bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Change in Aging: Identifying Gene–Environment Correlation and Nonshared Environment Mechanisms
Authors: Deater-Deckard Kirby , Mayr Ulrich
Published: June 2011

We describe gene–environment processes that may help account for individual differences in successful aging. Our emphasis is on successful aging in the cognitive domain, wherein individuals come to use a variety of strategies to cope with changes in cognitive capacities. We focus on the role of executive control in particular and define gene–environment correlation and nonshared environmental mechanisms. The quantitative genetic methods used to identify these mechanisms are described, with examples from research in childhood, where such studies are now common. Future work will be most effective if it is guided by life-span development frameworks that address these processes, such as the developmental genotype→environment theory of Scarr and McCartney and the selection/optimization/compensation theory of Baltes and Baltes.
Media Portrayals and Health Inequalities: A Case Study of Characterizations of Gene × Environment Interactions
Authors: Horwitz Allan V.
Published: June 2011

Objectives. This article examines how genetic and environmental interactions associated with health inequalities are constructed and framed in the presentation of scientific research.

Methods. It uses the example of a major article about depression in a longitudinal study of young adults that appeared in Science in 2003.

Results. This portrayal of findings related to health inequalities uses a genetic lens that privileges genetic influences and diminishes environmental ones.

Discussion. The emphasis on the genetic side of Gene × Environment interactions can serve to deflect attention away from the important impact of social inequalities on health.
The Health of U.S. Racial and Ethnic Populations
Authors: Williams David R.
Published: June 2011

This article provides an overview of racial and ethnic disparities in health in the United States. It describes limitations linked to the quality and method of presentation of the available data. It also considers the complex ways in which immigrant status, race, and SES combine to affect health and outlines important directions for research that would enhance our understanding of the ways in which social factors can lead to changes in health status.
Economic Status Over the Life Course and Racial Disparities in Health
Authors: Kahn Joan R. , Fazio Elena M.
Published: June 2011

Objectives. Racial and socioeconomic disparities in health have become a prominent feature of American society, though our understanding of the processes leading to such persistent disparities is still relatively limited. In this study, we focus on the impact of social and economic advantages and disadvantages over the life course on health disparities at older ages. In particular, we look at the roles of both cumulative and current financial resources and financial strains as determinants of a range of subjective and objective health assessments of physical conditions, functional impairment, and mental health.

Methods. Our data come from the 2001 Aging, Stress, and Health Study, which interviewed over 1,100 White and African American adults aged 65 years and older living in the Washington, D.C., metropolitan area.

Results and Discussion. Our results show that although racial and socioeconomic disparities in health do not follow a simple explanation, we do provide strong support for the fundamental importance of social and economic resources. Unlike previous studies that emphasize the role of financial resources such as income and wealth, we show that the lack of these resources, as indicated by high levels of financial strain, provides an important clue to how economic resources influence health.
Mental Health Disparities Across Education and Sex: A Prospective Analysis Examining How They Persist Over the Life Course
Authors: Miech Richard A. , Eaton William W. , Brennan Kathleen
Published: June 2011

Objectives. Higher levels of psychopathology among people with lower socioeconomic status and among women persist as cohorts age. In this analysis, we examine whether the persistence of these disparities as a cohort ages results from (a) a single set of people within a disadvantaged group who have chronic psychopathology or (b) continually changing sets of people within a disadvantaged group who have psychopathology of short duration.

Methods. Data for this analysis come from the Epidemiologic Catchment Area Study, which includes two psychological assessments (depressive syndrome and psychological distress) in a population sample of adults in Baltimore, Maryland, collected 13 years apart.

Results and Discussion. Results indicate that the persistence of disparities across education resulted primarily from one single set of respondents with chronic psychopathology over the 13 years of the survey, while the persistence of disparities across sex involved new sets of women as the cohort aged. We discuss implications of these results for theory and policy.
Association Mapping of Quantitative Resistance to Phaeosphaeria nodorum in Spring Wheat Landraces from the USDA National Small Grains Collection
Authors: Adhikari Tika B. , Jackson Eric W. , Gurung Suraj , Hansen Jana M. , Bonman J. Michael
Published: June 2011

Stagonospora nodorum blotch (SNB), caused by Phaeosphaeria nodorum, is a destructive disease of wheat (Triticum aestivum) found throughout the United States. Host resistance is the only economically feasible option for managing the disease; however, few SNB-resistant wheat cultivars are known to exist. In this study, we report findings from an association mapping (AM) of resistance to P. nodorum in 567 spring wheat landraces of diverse geographic origin. The accessions were evaluated for seedling resistance to P. nodorum in a greenhouse. Phenotypic data and 625 polymorphic diversity array technology (DArT) markers have been used for linkage disequilibrium (LD) and association analyses. The results showed that seven DArT markers on five chromosomes (2D, 3B, 5B, 6A, and 7A) were significantly associated with resistance to P. nodorum. Genetic regions on 2D, 3B, and 5B correspond to previously mapped quantitative trait loci (QTL) conferring resistance to P. nodorum whereas the remaining QTL appeared to be novel. These results demonstrate that the use of AM is an effective method for identifying new genomic regions associated with resistance to P. nodorum in spring wheat landraces. Additionally, the novel resistance found in this study could be useful in wheat breeding aimed at controlling SNB.
Stability and Fitness of Pyraclostrobin- and Boscalid-Resistant Phenotypes in Field Isolates of Botrytis cinerea from Apple
Authors: Kim Y. K. , Xiao C. L.
Published: June 2011

