bluuebunny/crossref_metadata_2025 huggingface dataset:
T Lymphocyte Autoreactivity in Inflammatory Mechanisms Regulating Atherosclerosis
Authors: Profumo Elisabetta , Buttari Brigitta , Saso Luciano , Capoano Raffaele , Salvati Bruno , Riganò Rachele
Published: December 2012

Atherosclerosis has been clearly demonstrated to be a chronic inflammatory disease of the arterial wall. Both cells of the innate and the acquired immune system, particularly monocytes and T lymphocytes, are implicated in the atherogenic process, producing different cytokines with pro- and anti-inflammatory effects. The majority of pathogenic T cells involved in atherosclerosis are of the Th1 profile, that has been correlated positively with coronary artery disease. Many studies conducted to evaluate the molecular factors responsible for the activation of T cells have demonstrated that the main antigenic targets in atherosclerosis are modified endogenous structures. These self-molecules activate autoimmune reactions mainly characterized by the production of Th1 cytokines, thus sustaining the inflammatory mechanisms involved in endothelial dysfunction and plaque development. In this paper we will summarize the different T-cell subsets involved in atherosclerosis and the best characterized autoantigens involved in cardiovascular inflammation.
Early Outcomes of Minimally Invasive Anterior Longitudinal Ligament Release for Correction of Sagittal Imbalance in Patients with Adult Spinal Deformity
Authors: Deukmedjian Armen R. , Dakwar Elias , Ahmadian Amir , Smith Donald A. , Uribe Juan S.
Published: December 2012

The object of this study was to evaluate a novel surgical technique in the treatment of adult degenerative scoliosis and present our early experience with the minimally invasive lateral approach for anterior longitudinal ligament release to provide lumbar lordosis and examine its impact on sagittal balance.Methods. All patients with adult spinal deformity (ASD) treated with the minimally invasive lateral retroperitoneal transpsoas interbody fusion (MIS LIF) for release of the anterior longitudinal ligament were examined. Patient demographics, clinical data, spinopelvic parameters, and outcome measures were recorded.Results. Seven patients underwent release of the anterior longitudinal ligament (ALR) to improve sagittal imbalance. All cases were split into anterior and posterior stages, with mean estimated blood loss of 125 cc and 530 cc, respectively. Average hospital stay was 8.3 days, and mean follow-up time was 9.1 months. Comparing pre- and postoperative 36′′ standing X-rays, the authors discovered a mean increase in global lumbar lordosis of 24 degrees, increase in segmental lumbar lordosis of 17 degrees per level of ALL released, decrease in pelvic tilt of 7 degrees, and decrease in sagittal vertical axis of 4.9 cm. At the last followup, there was a mean improvement in VAS and ODI scores of 26.2% and 18.3%.Conclusions. In the authors’ early experience, release of the anterior longitudinal ligament using the minimally invasive lateral retroperitoneal transpsoas approach may be a feasible alternative in correcting sagittal deformity.
Impact of genomic structural variation in Drosophila melanogaster based on population-scale sequencing
Authors: Zichner Thomas , Garfield David A. , Rausch Tobias , Stütz Adrian M. , Cannavó Enrico , Braun Martina , Furlong Eileen E.M. , Korbel Jan O.
Published: December 2012

Genomic structural variation (SV) is a major determinant for phenotypic variation. Although it has been extensively studied in humans, the nucleotide resolution structure of SVs within the widely used model organism Drosophila remains unknown. We report a highly accurate, densely validated map of unbalanced SVs comprising 8962 deletions and 916 tandem duplications in 39 lines derived from short-read DNA sequencing in a natural population (the “Drosophila melanogaster Genetic Reference Panel,” DGRP). Most SVs (>90%) were inferred at nucleotide resolution, and a large fraction was genotyped across all samples. Comprehensive analyses of SV formation mechanisms using the short-read data revealed an abundance of SVs formed by mobile element and nonhomologous end-joining-mediated rearrangements, and clustering of variants into SV hotspots. We further observed a strong depletion of SVs overlapping genes, which, along with population genetics analyses, suggests that these SVs are often deleterious. We inferred several gene fusion events also highlighting the potential role of SVs in the generation of novel protein products. Expression quantitative trait locus (eQTL) mapping revealed the functional impact of our high-resolution SV map, with quantifiable effects at >100 genic loci. Our map represents a resource for population-level studies of SVs in an important model organism.
An X-ray diffractometer coupled with diffuse reflectance infrared Fourier transform spectroscopy and gas chromatography forin situandin operandocharacterization: an innovative analytical laboratory instrument
Authors: Braconnier Laure , Clémençon Isabelle , Legens Christèle , Moizan Virginie , Diehl Fabrice , Pillière Henry , Echegut P. , De Sousa Meneses D. , Schuurman Yves
Published: December 2012

