bluuebunny/crossref_metadata_2025 huggingface dataset:
From southern refugia to the northern range margin: genetic population structure of the common wall lizard, Podarcis muralis
Authors: Gassert Franz , Schulte Ulrich , Husemann Martin , Ulrich Werner , Rödder Dennis , Hochkirch Axel , Engel Edmée , Meyer Jobst , Habel Jan Christian
Published: April 2013

Aim

Thermophilic species persisted in southern refugia during the cold phases of the Pleistocene, and expanded northwards during warming. These processes caused genetic imprints, such as a differentiation of genetic lineages and a loss of genetic diversity in the wake of (re)colonization. We used molecular markers and species distribution models (SDMs) to study the impact of range dynamics on the common wall lizard, Podarcis muralis, from southern refugia to the northern range margin.

Location

Parts of the Western Palaearctic.

Methods

We genotyped 10 polymorphic microsatellites in 282 individuals of P. muralis and sequenced the mitochondrial DNA (mtDNA) cytochrome b gene to study the genetic structure, divergence times and ancestral distributions. Furthermore, we generated SDMs for climate scenarios for 6 and 21 ka derived from two different global circulation models.

Results

We detected two major mtDNA lineages – a western France clade (Pyrenees to Brittany), and an eastern France clade (southern France to Germany, Belgium and Luxembourg). This split was dated to c. 1.23 Ma. The latter clade was divided into two subclades, which diverged c. 0.38 Ma. Genetic diversity of microsatellites within each clade was nested and showed a significant loss of genetic diversity from south to north, a strong pattern of allele surfing across nearly all loci, and an increase in genetic differentiation towards the northern range margin. Results from SDMs suggest that southward range retraction during the late glacial period split the distribution into geographically distinct refugia.

Main conclusions

The strong genetic differentiation mirrors the effects of long‐term isolation of P. muralis in multiple refugia. Post‐glacial recolonization of Northern Europe has taken place from two distinct refugia, most probably along river systems (Rhône, Rhine, Moselle) and along the Atlantic coastline, with subsequent nested elimination of genetic diversity and increasing genetic differentiation at the northern range margin.
Long‐term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients
Authors: López Esther , Berna‐Erro Alejandro , Bermejo Nuria , Brull José María , Martinez Rocío , Garcia Pino Guadalupe , Alvarado Raul , Salido Ginés María , Rosado Juan Antonio , Cubero Juan José , Redondo Pedro Cosme
Published: April 2013

The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti‐calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long‐term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura‐2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time‐dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long‐term administration of rapamycin to kidney transplant patients evokes alteration in platelet function.
Managing anticoagulation for atrial fibrillation: current issues and future strategies
Authors: John Camm A.
Published: April 2013

Although warfarin is superior to aspirin in reducing the risk of stroke in patients with atrial fibrillation, it can increase major bleeds. Hence, physicians stratify patients according to stroke risk to ensure a net benefit. In this review, the CHA2DS2‐VASc stratification scheme used in the latest European Society of Cardiology (2010/12) guidelines will be explained. The greater sensitivity of this scheme, compared to the previous CHADS2, more closely delineates patients for whom warfarin is appropriate. The review also anticipates that there will be a wider range of patients who may benefit from the new oral anticoagulants, which show similar or superior efficacy and/or safety to warfarin with a significant reduction in intracranial haemorrhage and do not require routine coagulation monitoring. The role of conventional and new anticoagulant options will also be discussed.
Relationship between vitamin D status and left ventricular geometry in a healthy population: results from the Baltimore Longitudinal Study of Aging
Authors: Ameri P. , Canepa M. , Milaneschi Y. , Spallarossa P. , Leoncini G. , Giallauria F. , Strait J. B. , Lakatta E. G. , Brunelli C. , Murialdo G. , Ferrucci L.
Published: April 2013

Objectives

The effects of vitamin D on the heart have been studied in patients with cardiac disease, but not in healthy persons. We investigated the relation between vitamin D status and left ventricular (LV) structure and function in community‐dwelling subjects without heart disease.

Design

The relationship between concentrations of 25‐hydroxyvitamin D [25(OH)D], a marker of vitamin D reserve, and LV transthoracic echocardiography measures was analysed in 711 participants in the Baltimore Longitudinal Study of Aging who were without cardiac disease.

Results

Mean 25(OH)D in the study population was 32.3 ± 11.4 ng mL−1; only 15.5% of subjects had moderate or severe vitamin D deficiency [25(OH)D < 20 ng mL−1]. Adjusting for age, body mass index, cardiovascular disease risk factors, physical activity, calcium and parathyroid hormone, 25(OH)D was positively correlated with LV thickness (β 0.095, SE 0.039, P < 0.05) and LV mass index (β 7.5, SE 2.6, P < 0.01). A significant nonlinear relation between 25(OH)D and LV concentric remodelling was observed. LV remodelling was more likely in participants with 25(OH)D levels <30 ng mL−1 [odds ratio (OR) 1.24; 95% confidence interval (CI) 0.83–1.85] or ≥38 ng mL−1 (OR 1.73; 95% CI 1.13–2.65), compared with those with 30–37 ng mL−1 25(OH)D. Consistently, LV relative wall thickness was significantly lower (P for trend=0.05), and LV diastolic internal diameter index (P for trend<0.05) and end‐diastolic volume index (P for trend<0.05) were significantly higher in subjects with 30–37 ng mL−1 25(OH)D compared to the rest of the study population. There was a significant interaction between 25(OH)D and hypertension on the risk of LV hypertrophy (P < 0.05).

