bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-operation between different targeting pathways during integration of a membrane protein
Authors: Keller Rebecca , de Keyzer Jeanine , Driessen Arnold J.M. , Palmer Tracy
Published: October 2012

Membrane protein assembly is a fundamental process in all cells. The membrane-bound Rieske iron-sulfur protein is an essential component of the cytochrome bc1 and cytochrome b6f complexes, and it is exported across the energy-coupling membranes of bacteria and plants in a folded conformation by the twin arginine protein transport pathway (Tat) transport pathway. Although the Rieske protein in most organisms is a monotopic membrane protein, in actinobacteria, it is a polytopic protein with three transmembrane domains. In this work, we show that the Rieske protein of Streptomyces coelicolor requires both the Sec and the Tat pathways for its assembly. Genetic and biochemical approaches revealed that the initial two transmembrane domains were integrated into the membrane in a Sec-dependent manner, whereas integration of the third transmembrane domain, and thus the correct orientation of the iron-sulfur domain, required the activity of the Tat translocase. This work reveals an unprecedented co-operation between the mechanistically distinct Sec and Tat systems in the assembly of a single integral membrane protein.
The Market for U.S. Livestock Feed Proteins
Authors: Mathews Kenneth H. , McConnell Michael J.
Published: October 2012

Parameters that characterize markets for livestock feed ingredients and inform an increasing array of policies motivated by a range of environmental, market, and animal disease issues are largely absent from the literature, which necessitates the use of often misleading assumptions in analyses of proposed feed‐market policies. Such parameters are derived here from a theoretically consistent, dual translog cost model of U.S. protein and energy feed markets. Own‐price elasticities ranged from a relatively inelastic −0.139 for feedgrains to a relatively elastic −0.568 for meat and bone meal (MBM). The cross elasticity for ethanol co‐products and oilseed meals (0.168) is larger than the elasticity with co‐products and feedgrains (0.024). Higher prices for protein feeds likely result in some substitution of feed grains for some protein (e.g. corn by oilseed meals = 0.125), which may also partially account for the relatively small feedgrains cross elasticity. Policies implemented as a result of bovine splongiform encephalopathy adversely affected the share of total costs attributed to MBM, but had a positive effect on oilseed meal cost share.
Predicting pseudoknotted structures across two RNA sequences
Authors: Sperschneider Jana , Datta Amitava , Wise Michael J.
Published: October 2012

Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity.

Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support.

Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw.

Contact:  janaspe@csse.uwa.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Nuclear transferred embryonic stem cells for analysis of B1 B-lymphocyte development
Authors: Takase Mitsuyo , Iida Ryuji , Maruya Mikako , Sakaue-Sawano Asako , Miyawaki Atsushi , Wakayama Teruhiko , Nishigami Satoshi , Fagarasan Sidonia , Kanagawa Osami
Published: October 2012

The transfer of nuclei of fully differentiated cells into enucleated oocytes is a well-recognized method for the generation of embryonic stem (ES) cells. Here, we demonstrate that nuclear transferred ES (NT-ES) cells can be established with high efficiency using innate-like B lymphocytes as donor cells. We established two mouse lines carrying rearranged immunoglobulin heavy and light chains using NT-ES cells containing nuclei from peritoneal cavity B1 cells. Analysis of B1 clone lines revealed that the B1-cell generation critically depends on the interaction between antigen (possibly self-antigen) and surface immunoglobulin, while the B1-cell maintenance requires the peritoneal environment. The B1-cell expansion takes place in spleen, and is held in check by competitor B2 cells. The results indicate that the NT-ES method could replace the transgenic or knock-in mouse approaches currently used to study the biology of cells that undergo somatic rearrangements of their antigen receptor genes.
An extended service recovery model: the moderating impact of temporal sequence of events
Authors: Prasongsukarn Kriengsin , Patterson Paul G.
Published: October 2012

Purpose

The purpose of this empirical paper is to explore for the first time, in a temporal sequence of events framework, how the various forms of justice (procedural, interactional and outcome) impact on customer satisfaction with service recovery.

Design/methodology/approach

Employing scenarios, an experimental design was employed with data collected from a student sample in an Eastern collectivist culture (Thailand).

Findings

The results reveal that affirmation of perceptions of all three forms of justice positively impact overall service recovery satisfaction. However, unlike previous models of recovery satisfaction, the findings presented here suggest a temporal sequence of events model involving the causal ordering of the three justice dimensions such that distributive justice mediates the relationship between procedural and interactional justice, and ultimate recovery satisfaction.

Research limitations/implications

Based on the findings here, future studies using the three forms of justice should consider the temporal element and undertake longitudinal analysis.

Practical implications

The findings suggest that organizations should pay special attention to delivering high levels of interactional and procedural justice as they precede, and have an impact on, subsequent perceptions of outcome justice (i.e. compensation, re‐done work, etc.) in a service recovery situation.

