm also that the greatest positive impact of trade liberalization will be on sectors that are close to the international technological frontier and that experienced a low level of product market competition before liberalization.
Constitutionalism in 3D: Mapping and Legitimating Our Lawmaking Underworld
Authors: Corkin Joseph
Published: April 2013

This article proposes a method for conceptualising the way lawmaking has ebbed away from our national parliamentary‐governmental complexes: horizontally, towards unelected officials, in a process of bureaucratisation; vertically, towards the EU, in a process of Europeanisation; and laterally, towards private actors that are left to regulate themselves, in a process of privatisation. The combined effect has been to diffuse lawmaking across many very diverse actors that interact in dense constellations across a 3D governance space described by these axes. The descriptive innovation of analysing these processes together points also to a common normative challenge; that of finding new ways to legitimate the outer reaches of this governance space, furthest removed from our traditional constitutional structures and the reasonably neat (electoral) lines of accountability they offer back to us. A tentative solution is proposed in creatively rethinking administrative and constitutional law while remaining faithful to the philosophical core of classical constitutionalism.
Article 260(2) TFEU: An Effective Judicial Procedure for the Enforcement of Judgements?
Authors: Jack Brian
Published: April 2013

Article 260(2) TFEU (ex 228(2) EC) enables the European Court of Justice to enforce compliance with its judgements. This article analyses its use in doing so and questions whether it could be applied more effectively. It commences by highlighting the principally economic and environmental context of the case‐law, and by examining the initiatives taken to tackle delays in bringing these cases before the Court. The article then critically evaluates the effectiveness of the financial sanctions available to the Court. In doing so, it aims to fill a gap in present research by looking beyond the procedural measures through which the Court and the Commission operate to examine the practical impact of Article 260(2) itself.
Political Reluctance and Judicial Activism in the Area of Free Movement of Persons: The Court as the Motor of EU–Turkey Relations?
Authors: Wiesbrock Anja
Published: April 2013

Progress in the EU–Turkey accession negotiations has been slow in recent years, with the free movement of persons constituting one of the most controversial issues. The political reluctance and public opposition towards opening up free movement rights to Turkish nationals have led to a deadlock in this area since the early 1980s. In the face of a reluctant legislator, the Court has taken an activist stance. In a number of recent cases, it has interpreted the rights of Turkish migrants extensively, allowing for a transformation of status from family member/student to worker and applying the standstill clauses to conditions of admission. This article explores the role of the Court in pushing forward the free movement agenda. It discusses the implications of the Court's rulings for the free movement of persons between the EU and Turkey, and for the division of tasks between the Court and the legislator.
The Shroud of Turin: A Historiographical Approach
Authors: Casabianca Tristan
Published: April 2013

Criteria of historical assessment are applied to the Turin Shroud to determine which hypothesis relating to the image formation process is the most likely. To implement this, a ‘Minimal Facts’ approach is followed that takes into account only physicochemical and historical data receiving the widest consensus among contemporary scientists. The result indicates that the probability of the Shroud of Turin being the real shroud of Jesus of Nazareth is very high; historians and natural theologians should therefore pay it increased attention.
Characteristics and outcomes of patients requiring unplanned transfer from subacute to acute care
Authors: Considine Julie , Mohr Marie , Lourenco Rosemary , Cooke Robynne , Aitken Mark
Published: April 2013

The study aims to identify the reasons for, and outcomes from, unplanned transfers from subacute care to acute care. A retrospective patient record review of patients requiring unplanned transfer from subacute to an acute care emergency department (ED) from 1 July 2008 to 30 June 2009 was undertaken. Data collected included patient demographics, clinical characteristics in preceding transfer, and on ED arrival and outcome data. There were 136 patients included in the study with a median age of 81 years. The most common reasons for transfer were respiratory problems and altered conscious state. In the 24 h preceding transfer, 92.6% of patients had ≥ 1 physiological abnormality and 10.3% of patients had no physiological parameters documented. On ED arrival, 75% of patients had physiological abnormalities. Hospital admission occurred in 75% of patients and the inpatient mortality rate was 14.7%. Factors associated with inpatient mortality were tachypnoea and severe hypoxaemia in 24 h preceding transfer and tachypnoea, hypoxaemia, hypoxaemia, severe hypoxaemia and hypothermia on ED arrival. Patients requiring unplanned transfer had higher inpatient mortality than older hospital users. Reasons for unplanned transfer reflect known predictors of in‐hospital adverse events so predictive use of physiological data and patient characteristics might optimize patient safety.
Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: a population‐based study of 9399 Finnish men
Authors: Wang J. , Stančáková A. , Soininen P. , Kangas A. J. , Paananen J. , Kuusisto J. , Ala‐Korpela M. , Laakso M.
Published: April 2013

Abstract.  Wang J, Stančáková A, Soininen P, Kangas AJ, Paananen J, Kuusisto J, Ala‐Korpela M, Laakso M (University of Eastern Finland and Kuopio University Hospital, Kuopio; Institute of Clinical Medicine, University of Oulu, Oulu; University of Eastern Finland, Kuopio; and Clinical Research Center, University of Oulu, Oulu; Finland). Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: a population‐based study of 9399 Finnish men. J Intern Med 2012; doi: 10.1111/j.1365‐2796.2012.02562.x.