Conclusions

In a population‐based sample of predominantly vitamin D‐sufficient subjects without heart disease, LV geometry was most favourable at intermediate 25(OH)D concentrations.
Determinants of HbA1c in nondiabetic Dutch adults: genetic loci and clinical and lifestyle parameters, and their interactions in the lifelines cohort study
Authors: Jansen H. , Stolk R. P. , Nolte I. M. , Kema I. P. , Wolffenbuttel B. H. R. , Snieder H.
Published: April 2013

Objectives

Glycated haemoglobin (HbA1c) is associated with cardiovascular disease risk in individuals without diabetes, and its use has been recommended for diagnosing diabetes. Therefore, it is important to gain further understanding of the determinants of HbA1c. The aim of this study was to investigate the effects of genetic loci and clinical and lifestyle parameters, and their interactions, on HbA1c in nondiabetic adults.

Design

Population‐based cohort study.

Setting

Three northern provinces of the Netherlands.

Subjects

A total of 2921 nondiabetic adults participating in the population‐based LifeLines Cohort Study.

Measurements

Body mass index (BMI), waist circumference, HbA1c, fasting plasma glucose (FPG) and erythrocyte indices were measured. Data on current smoking and alcohol consumption were collected through questionnaires. Genome‐wide genotyping was performed, and 12 previously identified single‐nucleotide polymorphisms (SNPs) were selected for replication and categorized as ‘glycaemic’ and ‘nonglycaemic’ SNPs according to their presumed mechanism(s) of action on HbA1c. Genetic risk scores (GRSs) were calculated as the sum of the weighted effect of HbA1c‐increasing alleles.

Results

Age, gender, BMI, FPG, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, current smoking and alcohol consumption were independent predictors of HbA1c, together explaining 26.2% of the variance in HbA1c, with FPG contributing 10.9%. We replicated three of the previously identified SNPs and the GRSs were also found to be independently associated with HbA1c. We found a smaller effect of the ‘nonglycaemic GRS' in females compared with males and an attenuation of the effect of the GRS of all 12 SNPs with increasing BMI.

Conclusions

Our results suggest that a substantial portion of HbA1c is determined by nonglycaemic factors. This should be taken into account when considering the use of HbA1c as a diagnostic test for diabetes.
Association between CD8+ T‐cell subsets and cardiovascular disease
Authors: Kolbus D. , Ljungcrantz I. , Andersson L. , Hedblad B. , Fredrikson G. N. , Björkbacka H. , Nilsson J.
Published: April 2013

Background

The findings of experimental studies suggest that the immune system plays a key role in atherosclerosis, but the clinical importance of different immune cells in cardiovascular disease remains poorly characterized. In this study we investigated the association between CD8+ T cells and carotid disease as well as development of cardiovascular disease events.

Methods

The study cohort comprised 700 subjects from the cardiovascular arm of the Malmö Diet and Cancer Study. Peripheral blood mononuclear cells, obtained at the 1991–1994 baseline investigation and stored at −140 °C, were thawed and the different CD8+ T‐cell populations analysed by flow cytometry. Baseline carotid intima–media thickness and stenosis were assessed by ultrasonography and clinical events were monitored through validated national registers.

Results

Subjects with a high fraction of CD8+ T cells were characterized by decreased cytokine release from activated leucocytes, metabolic signs of insulin resistance and increased incidence of coronary events; hazard ratios (95% confidence intervals) for the second and third tertiles of CD8+ T cells were 2.57 (1.16, 5.67) and 2.61 (1.19, 5,71), respectively, in a Cox proportional hazards regression model. Correlations were found between the fraction of CD8+CD25+ T cells and the degree of carotid stenosis (r = 0.11, P < 0.01), and between the CD8+CD56−IFN‐γ+ T‐cell fraction and the degree of stenosis (r = −0.18, P < 0.005). The association between CD8+CD56−IFN‐γ+ T cells and carotid stenosis remained significant after controlling for major cardiovascular disease risk factors.

Conclusion

This study provides prospective clinical evidence for a role of CD8+ T cells in cardiovascular disease and suggests the existence of CD8+ T‐cell subsets with different pathological functions.
Improvements in logistics could increase survival after out‐of‐hospital cardiac arrest in Sweden
Authors: Strömsöe A. , Afzelius S. , Axelsson C. , Södersved Källestedt M. L. , Enlund M. , Svensson L. , Herlitz J.
Published: April 2013

Objectives

In a review based on estimations and assumptions, to report the estimated number of survivors after out‐of‐hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden.

Design

An observational study.

Setting

All ambulance organisations in Sweden.

Subjects

Patients included in the Swedish Cardiac Arrest Registry who suffered an OHCA between January 1, 2008 and December 31, 2010. Approximately 80% of OHCA cases in Sweden in which CPR was started are included.

