bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mechanism for the Effect of Tropospheric Jet Structure on the Annular Mode–Like Response to Stratospheric Forcing
Authors: Simpson Isla R. , Blackburn Michael , Haigh Joanna D.
Published: March 2012

For many climate forcings the dominant response of the extratropical circulation is a latitudinal shift of the tropospheric midlatitude jets. The magnitude of this response appears to depend on climatological jet latitude in general circulation models (GCMs): lower-latitude jets exhibit a larger shift.

The reason for this latitude dependence is investigated for a particular forcing, heating of the equatorial stratosphere, which shifts the jet poleward. Spinup ensembles with a simplified GCM are used to examine the evolution of the response for five different jet structures. These differ in the latitude of the eddy-driven jet but have similar subtropical zonal winds. It is found that lower-latitude jets exhibit a larger response due to stronger tropospheric eddy–mean flow feedbacks.

A dominant feedback responsible for enhancing the poleward shift is an enhanced equatorward refraction of the eddies, resulting in an increased momentum flux, poleward of the low-latitude critical line. The sensitivity of feedback strength to jet structure is associated with differences in the coherence of this behavior across the spectrum of eddy phase speeds. In the configurations used, the higher-latitude jets have a wider range of critical latitude locations. This reduces the coherence of the momentum flux anomalies associated with different phase speeds, with low phase speeds opposing the effect of high phase speeds. This suggests that, for a given subtropical zonal wind strength, the latitude of the eddy-driven jet affects the feedback through its influence on the width of the region of westerly winds and the range of critical latitudes on the equatorward flank of the jet.
Supervised Learning Approaches to Classify Sudden Stratospheric Warming Events
Authors: Blume Christian , Matthes Katja , Horenko Illia
Published: March 2012

Sudden stratospheric warmings are prominent examples of dynamical wave–mean flow interactions in the Arctic stratosphere during Northern Hemisphere winter. They are characterized by a strong temperature increase on time scales of a few days and a strongly disturbed stratospheric vortex. This work investigates a wide class of supervised learning methods with respect to their ability to classify stratospheric warmings, using temperature anomalies from the Arctic stratosphere and atmospheric forcings such as ENSO, the quasi-biennial oscillation (QBO), and the solar cycle. It is demonstrated that one representative of the supervised learning methods family, namely nonlinear neural networks, is able to reliably classify stratospheric warmings. Within this framework, one can estimate temporal onset, duration, and intensity of stratospheric warming events independently of a particular pressure level. In contrast to classification methods based on the zonal-mean zonal wind, the approach herein distinguishes major, minor, and final warmings. Instead of a binary measure, it provides continuous conditional probabilities for each warming event representing the amount of deviation from an undisturbed polar vortex. Additionally, the statistical importance of the atmospheric factors is estimated. It is shown how marginalized probability distributions can give insights into the interrelationships between external factors. This approach is applied to 40-yr and interim ECMWF (ERA-40/ERA-Interim) and NCEP–NCAR reanalysis data for the period from 1958 through 2010.
Intermediate Zonal Jets in the Tropical Pacific Ocean Observed by Argo Floats*
Authors: Cravatte Sophie , Kessler William S. , Marin Frédéric
Published: March 2012

Argo float data in the tropical Pacific Ocean during January 2003–August 2011 are analyzed to obtain Lagrangian subsurface velocities at their parking depths. Maps of mean zonal velocities at 1000 and 1500 m are presented. At both depths, a series of alternating westward and eastward zonal jets with a meridional scale of 1.5° is seen at the basin scale from 10°S to 10°N. These alternating jets, with mean speeds about 5 cm s−1, are clearly present in the western and central parts of the basin but weaken and disappear approaching the eastern coast. They are stronger in the Southern Hemisphere. Along the equator at both 1000 and 1500 m, a westward jet is seen. The jets closer to the equator are remarkably zonally coherent across the basin, but the jets farther poleward appear broken in several segments. In the western half of the basin, the 1000-m zonal jets appear to slant slightly poleward from east to west. At the western boundary in the south (east of Solomon Islands and Papua New Guinea), the alternating jets appear to connect in narrow boundary currents. Seasonal zonal velocity anomalies at 1000 and 1500 m are observed to propagate westward across the basin; they are consistent with annual vertically propagating Rossby waves superimposed on the mean zonal jets. Their meridional structure suggests that more than one meridional mode is present.
Experimental Determination of Forecast Sensitivity and the Degradation of Forecasts through the Assimilation of Good Quality Data
Authors: Semple Adrian , Thurlow Michael , Milton Sean
Published: March 2012

