bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study
Authors: Walsh Timothy Simon , Salisbury Lisa G , Boyd Julia , Ramsay Pamela , Merriweather Judith , Huby Guro , Forbes John , Rattray Janice Z , Griffith David M , Mackenzie Simon J , Hull Alastair , Lewis Steff , Murray Gordon D
Published: July 2012

Introduction

Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life.

Methods and analysis

The authors plan a multicentre randomised parallel group complex intervention trial with concealment of group allocation from outcome assessors. Patients who required more than 48 h of mechanical ventilation and are deemed fit for intensive care unit discharge will be eligible. Patients with primary neurological diagnoses will be excluded. Participants will be randomised into one of the two groups: the intervention group will receive standard ward-based care delivered by the NHS service with additional treatment by a specifically trained generic rehabilitation assistant during ward stay and via telephone contact after hospital discharge and the control group will receive standard ward-based care delivered by the current NHS service. The intervention group will also receive additional information about their critical illness and access to a critical care physician. The total duration of the intervention will be from randomisation to 3 months postrandomisation. The total duration of follow-up will be 12 months from randomisation for both groups. The primary outcome will be the Rivermead Mobility Index at 3 months. Secondary outcomes will include measures of physical and psychological morbidity and function, quality of life and survival over a 12-month period. A health economic evaluation will also be undertaken. Groups will be compared in relation to primary and secondary outcomes; quantitative analyses will be supplemented by focus groups with patients, carers and healthcare workers.

Ethics and dissemination

Consent will be obtained from patients and relatives according to patient capacity. Data will be analysed according to a predefined analysis plan.

Trial registration

The trial is registered asISRCTN09412438and funded by the Chief Scientist Office, Scotland.
Understanding integrated care pathways in palliative care using realist evaluation: a mixed methods study protocol
Authors: Dalkin Sonia Michelle , Jones Diana , Lhussier Monique , Cunningham Bill
Published: July 2012

Introduction

Policy- and evidence-based guidelines have highlighted the need for improved palliative and end-of-life care. However, there is still evidence of individuals dying undignified deaths with little pain control, therefore inflicting unnecessary suffering. New commissioning powers have enabled a 2-year pilot of an innovative integrated care pathway (ICP) designed to improve arrangements for individuals with life-limiting illnesses requiring palliative care. A novel feature of the ICP is its focus on palliative care over the last 6 months of life, aiming to intervene early to prepare for and ensure a good death. What is not known is if this pathway works, how it works and who it works for.

Methods and analysis

A realist evaluation and a complex analytical framework will investigate and discover context, mechanism and outcome conjectures and configurations of the ICP and thus facilitate exploration of how it works and who it works for. A mixed methods approach will be used with small sample sizes to capture the breadth of the ICP. Phase 1 will identify if the pathway works through analysis of NHS MorbidityInformation Query and Export Syntax data, locality Death Audit data and the Quality of Dying and Death Questionnaire. Phase 2 employs soft systems methodology with data from focus groups with health professionals to identify how the pathway works. Phase 3 uses the Miller Behavioural Style Scale and interviews with palliative care patients and bereaved relatives to analyse communication in palliative care.

Ethics and dissemination

Ethical approval has been granted from the NHS local ethics committee (REC reference number:11/NE/0318). Research & Development approval has been gained from four different trusts, and relevant voluntary organisations and the local council have been informed about the research. This protocol illustrates the complexity inherent in evaluating a palliative care ICP. Identification of whether the pathway works, how it works and who it works for will be beneficial to all practices and other care providers involved as it will give objective data on the impact of the ICP. Results will be disseminated throughout the study for continuous quality improvement of the ICP. Outcomes from each data collection phase will be disseminated separately if analysis warrants it; all data collection will be utilised in the realist evaluation. The research provides a potential for the dissemination of the pathway to other localities through the transferable knowledge it will generate, from its focus on the contexts that are crucial for successful implementation, the mechanisms that facilitate implementation and the outcomes achieved.
Documentation of neurovascular status in supracondylar fractures and the development of an assessment proforma
Authors: Mayne Alistair Ivan William , Perry Daniel C , Stables Gareth , Dhotare Satish , Bruce Colin E
Published: July 2012

Background

Supracondylar fractures are associated with a high incidence of neurovascular complications. Comprehensive clinical evaluation is a necessity when children with these injuries present to the emergency department. Neurovascular assessment can be difficult due to pain, anxiety and the young age of these patients; however, it is crucial findings are well documented to identify patients requiring urgent surgical intervention, in addition to allowing the neurovascular status to be monitored over time. The aim of this study was to evaluate the preoperative neurovascular documentation in children presenting with displaced supracondylar fractures and devise an emergency department assessment proforma to facilitate comprehensive evaluation.

Methods

A retrospective case-note review was performed on patients with Gartland grades 2 and 3 supracondylar fractures observed in a 2-year period from July 2008 to July 2010.

Results

137 patients were included; only 12 patients (8.8%) and 19 patients (13.9%), respectively, had a complete preoperative neurological or vascular assessment documented. Regarding the individual nerves, 59 (43.1%) patients had median nerve integrity documented, 55 (40.1%) ulnar nerve and 49 (35.8%) radial nerve integrity documented. Only 18 patients (13.1%) had their anterior interosseous nerve (AIN) function documented.