Interventions

None

Results

In 11 005 patients, the 1‐month survival rate was 9.4%. There are approximately 5000 OHCA cases annually in which CPR is started and 30‐day survival is achieved in up to 500 patients yearly (6 per 100 000 inhabitants). Based on findings on survival in relation to the time to calling for the Emergency Medical Service (EMS) and the start of CPR and defibrillation, it was estimated that, if the delay from collapse to (i) calling EMS, (ii) the start of CPR, and (iii) the time to defibrillation were reduced to <2 min, <2 min, and <8 min, respectively, 300–400 additional lives could be saved.

Conclusion

Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300–400 additional OHCA patients yearly (4 per 100 000 inhabitants) could be saved in Sweden.
A prospective randomized toxicity study to compare reduced‐intensity and myeloablative conditioning in patients with myeloid leukaemia undergoing allogeneic haematopoietic stem cell transplantation
Authors: Ringdén O. , Erkers T. , Aschan J. , Garming‐Legert K. , Le Blanc K. , Hägglund H. , Omazic B. , Svenberg P. , Dahllöf G. , Mattsson J. , Ljungman P. , Remberger M.
Published: April 2013

Background

To our knowledge, no randomized toxicity studies have been conducted to compare myeloablative conditioning (MAC) and reduced‐intensity conditioning (RIC) in allogeneic haematopoietic stem cell transplantation (HSCT).

Methods

Adult patients ≤60 years of age with myeloid leukaemia were randomly assigned (1 : 1) to treatment with RIC (n = 18) or MAC (n = 19) in this Phase II single‐centre toxicity study.

Results

There was a maximum median mucositis grade of 1 in the RIC group compared with 4 in the MAC group (P < 0.001). Haemorrhagic cystitis occurred in eight of the patients in the MAC group and none in the RIC group (P < 0.01). Results of renal and hepatic tests did not differ significantly between the two groups. RIC‐treated patients had faster platelet engraftment (P < 0.01) and required fewer erythrocyte and platelet transfusions (P < 0.001) and less total parenteral nutrition (TPN) than those treated with MAC (P < 0.01). Cytomegalovirus (CMV) infection was more common in the MAC group (14/19) than in the RIC group (6/18) (P = 0.02). Donor chimerism was similar in the two groups with regard to CD19 and CD33, but was delayed for CD3 in the RIC group. Five‐year transplant‐related mortality (TRM) was approximately 11% in both groups, and rates of relapse and survival were not significantly different. Patients in the MAC group with intermediate cytogenetic acute myeloid leukaemia had a 3‐year survival of 73%, compared with 90% among those in the RIC group.

Conclusion

Reduced‐intensity conditioning had several advantages compared with MAC, including less mucositis, less haemorrhagic cystitis, faster platelet engraftment, the need for fewer transfusions and less TPN, and fewer CMV infections. Both regimens were tolerated and TRM was low.
Low blood pressure and antihypertensive treatment are independently associated with physical and mental health status in patients with arterial disease: the SMART study
Authors: Muller M. , Jochemsen H. M. , Visseren F. L. J. , Grool A. M. , Launer L. J. , van der Graaf Y. , Geerlings M. I. ,   The SMART‐study group
Published: April 2013

Objective

To investigate the independent effects of antihypertensive treatment and blood pressure (BP) levels on physical and mental health status in patients with arterial disease.

Design and setting

Cross‐sectional analyses were conducted within the single‐centre Secondary Manifestations of ARTerial disease (SMART) study, in a hospital care setting.

Subjects

A total of 5877 patients (mean age 57 years) with symptomatic and asymptomatic arterial disease underwent standardized vascular screening.

Main outcome measure

The primary outcome was self‐rated physical and mental health assessed using the 36‐item short‐form health survey.

Results

In the total population, antihypertensive drug use and increased intensity of antihypertensive treatment were associated with poorer health status independent of important confounders including BP levels; adjusted mean differences [95% confidence interval (CI)] in physical and mental health between n = 0 and n ≥ 3 antihypertensives were −1.2 (−2.1; −0.3) and −3.5 (−4.4; −2.6), respectively. Furthermore, both lower systolic and lower diastolic BP levels were related to poorer physical and mental health status independent of antihypertensive treatment. Mean differences (95% CI) in physical and mental health status per SD decrease in systolic BP were −0.56 (−0.84; −0.27) and −0.32 (−0.61; −0.03) and per SD decrease in diastolic BP were −0.50 (−0.78; −0.23) and −0.08 (−0.36; 0.20), respectively. The association between low BP and poor health status was particularly present in patients with coronary artery disease.

Conclusions

In a population of patients with asymptomatic and symptomatic arterial disease, antihypertensive treatment and lower BP levels are independently associated with poorer self‐rated physical and mental health. These findings suggest that different underlying mechanisms may explain these independent associations.
Exploring the experience of Canadian registered psychiatric nurses: a phenomenological study
Authors: Jackson J. , Morrissette P. J.
Published: April 2013

Accessible summary

This study was undertaken to explore the experience of registered psychiatric nurses in the province of Manitoba, Canada.

Results of this study revealed six predominant themes including how psychiatric nursing is perceived by the public and allied professionals, the aggressive behaviour and management of patients, the involvement of family members regarding the care of their loved ones, the relationship between physicians and psychiatric nurses, the sense of responsibility and worry associated with psychiatric nursing, and the gradual shift in educational standards and movement towards traditional medical intervention.