The case of a small vigorous cyclone crossing the United Kingdom on 1 November 2009 is investigated. Met Office Global Model forecasts at the time displayed a marked change in solutions at a forecast range of 72 h, with those at longer ranges being more representative of the correct solution and those at shorter ranges only gradually migrating toward it. The strong bimodal nature of the Global Model forecasts is enough to overwhelmingly dominate the solutions from the Met Office Global Ensemble on which it is based. An investigation into the case is used as a vehicle for developing an experimental method determining the critical location of assimilated data leading to the largest impact on forecast consistency and the origins of the bimodal solutions. It allows the identification of one global positioning system radio occultation (GPSRO) and three surface observations located around the developing low that have conclusively led to the degradation in forecast skill. An assessment of these observations concludes that they are of relatively good quality and correctly assimilated. The case is suggested to be an example of forecast degradation as a result of the addition of growing errors by the data assimilation scheme.
What We Know and Don’t Know About Corporate Social Responsibility
Authors: Aguinis Herman , Glavas Ante
Published: March 2012

The authors review the corporate social responsibility (CSR) literature based on 588 journal articles and 102 books and book chapters. They offer a multilevel and multidisciplinary theoretical framework that synthesizes and integrates the literature at the institutional, organizational, and individual levels of analysis. The framework includes reactive and proactive predictors of CSR actions and policies and the outcomes of such actions and policies, which they classify as primarily affecting internal (i.e., internal outcomes) or external (i.e., external outcomes) stakeholders. The framework includes variables that explain underlying mechanisms (i.e., relationship- and value-based mediator variables) of CSR–outcomes relationships and contingency effects (i.e., people-, place-, price-, and profile-based moderator variables) that explain conditions under which the relationship between CSR and its outcomes change. The authors’ review reveals important knowledge gaps related to the adoption of different theoretical orientations by researchers studying CSR at different levels of analysis, the need to understand underlying mechanisms linking CSR with outcomes, the need for research at micro levels of analysis (i.e., individuals and teams), and the need for methodological approaches that will help address these substantive knowledge gaps. Accordingly, they offer a detailed research agenda for the future, based on a multilevel perspective that aims to integrate diverse theoretical frameworks as well as develop an understanding of underlying mechanisms and microfoundations of CSR (i.e., foundations based on individual action and interactions). The authors also provide specific suggestions regarding research design, measurement, and data-analytic approaches that will be instrumental in carrying out their proposed research agenda.
Evaluation of Potential Gastrointestinal Biomarkers in a PAK4 Inhibitor-treated Preclinical Toxicity Model to Address Unmonitorable Gastrointestinal Toxicity
Authors: John-Baptiste Annette , Huang Wenhu , Kindt Erick , Wu Annette , Vitsky Allison , Scott Wes , Gross Cindy , Yang Amy H. , Schaiff W. Timothy , Ramaiah Shashi K.
Published: March 2012

Although gastrointestinal (GI) toxicity is a significant dose-limiting safety concern noted in multiple therapeutic areas, there are no GI biomarkers that can accurately track, precede, or reliably correlate with histologic evidence of injury. While significant efforts have been made within the pharmaceutical industry, academia, and consortia to address the biomarker gaps in other target organs such as liver, kidney, and muscle (cardiac and skeletal), there have been no concerted efforts in the area of GI biomarkers. Using PAK4 inhibitor as a preclinical rat model of gastric toxicity, selected candidate biomarkers from literature were evaluated to test their usefulness as gastric injury biomarkers in this study. Biomarkers selected in this study include plasma diamino oxidase and citrulline, fecal calprotectin, bile acids, and miRNA. Based on the results, L-citrulline and miR-194 results appear to correlate well with histopathology findings. Although these biomarkers will need additional assay validation and qualification to test if they truly predict the injury prior to histopathology, the results provide promise for further testing using additional GI toxicants. In addition, this article highlights important gaps in GI biomarkers and provides substrate and rationale for additional investments either for further testing of already available biomarkers or to pursue extensive biomarker discovery approaches.
No Evidence for the Diagnostic Value of Borrelia Serology in Patients with Sudden Hearing Loss
Authors: Bakker Renée , Aarts Mark C. J. , van der Heijden Geert J. M. G. , Rovers Maroeska M.
Published: March 2012

In this evidence‐based case report, we address the following clinical question: What is the predictive value of serological testing for Borrelia for diagnosing neuroborreliosis in patients with sudden sensorineural hearing loss? We searched for relevant articles in PubMed, Embase, and Web of Science. We retrieved 49 unique publications and screened the title and abstract of these articles for relevance. We included 2 of 12 studies initially considered relevant to answer our question. These 2 studies reported a seroprevalence of antibodies against Borrelia of 16% in patients with sudden sensorineural hearing loss (SHL) as compared with 13.5% in the general population, but in neither patients with definite neuroborreliosis were they found. To date, there is no evidence regarding the added value of routine diagnostic serologic testing for Borrelia in diagnosing neuroborreliosis in patients with sudden SHL. Neuroborreliosis seems to be a rare cause of sudden SHL, and routine screening of patients for borrelia antibodies in serum should therefore not be recommended.
Strength of Titanium Intramedullary Implant versus Miniplate Fixation of Mandibular Condyle Fractures
Authors: Frake Paul C. , Howell Rebecca J. , Joshi Arjun S.
Published: March 2012

Objective

To test the strength of internal fixation of mandibular condyle fractures repaired with titanium miniplates versus titanium intramedullary implants.

