bluuebunny/crossref_metadata_2025 huggingface dataset:
The wide but disjunct range of the European mountain plant Androsace lactea L. (Primulaceae) reflects Late Pleistocene range fragmentation and post‐glacial distributional stasis
Authors: Schneeweiss G. M. , Schönswetter P.
Published: July 2010

Aim  Our aim was to reconstruct the spatio‐temporal genetic diversification of Androsace lactea, a widely but disjunctly distributed European mountain plant, to test the hypothesis that its distribution is the result of vicariance, in the late Tertiary or during the Pleistocene, or alternatively of long‐distance dispersal. We also addressed the phylogeographic history of the Alps, emphasizing the role of Pleistocene refugia at their northern margin.

Location  The central and southern European mountain ranges.

Methods  We gathered amplified fragment length polymorphism (AFLP) data and plastid DNA sequences from one to four individuals of each of 26 populations spanning the entire distribution area. AFLP data were analysed with Bayesian clustering approaches, neighbour‐joining analysis and NeighbourNet. Plastid sequences were used to depict relationships among haplotypes in a statistical parsimony network, to test for population expansions, and to obtain age estimates in a Bayesian framework.

Results  The AFLP data suggested that many populations were genetically strongly differentiated. The internal structure, however, was weak, and only two major groups of populations, from the north‐western Alps and adjacent regions and from the easternmost Alps, were supported in the neighbour‐joining analysis. One of the Bayesian clustering approaches differentiated three groups of populations: Northern Alps, easternmost Alps and the remaining distribution area. Eleven closely related plastid haplotypes were found, separated by maximally four mutational steps, resulting in a star‐like parsimony network. None of several estimators suggested statistically significant population expansions. The diversification age was inferred to be (mean/median) 0.135/0.08 Ma (95% highest posterior density interval 0.364–0.006 Ma).

Main conclusions  We found no evidence that long‐distance dispersal shaped the disjunct distribution range; our data rather favoured a vicariance scenario. However, in contrast to the hypothesis that wide but disjunct distributions are old, we conclude that range fragmentation probably happened in the Late Pleistocene, perhaps during the last glaciation. In the Alps, most populations are at least close to formerly unglaciated areas. Our data support distributional stasis and suggest that important refugia were situated at the north‐eastern, but also at the northern and north‐western edges of the Alps, thereby strengthening the evidence for glacial refugia in this strongly glaciated region.
A community of practice: the nurses’ role on a medical assessment unit
Authors: Griffiths Pauline
Published: July 2010

Aim.  To explore the nurses’ role on a medical assessment unit.

Background.  Medical assessment units facilitate the acceptance of medical emergencies to one dedicated clinical space and are a response to politically driven strategies to enhance the provision of acute medical care in the UK. Despite the essential contribution that nurses make, there is a paucity of research‐based literature that has investigated the nurses’ role in these units.

Design.  An ethnographic study of a medical assessment unit in Wales, UK.

Method.  Data were collected over a three‐year period from 2003–2006 by participant observation (200 hours) with the researcher, a registered nurse and university lecturer, working alongside the nurses as a contributor to care delivery, semi‐structured interviews with nurses, doctors, paramedics and patients (n = 19) and the collection of documentary and artefact evidence.

Results.  Three main themes were identified: ‘making beds’: organising the clinical space; ‘knowing your stuff’: having professional knowledge; and ‘loving the buzz’: having the ability to work under pressure.

Conclusion.  A distinctive community of practice had developed to satisfy the workplace demands that the nurses faced in a culture that valued autonomous practice and provided a positive working environment. However, a cautionary note must be raised in that new approaches to care delivery, such as medical assessment units, whilst being operationally efficient, may not reflect a nursing ethos of holistic and individualised care delivery.