Originality/value

This study adds to the knowledge on how firms can best recover from a service failure situation.
“Shared Pathway” national pilot project: the experience of a secure learning disability service
Authors: Esan Fola , Pittaway Melanie , Nyamande Beatrice , Graham Alex
Published: October 2012

Purpose

This paper aims to describe the experience of a secure learning disability service in participating in the national Shared Pathway pilot project in secure services.

Design/methodology/approach

Some background drivers to the project are explored as well as the experience of service users and staff who were involved in the pilot project. Recommendations on service‐wide implementation of the Shared Pathway are made.

Findings

The Shared Pathway will lead to considerable changes in practice. This will also have resource implications.

Originality/value

The paper shows that the Shared Pathway may be useful in ensuring evidence based outcomes are routinely used by clinicians in secure services in collaboration with patients. It may also clarify to patients what their role is in engaging in treatment that helps them in moving through secure services.
Human Labour is Associated with a Decline in Myometrial Chemokine Receptor Expression: The Role of Prostaglandins, Oxytocin and Cytokines
Authors: Hua Renyi , Pease James E. , Cheng Weiwei , Sooranna Suren R. , Viney Jonathan M. , Nelson Scott M. , Myatt Les , Bennett Philip R. , Johnson Mark R.
Published: October 2012

Problem

Human labour is an inflammatory process with a heavy infiltration of immune cells into the myometrium and cervix induced by local chemokine production. Myometrial cells also express chemokine receptors, but there is little information about their behaviour or function during pregnancy and labour.

Method of Study

We studied the behaviour of the receptors (CCR2, CXCR1 and CXCR2) for the CCL2 and CXCL8 in human myometrium, because both have been shown to be important in labour.

Results

We found that there was a significant decline in the mRNA expression of all three receptors in the upper segment and a similar trend in the lower segment with the onset of term labour (TL). Chemokine receptor mRNA expression was increased by stretch, reduced by oxytocin and PGF2α acting via phospholipase C (PLC). CXCR2 declined with exposure to CXCL8, consistent with the negative relationship observed in labouring myometrial tissue. The mRNA changes were confirmed by western analysis and flow cytometry.

Conclusion

These data show that myometrial chemokine receptor expression is reduced with the onset of term labour probably in response to the increased activity of chemokines, oxytocin and PGF2α.
Ocean acidification increases the toxicity of contaminated sediments
Authors: Roberts David A. , Birchenough Silvana N. R. , Lewis Ceri , Sanders Matthew B. , Bolam Thi , Sheahan Dave
Published: October 2012

Ocean acidification (OA) may alter the behaviour of sediment‐bound metals, modifying their bioavailability and thus toxicity. We provide the first experimental test of this hypothesis with the amphipod Corophium volutator. Amphipods were exposed to two test sediments, one with relatively high metals concentrations (Σmetals 239 mg kg−1) and a reference sediment with lower contamination (Σmetals 82 mg kg−1) under conditions that mimic current and projected conditions of OA (390–1140 μatm pCO2). Survival and DNA damage was measured in the amphipods, whereas the flux of labile metals was measured in the sediment and water column (WC) using Diffusive Gradients in Thin‐films. The contaminated sediments became more acutely toxic to C. volutator under elevated pCO2 (1140 μatm). There was also a 2.7‐fold increase in DNA damage in amphipods exposed to the contaminated sediment at 750 μatm pCO2, as well as increased DNA damage in organisms exposed to the reference sediment, but only at 1140 μatm pCO2. The projected pCO2 concentrations increased the flux of nickel and zinc to labile states in the WC and pore water. However, the increase in metal flux at elevated pCO2 was equal between the reference and contaminated sediments or, occasionally, greater from reference sediments. Hence, the toxicological interaction between OA and contaminants could not be explained by e ffects of pH on metal speciation. We propose that the additive physiological effects of OA and contaminants will be more important than changes in metal speciation in determining the responses of benthos to contaminated sediments under OA. Our data demonstrate clear potential for near‐future OA to increase the susceptibility of benthic ecosystems to contaminants. Environmental policy should consider contaminants within the context of changing environmental conditions. Specifically, sediment metals guidelines may need to be reevaluated to afford appropriate environmental protection under future conditions of OA.
Breast surgeons' perceptions and attitudes towards contralateral prophylactic mastectomy
Authors: Musiello Toni , Bornhammar Emelie , Saunders Christobel
Published: October 2012

Background

The rates of contralateral prophylactic mastectomy (CPM) are increasing worldwide. This study investigated Australian and New Zealand's breast surgeons' perceptions, knowledge and attitudes towards CPM, and explored if demographic characteristics of surgeons were associated with an increased tendency to recommend or perform CPM.

Methods

A cross sectional research design was employed, with breast surgeons completing a self‐report questionnaire. The questionnaire collected information including surgeons' perceptions on CPM in their clinical practice, their attitudes and knowledge of CPM and surgeons' demographic information.

Results

 Eighty‐one of 220 (37%) breast surgeons contacted via BreastSurgANZ participated in this study. Forty‐four per cent of surgeons perceived that the rates of CPMs they performed had increased over the last year. CPM rates were found to be unrelated to surgeons' age (P = 0.773) or gender (P = 0.941). The main reasons a surgeon recommended a CPM to patients included known BRCA+ mutation, family history of breast cancer and patient factors including fear and anxiety and a desire to avoid further breast cancer treatment.