Results from this study can benefit patients, psychiatric nurses, and psychiatric nurse educators.

This paper describes a phenomenological study that was conducted in 2012 and investigated the experiences of registered psychiatric nurses working in the province of Manitoba. Ten registered psychiatric nurses participated in semistructured, audio‐recorded interviews, during which they described their experiences, yielding written protocols that were thematically analysed. Results from this study revealed six predominant themes that included (1) perception of psychiatric nursing; (2) patient aggression; (3) patient family involvement; (4) nurse–doctor relationship; (5) responsibility and worry; and (6) shift in practice and educational standards. The results of this study can assist in better understanding registered psychiatric nursing practice, inform educational programmes, and spawn future research.
Credential Effects and the Returns to Education in China
Authors: Xiu Lin , Gunderson Morley
Published: April 2013

Using the China Household Income Project (CHIP) data for 1995 and 2002, we examine the returns to education in China, separating out credential effects from pure years‐of‐schooling effects. The results are broadly consistent with the implications of China moving towards a market‐oriented economy: increasing returns to education where both years of schooling and credentials from completing key phases are rewarded; a decline in the importance of credentials as firms have more discretion to select the best‐suited employees irrespective of their credentials; more emphasis on credentials in the state sector; less emphasis on credentials for long‐tenured employees for whom the employer has more opportunity to assess productivity without relying on credentials; and a greater importance of credentials for females for whom the value of such signals may be more important.
Unrelated viral suppressors of RNA silencing mediate the control of ARGONAUTE1 level
Authors: Várallyay Éva , Havelda Zoltán
Published: April 2013

Various plant viruses ubiquitously mediate the induction of miR168, resulting in the control of ARGONAUTE 1 (AGO1), which is the pivotal component of the microRNA (miRNA) regulation pathway and can also exhibit antiviral function. Here, we demonstrate that miR168‐driven control of AGO1 can persist for a long time in virus‐infected plants and can be an important component of symptom development. We also show that infection of RNA viruses belonging to various genera is associated with the transcriptional induction of the MIR168 precursor gene. Moreover, in a transient expression study, we reveal that different unrelated viral suppressors of RNA silencing (VSRs) are responsible for the enhanced accumulation of miR168. The induction of miR168 accumulation is an early function of VSRs and this activity is associated with the control of the endogenous AGO1 protein level. The common ability of unrelated VSRs to induce the miR168 level implies that this activity might be a component of the host defence suppression in plant–virus interactions.
Arabidopsis phospholipase Dβ1 modulates defense responses to bacterial and fungal pathogens
Authors: Zhao Jian , Devaiah Shivakumar P. , Wang Cunxi , Li Maoyin , Welti Ruth , Wang Xuemin
Published: April 2013

Pathogen infection of higher plants often induces rapid production of phosphatidic acid (PA) and changes in lipid profiles, but the enzymatic basis and the function of the lipid change in pathogen–plant interactions are not well understood.

Infection of phospholipase D β1 (PLDβ1)‐deficient plants by Pseudomonas syringae tomato pv DC3000 (Pst DC30000) resulted in less bacterial growth than in wild‐type plants, and the effect was more profound in virulent Pst DC3000 than avirulent Pst DC3000 (carrying the avirulence gene avrRpt2) infection. The expression levels of salicylic acid (SA)‐inducible genes were higher, but those inducible by jasmonic acid (JA) showed lower expression in PLDβ1 mutants than in wild‐type plants.

However, PLDβ1‐deficient plants were more susceptible than wild‐type plants to the fungus Botrytis cinerea. The PLDβ1‐deficient plants had lower levels of PA, JA and JA‐related defense gene expression after B. cinerea inoculation.

PLDβ1 plays a positive role in pathogen‐induced JA production and plant resistance to the necrotrophic fungal pathogen B. cinerea, but a negative role in the SA‐dependent signaling pathway and plant tolerance to infection with biotrophic Pst DC3000. PLDβ1 is responsible for most of the increase in PA production in response to necrotrophic B. cinerea and virulent Pst DC3000 infection, but contributes less to avirulent Pst DC3000 (avrRpt2)‐induced PA production.
A systematic review of physical activity levels in Native American populations in Canada and the United States in the last 50 years
Authors: Foulds H. J. A. , Warburton D. E. R. , Bredin S. S. D.
Published: April 2013

Physical activity is beneficial for many chronic conditions. However, activity levels of Native Americans are not well known. This systematic review investigated if Native American populations achieve the recommended physical activity levels, compared current and past activity levels, and assessed the ability of exercise training programmes to improve health outcomes among this population. Electronic databases (e.g. MEDLINE, EMBASE) were searched and citations were cross‐referenced. Included articles reported physical activity levels or investigations among Native Americans. This search identified 89 articles: self‐report (n = 61), accelerometry and pedometry (n = 10), metabolic monitoring (n = 10) and physical activity interventions (n = 17). Few adults were found to meet the physical activity recommendations (27.2% [95% confidence interval = 26.9–27.5%] self‐report, 9% [4–14%] accelerometry). Among children/youth, 26.5% (24.6–28.4%) (self‐report) to 45.7% (42.3–49.1%) (pedometry/accelerometry) met the recommendations. Adults and children/youth were generally identified as physically inactive (via doubly labelled water). Overall, Native American adults reported lower activity levels since 2000, compared to 1990s, although similar to 1980s. Few physical activity interventions employed strong methodologies, large sample sizes and objective outcome measures. There is a clear need to increase Native American populations' physical activity. Additional research is required to evaluate exercise training programmes among this population.
Bronchial allergen provocation: A useful method to assess the efficacy of specific immunotherapy in children
Authors: Rosewich Martin , Arendt Sonja , El Moussaoui Samir , Schulze Johannes , Schubert Ralf , Zielen Stefan
Published: April 2013