In heterogeneous catalysis, chemical reactions take place at the surface of the material and can be influenced by its structure. To understand better the impact of the material surface and structure on catalytic properties, it is important to characterize them simultaneously. The association of X-ray diffraction and diffuse reflectance infrared Fourier transform spectroscopy, combined in a single dedicated high-temperature and high-pressure reaction cell with an online gas chromatograph, could be the answer to this challenge. For the first time, such an analytical tool has been developed for laboratory applications. The use of this device is illustrated, and it is validated through thein situstudy of the thermal decomposition of calcium oxalate.
Some properties of the neutron monochromatic beams obtained by multiple Bragg reflections realized in bent perfect single crystals
Authors: Mikula Pavol , Vrana Miroslav , Saroun Jan , Krejci Frantisek , Seong Baek-Seok , Woo Wanchuck , Furusaka Michihiro
Published: December 2012

Strong neutron multiple Bragg reflections (MBRs) excited by elastic bending have some excellent resolution properties that could be further exploited. MBR effects can create highly monochromatic and highly collimated beams of rather large cross section, which can find applications in high-resolution neutron scattering and neutron imaging instrumentation. The favourable properties of an MBR beam produced by means of bent perfect crystals of Si and Ge are demonstrated by the imaging of holes of diameter less than 1 mm in a Cd sheet, slits of width less than 1 mm in a Gd sheet and refraction effects on edges after the transmission of the MBR beam through office staples.
Mental health policy in California: the “millionaire's tax” and the Mental Health Services Oversight and Accountability Commission
Authors: Lee Deborah
Published: December 2012

Purpose

This article's aim is to describe the history, purpose, challenges, strategies, and progress of California's Mental Health Oversight and Accountability Commission (MHSOAC), created by California's pioneering Proposition 63 (Mental Health Services Act). California voters passed this initiative in 2004 to expand and transform public mental health services.

Design/methodology/approach

This case study is based on observations of the author, who has worked with the Commission since its inception, and the study is adapted from a 2009 article by one of the original Commissioners who served from 2005‐2008. The article focuses on challenges and opportunities for oversight in an environment of stakeholders' high and diverse expectations, limited direct state authority, and significant and broad budget challenges.

Findings

The Commission prioritizes evaluation as its principal strategy with a primary goal of using evaluation results for quality improvement. Implementing this strategy, with limited county reporting requirements, inadequate data systems, and insufficient funds designated for evaluation, is a continuing challenge. Other key challenges – and opportunities – include passionate stakeholders with high and divergent expectations, a de‐centralized public mental health, and a statewide fiscal and budget crisis.

Research limitations/implications

The paper relies on the observations of two key participants: a former Commissioner and the Commission's staff psychologist. Participant observation brings opportunities for bias as well as insight. Diverse stakeholders undoubtedly would provide different perspectives on the progress of Proposition 63 and on the MHSOAC.

Practical implications

The Commission developed a logic model that defines strategies for oversight and accountability and links these strategies to Proposition 63's intended outcomes for California's public mental health services system and clients.

Social implications

The success of California's Proposition 63 in transforming mental health delivery from a “fail first” crisis system to a “help first” proactive system has implications for integrated healthcare delivery that includes mental health.

Originality/value

The California emphasis on recovery, resilience, and wellness for diverse people with and at risk of serious mental illness is consistent with national and world‐wide recommendations and initiatives and is one of the largest efforts to transform a mental health system to reflect these values.
Western Australia's Mental Health Commission
Authors: van Schoubroeck Lesley
Published: December 2012

Purpose

Machinery of government changes and budget strategy are powerful levers to drive reform in the public sector. The purpose of this paper is to describe the rationale, progress and challenges in the establishment of Western Australia's Mental Health Commission in 2010 with policy, planning and purchasing powers to drive reform.

Design/methodology/approach

This case study is based on the observations of the author who had a lead role in the establishment of the Commission over its first two years. It sets this reform in the context of the whole of government reforms as well as demands for reform from stakeholders within the mental health sector.

Findings

It is demonstrated that externally imposed change is often necessary to fundamental reform. However, it also comes with risks of alienation of key stakeholders in powerful roles and an under‐estimation of the factors that will hamper change. Central government support has been essential to the establishment of the Commission.

Research limitations/implications

The paper relies on the observations of a key participant in the reform process. This brings the limitations of potential bias as well as the strength of understanding that is difficult for outsiders to access.

Practical implications

The paper identifies some of the practical strategies that mitigate the risks associated with system change.

Social implications

This reform has been useful to showcase a range of other social policy reforms demonstrating the opportunities that strong political leadership offers when linked to policy and administrative change.

Originality/value

This analysis of the progress of reform highlights a range of issues that can inform other governments and community stakeholders undertaking major reform in the public sector as well as particular issues for reform in mental health.
Mental Health Commissions of Different Sub‐species: can they effectively propagate mental health service reform? Provisional taxonomy and trajectories
Authors: Rosen Alan
Published: December 2012

Purpose

The aim is to provide a brief overview of a series of articles tracing the emergence of several Mental Health Commissions (MHCs) in developed countries over recent years, sometimes to enhance mental health law administration, but often in connection with mental health reform strategies. The paper seeks to review the functions of, and elicit a framework for, Mental Health Commissions (MHCs) as effective vehicles for effective operation and reform of a mental health service system.