Conclusions

Preoperative documentation of neurovascular status in children with displaced supracondylar fractures was poor. Documentation of AIN examination was particularly poor. The introduction of a proforma (Liverpool upper limb fracture assessment) is proposed to increase documentation of neurovascular assessment and optimise emergency department evaluation of children presenting with upper limb injuries.
Humanisation in the emergency department of an Italian hospital: new features and patient satisfaction
Authors: Lovato Emanuela , Minniti Davide , Giacometti Marika , Sacco Roberto , Piolatto Alberto , Barberis Bruno , Papalia Riccardo , Bert Fabrizio , Siliquini Roberta
Published: July 2012

Objectives

The goal of this study was to describe and analyse interventions performed in the emergency department (ED) of an Italian hospital with the aim of humanising the patient care pathway. The actions taken are described and the changes analysed to determine whether they resulted in an increased level of patient satisfaction.

Methods

An observational study was conducted between October 2010 and March 2011. The data were collected via a telephone questionnaire administered to patients who were admitted to the ED before and after humanisation interventions. The respondents were questioned about their general condition and their level of satisfaction.

Results

The study population included 297 patients (158 before and 139 after the interventions). The highest overall patient satisfaction after the interventions was highly correlated with the humanisation interventions and not with other factors such as gender, age, educational level or the severity code triage. Specifically, in patients who went to the ED after the changes had been made, there was a greater level of satisfaction regarding comfort in the waiting room, waiting time for the first visit and the privacy experienced during the triage.

Conclusion

The results demonstrate that the interventions implemented in this study, designed to humanise the ED, improved overall patient satisfaction. Interventions may be taken to reduce the depersonalisation of patients in the emergency room.
Does social capital affect the incidence of functional disability in older Japanese? A prospective population-based cohort study
Authors: Aida Jun , Kondo Katsunori , Kawachi Ichiro , Subramanian S V , Ichida Yukinobu , Hirai Hiroshi , Kondo Naoki , Osaka Ken , Sheiham Aubrey , Tsakos Georgios , Watt Richard G
Published: July 2012

Background

Recent increases in numbers of older people have been accompanied by increases in those with functional disability. No study has examined the association between community social capital and the onset of functional disability.

Methods

The association between community social capital and the onset of functional disability was examined using data from the Aichi Gerontological Evaluation Study, a prospective cohort established in 2003 in Japan. Perceptions of community social capital (indicators of social cohesion such as trust of others and extent of social participation) in 6953 men and 7636 women aged 65 years or older were surveyed. Multilevel survival analysis using the discrete-time hazard model was applied.

Results

During 4-year follow-up, onset of functional disability occurred in 759 men and 1146 women. Women living in communities with higher mistrust had 1.68 (95% CI 1.14 to 2.49) times higher OR of onset of disability, even after adjusting for covariates. Mediators did not substantially change this association. Lack of social participation seemed to affect the health of women, though the effect was marginal (OR for covariates adjusted model =1.12 (95% CI 0.96 to 1.31)). There were no significant ORs among men.

Conclusions

Lower community social capital was associated with higher incidence of onset of functional disability among older women but not among men. Community-based interventions to promote social capital may be useful for preventing functional disability of older Japanese women.
Navigating the swampy lowland: a framework for evaluating the effect of community mobilisation in female sex workers in Avahan, the India AIDS Initiative
Authors: Galavotti Christine , Wheeler Tisha , Kuhlmann Anne Sebert , Saggurti Niranjan , Narayanan Pradeep , Kiran Usha , Dallabetta Gina
Published: July 2012

Background

Few models of how community mobilisation works have been elaborated in the scientific literature, and evaluation of the impact of these programmes on HIV and other health outcomes is extremely limited. Avahan, the India AIDS Initiative, has been implementing community mobilisation as part of its prevention programming with groups of high-risk individuals across six states since 2005.

Purpose

To articulate a programme theory and evaluation framework for evaluation of Avahan's approach to community mobilisation among female sex workers in four southern states in India.

Methods

The authors use a goal-based evaluation approach to describe the programme goals and an underlying programme theory that specifies how the programme is expected to work. Using multilevel structural equation modelling with propensity score matching, the evaluation will compare what is observed in the data with the predicted relationships specified by the model.

Results

The Avahan model of community mobilisation posits that meaningful participation in high-risk group intervention, structural intervention and organisational development activities leads to identification, collectivisation and ownership, which in turn leads to improved programme outcomes. Strong community groups and an enabling environment reinforce social norm and behaviour change outcomes and lead to sustained impact.

Discussion

Specifying an explicit programme theory can aid in the evaluation of complex interventions, especially when the evaluation design is observational. In addition to articulating Avahan's community mobilisation approach in a model that can be tested, we recommend some specific measures and methods that could be used to improve evaluation efforts in the future.
How effective is community mobilisation in HIV prevention among highly diverse sex workers in urban settings? The Aastha intervention experience in Mumbai and Thane districts, India
Authors: Gaikwad Sanjeev Singh , Bhende Amrita , Nidhi Gaurav , Saggurti Niranjan , Ranebennur Virupax
Published: July 2012

Background

This paper examines the association between degree of confidence in collective efficacy and self-efficacy for condom use and empowerment among heterogeneous female sex workers (FSWs) in two metropolitan Indian cities with high HIV prevalence.