Conclusions

Breast surgeons perceived that rates of CPM were increasing in their own clinical practice. CPM rates were unrelated to surgeon demographics including age and gender. While surgeons are aware of the objective risk factors that make performing a CPM advisable, they also report taking into account subjective factors, including patient fear and anxiety and a desire for breast symmetry when recommending a CPM.
Non-Parametric Survival Analysis of Infectious Disease Data
Authors: Kenah Eben
Published: October 2012

The paper develops non-parametric methods based on contact intervals for the analysis of infectious disease data. The contact interval from person i to person j is the time between the onset of infectiousness in i and infectious contact from i to j, where we define infectious contact as a contact sufficient to infect a susceptible individual. The hazard function of the contact interval distribution equals the hazard of infectious contact from i to j, so it provides a summary of the evolution of infectiousness over time. When who infects whom is observed, the Nelson–Aalen estimator produces an unbiased estimate of the cumulative hazard function of the contact interval distribution. When who infects whom is not observed, we use an expectation–maximization algorithm to average the Nelson–Aalen estimates from all possible combinations of who infected whom consistent with the observed data. This converges to a non-parametric maximum likelihood estimate of the cumulative hazard function that we call the marginal Nelson–Aalen estimate. We study the behaviour of these methods in simulations and use them to analyse household surveillance data from the 2009 influenza A(H1N1) pandemic.
THE COMBINED INTRAVAGINAL SLING AND TUCK OPERATION. AN AMBULATORY PROCEDURE FOR CURE OF STRESS AND URGE INCONTINENCE
Authors: Petros Peter E. Papa , Ulmsten Ulf I.
Published: October 2012

Abstract Thirty patients with symptoms and signs of stress and urge incontinence were treated with a Combined Intravaginal Sling and Tuck procedure. Primarily, only the first part of the procedure, the Sling operation was undertaken. This procedure creates an artificial pubourethral ligament which is achieved by controlled deposition of collagen around a retropubically implanted, removable, 0.5 cm wide Mersilene tape, inserted through a special tunneler. This part, stage 1 of the combined surgical procedure is mainly performed under local anaesthesia without postoperative catheterization, and early return to work. Urgency symptoms were cured simultaneously with the stress symptoms.

The 50% success rate of the sling procedure was improved to 82% when the second part (stage 2) of this operation was undertaken. This procedure, the “Tuck” operation, tightens the suburethral vagina. The results of the combined procedure indicate that both an intact pubourethral ligament and tight suburethral vagina are equally important for cure as proposed in the Integral Theory of Female Urinary Incontinence.
THE TETHERED VAGINA SYNDROME, POST SURGICAL INCONTINENCE AND I‐PLASTY OPERATION FOR CURE
Authors: Petros Peter E. Papa , Ulmsten Ulf I.
Published: October 2012

Abstract Urinary incontinence was observed in 19 patients after bladder neck elevation or vaginal repair operations. Characteristically, patients could not suppress their urge to micturate on getting up in the morning, and they wet before arrival at the toilet. Urodynamically, a high posterior cough transmission ratio was noted. A 1.5 cm longitudinal incision in the vagina, dissected free and resutured horizontally (I‐plasty), immediately cured this particular condition, but ultimately failed in 1/3 cases. Most of these failed patients were subsequently cured by further adjustment of vaginal tension under local anaesthesia (Tuck procedure). These findings confirm the emphasis given by the Integral Theory of Female Urinary Incontinence as to maintain adequate elasticity in the zone of critical elasticity (ZCE) of the supralevator vagina. The ZCE acts as an elastic hinge, allowing (i.e. facilitates) the separate and opposite contractile forces of anterior pubococcygeus, and levator plate which are necesary to close off urethra and bladder neck respectively. Inadequate elasticity at the ZCE converts the ZCE's role from facilitation to opposition. The stronger levator muscle contraction counteracts the forward action of the weaker anterior part of pubococcygeus muscle, preventing bladder neck closure.
THE ROLE OF A LAX POSTERIOR VAGINAL FORNIX IN THE CAUSATION OF STRESS AND URGENCY SYMPTOMS: A PRELIMINARY REPORT
Authors: Petros Peter E. Papa , Ulmsten Ulf I.
Published: October 2012

Abstract Ten patients are presented with symptoms of urinary stress and/or urgency. Eight were cured by approximation of the uterosacral ligaments. This supports the contention of the Integral Theory of Female Urinary Incontinence that a loosely tethered supralevator vagina may be an important element in urinary incontinence, especially following hysterectomy.
A ptilochronological study of carry‐over effects of conditions during wintering on breeding performance in the barn swallowHirundo rustica
Authors: Saino Nicola , Romano Maria , Caprioli Manuela , Ambrosini Roberto , Rubolini Diego , Scandolara Chiara , Romano Andrea
Published: October 2012