Objectives.  We investigated serum concentrations of lipoprotein subclass particles and their lipid components determined by proton nuclear magnetic resonance spectroscopy in a population‐based study.

Design and methods.  A total of 9399 Finnish men were included in the study: 3034 men with normal fasting glucose and normal glucose tolerance; 4345 with isolated impaired fasting glucose (IFG); 312 with isolated impaired glucose tolerance (IGT); 1058 with both IFG and IGT; and 650 with newly diagnosed type 2 diabetes (New DM). Lipoprotein subclasses included chylomicrons (CM) and largest VLDL particles, other VLDL particles (five subclasses), intermediate‐density lipoprotein (IDL), LDL (three subclasses) and HDL (four subclasses). The phospholipid, triglyceride (TG), cholesterol, free cholesterol and cholesterol ester levels of the lipoprotein particles were measured.

Results.  Abnormal glucose tolerance (especially IGT and New DM) was significantly associated with increased concentrations of VLDL subclass particles and their components (with the exception of very small VLDL particles). After further adjustment for total TGs and HDL cholesterol, increased lipid concentrations in the CM/largest VLDL particles and in most of the other VLDL particles remained significant in individuals with isolated IGT, IFG+IGT and New DM. There was a consistent trend towards a decrease in large and an increase in small HDL particle concentrations in individuals with hyperglycaemia even after adjustment for serum total TGs and HDL cholesterol.

Conclusions.  Abnormal glucose tolerance modifies the concentrations of lipoprotein subclass particles and their lipid components in the circulation and is also related to compositional changes in these particles.
Hospitalization for physical illness and risk of subsequent suicide: a population study
Authors: Qin P. , Webb R. , Kapur N. , Sørensen H. T.
Published: April 2013

Objective

To examine suicide risk in relation to physical illness across a broad range of illnesses, including hospitalization history, specific organ or system illness and comorbidity.

Design

A nested case–control study.

Setting

Data were retrieved from five Danish national registers.

Subjects

On the basis of the entire population of Denmark, this study included 27 262 suicide cases, and 468 007 live controls matched for sex and date of birth.

Main outcome measures

Risk of suicide was assessed using conditional logistic regression.

Results

In the study population, 63.5% of suicide cases and 44.5% of comparison controls had a history of hospitalization for physical illness. A physical illness significantly increased the risk of subsequent suicide (incidence rate ratios 2.13, 95% CI 2.07–2.18) with a substantially greater effect in women than in men (P < 0.01). The elevated risk increased progressively with frequency and recency of hospitalization and was significant for diseases occurring in all organs or systems of the body. Comorbidity involving several organs or systems increased the risk substantially. The associated estimates were to some extent reduced but remained highly significant after adjustment for psychiatric history and socio‐economic status. Taking into account both prevalence and adjusted effect size, physical illness accounted for 24.4%, 21.0% and 32.3% of population attributable risk for suicide in total, male and female populations, respectively.

Conclusions

Physical illness constitutes a significant risk factor for suicide independent of psychiatric and socio‐economic factors. Clinicians treating physically ill patients should be aware of the risk, especially amongst those with multiple or recent hospitalizations, or multiple comorbidities.
Cadmium exposure is accompanied by increased prevalence and future growth of atherosclerotic plaques in 64‐year‐old women
Authors: Fagerberg Björn , Bergström Göran , Borén Jan , Barregard Lars
Published: April 2013

Objectives

There is currently widespread exposure to the toxic metal cadmium through the diet as well as through smoking, and it has been suggested that cadmium exposure may increase the risk of cardiovascular disease. Here we examined whether cadmium exposure is associated with prevalence and growth of atherosclerotic plaques in the carotid arteries.

Design and subjects

The analyses were performed in a screening‐based cohort of 64‐year‐old Caucasian women with stratified, random selection to groups with normal glucose tolerance, impaired glucose tolerance and diabetes (n = 599). We measured cadmium concentrations in blood and urine at baseline. In addition, we performed ultrasound examination to determine the prevalence and area of atherosclerotic plaques in the carotid arteries and assessed smoking history and other cardiovascular risk factors at baseline and at a follow‐up examination after a mean of 5.4 years.