Methods

The study utilises data from the Behavioural Tracking Survey, a cross-sectional behavioural study with 2106 FSWs recruited from 411 intervention sites in Mumbai and Thane. The key independent measures used determine the degree of confidence in collective efficacy (belief in the power to achieve goals and address problems together) and outcome measures included: self-efficacy for condom use with occasional clients and condom use with regular partners, self-confidence in handling a crisis situation and public speaking ability. Univariate and multivariate statistical methods were used to examine the study objectives.

Results

Of the analytical sample of 2106 FSWs, 532 (25.3%) reported high degree of collective efficacy for achieving certain goals and 1534 (72.8%) reported collective efficacy for addressing specific problems. FSWs reporting a higher collective efficacy as compared with those reporting lower collective efficacy were as follows: more likely to negotiate condom use with occasional clients (60.3% vs 19.7%; adjusted OR (AOR) =6.3, 95% CI 4.8 to 8.4) as well as regular partners (62.8% vs 20.2%; AOR =6.4, 95% CI 4.9 to 8.4); confident in facing troublesome stakeholders (73.5% vs 38.8%; AOR =4.3, 95% CI 3.3 to 5.6), confident in supporting fellow FSWs in a crisis (76.1% vs 49.6%; AOR =2.9, 95% CI 2.2 to 3.7), received help from other FSWs when a client or partner was violent (73.9% vs 46.3%; AOR =3.5, 95% CI 2.7 to 4.5) and had stood up to the police or madams/brokers to help fellow FSWs in the past 1 year (5.8% vs 3.3%; AOR =2.7, 95% CI 1.5 to 4.9).

Conclusion

The results suggest that the strategy of collectivisation in HIV prevention programme has much broader benefits than merely the promotion of safer sex practices. Future HIV prevention interventions in India and elsewhere may include collectivisation as the core strategy within HIV prevention programmes.
Residential racial segregation and racial differences in sexual behaviours: an 11-year longitudinal study of sexual risk of adolescents transitioning to adulthood
Authors: Biello Katie Brooks , Niccolai Linda , Kershaw Trace S , Lin Haiqun , Ickovics Jeannette
Published: July 2012

Background

Determining the underlying causes of racial disparities in sexually transmitted infections (STIs) is important. In the USA, rates of the most common STIs range from 5 to 20 times higher for African–Americans compared to Caucasians, and the health consequences of STIs can be serious. Residential racial segregation results in very different contexts for individuals and may be an important determinant of sexual risk. The purpose of this study was to examine how segregation and race interact to impact the age trajectory of sexual risk behaviours.

Methods

Using 11 years of data from the National Longitudinal Survey of Youth 1997 (1997–2007) and 2000 Census data, the authors performed three-level hierarchical linear regression to examine the associations between hypersegregation, race and a sexual risk behaviour index among black and white non-Hispanic adolescents as they transition to adulthood.

Results

Through most of the teenage years, African–Americans are at higher sexual risk than Caucasians. However, by age 19, Caucasians are at higher risk. Hypersegregation was not associated with increased sexual risk index score on average and did not impact the trajectory of the race–sexual risk association.

Conclusions

The authors did not find any evidence that hypersegregation was associated with the sex risk index or that it modified the race–sex risk association as individuals got older. Future studies should examine whether segregation is associated with other causes of STI/HIV acquisition risk, such as sexual network patterns.
Risk reduction and perceived collective efficacy and community support among female sex workers in Tamil Nadu and Maharashtra, India: the importance of context
Authors: Guha Mohua , Baschieri Angela , Bharat Shalini , Bhatnagar Tarun , Sane Suvarna Sanjay , Godbole Sheela V , S Saravanamurthy P , Mainkar Mandar Keshav , Williams Joseph , Collumbien Martine
Published: July 2012

Background

Empowering sex workers to mobilise and influence the structural context that obstructs risk reduction efforts is now seen an essential component of successful HIV prevention programmes. However, success depends on local programme environments and history.

Methods

The authors analysed data from the Integrated Behavioural and Biological Assessment Round I cross-sectional survey among female sex workers in Tamil Nadu and Maharashtra. The authors used propensity score matching to estimate the impact of participation in intervention activities on reduction of risk (consistent condom use) and vulnerability (perceived collective efficacy and community support).

Results

Background levels of risk and vulnerability as well as intervention impact varied widely across the different settings. The effect size ATT of attending meetings/trainings on consistent condom use was as high as 21% in Tamil Nadu (outside of Chennai) where overall use was lowest at 51%. Overall, levels of perceived collective efficacy were low at the time of the survey; perceived community support was high in Tamil Nadu and especially in Chennai (93%) contrasting with 33% in Mumbai. Consistent with previous research, the context of Mumbai seems least conducive to vulnerability reduction, yet self-help groups had a significant impact on consistent condom use (ATT=10%) and were significantly associated with higher collective efficacy (ATT=31%).