Relevance to clinical practice.  The concept of community of practice aids the exploration of the interplay of the goals of practice and the attendant social relations developed in nursing teams. Findings from this study have identified aspects of the role of the nurse in a medical assessment unit setting and so can help inform educational programmes. Further research is required to enable the development of this distinctive nursing role.
Chemical surface disinfection of eggs of Baltic cod, Gadus morhua L.
Authors: Overton J L , Bruun M S , Dalsgaard I
Published: July 2010

The effect of two disinfectants on eggs and larvae of Baltic cod, Gadus morhua, was investigated. The eggs were disinfected for 10 min using various concentrations of either glutaraldehyde (100, 200, 400, 600 and 800 mg L−1) or iodophor (10, 50, 100 and 150 mg L−1), 1–4‐days post‐fertilization. Bactericidal effect of disinfection, survival to hatching, hatching success and larval abnormalities were assessed. Larval survival was recorded at 5‐, 10‐ and 15‐days post‐hatch (dph). Although Baltic cod eggs have an unusually thin chorion, they could tolerate surface disinfection. A reduction in bacterial growth was observed with increased concentrations of disinfectant (3.0 × 107–1.6 × 101 CFU mL−1). Abnormalities in newly hatched larvae were not related to disinfection. Survival of the yolk sac larvae was significantly better for eggs treated with 400 mg L−1 glutaraldehyde for 10 min at 10 and 15 dph. Effective disinfection was also recorded using 100 mg L−1 Actomar K30. Egg batch effect rather than initial bacterial concentration, disinfectant type or incubation method determined the survival of the eggs to hatching and survival of larvae. Because of the carcinogenic effect of glutaraldehyde, iodophor is recommended for routine disinfection of cod eggs.
Comorbidity of Asperger syndrome: a preliminary report
Authors: Ghaziuddin M. , Weidmer‐Mikhail E. , Ghaziuddin N.
Published: July 2010

Asperger syndrome (AS) is a pervasive developmental disorder characterized by autistic social dysfunction and idiosyncratic interests in the presence of normal intelligence. There is no history of language delay. Although people with AS are known to suffer from comorbid psychiatric conditions, few studies have systematically addressed this topic. This preliminary report describes the occurrence of psychiatric disorders in a series of patients with AS diagnosed according to the ICD‐10/DSM‐IV criteria. Out of 35 patients (29 males and six females; mean age 15.1 years; mean verbal IQ 105.9; mean performance IQ 97.5; mean full‐scale IQ 102.7), 23 patients (65%) presented with symptoms of an additional psychiatric disorder at the time of evaluation or during the 2‐year follow‐up. Children were most likely to suffer from attention deficit hyperactivity disorder, while depression was the most common diagnosis in adolescents and adults. The implications of these findings are discussed.
Orthostatic hypotension and long‐term incidence of atrial fibrillation: the malmö preventive project
Authors: Fedorowski A. , Hedblad B. , Engström G. , Gustav Smith J. , Melander O.
Published: July 2010

Abstract.  Fedorowski A, Hedblad B, Engström G, Gustav Smith J, Melander O (Department of Clinical Sciences, Lund University, Malmö; and Skåne University Hospital, Malmö, Sweden). Orthostatic hypotension and long‐term incidence of atrial fibrillation: the Malmö Preventive Project. J Intern Med 2010; 268: 383–389.

Objectives.  Orthostatic hypotension (OH), a common manifestation of autonomic dysfunction, has been identified as an independent risk factor for all‐cause mortality and incident cardiovascular disease. However, the role of OH in the development of atrial fibrillation has not been studied.

Design.  We investigated the incidence of atrial fibrillation in relation to baseline presence of OH according to international consensus criteria in the Swedish population‐based prospective cohort of the Malmö Preventive Project. The study sample consisted of 33 346 individuals (67.3% men; mean age, 45.6 ± 7.4 years; range, 26–61 years). The association between OH and incidence of atrial fibrillation during follow‐up was assessed using the Kaplan–Meier method and multivariable Cox proportional hazard models, taking into account conventional risk factors for atrial fibrillation.

Results.  At baseline, 1987 participants (6.1%) met the diagnostic criteria for OH. Over a follow‐up period of approximately 24 years, 2312 individuals (3.0 events/1000 person‐years) were diagnosed with new‐onset atrial fibrillation. Of these, 196 had OH at baseline (4.6 events/1000 person‐years amongst all OH‐positive individuals). In a multivariable Cox regression analysis, OH predicted incidence of atrial fibrillation independently of other risk factors (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.05–1.61; P = 0.016), and this association was significant in hypertensive (HR: 1.44; 95%CI: 1.10–1.88; P = 0.008), but not in normotensive participants (HR: 1.10; 95%CI: 0.77–1.58; P = 0.60).