Design/methodology/approach

The approach of the paper is to identify the functions and limitations of Mental Health Commissions and then cluster them to form a typology of commissions.

Findings

There are broadly three types of MHCs: the first is more inspectorial and focussed on issues, concerns and complaints affecting the care of individuals, and is more restricted investigating the mental health service and the workings of mental health laws mainly to these ends; the second type is focussed on the entire mental health service system, including relevant all‐of‐government operations, concentrating on monitoring for and promoting system‐wide reform. While this appears to constitute a spectrum, with different MHCs mandated to work mainly at either end of it, there is conceivably a third type which has a combination of these functions. This occurs with some commissions, though an equal balance between these functions is unusual, so they usually can be assigned to a type on the basis of their predominant functions.

Research limitations/implications

There was a limited sample size, obliging a non‐statistical descriptive analysis which may well affect the validity of these distinctions.

Practical implications

There is sometimes a combination of functions encompassing some features of both of these types. While type I MHCs can ensure that individual rights are upheld and that mental health laws and regulations are adhered to, to improve service quality, type II MHCs are likely to be more effective in achieving system‐wide mental health service reform.

Social implications

MHCs can contribute to more holistic, evidence‐based and recovery‐oriented service delivery, which are more likely to lead to more desirable health and wellbeing outcomes for all mental health service users, their families and the community.

Originality/value

This typology provides a useful provisional framework for understanding the roles of MHCs in mental health services and in reform of the whole mental health service system and related systems.
Housing for all ages: why and how social landlords should build bridges between different generations
Authors: Fox Kirsty
Published: December 2012

Purpose

This paper's aim is to illustrate the importance of multigenerational activities within the social housing sector, and provide some examples of best practice.

Design/methodology/approach

From the perspective of a social landlord (Peaks & Plains Housing Trust) the paper explains the importance of intergenerational practice and the role that social landlords can play in helping to build bridges between, and within, communities.

Findings

The paper discusses some specific activities, including street soccer, a youth forum and a winter warmer event, that have engaged young people and multiple generations and provides some feedback to these.

Originality/value

The paper gives some examples for best practice that can be used by other housing providers and community activists.
Humic substance‐mediated reduction of iron(III) oxides and degradation of 2,4‐D by an alkaliphilic bacterium, Corynebacterium humireducens MFC‐5
Authors: Wu Chun‐yuan , Zhuang Li , Zhou Shun‐gui , Yuan Yong , Yuan Tian , Li Fang‐bai
Published: December 2012

With the use of an alkaliphilic bacterium, Corynebacterium humireducens MFC‐5, this study investigated the reduction of goethite (α‐FeOOH) and degradation of 2,4‐dichlorophenoxyacetic acid (2,4‐D) mediated by different humic substances (humics) and quinones in alkaline conditions (pH of 9.0). The results indicated that (i) using sucrose as the electron donor, the strain MFC‐5 was capable of reducing anthraquinone‐2,6‐disulfonic acid (AQDS), anthraquinone‐2‐disulfonic acid (AQS), anthraquinone‐2‐carboxylic acid (AQC), humic acid (HA) and fulvic acid (FA), and its reducing capability ranked as AQC > AQS > AQDS > FA > HA; (ii) the anaerobic reduction of α‐FeOOH and 2,4‐D by the strain was insignificant, while the reductions were greatly enhanced by the addition of quinones/humics serving as redox mediators; (iii) the Fe(III) reduction rate was positively related to the content of quinone functional groups and the electron‐accepting capacities (EAC) of quinones/humics based on fourier‐transform infrared spectroscopy (FT‐IR) and electrochemical analyses; however, such a relationship was not found in 2,4‐D degradation probably because quinone reduction was not the rate‐limiting step of quinone‐mediated reduction of 2,4‐D. Using the example of α‐FeOOH and 2,4‐D, this study well demonstrated the important role of humics reduction on the Fe(III)/Fe(II) biogeochemical cycle and chlorinated organic compounds degradation in alkaline reducing environments.
Systemic lupus erythematosus in Saudi children: long‐term outcomes
Authors: Al‐Mayouf Sulaiman M.
Published: December 2012

Objective

To report the long‐term outcome of Saudi children with systemic lupus erythematosus (SLE).

Methods

Charts of all children with SLE treated between 1990 and 2010 at King Faisal Specialist Hospital and Research Center Riyadh, were reviewed. The long‐term outcome measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics American College of Rheumatology Damage Index (pSDI) and death related to SLE were determined. The data included: gender, age at disease onset, clinical features and treatment at last follow‐up visit.