Conclusions

Significant risk reduction can be achieved by large-scale female sex worker interventions, but the impact depends on the history of programming, the complexity of the context in which sex work happens and pre-existing levels of support sex workers perceive from their peers.
Associations between maternal experiences of racism and early child health and development: findings from the UK Millennium Cohort Study
Authors: Kelly Yvonne , Becares Laia , Nazroo James
Published: July 2012

Background

Emerging evidence suggests that experienced racism might help explain observed ethnic inequalities in early child health and development. There are few studies outside the US context and none that consider mothers' experiences of racism in relation to a range of early childhood health and developmental markers.

Methods

The authors used cross-sectional data from the UK Millennium Cohort Study on 2136 mothers and their 5-year-old children from ethnic minority groups. Measures of racism tapped two dimensions of mothers' experience: perceived frequency of racist attacks in residential area and interpersonal racism. Markers of child health and development were obesity; socioemotional difficulties; cognitive: verbal, non-verbal and spatial ability test scores.

Results

There was a suggestion that the mothers' experience of interpersonal racism was associated with an increased risk of obesity (‘received insults’ OR=1.47; ‘treated unfairly’ OR=1.57; ‘disrespectful treatment by shop staff’ OR=1.55), but all CIs crossed 1.0, and size estimates were attenuated on further statistical adjustment. Perception of racism in the residential area was associated with socioemotional difficulties (fully adjusted coefficient=1.40, SE=0.47) and spatial abilities (fully adjusted coefficient=−1.99, SE=0.93) but not with verbal or non-verbal ability scores. Maternal experiences of racist insults were associated with non-verbal ability scores (fully adjusted coefficient=−1.70, SE=0.88).

Conclusion

The results suggest that mothers' experienced racism is linked to markers of early child health and development. Interventions that aim to improve early child development and address ethnic health inequalities need to incorporate approaches to tackling racism at all levels of society.
Carotid intima–media thickness: ultrasound measurement, prognostic value and role in clinical practice
Authors: Nair Satheesh Balakrishnan , Malik Rayaz , Khattar Rajdeep S
Published: July 2012

Ultrasound measurement of carotid intima–media thickness (IMT) has become a valuable tool for detecting and monitoring progression of atherosclerosis and recently published recommendations provide guidance for proper standardisation of these measurements. Important determinants of carotid IMT include age, gender, systolic blood pressure, diabetes mellitus and serum cholesterol levels. Many studies have shown carotid IMT to correlate with the severity of coronary atherosclerosis assessed by CT coronary calcification scores, coronary angiography and intravascular ultrasound. Consistent with its correlation with cardiovascular risk factors and coronary artery disease, a meta-analysis of large observational studies has shown carotid IMT to be a strong predictor of future cardiovascular events. Moreover, in patients with established coronary artery disease a reduction in carotid IMT has been shown to translate into a reduction in future cardiovascular events. Consensus statements now also recommend carotid IMT measurements to further refine the prognostic assessment of patients traditionally considered to be at an intermediate risk of cardiovascular disease.
Catheter ablation for atrial fibrillation: who, why and does it work?
Authors: Eyre-Brook S N , Rajappan K
Published: July 2012

Atrial fibrillation (AF) is the most common arrhythmia. For many years, treatment was predominantly pharmacological. The identification of signals from the pulmonary veins as critical to AF in many patients led to catheter ablation targeting these signals. Catheter ablation is more effective than antiarrhythmic drugs at restoring sinus rhythm, and may improve mortality, morbidity and quality of life in patients with symptomatic AF. There is evidence to suggest that catheter ablation would be even more beneficial if undertaken earlier in the disease process. Cost effectiveness of catheter ablation remains under assessment, but it does meet the NICE definition of cost efficacy and the figure improves as stroke risk rises. It is true that long-term data are lacking. However, until results of current long-term studies become available, ablation will continue to be reserved predominantly for patients with drug-refractory, symptomatic AF.
PSEUDORECURSIVE VARIETIES OF SEMIGROUPS — II
Authors: WELLS BENJAMIN
Published: July 2012

Constructions that yield pseudorecursiveness in [I] (Int. J. Algebra Comput.6 (1996) 457–510) are extended in this article. Finitely based varieties of semigroups with increasingly strict expansions by additional unary operation symbols or individual constants are shown to have the pseudorecursive property: the equational theory is undecidable, but the subsets obtained by bounding the number of distinct variables are all recursive. The most stringent case considered here is the single unary operation or distinguished element. New techniques of stratified reducibility and interpretation via rewriting rules are employed to show the property inherits along a chain of theories. Pure semigroup varieties that are both finitely based and pseudorecursive will be discussed in a later paper.
TWISTED ALEXANDER INVARIANTS OF TWISTED LINKS
Authors: SILVER DANIEL S. , WILLIAMS SUSAN G.
Published: July 2012

Let L = ℓ1 ∪⋯∪ℓd+1 be an oriented link in 𝕊3, and let L(q) be the d-component link ℓ1 ∪⋯∪ℓd regarded in the homology 3-sphere that results from performing 1/q-surgery on ℓd+1. Results about the Alexander polynomial and twisted Alexander polynomials of L(q) corresponding to finite-image representations are obtained. The behavior of the invariants as q increases without bound is described.
A TWO-PHASED FUZZY MULTICRITERIA SELECTION AMONG PUBLIC TRANSPORTATION INVESTMENTS FOR POLICY-MAKING AND RISK GOVERNANCE
Authors: KAYA İHSAN , ÖZTAYŞI BAŞAR , KAHRAMAN CENGIZ
Published: July 2012