Conclusions.  The presence of OH predicts the incidence of atrial fibrillation in middle‐aged hypertensive individuals, independently of conventional risk factors. Further studies of the association of autonomic dysfunction and OH with atrial fibrillation are needed.
Genomic signals of diversification along ecological gradients in a tropical lizard
Authors: FREEDMAN ADAM H. , THOMASSEN HENRI A. , BUERMANN WOLFGANG , SMITH THOMAS B.
Published: July 2010

Studies of rainforest diversification that simultaneously consider the effects of genetic drift and natural selection are rare. We use Amplified Fragment Length Polymorphism genome scans of the African rainforest lizardTrachylepis affinisfrom Cameroon to examine the spatial patterns and environmental associations of both neutrally evolving loci and those thought to be under selection. Bayesian selection scans revealed that approximately 7% of the genome may be under divergent selection. Using non‐linear environmental modelling techniques, we fit patterns of genetic differentiation recovered from the pooled neutral data and from individual loci showing a signature of natural selection. Neutral differentiation occurred along a cline from coastal lowland rainforest inland toward the gallery forests‐savanna mosaic (ecotone), and was associated with both geographic distance and changing precipitation patterns. Loci under selection were differentiated predominantly along the forest–ecotone gradient—in concordance with morphological divergence in traits related to fitness. A second set of these loci was differentiated between lowland and montane habitats. A third set of loci was indicative of divergent selection between rainforest refugia. Niche models and demographic signals in mitochondrial sequence data support a population expansion out of a core rainforest area into savanna since the last glacial maximum. Our findings indicate adaptive diversification inT. affinismay be taking place along the forest–ecotone gradient during range expansions or contractions, and that refugial isolation augmented by divergent adaptation to different rainforest environments appears to play a less significant role.
Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients
Authors: Carotti S. , Guarino M. P. L. , Cicala M. , Perrone G. , Alloni R. , Segreto F. , Rabitti C. , Morini S.
Published: July 2010

Background  Reduced gallbladder (GB) contractility and chronic inflammatory changes in the mucosa have been reported in patients with cholesterol gallstones (GS). Ursodeoxycholic acid (UDCA) restores GB contractility and antagonises liver macrophage activation. In the colon, hydrophobic bile acid, not hydrophilic UDCA, induces mast cell degranulation. We studied the presence of monocyte/macrophage infiltrate, cyclooxygenase (COX)‐2, inducible nitric oxide synthase (iNOS) expression, the number of total and degranulated mast cells in the GB muscle layer of cholesterol GS patients, and the effect of UDCA administration.

Methods  Gallbladder tissue was obtained from cholesterol GS patients, either treated or untreated with UDCA (10 mg kg−1 day−1) for 30 days prior to surgery. Gallbladders removed for neoplastic diseases, not involving GB, were evaluated for control purposes. The presence of monocytes/macrophages (CD68 positive), granulocytes, and mast cells, and the COX‐2 and iNOS expression, was determined immunohistochemically.

Key Results  The number of CD68, granulocytes, mast cells, COX‐2 and iNOS positive cells was significantly higher in the muscle layer of GS patients than in controls. Compared to untreated patients, those treated with UDCA showed significantly lower levels of CD68, COX‐2 positive cells and degranulated mast cells and a lesser number of iNOS positive cells and granulocytes.