Study Design

Prospective laboratory experimentation in urethane mandible models and human cadaveric mandibles.

Setting

Materials testing laboratory at an academic medical center.

Methods

Osteotomies of the mandibular condyle were created in 40 urethane hemimandible models and 24 human cadaveric specimens. Half of the samples in each group were repaired with traditional miniplates, and the other half were repaired with intramedullary titanium implants. Anteroposterior and mediolateral loads were applied to the samples, and the displacement was measured with reference to the applied force.

Results

Titanium intramedullary implants demonstrated statistically significant improved strength and stiffness versus miniplates in the urethane model experimental groups. Despite frequent plastic deformation and mechanical failures of the miniplates, a 1.6‐mm‐diameter titanium intramedullary pin did not mechanically fail in any of the cases. Intramedullary implantation failures were due to secondary fracture of the adjacent cortical bone or experimental design limitations including rotation of the smooth pin implant.

Conclusion

Mechanical implant failures that were encountered with miniplate fixation were not seen with titanium intramedullary implants. These intramedullary implants provide stronger and more rigid fixation of mandibular condyle fractures than miniplates in this in vitro model.
Transnational ties and ethnic activism: The case of Poland
Authors: Jasiewicz Joanna
Published: March 2012

The second half of the 20th century was characterized by debate on the implementation of minorities’ rights. Poland, similar to other Central Eastern European states, was not able to participate in this process until the 1990s. After 1989, there was a rapid increase in legislation on minorities’ rights in Poland. Simultaneously, ethnic groups entered the public sphere as actors who were able to legitimately voice their demands. While the anti-discrimination prescriptions created in the framework of supranational institutions and Poland’s democratic transformation facilitated the ethnic organizations’ activism, the supranational and domestic institutional environment was not decisive in determining different minorities’ levels of participation in the public sphere. This article argues that transnational linkages in which minorities are embedded variously empower them and allow them to break loose from the constraints imposed by the nation-state.
Identity, diversity and citizenship: A critical analysis of textbooks and curricula in Irish schools
Authors: Faas Daniel , Ross Wendy
Published: March 2012

Despite the long presence of migrant communities, Ireland was only transformed to a net-receiving immigration nation in 1996, and is currently experiencing net emigration in the wake of a sharp economic downturn. Debates about immigrant incorporation and educational responses are still at a relatively early stage. This study, which forms part of a larger project, set out to explore the role of schools and curricula in developing citizenship and the conception of Irish identity implicit therein. The article draws on citizenship curricula as well as some textbooks used in citizenship lessons. It argues that the curriculum at primary level emphasizes diversity and active citizenship in a plural society to a greater extent than the curriculum at secondary level. Moreover, there are discrepancies between the progressive rhetoric of policy documents and the content of textbooks and other curriculum material. This raises important questions of inclusivity in a still Catholic-dominated education system.
Defining the Excluded Middle: The Case of Ishmael in Jubilees
Authors: Francis Michael
Published: March 2012

This study explores the seemingly anomalous presentation of Ishmael in Jubilees. In a work in which an unbridgeable chasm separates Jewish and Gentile identities, the strikingly positive depiction of Abraham's natural firstborn is surprising. It is suggested that the genealogical considerations so prominent in Jubilees allow Ishmael to be treated as an unthreatening character: as son of an Egyptian mother, he cannot be mistaken for the primary covenant conduit; as brother of Isaac rather than the preeminent Jacob, his existence does not call into question the identity of the first Israelite proper. Beyond this, it is suggested that the favorable treatment of Ishmael in Jubilees is a matter of his full inclusion within the circle of covenant privilege. This is explained as a function of the laudable pedagogical instincts of Abraham, the friend of God, and, most significantly, the distinctive shape of covenant history in Jubilees.
Experimental studies on damping by parametric excitation using electromagnets
Authors: Dohnal F
Published: March 2012

Transient vibrations in mechanical systems are a common problem in engineering. Several theoretical studies have shown analytically and numerically that a vibrating system can be stabilised or its vibrations can be reduced when excited close to a specific parametric combination resonance frequency. At this operation, the transient vibrations are effectively damped by parametric excitation. The basic step in exploiting this method is its experimental implementation in mechanical systems. In this review, recent experiments are discussed for a simple chain mass system, a continuous cantilever and a flexible rotor system. The parametric excitation is realised by electromagnetic variable-stiffness actuators driven by a periodic open-loop control. It is demonstrated experimentally that a parametrically excited structure can exhibit enhanced damping properties. A certain level of the excitation amplitude has to be exceeded to achieve the damping effect in which the existing damping in the system is artificially amplified. Upon exceeding this value, the additional artificial damping provided to the system is significant and most effective for vibration suppression of the lower vibration modes.
Triggers of Students’ Efficacious Interaction in Collaborative Learning Situations
Authors: Määttä Elina , Järvenoja Hanna , Järvelä Sanna
Published: March 2012