The ecological conditions that a bird experiences during any stage of its life cycle may have consequences that become manifested at later life stages, and these ‘carry‐over effects’ may be major components of variance in individual performance. Condition‐dependent feather growth rate, as assessed by growth bars width (GBW), provides a unique, though largely under‐exploited tool to investigate carry‐over effects of ecological conditions and individual physiological state during molt. In this study of breeding barn swallowsHirundo rustica, which undergo a single complete annual molt of tail and wing feathers during wintering in sub‐Saharan Africa, we first show that old (≥ 2 yr) females have larger GBW than old males and yearlings. GBW was smaller with larger infestations by common ectoparasites of barn swallows, independent of the swallows’ age or sex, and larger GBW was associated with a higher index of body condition during the breeding season in males. Larger GBW predicted higher seasonal reproductive output of older males, but not reproductive output of younger males or females of any age class, with this higher reproductive output of older males mediated by higher offspring fledging success. However, no relationship with GBW was observed for seasonal reproductive output of males in the spring preceding the winter when the feathers were grown. Hence, this study suggests that the analysis of the rate of feathers growth (‘ptilochronology’) has a larger potential to serve as a powerful tool in the study of carry‐over effects than has been appreciated to date. Specifically, the present results support the idea that conditions experienced during wintering in Africa and proximately reflected by GBW have carry‐over effects on body condition and breeding success. These effects are sex and age specific, being more pronounced in older males, possibly as a consequence of differences in annual time routines and susceptibility to extrinsic factors among sex and age classes.
Candidates for detecting exoplanetary radio emissions generated by magnetosphere—ionosphere coupling
Authors: Nichols J. D.
Published: October 2012

In this Letter we consider the magnetosphere—ionosphere (M—I) coupling at Jupiter-like exoplanets with internal plasma sources such as volcanic moons, and we have determined the best candidates for detection of these radio emissions by estimating the maximum spectral flux density expected from planets orbiting stars within 25 pc using data listed in the NASA/IPAC/NExScI Star and Exoplanet Database (NStED). In total we identify 91 potential targets, of which 40 already host planets and 51 have stellar X-ray luminosity over 100 times the solar value. In general, we find that higher planetary field strength, combined with larger rotation rate, higher stellar XUV luminosity and lower stellar wind dynamic pressure, results in higher radio power. The top two targets that host planets are ε Eri and HIP 85523, and the top two targets that have X-ray luminosity over 100 times the solar value are CPD—28 332 and FF And.
Longitudinal in vivo developmental changes of metabolites in the hippocampus of Fmr1 knockout mice
Authors: Shi Da , Xu Su , Waddell Jaylyn , Scafidi Susanna , Roys Steven , Gullapalli Rao P. , McKenna Mary C.
Published: October 2012

Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is studied in the Fmr1 knockout (KO) mouse, which models both the anatomical and behavioral changes observed in FXS patients. In vitro studies have shown many alterations in synaptic plasticity and increased density of immature dendritic spines in the hippocampus, a region involved in learning and memory. In this study, magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopy (MRS) were used to determine in vivo longitudinal changes in volume and metabolites in the hippocampus during the critical period of early myelination and synaptogenesis at post‐natal days (PND) 18, 21, and 30 in Fmr1 KO mice compared with wild‐type (WT) controls. MRI demonstrated an increase in volume of the hippocampus in the Fmr1 KO mouse compared with controls. MRS revealed significant developmental changes in the ratios of hippocampal metabolites N‐acetylaspartate (NAA), myo‐inositol (Ins), and taurine to total creatine (tCr) in Fmr1 KO mice compared with WT controls. Ins was decreased at PND 30, and taurine was increased at all ages studied in Fmr1 KO mice compared with controls. An imbalance of brain metabolites in the hippocampus of Fmr1 KO mice during the critical developmental period of synaptogenesis and early myelination could have long‐lasting effects that adversely affect brain development and contribute to ongoing alterations in brain function.
Structural basis for selective GABA binding in bacterial pathogens
Authors: Planamente Sara , Mondy Samuel , Hommais Florence , Vigouroux Armelle , Moréra Solange , Faure Denis
Published: October 2012

GABA acts as an intercellular signal in eukaryotes and as an interspecies signal in host–microbe interactions. Structural characteristics of selective eukaryotic GABA receptors and bacterial GABA sensors are unknown. Here, we identified the selective GABA‐binding protein, called Atu4243, in the plant pathogen Agrobacterium tumefaciens. A constructed atu4243 mutant was affected in GABA transport and in expression of the GABA‐regulated functions, including aggressiveness on two plant hosts and degradation of the quorum‐sensing signal. The GABA‐bound Atu4243 structure at 1.28 Å reveals that GABA adopts a conformation never observed so far and interacts with two key residues, Arg203 and Asp226 of which the role in GABA binding and GABA signalling in Agrobacterium has been validated using appropriate mutants. The conformational GABA‐analogue trans‐4‐aminocrotonic acid (TACA) antagonizes GABA activity, suggesting structural similarities between the binding sites of the bacterial sensor Atu4243 and mammalian GABAC receptors. Exploration of genomic databases reveals Atu4243 orthologues in several pathogenic and symbiotic proteobacteria, such as Rhizobium, Azospirillum, Burkholderia and Pseudomonas. Thus, this study establishes a structural basis for selective GABA sensors and offers opportunities for deciphering the role of the GABA‐mediated communication in several host–pathogen interactions.
AVE 0991, a non‐peptide Mas‐receptor agonist, facilitates penile erection
Authors: da Costa Gonçalves Andrey C. , Fraga‐Silva Rodrigo A. , Leite Romulo , Santos Robson A. S.
Published: October 2012

New findings

What is the central question of this study?