Results

At baseline, blood cadmium levels were associated with increased risk of plaque and a large plaque area after adjustment for confounders. In women who had never smoked, blood cadmium levels correlated positively with plaque area at baseline. The occurrence of large plaques and the change in plaque area at follow‐up were associated with blood and creatinine‐corrected urinary cadmium concentrations at baseline after adjustment for confounders. Blood and urine cadmium levels added information to established cardiovascular risk factors in predicting progress of atherosclerosis.

Conclusions

We have shown that cadmium levels in blood and urine are independent factors associated with the development of atherosclerotic plaques at baseline as well as prospectively. This novel observation emphasizes the need to consider cadmium as a pro‐atherogenic pollutant.
Proteinuria modifies the effect of systolic blood pressure on total and cardiovascular disease mortality in patients with type 2 diabetes
Authors: Vepsäläinen T. , Laakso M. , Kantola I. , Lehto S. , Juutilainen A. , Rönnemaa T.
Published: April 2013

Objectives

Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long‐term population‐based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes.

Design

We prospectively followed 881 middle‐aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130–139, 140–159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L−1). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality.

Results

During follow‐up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality.

Conclusions

Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.
Cutaneous manifestations in patients with POEMS syndrome
Authors: Miest Rachel Y. N. , Comfere Nneka I. , Dispenzieri Angela , Lohse Christine M. , el‐Azhary Rokea A.
Published: April 2013

Background  Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome is a rare multisystem paraneoplastic condition associated with plasma cell dyscrasia.

Methods  From our institution’s dysproteinemia database, 107 patients met criteria for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome between January 1, 2000, and October 1, 2009. Medical records were reviewed for documented syndrome features at diagnosis. We assessed prevalence of skin findings and associations between dermatologic and other characteristic disease findings.

Results  Of the 107 patients, 96 (90%) had a recognized cutaneous manifestation. Hyperpigmentation and hemangioma were most common (47%), followed by hypertrichosis (38%). Vascular skin changes – acrocyanosis (34%), Raynaud phenomenon (20%), hyperemia/erythema (20%), flushing (16%), or rubor (11%) – occurred in 62%; white nails, sclerodermoid changes, and clubbing occurred in 30%, 26%, and 6%, respectively. Mean number of skin findings per patient was 2.9 (median, 3.0; range, 0–7). Presence of cutaneous manifestation was associated with abnormal pulmonary function tests (P < 0.001); immunoglobulin G gammopathy was associated with hyperpigmentation and hypertrichosis. No other significant associations were seen.

Conclusions  The high prevalence of skin findings (90%) shows the value of dermatologic evaluation in diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Our data indicate new associations between skin findings and other disease characteristics.
Blind to morphology: genetics identifies several widespread ecologically common species and few endemics among Indo‐Pacific cauliflower corals (Pocillopora, Scleractinia)
Authors: Pinzón Jorge H. , Sampayo Eugenia , Cox Evelyn , Chauka Leonard J. , Chen Chaolun Allen , Voolstra Christian R. , LaJeunesse Todd C.
Published: April 2013

Aim

Using high‐resolution genetic markers on samples gathered from across their wide distributional range, we endeavoured to delimit species diversity in reef‐building Pocillopora corals. They are common, ecologically important, and widespread throughout the Indo‐Pacific, but their phenotypic plasticity in response to environmental conditions and their nearly featureless microskeletal structures confound taxonomic assignments and limit an understanding of their ecology and evolution.

Location

Indo‐Pacific, Red Sea, Arabian/Persian Gulf.

Methods

Sequence analysis of nuclear ribosomal (internal transcribed spacer 2, ITS2) and mitochondrial (open reading frame) loci were combined with population genetic data (seven microsatellite loci) for Pocillopora samples collected throughout the Indo‐Pacific, Red Sea and Arabian Gulf, in order to assess the evolutionary divergence, reproductive isolation, frequency of hybridization and geographical distributions of the genus.

Results

Between five and eight genetically distinct lineages comparable to species were identified with minimal or no hybridization between them. Colony morphology was generally incongruent with genetics across the full range of sampling, and the total number of species is apparently consistent with lower estimates from competing morphologically based hypotheses (about seven or eight taxa). The most commonly occurring genetic lineages were widely distributed and exhibited high dispersal and gene flow, factors that have probably minimized allopatric speciation. Uniquely among scleractinian genera, this genus contains a monophyletic group of broadcast spawners that evolved recently from an ancestral brooder.