This article presents a case study that investigated primary school students’ social interaction while working in small groups in science. The aim was to identify what characterizes and triggers students’ efficacious interaction in collaborative learning situations. This was done by exploring and analyzing students’ and groups’ task involvement and the quality of their activity. The micro-level analysis proceeded first by identifying episodes of group task involvement and evaluating the quality of these interaction episodes. Next, the transitions between episodes were explored by identifying what triggered the shifts between task involvement levels. Ten hours of video observation data captured fourth-grade students, aged 9 to 10, in two groups of 3 students studying “the vital conditions of life” for 5 weeks. The main findings indicated that efficacious interaction demanded collaboration between group members and required active participation and productive on-task working. Three types of triggers were found to cause changes in students’ activity, of which the group progress trigger was the most powerful for increasing, and the contextual trigger the most powerful for decreasing the activity. These findings shed light on certain aspects of efficacious interaction that will help us to identify details of efficacious interaction in future studies.
A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper
Authors: Saccardi R , Freedman MS , Sormani MP , Atkins H , Farge D , Griffith LM , Kraft G , Mancardi GL , Nash R , Pasquini M , Martin R , Muraro PA
Published: March 2012

Background: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1–2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing–remitting phase than in those in the secondary progressive stage.

Objectives: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments.

Conclusions: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.
Natalizumab discontinuation after PML risk stratification: outcome from a shared and informed decision
Authors: Tur Carmen , Tintoré Mar , Vidal-Jordana Angela , Castilló Joaquín , Galán Ingrid , Río Jordi , Arrambide Georgina , Comabella Manuel , Arévalo Mª Jesús , Horno Rosalía , Vicente Mª José , Caminero Ana , Nos Carlos , Sastre-Garriga Jaume , Montalban Xavier
Published: March 2012

Multifocal progressive leukoencephalopathy (PML) is associated with JC virus (JCV) seropositivity, past immunosuppression, and natalizumab treatment for two years or more. The aim of our study was to investigate the rate of treatment discontinuation after stratifying for the three risk factors in a group of 104 natalizumab-treated patients with relapsing–remitting multiple sclerosis. We investigated JCV serological status in our population. We then divided patients into groups according to their PML risk. Treatment indication was reassessed. Of the patients, 64 (61.5%) were JCV seropositive. Amongst seropositive patients on natalizumab for 2 years or more, 10 had received immunosuppression (group A), and 38 had not (group B). After an informed and shared decision-making process, 6/10 (60%) from group A compared with 9/38 (23.7%) from group B discontinued treatment ( p=0.027). In groups A and B, discontinuation also depended upon doctors’ views ( p=0.019, group A; p=0.010, group B) and clinical outcomes ( p=0.021, group A). No-one from low–intermediate risk groups discontinued. The decision to discontinue natalizumab treatment is complex, even when clear PML risk rates are described. Clinical outcomes and doctors’ idiosyncrasies play a crucial part in patients’ final choice.
An initial look into party switching in Africa
Authors: Young Daniel J
Published: March 2012

What keeps politicians together in a political party? Shared ideologies and policy goals go far towards answering that question in established democracies, but in Africa political parties hardly differ from each other in their policy programmes. This leaves party cohesion as an open question. In this study, I attempt to explain the decisions to stay with or defect from political parties made by Members of Parliament in Malawi – a sub-Saharan African country that clearly lacks a salient ideological cleavage. I show that re-election prospects and joining the government significantly determine patterns of party switching. I find mixed evidence that ethno-regional linkages account for loyalty, and no evidence that governing party politicians leave their parties to avoid blame for poor government performance. This study adds to the existing literature on party switching with theory and evidence from a new region.
Renin and prorenin have no direct effect on aldosterone synthesis in the human adrenocortical cell lines H295R and HAC15
Authors: Jansen Pieter M , Hofland Johannes , van den Meiracker Anton H , de Jong Frank H , Danser AH Jan
Published: March 2012

Introduction:

Transgenic rats expressing the human (pro)renin receptor (h(P)RR) have elevated plasma aldosterone levels despite unaltered levels, in plasma and adrenal, of renin and angiotensin II.

Materials and methods:

To investigate whether renin/prorenin–(P)RR interaction underlies these elevated aldosterone levels, the effect of (pro)renin on steroidogenesis was compared with that of angiotensin II in two (P)RR-expressing human adrenocortical cell lines, H295R and HAC15. Angiotensin II rapidly induced extracellular signal-regulated kinase (ERK) phosphorylation and increased the expression of STAR, CYP21A2, CYP11B2, and CYP17A1 at 6 and 24 hours, whereas the expression of CYP11A1 and HSD3B2 remained unaltered. Incubation with renin or prorenin at nanomolar concentrations had no effect on the expression of any of the steroidogenic enzymes tested, nor resulted in ERK phosphorylation. Angiotensin II, but not renin or prorenin, induced aldosterone production.