The renin–angiotensin system plays a crucial role in erectile function. While angiotensin II contributes to the development of erectile dysfunction, angiotensin‐(1–7) mediates penile erection by activation of the Mas receptor. However, because of its peptidic nature, angiotensin‐(1–7) is not resistant to proteolytic enzymes, thus limiting its clinical applications. In this study, we have hypothesized that the synthetic non‐peptide Mas agonist, AVE 0991, would potentiate the penile erectile function.

What is the main finding and its importance

We demonstrated that AVE 0991 potentiates the rat penile erectile response through Mas in a nitric oxide‐dependent manner; therefore, our results suggest Mas agonists as potential targets for the treatment of erectile dysfunction.

The renin–angiotensin system plays a crucial role in erectile function. It has been shown that elevated levels of angiotensin II contribute to the development of erectile dysfunction both in humans and in aminals. On the contrary, the heptapeptide angiotensin‐(1–7) appears to mediate penile erection by activation of the Mas receptor. Recently, we have shown that the erectile function of Mas gene‐deleted mice was substantially reduced, which was associated with a marked increase in fibrous tissue in the corpus cavernosum. We have hypothesized that the synthetic non‐peptide Mas agonist, AVE 0991, would potentiate penile erectile function. We showed that intracavernosal injection of AVE 0991 potentiated the erectile response of anaesthetized Wistar rats, measured as the ratio between corpus cavernosum pressure and mean arterial pressure, upon electrical stimulation of the major pelvic ganglion. The facilitatory effect of AVE 0991 on erectile function was dose dependent and completely blunted by the nitric oxide synthesis inhibitor, l‐NAME. Importantly, concomitant intracavernosal infusion of the specific Mas receptor blocker, A‐779, abolished the effect of AVE 0991. We demonstrated that AVE 0991 potentiates the penile erectile response through Mas in an NO‐dependent manner. Importantly, these results suggest that Mas agonists, such as AVE 0991, might have significant therapeutic benefits for the treatment of erectile dysfunction.
Overexpression of peroxisome proliferator‐activated receptor α in pancreatic β‐cells improves glucose tolerance in diet‐induced obese mice
Authors: Hogh K‐Lynn N. , Uy Christopher E. , Asadi Ali , Baker Robert K. , Riedel Michael J. , Gray Sarah L.
Published: October 2012

New findings

What is the central question of this study?

Does overexpression of peroxisome proliferator‐activated receptor α (PPARα) specifically in pancreatic β‐cells of diet‐induced obese mice preserve pancreatic β‐cell function and delay the onset of obesity‐induced diabetes?

What is the main finding and its importance?

This study reports the phenotype of the first in vivo model of β‐cell‐specific PPARα overexpression in a murine model of diet‐induced obesity. We show that pancreatic β‐cell‐specific overexpression of PPARα significantly improves glucose tolerance in diet‐induced obese mice. These results suggest that activation of β‐cell PPARα may be an appropriate target to preserve β‐cell function in obesity‐induced diabetes.

Lipotoxicity is implicated in pancreatic β‐cell dysfunction in obesity‐induced type 2 diabetes. In vitro, activation of peroxisome proliferator‐activated receptor α (PPARα) has been shown to protect pancreatic β‐cells from the lipotoxic effects of palmitate, thereby preserving insulin secretion. Utilizing an adeno‐associated virus (dsAAV8), overexpression of PPARα was induced specifically in pancreatic β‐cells of adult, C57Bl/6 mice fed a high‐fat diet for 20 weeks and carbohydrate metabolism and β‐cell mass assessed. We show that overexpression of PPARα in pancreatic β‐cells in vivo preserves β‐cell function in obesity, and this improves glucose tolerance by preserving insulin secretion in comparison to control mice with diet‐induced obesity. No changes in β‐cell mass were observed in PPARα‐overexpressing mice compared with diet‐induced obese control animals. This model of β‐cell‐specific PPARα overexpression provides a useful in vivo model for elucidating the mechanisms underlying β‐cell lipotoxicity in obesity‐induced type 2 diabetes.
Thin film high dielectric constant metal oxides prepared by reactive sputtering
Authors: Wright Steven W. , Judge C. Philip , Lee Michael J. , Bowers Derek F. , Dunbar Mike , Wilson Craig D.
Published: October 2012