Phenotype stability, fitness, and competitive ability of pyraclostrobin- and boscalid-resistant isolates of Botrytis cinerea from apple were investigated. Stability of resistance was determined after consecutive transfers on potato dextrose agar (PDA) or being cycled on apple fruit. In vitro fitness components mycelial growth, osmotic sensitivity, conidial germination, and sporulation were evaluated on agar media. Pathogenicity, virulence and sporulation on apple fruit were evaluated at both 20 and 0°C. Competition between fungicide-resistant and -sensitive isolates on apple fruit also was evaluated. Resistance to the two fungicides was retained at levels similar to that of the initial generation after 20 and 10 transfers on PDA and five and three disease cycles on apple fruit at 20 and 0°C, respectively. Great variability in individual fitness components tested was observed among isolates within the same phenotype groups either sensitive or resistant to the fungicides but, when compared as phenotype groups, there were no significant differences in the mean values of these fitness components between resistant and sensitive phenotypes except that the phenotype resistant only to boscalid produced fewer conidia in vitro than sensitive isolates. Resistant isolates were as pathogenic and virulent on apple fruit as sensitive isolates. There was no significant correlation between the values of individual fitness components tested and the level of resistance to pyraclostrobin or boscalid, except that virulence at 20°C positively correlated with the level of resistance to the two fungicides. The final frequency of pyraclostrobin-resistant individuals in the populations was significantly decreased compared with the initial generation and no boscalid-resistant individuals were detected after four disease cycles on apple fruit inoculated with a pair mixture of a dual-sensitive isolate and one isolate each of the three phenotypes resistant to pyraclostrobin, boscalid, or both. The results suggest that resistance of B. cinerea to pyraclostrobin and boscalid was stable in the absence of the fungicides and that resistance to the two fungicides did not significantly impair individual fitness components tested. However, both pyraclostrobin- and boscalid-resistant isolates exhibited competitive disadvantage over the dual-sensitive isolate on apple fruit.
Genetic Differentiation at Microsatellite Loci Among Populations of Mycosphaerella graminicola from California, Indiana, Kansas, and North Dakota
Authors: Gurung Suraj , Goodwin Stephen B. , Kabbage Mehdi , Bockus William W. , Adhikari Tika B.
Published: June 2011

Mycosphaerella graminicola causes Septoria tritici blotch (STB) in wheat (Triticum aestivum) and is considered one of the most devastating pathogens of that crop in the United States. Although the genetic structures of M. graminicola populations from different countries have been analyzed using various molecular markers, relatively little is known about M. graminicola populations from geographically distinct areas of the United States and, in particular, of those from spring versus winter wheat. These are exposed to great differences in environmental conditions, length and season of host-free periods, and resistance sources used in geographically separated wheat breeding programs. Thus, there is more likely to be genetic differentiation between populations from spring versus winter wheat than there is among those within each region. To test this hypothesis, 330 single-spore isolates of M. graminicola representing 11 populations (1 from facultative winter wheat in California, 2 from spring wheat in North Dakota, and 8 from winter wheat in Indiana and Kansas) were analyzed for mating type frequency and for genetic variation at 17 microsatellite or simple-sequence repeat (SSR) loci. Analysis of clone-corrected data revealed an equal distribution of both mating types in the populations from Kansas, Indiana, and North Dakota, but a deviation from a 1:1 ratio in the California population. In total, 306 haplotypes were detected, almost all of which were unique in all 11 populations. High levels of gene diversity (H = 0.31 to 0.56) were observed within the 11 populations. Significant (P ≤ 0.05) gametic disequilibrium, as measured by the index of association (rBarD), was observed in California, one Indiana population (IN1), and three populations (KS1, KS2, and KS3) in Kansas that could not be explained by linkage. Corrected standardized fixation index (G″ST) values were 0.000 to 0.621 between the 11 populations and the majority of pairwise comparisons were statistically significant (P ≤ 0.001), suggesting some differentiation between populations. Analysis of molecular variance showed that there was a small but statistically significant level of genetic differentiation between populations from spring versus winter wheat. However, most of the total genetic variation (>98%) occurred within spring and winter wheat regions while <2% was due to genetic differentiation between these regions. Taken together, these results provide evidence that sexual recombination occurs frequently in the M. graminicola populations sampled and that most populations are genetically differentiated over the major spring- and winter-wheat-growing regions of the United States.
Significance of Molecular Testing for Congenital Chloride Diarrhea
Authors: Lechner Silvia , Ruemmele Frank M , Zankl Andreas , Lausch Ekkehart , Huber Wolf‐Dietrich , Mihatsch Walter , Phillips Alan D , Lewindon Peter , Querfeld Uwe , Heinz‐Erian Peter , Müller Thomas , Janecke Andreas R
Published: June 2011

Objectives:

Autosomal recessive, congenital chloride diarrhea (CLD) is a form of persistent secretory diarrhea, presenting with polyhydramnios and intractable diarrhea from birth. CLD is caused by mutations in the SLC26A3 gene, encoding a Na+‐independent Cl−/HCO3‐ exchanger. The diagnosis is generally made on the basis of high fecal chloride concentration in patients with serum electrolyte homoeostasis corrected by salt substitution. We aimed to evaluate the role of diagnostic genetic testing in CLD.