Conclusion:

Although the (P)RR is present in adrenocortical cells, renin and prorenin do not elicit ERK phosphorylation nor directly affect steroid production via this receptor at nanomolar concentrations. Thus, direct (pro)renin–(P)RR interaction is unlikely to contribute to the elevated aldosterone levels in human (P)RR transgenic rats. This conclusion also implies that the aldosterone rise that often occurs during prolonged renin–angiotensin system blockade is rather due to the angiotensin II ‘escape’ during such blockade.
Low serum mannose-binding lectin level is not associated with disease severity in non-cystic fibrosis bronchiectasis
Authors: Macfarlane James G , Jary Hannah , Hester Katharine LM , McAlinden Paul , Wake Jonathan , Small Therese , Walton Kathy E , Spickett Gavin , De Soyza Anthony
Published: March 2012

Deficiency of mannose-binding lectin (MBL), a serum protein involved in killing and promoting phagocytosis of pathogens, is associated with respiratory infection and disease progression in a number of acute and chronic lung diseases, including cystic fibrosis (CF)- associated bronchiectasis. No such association has been studied in non-CF bronchiectasis (nCF-Br). One hundred and thirty-three adult patients with nCF-Br were studied. Serum MBL levels were measured and deficiency defined using two cut-off levels, i.e. MBL ≤100 ng/ml and ≤600 ng/ml. Parameters of severity included lung function impairment, annual exacerbation and hospital admission rates, breathlessness, and Pseudomonas aeruginosa and Haemophilus influenzae infection rates. The incidence of MBL deficiency using cut-off levels of 100 ng/ml and 600 ng/ml was 10% and 26% respectively, similar to rates seen in the general population. There was no significant difference in mean FEV1% predicted between MBL deficient and sufficient patients at both cut-off levels (≤100 ng/ml: 63.8% vs . 64.6%, P = 0.91; ≤ 600 ng/ml: 66.5% vs . 63.9%, P = 0.56). In addition, exacerbation/hospital admission rates, symptoms of breathlessness and isolation/colonisation rates with P. aeruginosa and H. influenzae were similar in both groups at both cut-off levels. In conclusion, MBL deficiency is not associated with markers of disease severity in patients with nCF-Br.
Use of ethnographic approaches to the study of health experiences in relation to natural landscapes
Authors: O’Brien Liz , Varley Pete
Published: March 2012

Aims:

This paper discusses the use of ethnographic approaches to explore how engagement with natural landscapes might benefit people’s health.

Methods:

Drawing on a selected review of empirical research we identified 30 relevant research papers that utilised qualitative methods to explore health issues and engagement with nature. Three examples of ‘alternative’ – i.e. non-mainstream qualitative approaches – are used to illustrate how different methods can be used to explore people’s experiences of engaging with nature for health.

Results:

While quantitative methods are dominant in health research, qualitative approaches are becoming more widely used. Approaches such as autoethnography can add value to nature and health studies by providing opportunities for researchers to be self-critical of their role as a researcher. Accompanied visits and visual ethnography can afford the researcher rich data about bodily movement, facial expressions and journeys, as well as dialogues associated with the meanings of nature for health.

Conclusions:

The paper concludes by suggesting that ethnographic methods can provide useful and important insights into why people engage with the natural environment and the range of health benefits they may gain from contact with nature.
Beta-adrenergic blocking drugs in breast cancer: a perspective review
Authors: Barron Thomas I. , Sharp Linda , Visvanathan Kala
Published: March 2012

The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between β-blockers and breast cancer progression. Preclinical studies have shown that β-adrenergic receptor (β-AR) signalling can inhibit multiple cellular processes involved in breast cancer progression and metastasis, including extracellular matrix invasion, expression of inflammatory and chemotactic cytokines, angiogenesis and tumour immune responses. This has led to the hypothesis that the commonly prescribed class of β-AR antagonist drugs (β-blockers) may favourably impact cancer progression. A number of recent pharmacoepidemiological studies have examined the association between β-blocker exposure and breast cancer progression. The results from these studies have suggested a potential role for targeting the β-AR pathway in breast cancer patients. Larger observational studies are, however, required to confirm these results. Questions regarding the type of β-blocker, predictive biomarkers or tumour characteristics, appropriate treatment paradigms and, most importantly, efficacy must also be answered in randomized clinical studies before β-blockers can be considered a therapeutic option for patients with breast cancer.
CD4+ T-cell epitopes associated with antibody responses after intravenously and subcutaneously applied human FVIII in humanized hemophilic E17 HLA-DRB1*1501 mice
Authors: Steinitz Katharina N. , van Helden Pauline M. , Binder Brigitte , Wraith David C. , Unterthurner Sabine , Hermann Corinna , Schuster Maria , Ahmad Rafi U. , Weiller Markus , Lubich Christian , de la Rosa Maurus , Schwarz Hans Peter , Reipert Birgit M.
Published: March 2012