High dielectric constant, low loss dielectric thin film materials produced by reactive RF sputtering have been investigated for use as capacitor dielectrics in integrated circuits, using oxides of niobium, tantalum, titanium, hafnium, and zirconium and mixtures of these with aluminum oxide. High breakdown fields and low leakage currents are found for the best materials and a reduction in capacitor area of a factor of >3 compared with Si3N4 capacitors of the same value, using a simple production process compatible with semiconductor device manufacturing.
Multiresistant Uropathogenic Escherichia coli from a Region in India Where Urinary Tract Infections Are Endemic: Genotypic and Phenotypic Characteristics of Sequence Type 131 Isolates of the CTX-M-15 Extended-Spectrum-β-Lactamase-Producing Lineage
Authors: Hussain Arif , Ewers Christa , Nandanwar Nishant , Guenther Sebastian , Jadhav Savita , Wieler Lothar H. , Ahmed Niyaz
Published: October 2012

Escherichia coli
sequence type 131 (O25b:H4), associated with the CTX-M-15 extended-spectrum beta-lactamases (ESBLs) and linked predominantly to the community-onset antimicrobial-resistant infections, has globally emerged as a public health concern. However, scant attention is given to the understanding of the molecular epidemiology of these strains in high-burden countries such as India. Of the 100 clinical
E. coli
isolates obtained by us from a setting where urinary tract infections are endemic, 16 ST131
E. coli
isolates were identified by multilocus sequence typing (MLST). Further, genotyping and phenotyping methods were employed to characterize their virulence and drug resistance patterns. All the 16 ST131 isolates harbored the CTX-M-15 gene, and half of them also carried TEM-1; 11 of these were positive for
bla
OXA
groups 1 and 12 for
aac(6
′
)-Ib-cr
. At least 12 isolates were refractory to four non-beta-lactam antibiotics: ciprofloxacin, gentamicin, sulfamethoxazole-trimethoprim, and tetracycline. Nine isolates carried the class 1 integron. Plasmid analysis indicated a large pool of up to six plasmids per strain with a mean of approximately three plasmids. Conjugation and PCR-based replicon typing (PBRT) revealed that the spread of resistance was associated with the FIA incompatibility group of plasmids. Pulsed-field gel electrophoresis (PFGE) and genotyping of the virulence genes showed a low level of diversity among these strains. The association of ESBL-encoding plasmid with virulence was demonstrated in transconjugants by serum assay. None of the 16 ST131 ESBL-producing
E. coli
strains were known to synthesize carbapenemase enzymes. In conclusion, our study reports a snapshot of the highly virulent/multiresistant clone ST131 of uropathogenic
E. coli
from India. This study suggests that the ST131 genotypes from this region are clonally evolved and are strongly associated with the CTX-M-15 enzyme, carry a high antibiotic resistance background, and have emerged as an important cause of community-acquired urinary tract infections.
The spectrum of sleep-disordered breathing symptoms and respiratory events in infants with cleft lip and/or palate
Authors: MacLean Joanna E , Fitzsimons David , Fitzgerald Dominic A , Waters Karen A
Published: October 2012

Objective

To determine the prevalence of sleep-disordered breathing (SDB) symptoms and respiratory events during sleep in infants with cleft lip and/or palate (CL/P).

Design

Prospective observational study.

Setting

Cleft palate clinic, tertiary care paediatric hospital, before palate surgery.

Patients

Consecutive newborn infants with CL/P.

Main outcome measures

Demographics, clinical history, sleep symptoms, facial measurement and polysomnography (PSG; sleep study) data.

Results

Fifty infants completed PSG at 2.7±2.3 months; 56% were male, and 30% had a clinical diagnosis of Pierre Robin sequence (PRS) or a syndrome. The majority of infants (75%) were reported to snore frequently or constantly, while 74% were reported to have heavy or loud breathing during sleep. The frequency of parent-reported difficulty with breathing during sleep was 10% for infants with isolated CL/P, 33% for those with syndrome, and 43% for PRS (χ2 16.1, p<0.05). All infants had an Obstructive–Mixed Apnoea–Hypopnoea Index (OMAHI) >1 event/h, and 75% had an OMAHI >3 events/h. Infants with PRS had higher OMAHI (34.3±5.1) than infants with isolated CL/P (7.6±1.2) or infants with syndromes (15.6±5.7, F stat, p<0.001). Multivariate analysis showed that PRS was associated with higher OMAHI (B 0.53±0.22, p=0.022), but the majority of the variance for SDB was unexplained (constant B 1.31±0.55, p=0.024).