Patients and Methods:

Clinical and laboratory data were collected from 8 unrelated children diagnosed as having or suspected to have CLD. The evaluation included physical examination, routine clinical chemistry, and SLC26A3 mutation analysis by direct sequencing of DNA extracted from buccal swabs or peripheral leukocytes.

Results:

CLD was initially diagnosed on high fecal chloride concentrations in 7 patients, and by mutation analysis in 1 patient. In 3 of these patients the correct diagnosis was made more than 6 months after birth. We identified SLC26A3 mutations on both alleles in all 8 patients with CLD, including 3 novel missense and 4 novel truncating mutations. We present a compilation of reported SLC26A3 mutations and polymorphisms.

Conclusions:

The diagnosis and therapy of CLD were considerably delayed in 3 of 8 patients from this series, highlighting the potential of misdiagnosing CLD. We add 7 novel mutations, including 3 missense changes of highly conserved residues to a total of 41 mutations in this gene.

Molecular analysis is efficient and should be considered as a means of early diagnosis of CLD, especially if the clinical diagnosis remains uncertain.
Leukocytapheresis in Pediatric Patients With Ulcerative Colitis
Authors: Tomomasa Takeshi , Tajiri Hitoshi , Kagimoto Seiichi , Shimizu Toshiaki , Yoden Atsushi , Ushijima Kosuke , Uchida Keiichi , Kaneko Hiroaki , Abukawa Daiki , Konno Mutsuko , Maisawa Shun‐ichi , Kohsaka Takao , Kobayashi Akio ,   Japanese Study Group for Pediatric Ulcerative Colitis
Published: June 2011

Objective:

Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open‐label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC.

Patients and Methods:

Twenty‐three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid‐resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half‐volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements.

Results:

The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration.

Conclusions:

The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.
Two‐day Bowel Preparation With Polyethylene Glycol 3350 and Bisacodyl: A New, Safe, and Effective Regimen for Colonoscopy in Children
Authors: Phatak Uma P , Johnson Susanne , Husain Sohail Z , Pashankar Dinesh S
Published: June 2011

Objectives:

To assess the safety, efficacy, and acceptance of a 2‐day bowel preparation with polyethylene glycol (PEG) 3350 without electrolytes and bisacodyl for colonoscopy in children.

Patients and Methods:

In a prospective study, 111 children of mean age 11.9 years were given 2 g/kg of PEG and a 5‐mg tablet of bisacodyl daily for 2 days before colonoscopy. Stool frequency, consistency, and adverse effects were monitored for the duration of the bowel preparation. Compliance and quality of colonic preparation were assessed on the day of the colonoscopy.

Results:

The average daily stool frequency increased from a baseline of 2, to 4* on day 1, and 6.5* on day 2 of the bowel preparation (*P < 0.001 for difference vs baseline). The colonic preparations were rated as excellent or good in 92% and 93% of the patients in the right and left colon, respectively. Adverse effects were mild nausea (19%), abdominal pain (11%), and vomiting (4%). The compliance was rated as excellent in 95% of the patients.

Conclusions:

A 2‐day bowel preparation with PEG and bisacodyl is safe, effective, and well accepted for colonoscopy in children without any major adverse effects.
Epidemiological consequences of a newly discovered cryptic subgroup of
Anopheles gambiae
Authors: Yakob Laith
Published: June 2011

A cryptic subgroup of
Anopheles gambiae sensu stricto
mosquitoes was recently discovered in West Africa. This ‘GOUNDRY’ subgroup has increased susceptibility to
Plasmodium falciparum
, the most deadly form of malaria. Unusual for this major malaria vector, GOUNDRY mosquitoes also seem to bite exclusively outdoors. A mathematical model is developed to assess the epidemiological implications of current vector control tools, bednets and indoor residual spray, preferentially suppressing the more typical indoor biting mosquitoes. It is demonstrated that even if the GOUNDRY mosquitoes have a decreased preference for human blood, vector controls which select for increased GOUNDRY abundance relative to their indoor biting counterparts risks intensifying malaria transmission. Given the widely observed phenomenon of outdoor biting by major malaria vectors, this behaviour should not be ignored in future modelling efforts and warrants serious consideration in control programme strategy.
The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA
Authors: Splinter Erik , de Wit Elzo , Nora Elphège P. , Klous Petra , van de Werken Harmen J.G. , Zhu Yun , Kaaij Lucas J.T. , van IJcken Wilfred , Gribnau Joost , Heard Edith , de Laat Wouter
Published: June 2011