Today it is generally accepted that B cells require cognate interactions with CD4+ T cells to develop high-affinity antibodies against proteins. CD4+ T cells recognize peptides (epitopes) presented by MHC class II molecules that are expressed on antigen-presenting cells. Structural features of both the MHC class II molecule and the peptide determine the specificity of CD4+ T cells that can bind to the MHC class II–peptide complex. We used a new humanized hemophilic mouse model to identify FVIII peptides presented by HLA-DRB1*1501. This model carries a knockout of all murine MHC class II molecules and expresses a chimeric murine-human MHC class II complex that contains the peptide-binding sites of the human HLA-DRB1*1501. When mice were treated with human FVIII, the proportion of mice that developed antibodies depended on the application route of FVIII and the activation state of the innate immune system. We identified 8 FVIII peptide regions that contained CD4+ T-cell epitopes presented by HLA-DRB1*1501 to CD4+ T cells during immune responses against FVIII. CD4+ T-cell responses after intravenous and subcutaneous application of FVIII involved the same immunodominant FVIII epitopes. Interestingly, most of the 8 peptide regions contained promiscuous epitopes that bound to several different HLA-DR proteins in in vitro binding assays.
Ageing in general practice (AGP) trial: a cluster randomised trial to examine the effectiveness of peer education on GP diagnostic assessment and management of dementia
Authors: Pond Constance D , Brodaty Henry , Stocks Nigel P , Gunn Jane , Marley John , Disler Peter , Magin Parker , Paterson Nerida , Horton Graeme , Goode Susan , Paine Bronwen , Mate Karen E
Published: March 2012

Background

Dementia is increasing in prevalence as the population ages. An earlier rather than later diagnosis allows persons with dementia and their families to plan ahead and access appropriate management. However, most diagnoses are made by general practitioners (GPs) later in the course of the disease and are associated with management that is poorly adherent to recommended guidelines. This trial examines the effectiveness of a peer led dementia educational intervention for GPs.

Methods

The study is a cluster randomised trial, conducted across three states and five sites. All GPs will complete an audit of their consenting patients aged 75 years or more at three time points - baseline, 12 and 24 months. GPs allocated to the intervention group will receive two educational sessions from a peer GP or nurse, and will administer the GPCOG to consenting patients at baseline and 12 months. The first education session will provide information about dementia and the second will provide individualised feedback on audit results. GPs in the waitlist group will receive the RACGP Guidelines by post following the 12 month audit

Outcomes: Primary outcomes are carer and consumer quality of life and depression. Secondary outcomes include: rates of GP identification of dementia compared to a more detailed gold standard assessment conducted in the patient's home; GP identification of differential diagnoses including reversible causes of cognitive impairment; and GP referral to specialists, Alzheimers' Australia and support services. A "case finding" and a "screening" group will be compared and the psychometrics of the GPCOG will be examined.

Sample size: Approximately 2,000 subjects aged 75 years and over will be recruited through approximately 160 GPs, to yield approximately 200 subjects with dementia (reducing to 168 by 24 months).

Discussion

The trial outlined in this paper has been peer reviewed and supported by the Australian National Health and Medical Research Council. At the time of submission of this paper 2,034 subjects have been recruited and the intervention delivered to 114 GPs.

Trial registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000117415.
Impact of genital warts on health related quality of life in men and women in mainland China: a multicenter hospital-based cross-sectional study
Authors: Shi Ju-Fang , Kang Dian-Ju , Qi Shu-Zhen , Wu Hai-Yan , Liu Yan-Chun , Sun Li-Jun , Li Li , Yang Ying , Li Qing , Feng Xiang-Xian , Zhang Li-Qin , Li Jie , Li Xiao-Li , Yang Yun , Niyazi Mayinuer , Xu Ai-Di , Liu Jia-Hua , Xiao Qing , Li Lian-Kun , Wang Xin-Zheng , Qiao You-Lin
Published: March 2012

Background

Information on the health-related quality of life (HRQoL) of patients with genital warts (GW) in populations in mainland China is still limited. The aim of the study was to use a generic instrument to measure the impact of genital warts on HRQoL in men and women in this setting.

Methods

A multi-centre hospital-based cross-sectional study across 18 centers in China was conducted to interview patients using the European quality of life-5 dimension (EQ-5D) instrument; respondents' demographic and clinical data were also collected.

Results

A total of 1,358 GW patients (612 men, 746 women) were included in the analysis, with a mean age of 32.0 ± 10.6 years. 56.4% of the patients reported some problems in the dimension of Anxiety/Depression (highest), followed by Pain/Discomfort (24.7%) and Mobility (3.5%). The overall visual analogue scale (VAS) score of the study population was found to be 65.2 ± 22.0, and the EQ-5D index score was found to be 0.843 ± 0.129 using Japanese preference weights (the Chinese preference was unavailable yet). Patients with lower VAS means and EQ-5D index scores were more often female, living in urban area, and suffering multiple GW (all p values < 0.05), but the values did not differ notably by age (p values > 0.05).

Conclusions

The HRQoL of patients with GW was substantially lower, compared to a national representative general population in China (VAS = ~80); the findings of different subgroups are informative for future GW prevention and control efforts.
Community based needs assessment in an urban area; A participatory action research project
Authors: Ahari Saeid Sadeghieh , Habibzadeh Shahram , Yousefi Moharram , Amani Firouz , Abdi Reza
Published: March 2012

Background

Community assessment is a core function of public health. In such assessments, a commitment to community participation and empowerment is at the heart of the WHO European Healthy Cities Network, reflecting its origins in health for all and the Ottawa Charter for Health Promotion. This study employs a participation and empowerment plan in order to conduct community assessment.