Public transportation can be viewed as a key determinant and consequence of the social and spatial formation and development of contemporary cities and regions. Transportation policy generally combines four categories of instruments, i.e., investment, pricing, regulation and subsidy, to generate viable alternatives. Capital investment in public transportation supports the purchase of equipment and facilities including rolling stock, tracks, control equipment, and the construction of terminals, stations, parking lots, maintenance facilities and power generating facilities. Risk governance for public transportation investments looks at how risk-related decision-making unfolds when a range of actors is involved, requiring co-ordination and possibly reconciliation between a profusion of roles, perspectives, goals and activities. In this paper, a two-phased multicriteria methodology is proposed to select the best investment alternative for public transportation with respect to the predetermined criteria. In the first phase, a selection among transportation types is made, and in the second phase, a selection among transportation modes of the selected transportation type is made. A case study for Istanbul is given in the application section.
SPONTANEOUS SPATIAL FRACTAL PATTERN FORMATION IN ABSORPTIVE SYSTEMS
Authors: HUANG J. G. , CHRISTIAN J. M. , MCDONALD G. S.
Published: July 2012

We predict, for the first time to our knowledge, that purely-absorptive nonlinearity can support spontaneous spatial fractal pattern formation. A passive optical ring cavity with a thin slice of saturable absorber is analyzed. Linear stability analysis yields threshold curves for Turing (static) instabilities with features proposed as characteristics of potential fractal pattern formation. Numerical simulations of the fully-nonlinear dynamics, with both one and two transverse dimensions, confirm theoretical predictions.
MULTI-PLASMON RESONANCES SUPPORTING THE NEGATIVE REFRACTIVE INDEX IN "SINGLE-ATOM" METAMATERIALS
Authors: VIET D. T. , TUNG N. T. , HIEN N. T. , LEE Y. P. , TUNG B. S. , LAM V. D.
Published: July 2012

The search for a simple meta-system with negative refractive index has attracted a lot of attention recently. In this paper, we study a negative refractive transmission operating at 300 GHz by using "single-atom" metamaterials which were initially designed for achieving negative permeability. The nature of the negativity is discussed extensively by the effective medium analysis and confirmed by the dispersion diagram.
MODELING OF ENHANCEMENT OF FOM OF SILICA GLASS BY INTRODUCING CORE-SHELL NANOMETALS
Authors: JAFARI S. , SHAHMIRZAEE H. , GHARAATI A.
Published: July 2012

We investigate the effect of entering metallic core-shell nanoparticles in Silica glass to increase its nonlinear susceptibility (NLS). Third-order NLS and figure of merit (FOM) relations of this composite are driven with the T-Matrix method. Effect of nanoparticle volume fraction, shell-to-core radius ratio and core, clad and host material in the real and imaginary part of these parameters are studied. It is concluded that doping Silica with Copper core-Gold clad nanoparticles make the compound FOM-enhanced.
SUSTAINABLE IT SERVICES: DEVELOPING A STRATEGY FRAMEWORK
Authors: HARMON ROBERT R. , MOOLENKAMP NORA
Published: July 2012

Sustainable Information Technology (IT) refers to the practice of utilizing computing resources more efficiently while maintaining or increasing overall performance. Sustainable IT's first wave is often referred to as "green IT" and primarily focuses on reducing energy costs and carbon footprints of datacenters and IT operations. However, it is the emerging second wave, which emphasizes the role of IT services as an enabler of the overall corporate sustainability strategy that may hold the most promise for sustainability-based innovation. This paper provides a review of the literature on the current state of sustainable IT and presents a strategy framework for its future development.
A DETAILED CFD SIMULATION OF THE 2003 DAEGU METRO STATION FIRE
Authors: LEE MYUNGSUNG , HUR NAHMKEON
Published: July 2012

The Daegu metro station fire on 18 February 2003 was a tragic accident that claimed 192 lives in South Korea. The fire was set by an arsonist in a stopped train at the Daegu metro station, and spread to another train arriving at the station on the opposite track. The present numerical study aims to reproduce the Daegu metro station fire using a transient 3-D CFD simulation with detailed geometry of the station and tunnels in order to understand the behavior of the smoke and heat responsible for human losses in such accidents. The actual motion of the arriving train was also considered by using a moving mesh technique, and the fire development and CO gas generation were modeled with the enthalpy and scalar source terms. The evolutions of the temperature and CO gas distributions in the station were obtained in detail from the present simulation. The heat and CO concentrations at some critical locations (such as staircases) were shown and discussed in detail. The results of the present numerical study could provide useful data for future emergency plans of metro stations in case of fire.
Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis
Authors: Chandel Nirupama , Sharma Bipin , Salhan Divya , Husain Mohammad , Malhotra Ashwani , Buch Shilpa , Singhal Pravin C.
Published: July 2012