Background

The clinical efficacy of subcutaneous allergen‐specific immunotherapy (SCIT) varies between patients. New preparations are under development, and an objective tool with which to evaluate their efficacies in individual patients has become necessary. Our primary research question is whether bronchial allergen provocation (BAP) can be used to assess the efficacy of SCIT.

Methods

In 42 house dust mite (HDM) allergic children (average age: 8.6 yr) with asthma, we analysed the clinical and objective improvements of a standardised HDM allergoid. All patients underwent two BAPs, one before SCIT and another 1 yr after SCIT. Fourteen patients who were recommended but chose not to undergo SCIT represented the control group. The total and specific IgE were analysed before SCIT; in addition, after SCIT, specific IgG and IgG4 were analysed.

Results

After SCIT, the patients' allergen‐specific bronchial hyper‐reactivity (BHR) was significantly improved; specifically, their PD20FEV1 was 34.4 AU before and 63.3 AU after SCIT (p < 0.01). The PD20FEV1 of the control group remained unchanged. Although BHR improved significantly in the treatment group, we were able to differentiate between the responders (n = 17, 60.7%) and non‐responders (n = 11, no improvement in BAP). The patients in both groups stated that SCIT had led to a subjective improvement in their symptoms, in contrast to the untreated control group, but only the responders required less medication after SCIT (p < 0.01).

Conclusions

After 1 yr of SCIT against HDM, 60.7% of the patients observed in this study exhibited significant improvements, as defined by BAP. However, BAP was also able to identify the non‐responders to treatment. Thus, BAP is a useful and objective method of estimating the effectiveness of SCIT and is not influenced by a placebo effect.
The psychosocial impact of an activity holiday for young children with severe food allergy: a longitudinal study
Authors: Knibb Rebecca C. , Hourihane Jonathan O'B.
Published: April 2013

Background

Food allergy has been shown to severely affect quality of life (QoL) in children and their families. The Anaphylaxis Campaign UK supports families with allergic children and as part of that support ran an activity holiday for those with food allergy. This study investigated the effectiveness of this activity holiday for reducing anxiety and improving QoL and food allergy management for these children.

Methods

Measures were taken at baseline, at the start of the activity holiday, at the end of the holiday, at 3 and 6 months follow‐up. Children (n = 24) completed a paediatric food allergy–specific QoL questionnaire (PFA‐QL), a generic QoL questionnaire (PedsQL™), the Spence Children's Anxiety Scale (SCAS) and the Children's Health Locus of Control (CHLC) scale at all stages of the study.

Results

There were significant improvements in social QoL, food allergy–specific QoL, total CHLC and internal locus of control scores over time (p > 0.05). There were significant decreases in powerful others locus of control, total anxiety and obsessive compulsive disorder scores (p < 0.05). Greater anxiety significantly correlated with poorer QoL at all time points; no correlations with locus of control were significant at the 3‐ and 6‐month follow‐up.

Conclusions

The activity holiday was of significant benefit to the children who took part, providing support for the need for activity holidays such as this for children with severe food allergy. Ways in which adaptive locus of control and improved quality of life can be facilitated need to be further explored.
Ultraviolet Germicidal Irradiation: Future Directions for Air Disinfection and Building Applications
Authors: Miller Shelly L. , Linnes Jacqueline , Luongo Julia
Published: April 2013

Ultraviolet germicidal irradiation (UVGI) for air disinfection applications has relied on low‐pressure mercury vapor lamps for decades. New design requirements have generated the need for alternatives in some uses. This study describes the current state ofUVGItechnology and describes future directions for technology development, including the use of lamps produced from nontoxic materials and light‐emitting diode lamps. Important applications are discussed such as the use of ultraviolet germicidal lamps in developing countries, in heating, ventilating and air‐conditioning systems to improve energy efficiency and indoor air quality, and for whole room disinfection.
Separating mismatch negativity (MMN) response from auditory obligatory brain responses in school‐aged children
Authors: Lohvansuu Kaisa , Hämäläinen Jarmo A. , Tanskanen Annika , Bartling Jürgen , Bruder Jennifer , Honbolygó Ferenc , Schulte‐Körne Gerd , Démonet Jean‐Francois , Csépe Valéria , Leppänen Paavo H. T.
Published: April 2013