Methods

The method of participatory action research (PAR) was used. The study was carried out in an area of high socio-economic deprivation in Ardabil, a city in the northwest of Iran, which is currently served by a branch of the Social Development Center (SDC). The steering committee of the project was formed by some university faculty members, health officials and delegates form Farhikhteh non-governmental organization and representatives from twelve blocks or districts of the community. Then, the representatives were trained and then conducted focus groups in their block. The focus group findings informed the development of the questionnaire. About six hundred households were surveyed and study questionnaires were completed either during face-to-face interviews by the research team (in case of illiteracy) or via self-completion. The primary question for the residents was: 'what is the most important health problem in your community? Each health problem identified by the community was weighted based on the frequency it was selected on the survey, and steering committee perception of the problem's seriousness, urgency, solvability, and financial load.

Results

The main problems of the area appeared to be the asphalt problem, lack of easy access to medical centers, addiction among relatives and unemployment of youth. High participation rates of community members in the steering committee and survey suggest that the PAR approach was greatly appreciated by the community and that problems identified through this research truly reflect community opinion.

Conclusions

Participatory action research is an effective method for community assessments. However, researchers must rigorously embrace principles of mutual cooperation, respect for public ideas, and a robust belief in community empowerment in order to pave the way for responsible and active citizen participation in the various stages of research.
Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes
Authors: Sinclair Alan J , Alexander Charles M , Davies Michael J , Zhao Changgeng , Mavros Panagiotis
Published: March 2012

Aim

To assess the factors associated with antihyperglycaemic medication initiation in UK patients with newly diagnosed type 2 diabetes.

Methods

In a retrospective cohort study, patients with newly diagnosed type 2 diabetes were identified during the index period of 2003-2005. Eligible patients were ≥ 30 years old at the date of the first observed diabetes diagnosis (referred to as index date) and had at least 2 years of follow-up medical history (N = 9,158). Initiation of antihyperglycaemic medication (i.e., treatment) was assessed in the 2-year period following the index date. Adjusted Cox regression models were used to examine the association between time to medication initiation and patient age and other factors.

Results

Mean (SD) HbA1c at diagnosis was 8.1% (2.3). Overall, 51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%, 46% and 40% for patients in the 30- < 45, 45- < 65, 65- < 75, 75+ age groups, respectively). Among the treated patients, median (25th, 75th percentile) time to treatment initiation was 63 (8, 257) days. Of the patients with HbA1c ≥ 7.5% at diagnosis, 87% initiated treatment within 2 years. These patients with a higher HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR) = 2.44 [95% confidence interval (CI): 1.61, 3.70]; p < 0.0001). Increasing age (in years) was negatively associated with time to treatment initiation (HR = 0.98 [95% CI: 0.97, 0.99]; p < 0.001). Factors significantly associated with shorter time to treatment initiation included female gender and use of cardiovascular medications at baseline or initiated during follow up.

Conclusions

In this UK cohort of patients with newly diagnosed type 2 diabetes, only 51% had antihyperglycaemic medication initiated over a 2-year period following diagnosis. Older patients were significantly less likely to have been prescribed antihyperglycaemic medications. Elevated HbA1c was the strongest factor associated with initiating antihyperglycaemic medication in these patients.
Prognostic significance of the Complex "Visceral Adiposity Index" vs. simple anthropometric measures: Tehran lipid and glucose study
Authors: Mohammadreza Bozorgmanesh , Farzad Hadaegh , Davoud Khalili , Prof Azizi Fereidoun
Published: March 2012

Background

Visceral adiposity index (VAI) has recently been suggested to be used as a surrogate of visceral adiposity. We examined if VAI could improve predictive performances for CVD of the Framingham's general CVD algorithm (a multivariate model incorporating established CVD risk factors). We compared the predictive abilities of the VAI with those of simple anthropometric measures i.e. BMI, waist-to-height ratio (WHtR) or waist-to-hip ratio (WHpR).

Design and methods

In a nine-year population-based follow-up, 6 407 (2 778 men) participants, free of CVD at baseline, aged ≥ 30 years were eligible for the current analysis. The risk of CVD was estimated by incorporating VAI, BMI, WHpR, and WHtR, one at a time, into multivariate accelerated failure time models.

Results

We documented 534 CVD events with the annual incidence rate (95%CIs) being 7.3 (6.4-8.3) among women and 13.0 (11.7-14.6) among men. Risk of future CVD increased with increasing levels of VAI among both men and women. VAI was associated with multivariate-adjusted increased risk of incident CVD among women. However, the magnitude of risk conferred by VAI was not significantly higher than those conferred by BMI, WHpR, or WHtR. Among men, after adjustment for established CVD risk factors, VAI was no longer associated with increased risk of CVD. VAI failed to add to the predictive ability of the Framingham general CVD algorithm.