Opiates have been reported to induce T cell loss. We evaluated the role of vitamin D receptor (VDR) and the activation of the renin-angiotensin system (RAS) in morphine-induced T cell loss. Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS. On the other hand, a VDR agonist (EB1089) enhanced T cell VDR expression both under basal and morphine-stimulated states. Since T cells with silenced VDR displayed the activation of the RAS, whereas activation of the VDR was associated with downregulation of the RAS, it appears that morphine-induced T cell RAS activation was dependent on the VDR status. Morphine enhanced reactive oxygen species (ROS) generation in a dose-dependent manner. Naltrexone (an opiate receptor antagonist) inhibited morphine-induced ROS generation and thus, suggested the role of opiate receptors in T cell ROS generation. The activation of VDR as well as blockade of ANG II (by losartan, an AT1 receptor blocker) also inhibited morphine-induced T cell ROS generation. Morphine not only induced double-strand breaks (DSBs) in T cells but also attenuated DNA repair response, whereas activation of VDR not only inhibited morphine-induced DSBs but also enhanced DNA repair. Morphine promoted T cell apoptosis; however, this effect of morphine was inhibited by blockade of opiate receptors, activation of the VDR, and blockade of the RAS. These findings indicate that morphine-induced T cell apoptosis is mediated through ROS generation in response to morphine-induced downregulation of VDR and associated activation of the RAS.
AMP kinase regulation of sugar transport in brain capillary endothelial cells during acute metabolic stress
Authors: Cura Anthony J. , Carruthers Anthony
Published: July 2012

AMP-dependent kinase (AMPK) and GLUT1-mediated sugar transport in blood-brain barrier endothelial cells are activated during acute cellular metabolic stress. Using murine brain microvasculature endothelium bEnd.3 cells, we show that AMPK phosphorylation and stimulation of 3- O-methylglucose transport by the AMPK agonist AICAR are inhibited in a dose-dependent manner by the AMPK antagonist Compound C. AMPK α1- or AMPK α2-knockdown by RNA interference or AMPK inhibition by Compound C reduces AMPK phosphorylation and 3- O-methylglucose transport stimulation induced by cellular glucose-depletion, by potassium cyanide (KCN), or by carbonyl cyanide- p-trifluoromethoxy-phenylhydrazone (FCCP). Cell surface biotinylation studies reveal that plasma membrane GLUT1 levels are increased two- to threefold by cellular glucose depletion, AICAR or KCN treatment, and that these increases are prevented by Compound C and by AMPK α1- or α2-knockdown. These results support the hypothesis that AMPK activation in blood-brain barrier-derived endothelial cells directs the trafficking of GLUT1 intracellular pools to the plasma membrane, thereby increasing endothelial sugar transport capacity.
Food intake reductions and increases in energetic responses by hindbrain leptin and melanotan II are enhanced in mice with POMC-specific PTP1B deficiency
Authors: De Jonghe Bart C. , Hayes Matthew R. , Zimmer Derek J. , Kanoski Scott E. , Grill Harvey J. , Bence Kendra K.
Published: July 2012

Leptin regulates energy balance through central circuits that control food intake and energy expenditure, including proopiomelanocortin (POMC) neurons. POMC neuron-specific deletion of protein tyrosine phosphatase 1B (PTP1B) ( Ptpn1 loxP/loxP POMC-Cre), a negative regulator of CNS leptin signaling, results in resistance to diet-induced obesity and improved peripheral leptin sensitivity in mice, thus establishing PTP1B as an important component of POMC neuron regulation of energy balance. POMC neurons are expressed in the pituitary, the arcuate nucleus of the hypothalamus (ARH), and the nucleus of the solitary tract (NTS) in the hindbrain, and it is unknown how each population might contribute to the phenotype of POMC-Ptp1b −/− mice. It is also unknown whether improved leptin sensitivity in POMC-Ptp1b −/− mice involves altered melanocortin receptor signaling. Therefore, we examined the effects of hindbrain administration (4th ventricle) of leptin (1.5, 3, and 6 μg) or the melanocortin 3/4R agonist melanotan II (0.1 and 0.2 nmol) in POMC-Ptp1b −/− (KO) and control PTP1Bfl/fl (WT) mice on food intake, body weight, spontaneous physical activity (SPA), and core temperature (TC). The results show that KO mice were hypersensitive to hindbrain leptin- and MTII-induced food intake and body weight suppression and SPA compared with WT mice. Greater increases in leptin- but not MTII-induced TC were also observed in KO vs. WT animals. In addition, KO mice displayed elevated hindbrain and hypothalamic MC4R mRNA expression. These studies are the first to show that hindbrain administration of leptin or a melanocortin receptor agonist alters energy balance in mice likely via participation of hindbrain POMC neurons.
Regulation of hindbrainPyyexpression by acute food deprivation, prolonged caloric restriction, and weight loss surgery in mice
Authors: Gelegen C. , Chandarana K. , Choudhury A. I. , Al-Qassab H. , Evans I. M. , Irvine E. E. , Hyde C. B. , Claret M. , Andreelli F. , Sloan S. E. , Leiter A. B. , Withers D. J. , Batterham R. L.
Published: July 2012