Three-dimensional topology of DNA in the cell nucleus provides a level of transcription regulation beyond the sequence of the linear DNA. To study the relationship between the transcriptional activity and the spatial environment of a gene, we used allele-specific chromosome conformation capture-on-chip (4C) technology to produce high-resolution topology maps of the active and inactive X chromosomes in female cells. We found that loci on the active X form multiple long-range interactions, with spatial segregation of active and inactive chromatin. On the inactive X, silenced loci lack preferred interactions, suggesting a unique random organization inside the inactive territory. However, escapees, among which is Xist, are engaged in long-range contacts with each other, enabling identification of novel escapees. Deletion of Xist results in partial refolding of the inactive X into a conformation resembling the active X without affecting gene silencing or DNA methylation. Our data point to a role for Xist RNA in shaping the conformation of the inactive X chromosome at least partially independent of transcription.
‘Have You Talked with a Teacher Yet?’: How Helpline Counsellors Support Young Callers Being Bullied at School
Authors: Danby Susan , Butler Carly W. , Emmison Michael
Published: June 2011

When seeking help and support about being bullied, children and young people weigh up the benefits and risks of talking to their friends, parents, teachers and counsellors about their experiences. The focus of this article is calls to an Australian helpline for children and young people where the strategy of ‘talking to the teacher’ is discussed by callers and counsellors as a possible way of dealing with the caller’s bullying situation at school. Transcribed and analysed data extracts of calls show how the young callers’ bullying experiences are being heard by the counsellor and also reveals the skill of the counsellors in managing these calls within the philosophy and guidelines of the service.
Evaluation of a novel needle guide for ultrasound‐guided phantom vessel cannulation*
Authors: Luyet C. , Hartwich V. , Urwyler N. , Schumacher P. M. , Eichenberger U. , Vogt A.
Published: June 2011

We evaluated a novel, sled‐mounted needle guide for ultrasound‐guided vessel cannulation. Fifty medical students were randomly assigned to use ultrasound with the sled (sled group, n = 23) or ultrasound without the sled (control group, n = 27) for vessel cannulation in a phantom. For each of 15 attempts we recorded cannulation time and designated a successful cannulation as 1 and a failure as 0. Our primary outcome was the mean overall success rate. The median (IQR [range]) number of successes in the sled group and control group were 15.0 (13.0–15.0 [11.0–15.0]) and 11.0 (9.0–13.0 [6.0–15.0]), respectively (p < 0.001). Cannulation time decreased from the first to the last attempt in the sled group from 7.0 s (6.0–10.0 [4.0–16]) s to 4.0 s (3.0–4.0 [1.0–6.0]) s and in the control group from 35.0 s (27.0–35.0 [11.0–35.0]) s to 7.0 s (5.0–10.0 [3.0–25.0]) s. The sled group demonstrated a shorter cannulation time at each attempt (p < 0.001). The novel sled improved the success rate and efficiency of ultrasound‐guided phantom vessel cannulation.
Ideal versus corrected body weight for dosage of sugammadex in morbidly obese patients
Authors: Van Lancker P. , Dillemans B. , Bogaert T. , Mulier J. P. , De Kock M. , Haspeslagh M.
Published: June 2011

To date, the dosing of sugammadex is based on real body weight without taking fat content into account. We compared the reversal of profound rocuronium‐induced neuromuscular blockade in morbidly obese patients using doses of sugammadex based on four different weight corrections. One hundred morbidly obese patients, scheduled for laparoscopic bariatric surgery under propofol‐sufentanil anaesthesia, were randomly assigned four groups: ideal body weight; ideal body weight + 20%; ideal body weight + 40%; and real body weight. Patients received sugammadex 2 mg.kg−1, when adductor pollicis monitoring showed two responses. The primary endpoint was full decurarisation. Secondary endpoints were the ability to get into bed independently on arrival to the post‐anaesthetic care unit and clinical signs of residual paralysis. There was no residual paralysis in any patient. Morbidly obese patients can safely be decurarised from rocuronium‐induced neuromuscular blockade T1‐T2 with sugammadex dosed at 2 mg.kg−1 ideal body weight + 40% (p < 0.0001).
Postoperative hypothermia and patient outcomes after elective cardiac surgery
Authors: Karalapillai D. , Story D. , Hart G. K. , Bailey M. , Pilcher D. , Cooper D. J. , Bellomo R.
Published: June 2011

Hypothermia after elective cardiac surgery is an important physiological abnormality and is associated with increased morbidity and mortality. The Australian and New Zealand intensive care adult patient database was studied to obtain the lowest and highest temperature in the first 24 h after surgery. Hypothermia was defined as core temperature < 36 °C; transient hypothermia as temperature < 36 °C that was corrected within 24 h; and persistent hypothermia as hypothermia that was not corrected within 24 h. Hypothermia occurred in 28 587 out of a total of 43 158 consecutive patients (66%) and was persistent in 111 (0.3%). Transient hypothermia was not independently associated with increased hospital mortality (OR = 0.9, 95% CI 0.8–1.1), whereas persistent hypothermia was associated with markedly increased risk of death (OR = 6.3, 95% CI = 3.3–12.0). Hypothermia is common in postoperative cardiac surgery patients during the first 24 h after ICU admission but, if transient, is not independently associated with an increased risk of death.
Use of modelling and simulation techniques to support decision making on the progression of PF‐04878691, a TLR7 agonist being developed for hepatitis C
Authors: Jones Hannah M. , Chan Phylinda L. S. , van der Graaf Piet H. , Webster Robert
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• While several clinical studies have been published on toll‐like receptor 7 (TLR7) agonists, there is no information on the quantitative link between 2′,5′‐oligoadenylate synthetase (OAS) and antiviral efficacy (viral load).