Results

One hundred and fifty‐two patients (129 girls and 23 boys) were included. The mean age at onset of SLE was 8.8 ± 2.6 years, while the mean age at diagnosis was 9.5 ± 2.6 years and the mean disease duration was 7.5 ± 4.6 years. All patients were treated with corticosteroid and immunosuppressive drugs. Eighty (52.6%) patients had damage with a mean SDI score of 1.3 ± 1.7. Damage accrual was mostly in the growth (26.8%), renal (17.1%) and neuropsychiatric (15.8%) domains. Due to progressive renal disease, 14 patients required dialysis; five of them underwent renal transplant. There were nine deaths related to SLE, eight of them due to infection. Based on logistic regression, patient disease damage was significantly associated with young age at disease onset and long disease duration. Similarly, death related to SLE was influenced by early‐onset disease. In contrast, gender, disease duration and therapy did not affect the suggested outcome measures.

Conclusion

Our results are comparable to reports from other tertiary centers. Early‐onset disease probably influences the long‐term outcome of SLE in children. Infection remains an important cause of death in children with SLE.
Methadone dosing and prescribed medication use in a prospective cohort of opioid‐dependent pregnant women
Authors: Cleary Brian J. , Reynolds Kieran , Eogan Maeve , O'Connell Michael P. , Fahey Tom , Gallagher Paul J. , Clarke Tom , White Martin J. , McDermott Christine , O'Sullivan Anne , Carmody Deirdre , Gleeson Justin , Murphy Deirdre J.
Published: December 2012

Aims

This study aimed to (i) describe methadone dosing before, during and after pregnancy, (ii) to compare the incidence of neonatal abstinence syndrome (NAS) between those with dose decreases and those with steady or increasing doses and (iii) to describe prescribed medication use among opioid‐dependent pregnant women.

Design

Prospective cohort study.

Setting

Two Irish tertiary care maternity hospitals.

Participants

A total of 117 pregnant women on methadone maintenance treatment (MMT) recruited between July 2009 and July 2010.

Measurements

Electronic dispensing records from addiction clinics and the Primary Care Reimbursement Service were used to determine methadone doses and dispensed medications in the year preceding and the month following delivery. The Finnegan score was used to determine need for medical treatment of NAS.

Findings

Of the 117 participants, sufficient dosing data were available for 89 women treated with MMT throughout pregnancy; 36 (40.4%) had their dose decreased from a mean pre‐pregnancy dose of 73.3 mg [standard deviation (SD) 25.5] to a third‐trimester dose of 58.0 mg (SD 26.0). The corresponding figures for those with increased doses (n = 31, 34.8%) were 70.7 mg (SD 25.3) and 89.7 mg (SD 21.0), respectively. The incidence of medically treated NAS did not differ between dosage groups. Antidepressants were dispensed for 29 women (25.7%) during pregnancy, with the rate decreasing from pre‐pregnancy to postpartum. Benzodiazepines were prescribed for 43 women (38.0%).

Conclusion

In the Irish health service, opioid‐dependent women frequently have their methadone dose decreased during pregnancy but this does not appear to affect the incidence of the neonatal abstinence syndrome in their babies.
Genetic diversity and investigation of polledness in divergent goat populations using 52 088 SNPs
Authors: Kijas James W. , Ortiz Judit S. , McCulloch Russell , James Andrew , Brice Blair , Swain Ben , Tosser‐Klopp Gwenola ,   the International Goat Genome Consortium
Published: December 2012

The recent availability of a genome‐wide SNP array for the goat genome dramatically increases the power to investigate aspects of genetic diversity and to conduct genome‐wide association studies in this important domestic species. We collected and analysed genotypes from 52 088 SNPs in Boer, Cashmere and Rangeland goats that had both polled and horned individuals. Principal components analysis revealed a clear genetic division between animals for each population, and model‐based clustering successfully detected evidence of admixture that matched aspects of their recorded history. For example, shared co‐ancestry was detected, suggesting Boer goats have been introgressed into the Rangeland population. Further, allele frequency data successfully tracked the altered genetic profile that has taken place after 40 years of breeding Australian Cashmere goats using the Rangeland animals as the founding population. Genome‐wide association mapping of the POLL locus revealed a strong signal on goat chromosome 1. The 769‐kb critical interval contained the polled intersex syndrome locus, confirming the genetic basis in non‐European animals is the same as identified previously in Saanen goats. Interestingly, analysis of the haplotypes carried by a small set of sex‐reversed animals, known to be associated with polledness, revealed some animals carried the wild‐type chromosome associated with the presence of horns. This suggests a more complex basis for the relationship between polledness and the intersex condition than initially thought while validating the application of the goat SNP50 BeadChip for fine‐mapping traits in goat.
Optimizing drug development of anti‐cancer drugs in children using modelling and simulation
Authors: van Hasselt Johan G.C. , van Eijkelenburg Natasha K.A. , Beijnen Jos H. , Schellens Jan H.M. , Huitema Alwin D.R.
Published: December 2012