PYY is a gut-derived putative satiety signal released in response to nutrient ingestion and is implicated in the regulation of energy homeostasis. Pyy-expressing neurons have been identified in the hindbrain of river lamprey, rodents, and primates. Despite this high evolutionary conservation, little is known about central PYY neurons. Using in situ hybridization, PYY-Cre;ROSA-EYFP mice, and immunohistochemistry, we identified PYY cell bodies in the gigantocellular reticular nucleus region of the hindbrain. PYY projections were present in the dorsal vagal complex and hypoglossal nucleus. In the hindbrain, Pyy mRNA was present at E9.5, and expression peaked at P2 and then decreased significantly by 70% at adulthood. We found that, in contrast to the circulation, PYY-(1–36) is the predominant isoform in mouse brainstem extracts in the ad libitum-fed state. However, following a 24-h fast, the relative amounts of PYY-(1–36) and PYY-(3–36) isoforms were similar. Interestingly, central Pyy expression showed nutritional regulation and decreased significantly by acute starvation, prolonged caloric restriction, and bariatric surgery (enterogastroanastomosis). Central Pyy expression correlated with body weight loss and circulating leptin and PYY concentrations. Central regulation of energy metabolism is not limited to the hypothalamus but also includes the midbrain and the brainstem. Our findings suggest a role for hindbrain PYY in the regulation of energy homeostasis and provide a starting point for further research on gigantocellular reticular nucleus PYY neurons, which will increase our understanding of the brain stem pathways in the integrated control of appetite and energy metabolism.
Selective cannabinoid-1 receptor blockade benefits fatty acid and triglyceride metabolism significantly in weight-stable nonhuman primates
Authors: Vaidyanathan Vidya , Bastarrachea Raul A. , Higgins Paul B. , Voruganti V. Saroja , Kamath Subhash , DiPatrizio Nicholas V. , Piomelli Daniele , Comuzzie Anthony G. , Parks Elizabeth J.
Published: July 2012

The goal of this study was to determine whether administration of the CB1 cannabinoid receptor antagonist rimonabant would alter fatty acid flux in nonhuman primates. Five adult baboons ( Papio Sp) aged 12.1 ± 4.7 yr (body weight: 31.9 ± 2.1 kg) underwent repeated metabolic tests to determine fatty acid and TG flux before and after 7 wk of treatment with rimonabant (15 mg/day). Animals were fed ad libitum diets, and stable isotopes were administered via diet (d31-tripalmitin) and intravenously (13C4-palmitate, 13C1-acetate). Plasma was collected in the fed and fasted states, and blood lipids were analyzed by GC-MS. DEXA was used to assess body composition and a hyperinsulinemic euglycemic clamp used to assess insulin-mediated glucose disposal. During the study, no changes were observed in food intake, body weight, plasma, and tissue endocannabinoid concentrations or the quantity of liver-TG fatty acids originating from de novo lipogenesis (19 ± 6 vs. 16 ± 5%, for pre- and posttreatment, respectively, P = 0.39). However, waist circumference was significantly reduced 4% in the treated animals ( P < 0.04), glucose disposal increased 30% ( P = 0.03), and FFA turnover increased 37% ( P = 0.02). The faster FFA flux was consistent with a 43% reduction in these fatty acids used for TRL-TG synthesis (40 ± 3 vs. 23 ± 4%, P = 0.02) and a twofold increase in TRL-TG turnover (1.5 ± 0.9 vs. 3.1 ± 1.4 μmol·kg−1·h−1, P = 0.03). These data support the potential for a strong effect of CB1 receptor antagonism at the level of adipose tissue, resulting in improvements in fasting turnover of fatty acids at the whole body level, central adipose storage, and significant improvements in glucose homeostasis.
Abdominal fat analyzed by DEXA scan reflects visceral body fat and improves the phenotype description and the assessment of metabolic risk in mice
Authors: Chen Weiyi , Wilson Jenny L. , Khaksari Mohammad , Cowley Michael A. , Enriori Pablo J.
Published: July 2012

Clinical studies have demonstrated a strong relationship between visceral fat content and metabolic diseases, such as type 2 diabetes and liver steatosis. Obese mouse models are an excellent tool to study metabolic diseases; however, there are limited methods for the noninvasive measurement of fat distribution in mice. Although micromagnetic resonance imaging and microcomputed tomography are the “gold standards” in the measurement of fat distribution, more economical and accessible methods are required. Dual energy X-ray absorptiometry (DEXA) is an effective method in characterizing fat content; however, it cannot discriminate between visceral and subcutaneous fat depots. We demonstrate that an evaluation of abdominal fat content measured by DEXA through the selection of one localized abdominal area strongly correlates with visceral fat content in C57BL/6J mice. We found that DEXA is able to measure fat pad volume ex vivo with high accuracy; however, the measurement of visceral fat in vivo shows an overestimation caused by subcutaneous tissue interference. The overestimation is almost constant for a wide range of values, and thus it is possible to correct the data for a more accurate estimation of visceral fat content. We demonstrate the utility of this technique in characterizing phenotypes of several obese mouse models ( ob/ob, db/db, MC4R-KO, and DIO) and evaluating the effect of treatments on visceral fat content in longitudinal studies. Additionally, we also establish abdominal obesity as a potential biomarker for metabolic abnormalities (liver fat accumulation, insulin resistance/diabetes) in mice, similar to that described in humans.
Effects of ambient temperature on adaptive thermogenesis during maintenance of reduced body weight in mice
Authors: Ravussin Yann , LeDuc Charles A. , Watanabe Kazuhisa , Leibel Rudolph L.
Published: July 2012