WHAT THIS STUDY ADDS

• This study provides the only quantitative dynamic clinical relationship between the pharmacokinetics (PK) of PF‐04878691 and OAS and lymphocyte levels, together with the only published clinical relationship between markers of anti‐viral pharmacology (OAS) and antiviral efficacy (viral load). This study highlights how modelling and simulation can be used to impact compound progression decisions in clinical development.

AIM

To use non‐linear mixed effects modelling and simulation techniques to predict whether PF‐04878691, a toll‐like receptor 7 (TLR7) agonist, would produce sufficient antiviral efficacy while maintaining an acceptable side effect profile in a ‘proof of concept’ (POC) study in chronic hepatitis C (HCV) patients.

METHODS

A population pharmacokinetic–pharmacodynamic (PKPD) model was developed using available ‘proof of pharmacology’ (POP) clinical data to describe PF‐04878691 pharmacokinetics (PK) and its relationship to 2′,5′‐oligoadenylate synthetase (OAS; marker of pharmacology) and lymphocyte levels (marker of safety) following multiple doses in healthy subjects. A second model was developed to describe the relationship between change from baseline OAS expressed as fold change and HCV viral RNA concentrations using clinical data available in HCV patients for a separate compound, CPG‐10101 (ACTILON™), a TLR9 agonist. Using these models the antiviral efficacy and safety profiles of PF‐04878691 were predicted in HCV patients.

RESULTS

The population PKPD models described well the clinical data as assessed by visual inspection of diagnostic plots, visual predictive checks and precision of the parameter estimates. Using these relationships, PF‐04878691 exposure and HCV viral RNA concentration was simulated in HCV patients receiving twice weekly administration for 4 weeks over a range of doses. The simulations indicated that significant reductions in HCV viral RNA concentrations would be expected at doses >6 mg. However at these doses grade ≥3 lymphopenia was also predicted.

CONCLUSIONS

The model simulations indicate that PF‐04878691 is unlikely to achieve POC criteria and support the discontinuation of this compound for the treatment of HCV.
A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria
Authors: Kim S-H. , Son J.K. , Yang E-M. , Kim J-E. , Park H-S.
Published: June 2011

Background Urticaria is the commonest cutaneous reaction caused by aspirin or other nonsteroidal anti-inflammatory drugs. The pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, but appears to involve mast cell activation and neutrophil infiltration.

Objectives To investigate the genetic contribution of interleukin (IL)-18, which can amplify acute inflammation by promoting mast cell activation, neutrophil migration and cytokine production, to the pathogenesis of AIU.

Methods A case–control association study was performed using 275 patients with AIU and 196 normal healthy controls in a Korean population. Two promoter polymorphisms of the IL18 gene (−607A/C and −137G/C) were genotyped using the primer extension method. The functional effect of the IL18 gene promoter polymorphism was investigated through in vitro studies including a luciferase reporter assay and electrophoretic mobility shift assays (EMSAs) and ex vivo studies involving neutrophil chemotaxis assays.

Results A significant association was detected between both AIU in general and the aspirin-intolerant acute urticaria (AIAU) phenotype and the IL18 promoter polymorphism −607A/C. Patients with AIAU showed higher frequencies of the C−607G−137 haplotype, ht1 [CG], compared with controls (P =0·02). Moreover, ht1 [CG] showed a high transcript haplotype by the luciferase activity assay, and EMSAs identified a −607C allele-specific DNA-binding protein as CREB2. Neutrophil chemotactic activity was highest in subjects with AIU exhibiting the high transcript haplotype, ht1 [CG] (P =0·019).

Conclusions The high transcript haplotype ht1 [CG] of the IL18 gene may contribute to the development of acute cutaneous inflammation sensitive to aspirin, leading to the clinical presentation of AIAU.
Comparative proteomics reveals deficiency of SLC9A1 (sodium/hydrogen exchanger NHE1) in β‐adducin null red cells
Authors: Wooden Jason M. , Finney Greg L. , Rynes Eric , MacCoss Michael J. , Lambert Amy J. , Robledo Raymond F. , Peters Luanne L. , Gilligan Diana M.
Published: June 2011