Main conclusions

The delineation of species diversity guided by genetics fundamentally advances our understanding of Pocillopora geographical distributions, ecology and evolution. Because traditional diagnostic features of colony and branch morphology are proving to be of limited utility, the identification of Pocillopora species for future ecological and experimental work should rely on genetic characters that will improve research and aid in conservation strategies for these and other reef‐building corals, including the detection of real and mistaken endemic populations.
Glycosylphosphatidylinositol‐anchored high‐density lipoprotein‐binding protein 1 and the intravascular processing of triglyceride‐rich lipoproteins
Authors: Adeyo O. , Goulbourne C. N. , Bensadoun A. , Beigneux A. P. , Fong L. G. , Young S. G.
Published: April 2013

Lipoprotein lipase (LPL) is produced by parenchymal cells, mainly adipocytes and myocytes, but is involved in hydrolysing triglycerides in plasma lipoproteins at the capillary lumen. For decades, the mechanism by which LPL reaches its site of action in capillaries was unclear, but this mystery was recently solved. Glycosylphosphatidylinositol‐anchored high‐density lipoprotein‐binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol‐anchored protein of capillary endothelial cells, ‘picks up’ LPL from the interstitial spaces and shuttles it across endothelial cells to the capillary lumen. When GPIHBP1 is absent, LPL is mislocalized to the interstitial spaces, leading to severe hypertriglyceridaemia. Some cases of hypertriglyceridaemia in humans are caused by GPIHBP1 mutations that interfere with the ability of GPIHBP1 to bind to LPL, and some are caused by LPL mutations that impair the ability of LPL to bind to GPIHBP1. Here, we review recent progress in understanding the role of GPIHBP1 in health and disease and discuss some of the remaining unresolved issues regarding the processing of triglyceride‐rich lipoproteins.
Genetically engineered T cells for the treatment of cancer
Authors: Essand M. , Loskog A. S. I.
Published: April 2013

T‐cell immunotherapy is a promising approach to treat disseminated cancer. However, it has been limited by the ability to isolate and expand T cells restricted to tumour‐associated antigens. Using ex vivo gene transfer, T cells from patients can be genetically engineered to express a novel T cell receptor or chimeric antigen receptor to specifically recognize a tumour‐associated antigen and thereby selectively kill tumour cells. Indeed, genetically engineered T cells have recently been successfully used for cancer treatment in a small number of patients. Here we review the recent progress in the field, and summarize the challenges that lie ahead and the strategies being used to overcome them.
Manganese toxicity in the central nervous system: the glutamine/glutamate‐γ‐aminobutyric acid cycle
Authors: Sidoryk‐Wegrzynowicz M. , Aschner M.
Published: April 2013

Manganese (Mn) is an essential trace element that is required for maintaining proper function and regulation of numerous biochemical and cellular reactions. Despite its essentiality, at excessive levels Mn is toxic to the central nervous system (CNS). Increased accumulation of Mn in specific brain regions, such as the substantia nigra, globus pallidus and striatum, triggers neurotoxicity resulting in a neurological brain disorder, termed manganism. Mn has been also implicated in the pathophysiology of several other neurodegenerative diseases. Its toxicity is associated with disruption of the glutamine (Gln)/glutamate (Glu)‐γ‐aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons, thus leading to changes in Glu‐ergic and/or GABAergic transmission and Gln metabolism. Here we discuss the common mechanisms underlying Mn‐induced neurotoxicity and their relationship to CNS pathology and GGC impairment.
High levels of cystatin C predict the metabolic syndrome: the prospective Malmö Diet and Cancer Study
Authors: Magnusson M. , Hedblad B. , Engström G. , Persson M. , Nilsson P. , Melander O.
Published: April 2013

Objective

Cystatin C is a novel marker of cardiovascular disease (CVD); however, the underlying mechanisms remain unclear. Here, we prospectively investigated whether plasma levels of cystatin C predict new‐onset metabolic syndrome (MetS) as well as long‐term progression and incidence of the different components of the MetS.

Methods

Cystatin C was measured in 1502 individuals included in the Malmö Diet and Cancer cardiovascular cohort (mean age 56 years, 59% women) who were free from the MetS at baseline and subsequently underwent a follow‐up examination after a median of 16 years. MetS was defined according to the NCEP‐ATP‐III guidelines. Logistic regression was used to adjust for covariates.

Main outcome measures

Metabolic syndrome and long‐term progression as well as incidence of the different components of the MetS.

Results

During follow‐up, 428 subjects developed new‐onset MetS. In age‐ and sex‐adjusted analysis, compared with the lowest quartile of cystatin C, the odds ratios (95% confidence interval) for incident MetS in subjects with cystatin C levels in quartiles 2, 3 and 4 were 1.00 (0.71–1.40), 1.48 (1.06–2.07) and 1.91 (1.37–2.68), respectively (Ptrend < 0.001); this linear association remained significant even after full multivariate adjustment (Ptrend = 0.041). Interestingly, in this fully adjusted model, long‐term progression of abdominal obesity was the only component of the MetS significantly associated with increasing quartiles of baseline cystatin C levels (Ptrend = 0.008).

Conclusion

These findings suggest that cystatin C may adversely affect metabolic factors, particularly abdominal obesity, thus contributing to development of the MetS. Our results may help to explain the link between cystatin C and development of CVD.