Conclusions & Inferences  An inflammatory monocyte/macrophage, mast cell and granulocyte infiltrate is present in the GB muscle layer of GS patients. Ursodeoxycholic acid decreases macrophages, degranulated mast cells and COX‐2 expression. These results suggest that monocytes/macrophages and degranulating mast cells contribute to muscle cell dysfunction in cholesterol GS patients and support the anti‐inflammatory effect of UDCA.
Improved Immunogenicity of Recombinant Mycobacterium bovis Bacillus Calmette‐Guérin Strains Expressing Fusion Protein Ag85A‐ESAT‐6 of Mycobacterium tuberculosis
Authors: Deng Y. H. , Sun Z. , Yang X. L. , Bao L.
Published: July 2010

Early secretory antigen target 6 (ESAT‐6) is a dominant target for cell‐mediated immunity in the early phase of tuberculosis (TB) in patients with TB, causing T‐cell proliferation and gamma interferon (IFN‐γ) production, which has been considered to be a protective antigen that can be used for future vaccine development. Ag85A is the most essential component for bacterial survival within macrophages and has been used in numerous vaccine preparations, which can induce strong cellular immune responses. In this study, we constructed a new recombinant bacilli Calmette‐Guérin (BCG) strain (rBCG‐AE) that could express fusion protein Ag85A‐ESAT‐6 of Mycobacterium tuberculosis and evaluated its immunogenicity in BALB/c mice. There was no evidence for increased virulence of this rBCG. Our experiments illustrated that the rBCG‐AE was able to induce higher titer of antibody and elicit more long‐lasting and stronger Th1 type cellular immune responses than the parental BCG strain, or rBCG‐A (expressing Ag85A) strain, or rBCG‐E (expressing ESAT‐6) strain, which are characterized by the strong antibody response, the proliferation rate of splenocytes, the ratio of CD4+ T and CD8+ T cells stimulated by tuberculin‐purified protein derivative and elevated levels of IFN‐γ in antigen‐stimulated splenocyte cultures. The results show that rBCG‐AE is an improved TB vaccine for further study.
Cyclosporine‐A in severe chronic urticaria: the option for long‐term therapy
Authors: Kessel A. , Toubi E.
Published: July 2010

To cite this article: Kessel A, Toubi E. Cyclosporine‐A in severe chronic urticaria: the option for long‐term therapy. Allergy 2010; 65: 1478–1482.

Background:  The treatment of severe chronic urticaria (CU) remains a difficult goal to achieve. Many patients do not respond to anti‐histamine therapy, even when off‐label doses are given. Thus, cyclosporine‐A (CsA) becomes a good therapeutic option for severe patients and for some, long‐term therapy is required. We evaluated the effectiveness and safety of low‐dose CsA, when treatment cannot be discontinued and long‐term CsA therapy is needed to maintain severe CU in remission.

Methods:  Among 2000 patients with CU who were referred to our outpatient clinic, 120 patients who suffered from a very severe CU began treatment with CsA 3 mg/kg. A clinical and laboratory followup was performed during this period of treatment.

Results:  In 20 patients, CsA was discontinued within 2–15 days after initiation because of side‐effects. Among 62 of the remaining 100 patients (62%), CsA was administered for a period of 3 months with a highly beneficial outcome. In another 20 patients (20%), CsA was considered beneficial; however, it was required for a longer period of time, 5–10 years for some of the cases. In all cases, CsA was well tolerated and most important, it was safe. For 18 patients (18%), CsA therapy was reported as failed.

Conclusion:  A low dose of CsA is a good option for patients who suffer from especially severe CU. In most cases, this therapy regimen is considered effective and safe. For a small group of patients, long‐term therapy is needed, and until now it is considered safe.
Exome sequencing: expanding the genetic testing toolbox
Authors: Kobelka CE
Published: July 2010

Exome sequencing identifies the cause of a Mendelian disorder

Ng et al. (2009)

Nature Genetics 41(1):30–36
Evaluation of phone‐based genetic counselling in African American women using culturally tailored visual aids
Authors: Pal T , Stowe C , Cole A , Lee J‐H , Zhao X , Vadaparampil S
Published: July 2010

Pal T, Stowe C, Cole A, Lee J‐H, Zhao X, Vadaparampil S. Evaluation of phone‐based genetic counselling in African American women using culturally tailored visual aids.