Spherocytosis is one of the most common inherited disorders, yet presents with a wide range of clinical severity. While several genes have been found mutated in patients with spherocytosis, the molecular basis for the variability in severity of haemolytic anaemia is not entirely understood. To identify candidate proteins involved in haemolytic anaemia pathophysiology, we utilized a label‐free comparative proteomic approach to detect differences in red blood cells (RBCs) from normal and β‐adducin (Add2) knock‐out mice. We detected seven proteins that were decreased and 48 proteins that were increased in β‐adducin null RBC ghosts. Since haemolytic anaemias are characterized by reticulocytosis, we compared reticulocyte‐enriched samples from phenylhydrazine‐treated mice with mature RBCs from untreated mice. Among the 48 proteins increased in Add2 knockout RBCs, only 11 were also increased in reticulocytes. Of the proteins decreased in Add2 knockout RBCs, α‐adducin showed the greatest intensity difference, followed by SLC9A1, the sodium‐hydrogen exchanger previously termed NHE1. We verified these mass spectrometry results by immunoblot. This is the first example of SLC9A1deficiency in haemolytic anaemia and suggests new insights into the mechanisms leading to fragile RBCs.
NT‐pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease
Authors: Machado Roberto F. , Hildesheim Mariana , Mendelsohn Laurel , Remaley Alan T. , Kato Gregory J. , Gladwin Mark T.
Published: June 2011

Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N‐terminal‐pro brain natriuretic peptide (NT‐proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT‐pro‐BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT‐proBNP level ≥160 ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P < 0·001), high lactate dehydrogenase (P < 0·001), and high total bilirubin levels (P < 0·007). A NT‐proBNP level ≥160 ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9–13·3, P < 0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population.
A test of a field‐based 15N–nitrous oxide pool dilution technique to measure gross N2O production in soil
Authors: Yang Wendy H. , Teh Yit Arn , Silver Whendee L.
Published: June 2011

Soils are both a major source and sink of nitrous oxide (N2O), but the proportion of soil N2O production released to the atmosphere (termed the N2O yield) is poorly constrained due to the difficulty in measuring gross N2O production. The quantification of gross N2O fluxes would greatly improve our ability to predict N2O dynamics across the soil‐atmosphere interface. We report a new approach, the 15N2O pool dilution technique, to measure rates of gross N2O production and consumption under laboratory and field conditions. In the laboratory, gross N2O production and consumption compared well between the 15N2O pool dilution and acetylene inhibition methods whereas the 15NO3− tracer method measured significantly higher rates. In the field, N2O emissions were not significantly affected by increasing chamber headspace concentrations up to 100 ppb 15N2O. The pool dilution model estimates of 14N2O and 15N2O concentrations as well as net N2O fluxes fit observed data very well, suggesting that the technique yielded robust estimates of gross N2O production. Estimated gross N2O consumption rates were underestimated relative to rates calculated as the difference between gross and net N2O production rates, possibly due to heterogeneous and/or inadequate tracer diffusion to deeper layers in the soil profile. Gross N2O production rates were high, averaging 8.4 ± 3.2 mg N m−2 day−1, and were most strongly correlated to mineral nitrogen concentrations and denitrifying enzyme activity (R2 = 0.73). Gross N2O production rates varied spatially, with the highest rates in soils with the best drainage and the highest mineral N availability. Estimated and calculated N2O consumption rates constrained the average N2O yield from 0.70 to 0.84. Our results demonstrate that the 15N2O pool dilution technique can provide well‐constrained estimates of N2O yields and field rates of gross N2O production correlated to soil characteristics, improving our understanding of terrestrial N2O dynamics.
Haemophilia Utilization Group Study – Part Va (HUGS Va): design, methods and baseline data
Authors: ZHOU Z.‐Y. , WU J. , BAKER J. , CURTIS R. , FORSBERG A. , HUSZTI H. , KOERPER M. , LOU M. , MILLER R. , PARISH K. , RISKE B. , SHAPIRO A. , ULLMAN M. , JOHNSON K.
Published: June 2011

Summary.  To describe the study design, procedures and baseline characteristics of the Haemophilia Utilization Group Study – Part Va (HUGS Va), a US multi‐center observational study evaluating the cost of care and burden of illness in persons with factor VIII deficiency. Patients with factor VIII level ≤30%, age 2–64 years, receiving treatment at one of six federally supported haemophilia treatment centres (HTCs) were enrolled in the study. Participants completed an initial interview including questions on socio‐demographical characteristics, health insurance status, co‐morbidities, access to care, haemophilia treatment regimen, factor utilization, self‐reported joint pain and motion limitation and health‐related quality of life. A periodic follow‐up survey collected data regarding time lost from usual activities, disability days, health care utilization and outcomes of care. HTC clinicians documented participants’ baseline clinical characteristics and pharmacy dispensing records for 2 years. Between July 2005 and July 2007, 329 participants were enrolled. Average age was 9.7 years for children and 33.5 years for adults; two‐thirds had severe haemophilia. The distributions of age, marital status, education level and barriers to haemophilia care were relatively consistent across haemophilic severity categories. Differences were found in participants’ employment status, insurance status and income. Overall, children with haemophilia had quality of life scores comparable to healthy counterparts. Adults had significantly lower physical functioning than the general US population. As one of the largest economic studies of haemophilia care, HUGS Va will provide detailed information regarding the burden of illness and health care utilization in the US haemophilia A population.
Registered nurses’ thinking strategies on malnutrition and pressure ulcers in nursing homes: a scenario‐based think‐aloud study
Authors: Fossum Mariann , Alexander Gregory L , Göransson Katarina E , Ehnfors Margareta , Ehrenberg Anna
Published: June 2011

Aim.  The aim of this study was to explore the thinking strategies and clinical reasoning processes registered nurses use during simulated care planning for malnutrition and pressure ulcers in nursing home care.