Conclusions

The results highlight that infants across the spectrum of CL/P have a high risk of SDB symptoms and obstructive respiratory events before palate surgery. Clinicians should enquire about symptoms of SDB and consider investigation with polysomnography in all infants with CL/P.
Diagnosis and management of the epilepsies in children: a summary of the partial update of the 2012 NICE epilepsy guideline
Authors: Appleton Richard E , Freeman Amanda , Cross J Helen
Published: October 2012

The epilepsies of childhood are a heterogeneous group of disorders with different causes, treatments and outcomes. The choice of anti-epileptic drug is largely determined by its effectiveness in a specific epilepsy syndrome, or seizure type(s) if a syndrome cannot be readily identified, and the drug's safety profile. There are minimal randomised controlled trial data to help inform this decision. In January 2012, the National Institute for Health and Clinical Excellence (NICE) published its partially revised and updated clinical guideline on the pharmacological treatment of the epilepsies in children and adults. This partial update provides additional data and also specific recommendations that improve the evidence base for the use of specific anti-epileptic drugs in treating the epilepsies of childhood.
A cross-sectional study of the association of age, race and ethnicity, and body mass index with sex steroid hormone marker profiles among men in the National Health and Nutrition Examination Survey (NHANES III)
Authors: Ritchey Jamie , Karmaus Wilfried , Sabo-Attwood Tara , Steck Susan E , Zhang Hongmei
Published: October 2012

Objectives

Since sex hormone markers are metabolically linked, examining sex steroid hormones singly may account for inconsistent findings by age, race/ethnicity and body mass index (BMI) across studies. First, these markers were statistically combined into profiles to account for the metabolic relationship between markers. Then, the relationships between sex steroid hormone profiles and age, race/ethnicity and BMI were explored in multinomial logistic regression models.

Design

Cross-sectional survey.

Setting

The US Third National Health and Nutrition Examination Survey (NHANES III).

Participants

1538 Men, >17 years.

Primary outcome measure

Sex hormone profiles.

Results

Cluster analysis was used to identify four statistically determined profiles with Blom-transformed T, E, sex hormone binding globulin (SHBG), and 3-α diol G. We used these four profiles with multinomial logistic regression models to examine differences by race/ethnicity, age and BMI. Mexican American men >50 years were associated with the profile that had lowest T, E and 3-α diol G levels compared to other profiles (p<0.05). Non-Hispanic Black, overweight (25–29.9 kg/m2) and obese (>30 kg/m2) men were most likely to be associated with the cluster with the lowest SHBG (p<0.05).

Conclusion

The associations of sex steroid hormone profiles by race/ethnicity are novel, while the findings by age and BMI groups are largely consistent with observations from single hormone studies. Future studies should validate these hormone profile groups and investigate these profiles in relation to chronic diseases and certain cancers.
Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials
Authors: Mak Koon-Hou
Published: October 2012

Objective

Oral direct thrombin and anti-Xa inhibitors have been shown to be efficacious in the prevention and treatment of venous thromboembolism, and prevention of embolic events in atrial fibrillation. Recent studies showed that dabigatran may be associated with increased rates of myocardial infarction (MI). Coronary risk for the other agents was unclear. The aim of the study is to determine the coronary risk among four novel antithrombotic agents.

Design

Mixed treatment comparison meta-analysis.

Data sources and study selection

Randomised controlled trials (RCTs) on ximelagatran, dabigatran, rivaroxaban and apixaban were obtained from PubMed search (February 2012) and major scientific meeting in 2011. The random-effects model was used to evaluate the effect of these agents on MI or acute coronary syndrome (MI/ACS), major bleeding complication and all-cause mortality.

Results

From 28 RCTs (n=138 948), the risk for MI/ACS was higher for dabigatran (OR 1.30; 95% CI 1.04 to 1.63; p=0.021) but lower for rivaroxaban (OR 0.78; 95% CI 0.69 to 0.89; p<0.001). Ximelagatran showed a higher risk for MI/ACS, which was not statistically significant, while apixaban demonstrated a non-significant lower likelihood. Among the RCTs for MI/ACS among the four agents, only those pertaining to ximelagatran showed heterogeneity. Major bleeding complication rates varied considerably among different agents. Importantly, these agents were associated with a lower all-cause mortality, without heterogeneity among the studies.

Conclusions

The risk for coronary events was significantly higher for dabigatran but not significantly higher for ximelagatran. Conversely, this risk was lower among anti-Xa inhibitors. All-cause mortality was lower among those receiving novel antithrombotic agents. This information may be useful in selecting agents for specific subsets of patients requiring anticoagulation.
How to design and implement palliative care public health programmes: foundation measures. An operational paper by the WHO Collaborating Centre for Public Health Palliative Care Programmes at the Catalan Institute of Oncology
Authors: Gómez-Batiste Xavier , Stjernsward Jan , Espinosa Jose , Martínez-Muñoz Marisa , Trelis Jordi , Constante Carles
Published: October 2012

This paper summarises the recommendations of the WHO Collaborating Centre for Palliative Care Public Health Programmes with respect to design and implementation of palliative care national or regional public health palliative care programmes in their initial phases. We describe the elements of a programme (leadership and aims; needs and context assessment; definition of the target patients; general measures in conventional services; specialist services in different settings; sectorised networks; education and training; availability and accessibility of opioids and essential drugs; legislation; standards; budget; valuation and improvement of quality; and evaluation of results and indicators) and the specific recommendations to implement the first steps of each component. Palliative care planning needs to be systematic, inserted in all levels of the healthcare system and adapted to the cultural and organisational status of the system. Coverage for all types of patients in need, together with equity and quality, are the main aims of programmes.
Effects of a free school breakfast programme on children's attendance, academic achievement and short-term hunger: results from a stepped-wedge, cluster randomised controlled trial
Authors: Mhurchu Cliona Ni , Gorton Delvina , Turley Maria , Jiang Yannan , Michie Jo , Maddison Ralph , Hattie John
Published: October 2012

Background

Free school breakfast programmes (SBPs) exist in a number of high-income countries, but their effects on educational outcomes have rarely been evaluated in randomised controlled trials.