Mismatch negativity (MMN) overlaps with other auditory event‐related potential (ERP) components. We examined the ERPs of 50 9‐ to 11‐year‐old children for vowels /i/, /y/ and equivalent complex tones. The goal was to separate MMN from obligatory ERP components using principal component analysis and equal probability control condition. In addition to the contrast of the deviant minus standard response, we employed the contrast of the deviant minus control response, to see whether the obligatory processing contributes to MMN in children. When looking for differences in speech deviant minus standard contrast, MMN starts around 112 ms. However, when both contrasts are examined, MMN emerges for speech at 160 ms whereas for nonspeech MMN is observed at 112 ms regardless of contrast. We argue that this discriminative response to speech stimuli at 112 ms is obligatory in nature rather than reflecting change detection processing.
Economic Insecurity in Transition: A Primary Commodities Perspective
Authors: Ivlevs Artjoms
Published: April 2013

This paper studies the individual and household‐level determinants of economic insecurity in post‐socialist countries. Exploring subjective, backward‐ and forward‐looking measures of economic insecurity, the paper focuses on: (1) the perceptions of past affordability of primary commodities; and (2) worries about their consumption in the future. We find that low affordability of primary commodities and big worries about their future consumption are experienced by rural residents, people with poor health, and households headed by females, less‐educated, and unemployed persons. In addition, low affordability is reported by people with low incomes and non‐Russian ethnic minorities, while high affordability is reported by people for whom remittances are the main source of income. Worries about primary commodities are more prevalent among “younger” households, big‐city dwellers and people receiving moderate amounts of remittances. People who have experienced lower affordability of primary commodities in the recent past report higher worries about their consumption in the future.
Formation and preservation of an overstepped segmented lagoon complex on a high‐energy continental shelf
Authors: Green Andrew N. , Cooper J. Andrew G. , Leuci Rio , Thackeray Zane
Published: April 2013

The duration of shoreline occupation at a given sea‐level, coastal response to sea‐level change and the controls on preservation of various shoreline elements can be recognized by detailed examination of submerged shorelines on the continental shelf. Using bathymetric and seismic observations, this article documents the evolution and preservation of an incised valley and lithified barrier complex between −65 m and −50 m mean sea‐level on a wave‐dominated continental shelf. The barrier complex is preserved as a series of aeolianite or beachrock ridges backed by laterally extensive back‐barrier sediments. The ridges include prograded cuspate lagoonal shoreline features similar to those found in contemporary lagoons. The incised valley trends shore‐parallel behind the barrier complex and records an early phase of valley filling, followed by a phase of extensive lagoonal sedimentation beyond the margins of the incised bedrock valley. Sea‐level stability at the outer barrier position (ca −65 m) enabled accumulation of a substantial coastal barrier that remained intact during a phase of subsequent slow sea‐level rise to −58 m when the lagoon formed. These lagoonal sediments are stripped seawards by bay ravinement processes which caused the formation of several prograded marginal cuspate features. An abrupt rise in sea‐level to −40 m, correlated with melt‐water pulse 1B, enabled the preservation of thick lagoonal sediments at the top of the incised valley fill and preservation on the sea bed of the cemented core of the barriers. This situation is unique to subtropical coastlines where early diagenesis is possible. The overlying sandy sediment from the uncemented upper portion of the barriers is dispersed by ravinement, partly burying the ridges and protecting the underlying sediments. The high degree of barrier or shoreline preservation is attributed to rapid overstepping of the shoreline, early cementation in favourable climatic conditions and the protection of the barrier cores by sand sheet draping.
Quantitation of fetomaternal haemorrhage and F cells in unusual maternal blood samples by flow cytometry using anti‐D and anti‐HbF
Authors: Kumpel B. M. , MacDonald A. P. , Bishop D. R. , Yates A. F. , Lee E.
Published: April 2013

Background

Fetomaternal haemorrhage (FMH) assessment by the Kleihauer–Betke test (KBT) is rapid but semi‐quantitative and liable to false positive results.

Objectives

To compare FMH estimated by KBT with flow cytometry (FC) quantitation for 37 patients with massive FMH, obstetric risk factors or technical problems.

Methods

Maternal blood was sent for analysis by FC after KBT. A variety of reagents including anti‐haemoglobin F (HbF), anti‐D and combined anti‐HbF/anti‐carbonic anhydrase (CA) were used.

Results

Eight cases of massive FMH (>100 mL fetal cells) causing fetal death or severe neonatal anaemia in late gestation were confirmed by FC. Anti‐HbF FC identified maternal F cells and fetal cells. In some cases these red cell populations merged but they could be differentiated by anti‐CA, labelling F cells only. Using KBT, false positive FMH results were obtained for 12 patients, who had strongly stained cells that were then shown by FC to be maternal F cells. All these patients had increased F cells (>5% of total red cells) whereas only 16% of patients with FMH and 22% of donors had elevated F cells. In contrast, anti‐D FC was simple and rapid, quantitating D‐positive FMH in all 15 D‐negative patients except one with massive FMH of weak D fetal cells. Leucocytes in four samples bound anti‐D, variably, giving erroneously high FMH, but they could be eliminated from FC analysis using combined anti‐D/anti‐CD45.

Conclusion

FMH quantitation using anti‐D by FC is suitable for the majority of maternal samples and could enable accurate targeted dosing of anti‐D prophylaxis.
Blood group typing in five Afghan populations in the North Hindu‐Kush region: implications for blood transfusion practice
Authors: Mazières S. , Temory S. A. , Vasseur H. , Gallian P. , Di Cristofaro J. , Chiaroni J.
Published: April 2013

Background and Objectives

Blood incompatibility arises from individual and ethnic differences in red blood cell (RBC) antigen profiles. This underlines the importance of documenting RBC antigen variability in various ethnic groups. Central Asia is an area with a long and complex migratory history. The purpose of this article is to describe key antigen frequencies of Afghan ethnic groups in the Hindu‐Kush region of Afghanistan as a basis for improving blood transfusion practices in that area.