Background.  Clinical reasoning is an essential component of nursing practice. Registered nurses’ thinking strategies and clinical reasoning have received limited attention in nursing science. Further research is needed to understand registered nurses’ clinical reasoning, especially for prevention of malnutrition and pressure ulcers as they are important quality indicators of resident care in nursing homes.

Design.  A qualitative explorative design was used with a think‐aloud interview technique.

Methods.  The transcribed verbalisations were analysed with qualitative deductive content analysis. Data were collected during six months in 2007–2008 from 30 registered nurses at nine nursing homes in Norway.

Results.  The registered nurses used a variety of thinking strategies, but there were differences in the frequency of use of the different strategies. The three most commonly used thinking strategies were ‘making choices’, ‘forming relationships’ and ‘drawing conclusions’. None of the nurses performed a structured risk assessment of malnutrition or pressure ulcers. Registered nurses started with assessing data from the scenarios, but after a short and elementary assessment they moved directly to planning.

Conclusion.  Many different thinking strategies were used in registered nurses’ clinical reasoning for prevention of malnutrition and pressure ulcers. The thinking strategy ‘making choices’ was most commonly used and registered nurses’ main focus in their reasoning was on planning nursing interventions.

Relevance to clinical practice.  This study showed that most of the registered nurses go directly to planning when reasoning clinically about residents in nursing homes. A lack of systematic risk assessments was identified. The insight gained from this study can be used to recommend improvements in tools designed for nursing homes to support the registered nurses.
Computerized physician order entry system combined with on‐ward pharmacist: analysis of pharmacists' interventions
Authors: Bedouch Pierrick , Tessier Alexandre , Baudrant Magalie , Labarere José , Foroni Luc , Calop Jean , Bosson Jean‐Luc , Allenet Benoît
Published: June 2011

Rationale, aims and objectives  To analyse pharmacists' interventions in a setting where a computerized physician order entry system (CPOE) is in use and a pharmacist works on the ward.

Method  A prospective cohort study was conducted in seven wards of a French teaching hospital using CPOE along with the presence of a full‐time on‐ward pharmacy resident. We documented the characteristics of pharmacists' interventions communicated to physicians during the medication order validation process whenever a drug‐related problem was identified. Independent predictors of the physician's acceptance of the pharmacist's intervention were assessed using multiple logistic regression analysis.

Results  The 448 pharmacists' interventions concerned: non‐conformity to guidelines or contraindications (22%), too high doses (19%), drug interactions (15%) and improper administration (15%). The interventions consisted of changes in drug choice (41%), dose adjustment (23%), drug monitoring (19%) and optimization of administration (17%). Interventions were communicated via the CPOE in 57% of cases and 43% orally. The rate of physicians' acceptance was 79.2%. In multivariate analysis, acceptance was significantly associated with the physician's status [higher for residents vs. seniors: OR = 7.23, CI 95 (2.37–22.10), P < 0.01], method of communication [higher for oral vs. computer communication: OR = 12.5, CI 95 (4.16–37.57), P < 0.01] and type of recommendation [higher for drug monitoring vs. drug choice recommendations: OR = 10.32, CI 95 (3.20–33.29), P < 0.01].

Conclusions  When a clinical pharmacist is present on a ward in which a CPOE is in use, the pharmacists' interventions are well accepted by physicians. Specific predictors of the acceptance by physicians emerge, but further research as to the impact of CPOE on pharmacist–physician communication is needed.
Physical violence between intimate partners during pregnancy and postpartum: a prediction model for use in primary health care facilities
Authors: Moraes Claudia L. , Tavares da Silva Tatiana de S. , Reichenheim Michael E. , Azevedo Gustavo L. , Dias Oliveira Alessandra S. , Braga José U.
Published: June 2011

Moraes CL, Tavares da Silva TS, Reichenheim ME, Azevedo GL, Dias Oliveira AS, Braga JU. Physical violence between intimate partners during pregnancy and postpartum: a prediction model for use in primary health care facilities. Paediatric and Perinatal Epidemiology 2011; 25: 478–486.