Modelling and simulation (M&S)‐based approaches have been proposed to support paediatric drug development in order to design and analyze clinical studies efficiently. Development of anti‐cancer drugs in the paediatric population is particularly challenging due to ethical and practical constraints. We aimed to review the application of M&S in the development of anti‐cancer drugs in the paediatric population, and to identify where M&S‐based approaches could provide additional support in paediatric drug development of anti‐cancer drugs. A structured literature search on PubMed was performed. The majority of identified M&S‐based studies aimed to use population PK modelling approaches to identify determinants of inter‐individual variability, in order to optimize dosing regimens and to develop therapeutic drug monitoring strategies. Prospective applications of M&S approaches for PK‐bridging studies have scarcely been reported for paediatric oncology. Based on recent developments of M&S in drug development there are several opportunities where M&S could support more informative bridging between children and adults, and increase efficiency of the design and analysis of paediatric clinical trials, which should ultimately lead to further optimization of drug treatment strategies in this population.
Organizational hierarchies in Bulgarian hospitals and perceptions of justice
Authors: Todorova Irina L. G. , Alexandrova‐Karamanova Anna , Panayotova Yulia , Dimitrova Elitsa
Published: December 2012

Objectives

Health care reform in Bulgaria has been ongoing for two decades. Since 1990, it has been transforming from a socialized system of medical care with free access, to one which is decentralized, includes private health care services, the general practitioner model and a National Health Insurance Fund. In this context, we are conducting an international EC Framework 7 project: ‘Improving quality and safety in the hospital: The link between organizational culture, burnout, and quality of care’. We focus on health professionals’ perceptions of organizational hierarchies in Bulgarian hospitals and how doctors and nurses connect these to organizational justice.

Methods

We conducted seven focus groups and four interviews, with a total of 42 participants (27 nurses, 15 physicians and medical residents) in three hospitals. Data were analysed through thematic analysis and discourse analysis with Atlas.ti.

Results

From the perspective of health professionals, health reform has intensified traditional hierarchies and inequalities and has created new ones in Bulgarian hospitals. These hierarchies are continuously (re)constructed through language and practices and also destabilized through resistance. The health professionals protest fact that these hierarchies are permeated with unfairness and silence voices. All health professions (nurses, doctors, residents) in our study experience being unjustly positioned and disempowered in various hierarchies. They connect these experiences to stress and anxiety.

Conclusions

Participatory action research needs to address multiple dimensions of organizational relationships in Bulgarian hospitals, including hierarchical relationships and ways of promoting organizational justice.

Statement of Contribution

What is already known on this subject? Health care organizations are hierarchically organized. Organizational injustice can contribute to burnout in health professionals. There is a high level of stress and burnout for health professionals in Bulgaria.

What does this study add? This study adds understanding of changing hierarchies in hospitals during health care reform in the post‐socialist period. Illuminates how health professionals' discourse sustains and resists hierarchical relationships in Bulgarian hospitals. Adds understanding of health professionals' perspectives on implications of injustice for their well‐being.
A history of heart interventions moderates the relationship between psychological variables and the presence of chest pain in older women with self‐reported coronary heart disease
Authors: Strodl Esben , Kenardy Justin
Published: December 2012

Objectives

This study examines the hypothesis that a past history of heart interventions will moderate the relationship between psychosocial factors (stressful life events, social support, perceived stress, having a current partner, having a past diagnosis of depression or anxiety over the past 3 years, time pressure, education level, and the mental health index) and the presence of chest pain in a sample of older women.

Design

Longitudinal survey over a 3‐year period.

Methods

The sample was taken from a prospective cohort study of 10,432 women initially aged between 70 and 75 years, who were surveyed in 1996 and then again in 1999. Two groups of women were identified: those reporting to have heart disease but no past history of heart interventions (i.e., coronary artery bypass graft/angioplasty) and those reporting to have heart disease with a past history of heart interventions.

Results

Binary logistic regression analysis was used to show that for the women with self‐reported coronary heart disease but without a past history of heart intervention, feelings of time pressure as well as the number of stressful life events experienced in the 12 months prior to 1996 were independent risk factors for the presence of chest pain, even after accounting for a range of traditional risk factors. In comparison, for the women with self‐reported coronary heart disease who did report a past history of heart interventions, a diagnosis of depression in the previous 3 years was the significant independent risk factor for chest pain even after accounting for traditional risk factors.

Conclusion

The results indicate that it is important to consider a history of heart interventions as a moderator of the associations between psychosocial variables and the frequency of chest pain in older women.

Statement of contribution

What is already known on this subject? Psychological factors have been shown to be independent predictors of a range of health outcomes in individuals with coronary heart disease, including the presence of chest pain. Most research has been conducted with men or with small samples of women; however, the evidence does suggest that these relationships exist in women as well as in men.