Materials and Methods

The key ABO, Rh and Kell antigens were investigated in five Afghan populations. In order to depict accurately the blood group gene diversity in the area, DNA from eight additional Pakistani populations were included, and the entire sample set screened using two multiplex polymerase chain reactions sensitive for 17 alleles in 10 blood group genetic systems (MNS, Kell, Duffy, Kidd, Cartwright, Dombrock, Indian, Colton, Diego and Landsteiner–Wiener).

Results

Phenotype and allele frequencies fell within the ranges observed in Western European and East Asian populations. Occurrence of DI*01, IN*01, LW*07 and FY*02N.01 and prevalence of ABO*B were consistent with migratory history as well as with putative environmental adaptation in the subtropical environment Hindu‐Kush region.

Conclusion

These findings expand the current knowledge about key antigen frequencies. Regarding occurrence of viral markers, further blood transfusion in the region requires rigorous typing.
A local regulatory network around threeNACtranscription factors in stress responses and senescence inArabidopsis leaves
Authors: Hickman Richard , Hill Claire , Penfold Christopher A. , Breeze Emily , Bowden Laura , Moore Jonathan D. , Zhang Peijun , Jackson Alison , Cooke Emma , Bewicke‐Copley Findlay , Mead Andrew , Beynon Jim , Wild David L. , Denby Katherine J. , Ott Sascha , Buchanan‐Wollaston Vicky
Published: April 2013

A model is presented describing the gene regulatory network surrounding three similarNACtranscription factors that have roles in Arabidopsis leaf senescence and stress responses.ANAC019,ANAC055andANAC072belong to the same clade ofNACdomain genes and have overlapping expression patterns. A combination of promoterDNA/protein interactions identified using yeast 1‐hybrid analysis and modelling using gene expression time course data has been applied to predict the regulatory network upstream of these genes. Similarities and divergence in regulation during a variety of stress responses are predicted by different combinations of upstream transcription factors binding and also by the modelling. Mutant analysis with potential upstream genes was used to test and confirm some of the predicted interactions. Gene expression analysis in mutants ofANAC019andANAC055at different times during leaf senescence has revealed a distinctly different role for each of these genes. Yeast 1‐hybrid analysis is shown to be a valuable tool that can distinguish clades of binding proteins and be used to test and quantify protein binding to predicted promoter motifs.
Application of Kriging and Radial Basis Function for Reliability Optimization in Power Modules
Authors: Rajaguru Pushparajah , Stoyanov Stoyan , Lu Hua , Bailey Chris
Published: April 2013

This paper discusses the design for reliability of a wire bond structure in a power electronic module based on computational approach that integrates methods for high fidelity analysis, reduced order modeling, numerical risk analysis, and optimization. This methodology is demonstrated on a wire bond structure in a power electronic module with the aim of reducing the chance of failure due to the wire bond lift off in a power electronic module. In particular, wire bond reliability of the power module related to the thermal fatigue material degradation of aluminum wire is one of the main concerns. Understanding the performance, reliability, and robustness of wire bond is a key factor for the future development and success of the power electronic module technology. The main focus in this study is on the application of reduced order modeling techniques and the development of the associated models for fast design evaluation and analysis. The discussion is on methods for approximate response surface modeling based on interpolation techniques using Kriging and radial basis functions. The reduced order modeling approach uses prediction data for the electrothermomechanical behavior of the power module wire bond design obtained through nonlinear transient finite element simulations, in particular, for the fatigue lifetime of the aluminum wire attached to the silicon chip and the warpage (displacement) of the wire in the module. These reduced order models are used for the analysis of the effect of design uncertainties on the reliability of these advanced electronics modules. To assess the effect of uncertain design data, different methods for estimating the variation of reliability-related metrics of the wire bond model are researched and tested. Sample-based methods, such as full-scale Monte Carlo and Latin hypercube, and analytical approximate methods, such as first order second moment (FOSM) and point estimation method (PEM), are investigated, and their accuracy is compared. The optimization modeling analyzes the probabilistic nature of the reliability problem of the aluminum wire bond structures under investigation. Optimization tasks with design uncertainty are identified and solved using a particle swarm optimization algorithm. The probabilistic optimization deals with two different characteristic performance metrics of the design, the electrothermomechanical fatigue reliability of the aluminum wire attached to the chip and the thermally induced warpage of the wire in the module structure. The objective in this analysis is to ensure that the design has the required reliability and meets a number of additional requirements.
Computationally Assisted Identification of Functional Inorganic Materials
Authors: Dyer Matthew S. , Collins Christopher , Hodgeman Darren , Chater Philip A. , Demont Antoine , Romani Simon , Sayers Ruth , Thomas Michael F. , Claridge John B. , Darling George R. , Rosseinsky Matthew J.
Published: April 2013

Modules of Desire

Using computational methods to design materials with specific properties has found some limited success.

Dyer
et al.