Genetic counselling (GC) services for inherited breast and ovarian cancer (HBOC) are underutilized by African American (AA) women. We sought to evaluate factors associated with knowledge gain in a sample of AA women diagnosed with early‐onset breast cancer, in whom GC for HBOC was provided, using a culturally targeted genetic counselling aid (GCA). Through a cancer registry‐based study, phone‐based GC for HBOC was offered to AA women with breast cancer ≤50. A questionnaire to assess knowledge about HBOC was completed prior to GC. All women were provided a GCA about HBOC developed by the investigative team for use during the GC session. Following GC, a personalized summary letter was mailed to all study participants and the same knowledge questionnaire was completed. A total of 37 study participants completed the pre‐ and post‐GC knowledge questionnaires with significant gains in knowledge following the GC process (p < 0.0001). Statistically significant factors associated with knowledge gain included earlier stage of diagnosis of breast cancer and education level. Our results indicate that phone‐based GC supplemented by a culturally targeted visual aid is an effective means of improving knowledge about HBOC in young AA women with invasive breast cancer.
Management of major blood loss: An update
Authors: JOHANSSON P. I. , OSTROWSKI S. R. , SECHER N. H.
Published: July 2010

Haemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved, prioritizing the early control of the cause of bleeding by non‐definitive means, while haemostatic control resuscitation seeks early control of coagulopathy. Haemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells (RBCs) in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Transfusion of RBCs, plasma and platelets in a similar proportion as in whole blood prevents both hypovolaemia and coagulopathy. Although an early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking. Results from recent before‐and‐after studies in massively bleeding patients indicate that trauma exsanguination protocols involving the early administration of plasma and platelets are associated with improved survival. Furthermore, viscoelastic whole blood assays, such as thrombelastography (TEG)/rotation thromboelastometry (ROTEM), appear advantageous for identifying coagulopathy in patients with severe haemorrhage, as opposed to conventional coagulation assays. In our view, patients with uncontrolled bleeding, regardless of its cause, should be treated with goal‐directed haemostatic control resuscitation involving the early administration of plasma and platelets and based on the results of the TEG/ROTEM analysis. The aim of the goal‐directed therapy should be to maintain a normal haemostatic competence until surgical haemostasis is achieved, as this appears to be associated with reduced mortality.
Adrenocortical Response in Cows after Intramuscular Injection of Long‐Acting Adrenocorticotropic Hormone (Tetracosactide Acetate Zinc Suspension)
Authors: Thinh NC , Yoshida C , Long ST , Yusuf M , Nakao T
Published: July 2010

Contents

The objectives of this study were first to show adrenocortical response to a long‐acting adrenocorticotropic hormone preparation (tetracosactide acetate zinc suspension) (ACTH‐Z) and its effect on adrenocortical function in beef cows (Experiment 1) and second to apply the ACTH‐Z challenge in dairy cows based on cortisol concentrations in milk collected at routine milking (Experiment 2). InExperiment 1, four beef cows in luteal phase were challenged with ACTH‐Z, and plasma cortisol concentrations were determined for 48 h after the injection at 30‐min to 2‐h intervals. A rapid ACTH test was conducted 3 days before and 2 h after the completion of ACTH‐Z injection for 48 h to investigate the effect on adrenocortical function. Plasma cortisol concentrations increased significantly 30 min after ACTH‐Z injection (p < 0.001), and the high cortisol levels were maintained for approximately 10 h after the injection. InExperiment 2, eight dairy cows were subjected to ACTH‐Z challenge 1–2 weeks and 4–5 weeks post‐partum. Blood and milk samples were taken at morning and afternoon milking. All the cows showed a significant increase in cortisol concentrations in plasma as well as in skim milk 8 h after ACTH‐Z injection 1–2 weeks and 4–5 weeks post‐partum (p < 0.001). There was a significant correlation between plasma and skim milk cortisol concentrations 8 h after ACTH‐Z challenge (r = 0.74, p < 0.001). The results obtained in this study suggest that elevated levels of plasma cortisol are maintained for approximately 10 h after ACTH‐Z treatment without adverse effect on adrenocortical function and a long‐acting ACTH‐Z challenge based on cortisol concentrations in milk, which were collected at the morning and the afternoon milking, can be a useful tool to monitor adrenocortical function in cows.
Telegony, the Sire Effect and non‐Mendelian Inheritance Mediated by Spermatozoa: A Historical Overview and Modern Mechanistic Speculations
Authors: Liu YS
Published: July 2010