What does this study add? Most studies have looked at overall relationships between psychological variables and health outcomes. The few studies that have looked at moderators have mainly examined gender as a moderator. To our knowledge, this is the first published study to examine a history of heart interventions as a moderator of the relationship between psychological variables and the presence of chest pain.
Response diversity determines the resilience of ecosystems to environmental change
Authors: Mori Akira S. , Furukawa Takuya , Sasaki Takehiro
Published: December 2012

A growing body of evidence highlights the importance of biodiversity for ecosystem stability and the maintenance of optimal ecosystem functionality. Conservation measures are thus essential to safeguard the ecosystem services that biodiversity provides and human society needs. Current anthropogenic threats may lead to detrimental (and perhaps irreversible) ecosystem degradation, providing strong motivation to evaluate the response of ecological communities to various anthropogenic pressures. In particular, ecosystem functions that sustain key ecosystem services should be identified and prioritized for conservation action. Traditional diversity measures (e.g. ‘species richness’) may not adequately capture the aspects of biodiversity most relevant to ecosystem stability and functionality, but several new concepts may be more appropriate. These include ‘response diversity’, describing the variation of responses to environmental change among species of a particular community. Response diversity may also be a key determinant of ecosystem resilience in the face of anthropogenic pressures and environmental uncertainty. However, current understanding of response diversity is poor, and we see an urgent need to disentangle the conceptual strands that pervade studies of the relationship between biodiversity and ecosystem functioning. Our review clarifies the links between response diversity and the maintenance of ecosystem functionality by focusing on the insurance hypothesis of biodiversity and the concept of functional redundancy. We provide a conceptual model to describe how loss of response diversity may cause ecosystem degradation through decreased ecosystem resilience. We explicitly explain how response diversity contributes to functional compensation and to spatio‐temporal complementarity among species, leading to long‐term maintenance of ecosystem multifunctionality. Recent quantitative studies suggest that traditional diversity measures may often be uncoupled from measures (such as response diversity) that may be more effective proxies for ecosystem stability and resilience. Certain conclusions and recommendations of earlier studies using these traditional measures as indicators of ecosystem resilience thus may be suspect. We believe that functional ecology perspectives incorporating the effects and responses of diversity are essential for development of management strategies to safeguard (and restore) optimal ecosystem functionality (especially multifunctionality). Our review highlights these issues and we envision our work generating debate around the relationship between biodiversity and ecosystem functionality, and leading to improved conservation priorities and biodiversity management practices that maximize ecosystem resilience in the face of uncertain environmental change.
Protecting against plague: towards a next-generation vaccine
Authors: Williamson E D , Oyston P C F
Published: December 2012

The causative organism of plague is the bacterium Yersinia pestis. Advances in understanding the complex pathogenesis of plague infection have led to the identification of the F1- and V-antigens as key components of a next-generation vaccine for plague, which have the potential to be effective against all forms of the disease. Here we review the roles of F1- and V-antigens in the context of the range of virulence mechanisms deployed by Y. pestis, in order to develop a greater understanding of the protective immune responses required to protect against plague.
Ex-vivo analysis of human Natural Killer T cells demonstrates heterogeneity between tissues and within established CD4+ and CD4− subsets
Authors: Chan A C , Leeansyah E , Cochrane A , d' Udekem d' Acoz Y , Mittag D , Harrison L C , Godfrey D I , Berzins S P
Published: December 2012

Our understanding of human type 1 natural killer T (NKT) cells has been heavily dependent on studies of cells from peripheral blood. These have identified two functionally distinct subsets defined by expression of CD4, although it is widely believed that this underestimates the true number of subsets. Two recent studies supporting this view have provided more detail about diversity of the human NKT cells, but relied on analysis of NKT cells from human blood that had been expanded in vitro prior to analysis. In this study we extend those findings by assessing the heterogeneity of CD4+ and CD4− human NKT cell subsets from peripheral blood, cord blood, thymus and spleen without prior expansion ex vivo, and identifying for the first time cytokines expressed by human NKT cells from spleen and thymus. Our comparative analysis reveals highly heterogeneous expression of surface antigens by CD4+ and CD4− NKT cell subsets and identifies several antigens whose differential expression correlates with the cytokine response. Collectively, our findings reveal that the common classification of NKT cells into CD4+ and CD4− subsets fails to reflect the diversity of this lineage, and that more studies are needed to establish the functional significance of the antigen expression patterns and tissue residency of human NKT cells.
Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers
Authors: Rong G-H , Yang G-X , Ando Y , Zhang W , He X-S , Leung P S C , Coppel R L , Ansari A A , Zhong R , Gershwin M E
Published: December 2012

The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non-professional phagocytic cells, including epithelial cells, can both take up and process apoptotic bodies, including the release of anti-inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up-regulation of the chemokines CCL2 [monocyte chemotactic protein-1 (MCP-1)] and CXCL8 [interleukin (IL)-8]. In particular, HiBEC cells express the phagocytosis-related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the ‘eat-me’ signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen-presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll-like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis.
Time‐dependent morphological alterations and viability of cultured human trabecular cells after exposure to Trypan blue
Authors: Tsaousis Konstantinos T , Kopsachilis Nikolaos , Tsinopoulos Ioannis T , Dimitrakos Stavros A , Kruse Friedrich E , Welge‐Luessen Ulrich
Published: December 2012

Background

To determine the time‐dependent toxicity of Trypan blue at 0.06% concentration in cultured human trabecular meshwork cells.