(p.
847
, published online 11 April) have devised a method, based on extended module materials assembly, that combines chemical intuition and
ab initio
calculations starting from fragments or modules of structure types that show the desired functionality. The method was tested by identifying materials suitable for a solid oxide fuel cell cathode.
Wnt Stabilization of β-Catenin Reveals Principles for Morphogen Receptor-Scaffold Assemblies
Authors: Kim Sung-Eun , Huang He , Zhao Ming , Zhang Xinjun , Zhang Aili , Semonov Mikhail V. , MacDonald Bryan T. , Zhang Xiaowu , Abreu Jose Garcia , Peng Leilei , He Xi
Published: April 2013

Signal Scaffolds

Scaffolds in cellular signaling pathways are turning out to do way more than just hold proteins together in a complex.

Kim
et al.

(p.
867
, published online 11 April) showed the importance of the scaffold protein Axin as an active participant controlling the kinetics of activation of signaling through the pathways. Axin is part of two protein complexes that have opposing actions that may regulate the timing of signaling—either activating Wnt signaling, thus protecting β-catenin from destruction, or causing proteolytic destruction of β-catenin.

Rock
et al.

(p.
871
, published online 11 April) characterized the role of the scaffold protein Nud1 in the mitotic exit network and found that the kinase that produces the output from the signaling complex only interacts with a scaffold that is primed by its activator protein kinase, already bound to the scaffold and creating a docking site.
Genome Sequence of the Obligate Gammaproteobacterial Methanotroph Methylomicrobium album Strain BG8
Authors: Kits K. Dimitri , Kalyuzhnaya Marina G. , Klotz Martin G. , Jetten Mike S. M. , Op den Camp Huub J. M. , Vuilleumier Stéphane , Bringel Françoise , DiSpirito Alan A. , Murrell J. Colin , Bruce D. , Cheng J.-F. , Copeland A. , Goodwin Lynne , Hauser Loren , Lajus Aurélie , Land M. L. , Lapidus A. , Lucas S. , Médigue Claudine , Pitluck S. , Woyke Tanja , Zeytun A. , Stein Lisa Y.
Published: April 2013

The complete genome sequence of
Methylomicrobium album
strain BG8, a methane-oxidizing gammaproteobacterium isolated from freshwater, is reported. Aside from a conserved inventory of genes for growth on single-carbon compounds,
M. album
BG8 carries a range of gene inventories for additional carbon and nitrogen transformations but no genes for growth on multicarbon substrates or for N fixation.
Gitelman syndrome
Authors: Cotovio Patricia , Silva Cristina , Oliveira Nuno , Costa Fátima
Published: April 2013

Hypokalaemia is a common clinical disorder, the cause of which can usually be determined by the patient's clinical history. Gitelman syndrome is an inherited tubulopathy that must be considered in some settings of hypokalaemia. We present the case of a 60-year-old male patient referred to our nephrology department for persistent hypokalaemia. Clinical history was positive for symptoms of orthostatic hypotension and polyuria. There was no history of drugs consumption other than potassium supplements. Complementary evaluation revealed hypokalaemia (2.15 mmol/l), hypomagnesaemia (0.29 mmol/l), metabolic alkalosis (pH 7.535, bicarbonate 34.1 mmol/l), hypereninaemia (281.7 U/ml), increased chloride (160 mmol/l) and sodium (126 mmol/l) urinary excretion and reduced urinary calcium excretion (0.73 mmol/l). Renal function, remainder serum and urinary ionogram, and renal ultrasound were normal. A diagnosis of Gitelman syndrome was established. We reinforced oral supplementation with potassium chloride and magnesium sulfate. Serum potassium stabilised around 3 mmol/l. The aim of our article is to remind Gitelman syndrome in the differential diagnosis of persistent hypokalaemia.
Survey of UK histopathologists’ approach to the reporting of resection specimens for carcinomas of the pancreatic head
Authors: Feakins Roger , Campbell Fiona , Verbeke Caroline S
Published: April 2013

To assess UK histopathologists’ approach to reporting resection specimens for carcinomas of the pancreatic head. Questions were asked using an online survey service. The responses revealed considerable variation in dissection and sampling procedures, interpretation of histology, and the structure of services in the UK. Assessment of resection margins was a notable area of inconsistency. Information in guidelines and better support for some centres could help reduce the observed differences in practice.
Imprisonment for non-intentional transmission of HIV: can it be supported using established principles for justifying criminal sentencing?
Authors: Phillips Matthew , Sukthankar Ashish
Published: April 2013

In England, Wales and Scotland, those who unintentionally transmit HIV through sexual intercourse are at risk of criminal prosecution, and furthermore may be at risk of imprisonment under the Offences Against the Person Act 1861. These sentences have ranged between 1 and 10 years. There has been a long debate on whether this is an acceptable use of the law, and indeed whether those who transmit HIV in this manner should be subjected to legal proceedings. Previous debate has embraced the rhetoric of shared responsibility and public health. In this paper, we wished instead to apply traditional justifications for sentencing (including retribution, deterrence, rehabilitation, incapacitation and reparation) to imprisonment for non-intentional transmission of HIV through consensual sexual intercourse. We argue that when these principles are applied to imprisonment for this ‘crime’, we are unable to justify imprisonment sufficiently, and therefore, that imprisonment is a misguided response to HIV transmission.