This article offers a simple predictive model of physical intimate partner violence (PIPV) to be used by primary health care (PHC) professionals. The sample comprised 811 mothers of children <5 months old attending PHC facilities in Rio de Janeiro, Brazil. A multinomial logit model was used. Measured by the Revised Conflict Tactics Scales, PIPV was classified in three levels (absence, at least one episode during pregnancy or postpartum, and presence in both periods). Socio‐economic, demographic and life style variables were considered as potential predictors. Maternal age <20 years, an education of <8 years of schooling, raising >2 children under 5, tobacco smoking, alcohol misuse and illicit drug use by the mother and/or partner, and perception of baby's ill‐health were identified as predictors of PIPV. The model‐projected prevalence of PIPV for pregnancy and/or postpartum was just 10.1% in the absence of these characteristics, whereas this increased to 96.4% when all the seven characteristics were present. Child, maternal and family characteristics greatly increase the likelihood of PIPV and could be used together as screening indicators.
Spatial analysis and incidence–density relationships for downy mildew on hop
Authors: Gent D. H. , Farnsworth J. L. , Johnson D. A.
Published: June 2011

The spatial pattern of downy mildew (Pseudoperonospora humuli) on hop (Humulus lupulus) was characterized over 4 years to aid in deriving an appropriate incidence–density relationship. From 472 disease assessments (datasets), discrete distributions were fitted to the datasets to determine aggregation of disease density. Where distributions were able to be fitted, the Poisson distribution fitted 4% of the datasets and the negative binomial distribution fitted 87% of the datasets. Larger‐scale patterns of disease were assessed by autocorrelation and runs analysis; both indicated aggregation of diseased plants was less common than aggregation of disease within plants. Taylor’s power law indicated disease density was aggregated and related to mean disease density in all years. Disease incidence and density were linked by saturation‐type relationships based on the zero term of the negative binomial distribution or an empirical regression. Certain individual datasets were not described well by any incidence–density model, particularly when disease density was greater than about 0·8 diseased shoots per plant with the cultivar Cascade. When applied to 56 validation datasets, 88% of the variation in observed disease incidence was explained by the incidence–density models. Under conditions where sampling would be implemented for disease management, the requisite conditions appear to be in place for a binomial sampling plan for downy mildew.
Detection of Dickeya spp. latent infection in potato seed tubers using PCR or ELISA and correlation with disease incidence in commercial field crops under hot‐climate conditions
Authors: Tsror (Lahkim) L. , Erlich O. , Hazanovsky M. , Ben Daniel B. , Zig U. , Lebiush S.
Published: June 2011

Over a 5‐year period (2006–2010), 277 certified, visually healthy potato seed lots, imported from Europe to Israel for commercial use, were tested for Dickeya spp. latent infection by PCR analysis (277 seed lots) and ELISA (154 seed lots). Seeds from these lots were grown in commercial potato fields which were inspected twice a season by Plant Protection and Inspection Services (PPIS). Stem samples were tested for the presence of Dickeya spp. by PCR analysis. PCR and ELISA results from seed lot testing correlated with disease expression in 74 and 83·8% of the cases, respectively. Positive laboratory results with no disease symptoms in the field (‘+lab/−field’ results) comprised 24·7 and 9·7% of the PCR and ELISA analyses, respectively, whereas negative laboratory results with disease symptoms in the field results (‘−lab/+field’) were obtained in 1·3 and 6·5%, of cases respectively. Maximum disease incidence, as well as the number of cultivars expressing disease symptoms, increased over the years of this study, indicating an increase in the prevalence of the disease. Severe disease incidence was observed on cvs Dita, Rodeo, Desiree, Mondial, Tomensa and Jelly. Of the 55 imported seed lots from which disease was recorded in the field, 49 originated from the Netherlands, four from Germany and two from France. None originated from Scotland.
Genetic structure of the fungal grapevine pathogen Eutypa lata from four continents
Authors: Travadon R. , Baumgartner K. , Rolshausen P. E. , Gubler W. D. , Sosnowski M. R. , Lecomte P. , Halleen F. , Péros J.‐P.
Published: June 2011

The generalist ascomycete fungus Eutypa lata causes Eutypa dieback of grapevine (Vitis vinifera) worldwide. To decipher the cosmopolitan distribution of this fungus, the population genetic structure of 17 geographic samples was investigated from four continental regions (Australia, California, Europe and South Africa), based on analysis of 293 isolates genotyped with nine microsatellite markers. High levels of haplotypic richness (R = 0·91–1) and absence of multilocus linkage disequilibrium among loci supported the preponderance of sexual reproduction in all regions examined. Nonetheless, the identification of identical multilocus haplotypes with identical vegetative compatibility groups, in some vineyards in California and South Africa, suggests that asexual dispersal of the fungus among neighbouring plants could be a rare means of disease spread. The greatest levels of allelic richness (A = 4·89–4·97) and gene diversity (H = 0·66–0·69) were found in Europe among geographic samples from coastal areas surrounding the Mediterranean Sea, whereas the lowest genetic diversity was found in South Africa and Australia (A = 2·78–3·74; H = 0·49–0·57). Samples from California, Australia and South Africa, which had lower genetic diversity than those of Europe, were also characterized by demographic disequilibrium and, thus, may represent founding populations of the pathogen. Low but significant levels of genetic differentiation among all samples (DEST = 0·12, P = 0·001; FST = 0·03, P = 0·001) are consistent with historical gene flow preventing differentiation at continental scales. These findings suggest that global, human‐mediated spread of the fungus may have resulted in its current global distribution.