Methods

Human trabecular meshwork cells cultured in vitro were exposed to Trypan blue and acute toxicity was evaluated. Cells were exposed for 5, 30, 60 s and for 5, 15, 30, 60 min to a commercially available Trypan blue preparation (Vision Blue; DORC International Zuidland, The Netherlands). Morphology was observed by phase‐contrast microscopy and cell viability was measured using Hoechst 33342 (Intergen; Purchase, NY, USA) and propidium iodide assays to determine the percentage of living and dead cells.

Results

Morphological changes occurred mainly after 5 min of exposure to Trypan blue. Viability was 96.0% ± 3.6%, 94.8% ± 3.5% and 92.5% ± 4.4% after 5, 30 and 60 s of exposure, respectively; a significant toxic effect of Trypan blue was observed after 5, 15, 30 and 60 min of exposure with a viability of 85.0% ± 3.7%, 77.0% ± 6.7%, 70.8% ± 5.9% and 68.3% ± 8.7%, respectively.

Conclusions

Trypan blue is not toxic, in terms of cell viability, over an exposure time of up to 60 s; however, further exposure results in a gradual increase in damage of cultured human trabecular meshwork cells.
Poverty, caregiver depression and stress as predictors of children's externalizing behaviours in a low‐income sample
Authors: Henninger William R. , Luze Gayle
Published: December 2012

Previous research suggests a relationship between poverty, caregiver depression, caregiver stress and children's externalizing behaviour. However, little research exists to suggest the manner in which these concepts are interrelated. Latent growth curve analyses were conducted on caregiver–child dyads data from the Early Head Start Research and Evaluation Project to identify the path through which poverty, caregiver depression, caregiver stress and child externalizing behaviours were related. Analyses identified a path through which caregiver stress and depression mediated the effect of poverty on child externalizing behaviours. In addition, the influence of caregiver depression on child externalizing behaviours was mediated by caregiver stress. Implications and limitations of these findings are discussed.
The utility of elastic Verhoeff‐Van Gieson staining in dermatopathology
Authors: Kazlouskaya Viktoryia , Malhotra Saurabh , Lambe Jennifer , Idriss Munir Hassen , Elston Dirk , Andres Christian
Published: December 2012

Elastic fibers are important components of the skin and are responsible for skin elasticity. Genetic defects are well‐known in numerous hereditary elastic tissue disorders and skin biopsies are often the first step in the evaluation of those disorders. Verhoeff‐Van Gieson elastic staining is a simple method that is used for visualizing elastic fibers. With the development of modern immunohistochemical methods, the value of routine histochemical staining is sometimes underestimated. Histochemical stains are less expensive, easy to perform and help to resolve numerous diagnostic quandaries in dermatopathology. This article focuses on the value of elastic tissue staining in dermatopathology, with a focus on primary elastic tissue disorders, alopecia, inflammatory skin disorders and neoplastic proliferations.
Towards a new transition economics
Authors: Pistor Katharina
Published: December 2012

In these brief comments, I take issue with the thesis expressed in Konstantin Sonin’s conference review that economic transition is a thing of the past. To the contrary, I argue that it has only just begun, and so has the process of rethinking the economic theories and models that have framed the subfield of transition economics. Specifically, I point out that the many surprises economists have encountered when confronted with the actual results of the transition process reveal deep flaws in the analytical framework that informs their analyses and policy prescriptions. If protecting existing theories and models is of primary importance, we should indeed call an end to economic transition and the subfield it has engendered. If, however, the issue is to understand real economies and their dynamic change over time and to improve the results of contemporary and future reform efforts there is a strong case for a New Transition Economics.
Distribution of the black pecan aphid, Melanocallis caryaefoliae, on the upper and lower surface of pecan foliage
Authors: Paulsen C.M. , Cottrell T.E. , Ruberson J.R.
Published: December 2012

Three aphid species regularly feed on pecan [Carya illinoinensis (Wangenh.) K. Koch (Juglandaceae)] foliage: the black pecan aphid, Melanocallis caryaefoliae (Davis), the yellow pecan aphid, Monelliopsis pecanis Bissell, and the blackmargined aphid, Monellia caryella (Fitch) (all Hemiptera: Aphididae). Adults of M. caryaefoliae and both the nymphs and adults of M. pecanis and M. caryella mainly feed on the lower surface of leaves. Nymphs of M. caryaefoliae appear unique by frequently feeding on the upper surface of pecan leaves. This is risky behavior given the environmental hazards (e.g., rain, solar radiation, and dislodgement) associated with the upper surface. Thus, we determined the leaf surface distribution of M. caryaefoliae on trees in an orchard and on pecan seedlings in the laboratory. A pecan orchard survey found all three aphid species and stages predominantly on the lower leaf surface, except for the nymphs of M. caryaefoliae, which were evenly distributed between upper and lower leaf surfaces. This survey also found aphidophagous lacewing (Neuroptera) larvae predominantly on the lower leaf surface, whereas ladybird beetle (Coleoptera: Coccinellidae) larvae were more evenly distributed between upper and lower surfaces. Laboratory experiments using single or multiple pecan aphid species revealed M. caryaefoliae distribution on pecan seedlings similar to orchard data. Nymphal M. caryaefoliae require nearly 2 days to elicit chlorotic feeding lesions on leaves; without these lesions, nymphal development is hindered. The similar distribution of nymphs of M. caryaefoliae on both leaf surfaces likely reflects a strategy of predator avoidance allowing a proportion of the population to survive.
Epigenetics and epilepsy
Authors: Roopra Avtar , Dingledine Raymond , Hsieh Jenny
Published: December 2012