Methods

A 1-year stepped-wedge, cluster randomised controlled trial was undertaken in 14 New Zealand schools in low socioeconomic resource areas. Participants were 424 children, mean age 9±2 years, 53% female. The intervention was a free daily SBP. The primary outcome was children's school attendance. Secondary outcomes were academic achievement, self-reported grades, sense of belonging at school, behaviour, short-term hunger, breakfast habits and food security.

Results

There was no statistically significant effect of the breakfast programme on children's school attendance. The odds of children achieving an attendance rate <95% was 0.76 (95% CI 0.56 to 1.02) during the intervention phase and 0.93 (95% CI 0.67 to 1.31) during the control phase, giving an OR of 0.81 (95% CI 0.59 to 1.11), p=0.19. There was a significant decrease in children's self-reported short-term hunger during the intervention phase compared with the control phase, demonstrated by an increase of 8.6 units on the Freddy satiety scale (95% CI 3.4 to 13.7, p=0.001). There were no effects of the intervention on any other outcome.

Conclusions

A free SBP did not have a significant effect on children's school attendance or academic achievement but had significant positive effects on children's short-term satiety ratings. More frequent programme attendance may be required to influence school attendance and academic achievement.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR)—ACTRN12609000854235.
Improvements in recanalization with modern stroke therapy: a review of prospective ischemic stroke trials during the last two decades
Authors: Fargen Kyle M , Meyers Philip M , Khatri Pooja , Mocco J
Published: October 2012

Introduction

A number of recent trials evaluating intra-arterial therapies for acute ischemic stroke have been completed. We present a review of prospective acute ischemic stroke trials reported in a peer-reviewed forum during the last 20 years to provide insight into the general direction of this rapidly evolving field.

Methods

Prospective trials evaluating acute stroke intra-arterial therapies since 1999 were included, with the National Institute of Neurological Disorders and Stroke rtPA trial published in 1995 as a baseline comparator. Patient presenting factors and outcome data were analyzed based on year of publication and best-fit lines and linear regression analyses were generated.

Results

Thirteen prospective trials were included. Regression analyses demonstrated no appreciable change in the median NIH Stroke Scale score of subjects at the time of enrollment since 1995 (p=0.44) and no appreciable improvements in good outcome based on a modified Rankin score of 0–2 at 90 days (p=0.66) or mortality at 90 days (p=0.55). A significant increase in time from onset of symptoms to treatment among enrolled patients was noted from 1995 to 2012 (p=0.03). In addition, a significant improvement in recanalization/reperfusion was noted over the last two decades (p=0.02).

Conclusions

This review of prospective acute ischemic stroke trials since 1999 indicates a substantial improvement in revascularization in the setting of a significant increase in time to therapy onset, but no appreciable change in good functional outcome.
Statin-induced lung injury: diagnostic clue and outcome
Authors: Huang Li-Kuo , Tsai Ming-Ji , Tsai Han-Chen , Chao Heng-Sheng , Lin Fang-Chi , Chang Shi-Chuan
Published: October 2012

Background

Statin-induced lung injury (SILI) is an uncommon but serious complication of statins. The clinical features and outcome of patients with SILI vary widely. Clinical data relevant to diagnosis and outcome of patients with SILI were investigated in this study.

Method

Four cases of SILI diagnosed at our institute and 12 cases reported in the English literature from 1995 to 2010 were studied. The patients were further divided into favourable and unfavourable outcome groups and compared.

Results

Compared with the 12 previously reported cases, fever (p=0.008) and consolidation (p=0.027) were more common and duration of statin treatment was significantly shorter (p=0.030) in our patients. Foamy alveolar macrophages in bronchoalveolar lavage fluid (BALF) were found in our four patients. Patients with cough (p=0.024), fever (p=0.026) and alveolar infiltrates (p=0.036), especially ground-glass opacity (GGO) (p=0.001) shown on thoracic high-resolution CT (HRCT), had a favourable outcome. Conversely, those with fibrosis shown on HRCT (p=0.008) had an unfavourable outcome. Stepwise logistic regression analysis demonstrated that cough (p=0.011), fever (p=0.005), and alveolar infiltrates (p=0.017), GGO (p<0.001) and fibrosis (p=0.002) shown on thoracic HRCT were independent factors affecting the outcome of SILI.

Conclusions

For patients with SILI, pulmonary phospholipidosis, as shown by foamy alveolar macrophages in BALF, may be valuable in diagnosis, and clinical symptoms and thoracic HRCT findings are of value in predicting the outcome.