Conclusions

Using VAI instead of simple anthropometric measures may lead to loss of much information needed for predicting incident CVD.
Quantitative study of cytotoxic T-lymphocyte immunotherapy for nasopharyngeal carcinoma
Authors: Shengjun Wang , Yunbo Guo , Liyan Song , Jinming Li , Qinkai Deng
Published: March 2012

Background

In clinical practice, the common strategy for immunotherapy of nasopharyngeal carcinoma (NPC) is to infuse cytotoxic T-lymphocyte (CTL) lines several times by intravenous injection, but it is difficult by laboratory research to investigate the relationship between treatment time-point, the amount of CTL added and the therapeutic effect. The objective of this study is to establish a mathematical model to study the therapeutic effect of different treatment time-points and amounts of CTL, and to predict the change in therapeutic effect when the percentage of EBV LMP2-specific CTL is increased from 10% to 20%.

Results

The concentration of epidermal growth factor receptor (EGFR) in the tumor cell cytomembranes increases after CTL is added. Concurrently, there is a marked downward trend of the phosphorylated transforming growth factor-α (TGFα)-EGFR complex in the tumor cell cytomembranes, which indicates restriction of tumor growth after CTL immunotherapy. The relationships among the time of addition of CTL, the amount of CTL added, different CTL specificities for LMP2 and the increment rate k of the total number of tumor cells were evaluated.

Conclusions

The simulation results quantify the relationships among treatment time-points, amount of CTL added, and the corresponding therapeutic effect of immunotherapy for NPC.
Occurrence and characteristics of extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae in food producing animals, minced meat and raw milk
Authors: Geser Nadine , Stephan Roger , Hächler Herbert
Published: March 2012

Background

The impact of food animals as a possible reservoir for extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, and the dissemination of such strains into the food production chain need to be assessed. In this study 334 fecal samples from pigs, cattle, chicken and sheep were investigated at slaughter. Additionally, 100 raw milk samples, representing bulk tank milk of 100 different dairy farms, 104 minced meat (pork and beef) samples and 67 E. coli isolates from cattle E. coli mastitis were analyzed.

Results

As many as 15.3% of the porcine, 13.7% of the bovine, 8.6% of the sheep and 63.4% of the chicken fecal samples yielded ESBL producers after an enrichment step. In contrast, none of the minced meat, none of the bulk tank milk samples and only one of the mastitis milk samples contained ESBL producing strains. Of the total of 91 isolates, 89 were E. coli, one was Citrobacter youngae and one was Enterobacter cloacae. PCR analysis revealed that 78 isolates (85.7%) produced CTX-M group 1 ESBLs while six isolates (6.6%) produced CTX-M group 9 enzymes. Five detected ESBLs (5.5%) belonged to the SHV group and 2 isolates (2.2%) contained a TEM-type enzyme. A total of 27 CTX-M producers were additionally PCR-positive for TEM-beta-lactamase. The ESBL-encoding genes of 53 isolates were sequenced of which 34 produced CTX-M-1, 6 produced CTX-M-14, 5 produced CTX-M-15 and also 5 produced SHV-12. Two isolates produced TEM-52 and one isolate expressed a novel CTX-M group 1 ESBL, CTX-M-117. One isolate--aside from a CTX-M ESBL-- contained an additional novel TEM-type broad-spectrum beta-lactamase, TEM-186.

Conclusions

The relatively high rates of ESBL producers in food animals and the high genetic diversity among these isolates are worrisome and indicate an established reservoir in farm animals.
Riedel's thyroiditis - a case report with genes' expression studies
Authors: Wojciechowska-Durczyńska Katarzyna , Durczyński Adam , Sporny Stanisław , Strzelczyk Janusz , Lewiński Andrzej
Published: March 2012

Background

Genetic background of Riedel's thyroiditis remains unknown. Herein, we describe our results of studies on genes expression levels in Riedel's thyroiditis.

Case report and genetic findings

We report the case of 48-year old woman with Riedel's thyroiditis who has presented unusual course of disease with non-specific cervical discomfort, though as with no pain and/or no compression symptoms. After surgery, thyroid specimens were quantitatively evaluated, regardingPIK3CA, PIK3CD, PIK3CG, Tg, TGFB1, THRB, COL1, CDKN1C, CDH3andCACNA2D2genes expression levels, by real-time PCR in the ABI PRISM®7500 Sequence Detection System. Out of 10 above genes, in 2 cases the expression was higher than in respective Controls of unchanged thyroid tissue. In the remaining 8 cases, expression in question became comparable or lower as in Controls.

Discussion

The association between increased expression levels ofPIK3CAandCDH3genes and Riedel's thyroiditis is not well-defined. However, the increased expression ofPIK3CAandCDH3genes in our case report and in previous studies of other authors on various malignancies may suggest possible molecular relation between Riedel's thyroiditis and certain neoplastic processes, the relation of which requires further genetic evaluation. It is to be stressed that gene expression studies in Riedel's thyroiditis are difficult to perform, mainly due to fibrosis, resulting in scarce thyroid specimens and - in consequence - small amount of genetic material.