Seizures can give rise to enduring changes that reflect alterations in gene‐expression patterns, intracellular and intercellular signaling, and ultimately network alterations that are a hallmark of epilepsy. A growing body of literature suggests that long‐term changes in gene transcription associated with epilepsy are mediated via modulation of chromatin structure. One transcription factor in particular, repressor element 1‐silencing transcription factor (REST), has received a lot of attention due to the possibility that it may control fundamental transcription patterns that drive circuit excitability, seizures, and epilepsy. REST represses a suite of genes in the nervous system by utilizing nuclear protein complexes that were originally identified as mediators of epigenetic inheritance. Epigenetics has traditionally referred to mechanisms that allow a heritable change in gene expression in the absence of DNA mutation. However a more contemporaneous definition acknowledges that many of the mechanisms used to perpetuate epigenetic traits in dividing cells are utilized by neurons to control activity‐dependent gene expression. This review surveys what is currently understood about the role of epigenetic mechanisms in epilepsy. We discuss how REST controls gene expression to affect circuit excitability and neurogenesis in epilepsy. We also discuss how the repressor methyl‐CpG‐binding protein 2 (MeCP2) and activator cyclic AMP response element binding protein (CREB) regulate neuronal activity and are themselves controlled by activity. Finally we highlight possible future directions in the field of epigenetics and epilepsy.
Possible alterations in GABAA receptor signaling that underlie benzodiazepine‐resistant seizures
Authors: Deeb Tarek Z. , Maguire Jamie , Moss Stephen J.
Published: December 2012

Benzodiazepines have been used for decades as first‐line treatment for status epilepticus (SE). For reasons that are not fully understood, the efficacy of benzodiazepines decreases with increasing duration of seizure activity. This often forces clinicians to resort to more drastic second‐ and third‐line treatments that are not always successful. The antiseizure properties of benzodiazepines are mediated by γ‐aminobutyric acid type A (GABAA) receptors. Decades of research have focused on the failure of GABAergic inhibition after seizure onset as the likely cause of the development benzodiazepine resistance during SE. However, the details of the deficits in GABAA signaling are still largely unknown. Therefore, it is necessary to improve our understanding of the mechanisms of benzodiazepine resistance so that more effective strategies can be formulated. In this review we discuss evidence supporting the role of altered GABAA receptor function as the major underlying cause of benzodiazepine‐resistant SE in both humans and animal models. We specifically address the prevailing hypothesis, which is based on changes in the number and subtypes of GABAA receptors, as well as the potential influence of perturbed chloride homeostasis in the mature brain.
GABAA receptor modulation by neurosteroids in models of temporal lobe epilepsies
Authors: Ferando Isabella , Mody Istvan
Published: December 2012

Epilepsies consist of a spectrum of neurologic disorders typically characterized by unpredictable and dysfunctional network behaviors in the central nervous system (CNS), which lead to discrete episodes of large bouts of uncontrolled neuronal synchrony that interfere with the normal functioning of the brain. Temporal lobe epilepsy (TLE) is accompanied by changes in interneuronal innervation and modifications in different γ‐aminobutyric acid (GABA)A receptor subunits. Hormones play an important role in modulating the overall excitability of neurons, and at the same time hormonal pathways are frequently modified during epilepsy. This review focuses on TLE‐correlated modifications of GABAergic transmission, and in particular on the implications of some of our own findings related to GABAARs containing the δ subunits (δ‐GABAARs). These are extra‐ or perisynaptic GABAARs that mediate tonic inhibition, a major component of the inhibitory mechanism in the brain. The most potent endogenous modulators of δ‐GABAARs are neurosteroids, which act as positive allosteric modulators. Plasticity of δ‐GABAARs during TLE consists of down‐regulation of the subunit in the dentate gyrus granule cells (DGGCs), while being up‐regulated in interneurons. Surprisingly, the level of tonic inhibition in DGGCs remains unchanged, consistent with the idea that it becomes mediated by GABAARs containing other subunits. In parallel, tonic inhibition in a TLE model ceases to be sensitive to neurosteroid potentiation. In contrast, as predicted by the anatomic plasticity, interneuronal tonic current is increased, and remains sensitive to neurosteroids. These findings have important pharmacologic implications. Where neurosteroids normally have sedative and anticonvulsant effects, bimodal and cell‐type specific modulations in their natural targets might weaken the inhibitory control on the dentate gate, under circumstances of altered neurosteroids levels (stress, ovarian cycle, or the postpartum period).