We showed previously that, at ambient room temperature (22°C), mice maintained at 20% below their initial body weight by calorie restriction expend energy at a rate below that which can be accounted for by the decrease of fat and fat-free mass. Food-restricted rodents may become torpid at subthermoneutral temperatures, a possible confounding factor when using mice as human models in obesity research. We examined the bioenergetic, hormonal, and behavioral responses to maintenance of a 20% body weight reduction in singly housed C57BL/6J +/+ and Lep ob mice housed at both 22°C and 30°C. Weight-reduced high-fat-fed diet mice (HFD-WR) showed similar quantitative reductions in energy expenditure—adjusted for body mass and composition—at both 22°C and 30°C: −1.4 kcal/24 h and −1.6 kcal/24 h below predicted, respectively, and neither group entered torpor. In contrast, weight-reduced Lep ob mice (OB-WR) housed at 22°C became torpid in the late lights-off period (0200–0500) but did not when housed at 30°C. These studies indicate that mice with an intact leptin axis display similar decreases in “absolute” energy expenditure in response to weight reduction at both 22°C and 30°C ambient temperature. More importantly, the “percent” decrease in total energy expenditure observed in the HFD-WR compared with AL mice is much greater at 30°C (−19%) than at 22°C (−10%). Basal energy expenditure demands are ∼45% lower in mice housed at 30°C vs. 22°C, since the mice housed at thermoneutrality do not allocate extra energy for heat production. The higher total energy expenditure of mice housed at 22°C due to these increased thermogenic demands may mask physiologically relevant changes in energy expenditure showing that ambient temperature must be carefully considered when quantifying energy metabolism in both rodents and humans.
Female spontaneously hypertensive rats have greater renal anti-inflammatory T lymphocyte infiltration than males
Authors: Tipton Ashlee J. , Baban Babak , Sullivan Jennifer C.
Published: July 2012

T cells contribute to hypertension in male experimental models; data in females is lacking even though women are more likely to develop immune disorders. The goal of this study was to determine whether immune cells contribute to hypertension in female spontaneously hypertensive rats (SHR) and define the T cell profile in whole blood and kidneys of male and female SHR. We hypothesized that inflammatory cells contribute to hypertension in female SHR; however, male SHR have a higher blood pressure so we hypothesize they will have a heightened inflammatory profile. The lymphocyte inhibitor mycophenolate mofetil (MMF) was administered in a dose-dependent manner to SHR. At the highest dose (50 mg·kg−1·day−1), blood pressure was significantly decreased in both sexes, yet the percent decrease in blood pressure was greater in females (female: 12 ± 1%; males: 7 ± 1%, P = 0.01). Circulating and renal T cell profiles were defined using analytical flow cytometry. Female SHR had more circulating CD3+, CD4+, and pro-inflammatory CD3+CD4+RORγ+Th17 cells, whereas males had more immune-suppressive CD3+CD4+Foxp3+T regulatory cells. In the kidney, females had greater numbers of CD8+and T regulatory cells than males, whereas males had greater CD4+and Th17 cell infiltration. MMF decreased circulating and renal T cells in both sexes ( P < 0.0001), although the effect of MMF on T cell subtypes was sex specific with females having greater sensitivity to MMF-induced decreases in lymphocytes. In conclusion, there is a lymphocyte contribution to the maintenance of hypertension in the female SHR and sex of the animal impacts the T cell profile.
Upregulation of HNF-1β during experimental acute kidney injury plays a crucial role in renal tubule regeneration
Authors: Ogata Koji , Shimamura Yoshiko , Hamada Kazu , Hisa Masayuki , Bun Masayuki , Okada Nazuki , Inoue Kosuke , Taniguchi Yoshinori , Ishihara Masayuki , Kagawa Toru , Horino Taro , Fujimoto Shimpei , Terada Yoshio
Published: July 2012

Hepatocyte nuclear factor-1β (HNF-1β) is a transcription factor expressed in the kidney, liver, pancreas, and other organs. Mutations of HNF-1β cause maturity-onset diabetes of the young type 5 (MODY5). The aims of this study were to investigate the functional roles of the HNF-1β/suppressor of cytokine signaling-3 (SOCS-3) pathway in tubule damage after acute kidney injury (AKI) both in vivo and in vitro and to examine the effect of HNF-1β on renal tubule formation. To clarify the significance of the HNF-1β/SOCS-3 pathway in AKI, we used a rat ischemia/reperfusion (I/R) AKI model and cultured renal tubular cells (NRK-52E cells). Western blot analysis showed that HNF-1β and polycystic kidney disease 2 (PKD2) expressions were increased at 3–12 h and 12–24 h after I/R, respectively. The expression level of SOCS-3 was decreased at 3–48 h. Immunohistological examination revealed that expression of HNF-1β was increased in proximal tubules. Overexpression of HNF-1β resulted in decreased SOCS-3 expression, activation of signal transducer and activator of transcription 3 (STAT3) and Erk, and increased [3H]thymidine uptake in the presence of hepatocyte growth factor. Furthermore, tubule formation in three-dimensional gels was inhibited by dominant-negative HNF-1β. Our study shows that HNF-1β is upregulated after AKI in proximal tubular cells and that HNF-1β controls cellular proliferation and tubule formation by regulating SOCS-3 expression and STAT3/Erk activation. Therefore, the current study unravels the physiological and pathological significance of the HNF-1β pathway in AKI.