Contents

Telegony is the belief that the sire first mated to a female will have an influence upon some of that female’s later offspring by another male. Although the reality of telegony was acknowledged by such authorities as Darwin, Spencer, Romanes and many experienced breeders, it has been met with scepticism because of Weismann’s unfavourable comments and negative results obtained in several test experiments. In this article, alleged cases of telegony are provided. A search of the literature of cell biology and biochemistry reveals several plausible mechanisms that may form the basis for telegony. These involve the penetration of spermatozoa into the somatic tissues of the female genital tract, the incorporation of the DNA released by spermatozoa into maternal somatic cells, the presence of foetal DNA in maternal blood, as well as sperm RNA‐mediated non‐Mendelian inheritance of epigenetic changes.
Interleukin‐1B and interleukin‐1 RN polymorphisms and gastric carcinoma risk: A meta‐analysis
Authors: Xue Huiping , Lin Bin , Ni Peihua , Xu Hong , Huang Gang
Published: July 2010

Background and Aim:  We aimed to explore the role of interleukin (IL)‐1B cluster gene polymorphisms at positions −511, −31, and +3954 and the receptor IL‐1RN variable number tandem repeat polymorphisms in the susceptibility to gastric carcinoma through a systematic review and meta‐analysis.

Methods:  Each initially included article was scored for quality appraisal. The desirable data were extracted and registered into databases. Studies that deviated from Hardy–Weinberg equilibrium were excluded. Eighteen studies were ultimately eligible for the meta‐analysis of IL1B–511, 21 studies for IL1B‐31, 10 studies for IL1B+3954, and 20 studies for IL1RN variable number tandem repeat genetic polymorphisms, respectively. Original groups were collapsed and re‐grouping was adopted in line with the most probably appropriate genetic models. Potential sources of heterogeneity were sought out via stratification and sensitivity analyses, and biases across studies were estimated.

Results:  The pooled odds ratios (95% confidence intervals, P‐value) associated with IL‐1B −511 T carriers versus CC genotypes and with RN *2 carriers versus L/L were 1.23 (1.04–1.45, P = 0.015) and 1.26 (1.06–1.51, P = 0.010), respectively, for overall gastric carcinoma; 1.31 (1.04–1.64, P = 0.020) and 1.47 (1.21–1.79, P = 0.000), respectively, for non‐cardia gastric cancer; 1.55 (1.05–2.28, P = 0.026) and 1.66 (1.23–2.25, P = 0.001), respectively, for intestinal type gastric carcinoma; and 1.33 (1.04–1.71, P = 0.023) and 1.31 (1.07–1.61, P = 0.010), respectively, in Caucasians for overall gastric carcinoma. The pooled odds ratio (95% confidence interval, P‐value) regarding IL‐1B−31 CC plus TT versus CT was 0.73 (0.60–0.89, P = 0.002) for intestinal type gastric carcinoma. Genotyping methods and publication time could constitute the sources of heterogeneity across studies. Publication biases were not found.

Conclusion:  IL‐1B −511 T allele and IL‐1 RN *2 VNTR are significantly associated with an increased risk of developing gastric carcinoma and even more significantly with non‐cardia gastric carcinoma or with intestinal‐type gastric carcinoma. Both are significantly associated with an increased risk of developing gastric carcinoma among Caucasians, but not among Asians or Hispanics.
Increased myocardial methionine‐enkephalin with reduced arterial oxygenation in congenital heart disease
Authors: van den Brink Olivier WV , Cochrane Andrew D , Rosenfeldt Franklin L , Penny Daniel J , Pepe Salvatore
Published: July 2010

Background:  Cardiac opioid peptides have been identified to exert important adaptive metabolic signalling for cardioprotection against ischaemia or hypoxia‐related injury.

Aims:  To determine myocardial methionine‐enkephalin content in children with hypoxemic congenital heart defects and to correlate myocardial content of methionine‐enkephalin with the extent of arterial oxygen desaturation.

Methods:  Children (n= 20, median age of 16 months), undergoing cardiac surgical repair (tetralogy of Fallot, 17/20), were included in this study. Arterial oxygen saturation was measured on admission. Myocardial samples obtained during surgery were assayed via radioimmunochemistry for methionine‐enkephalin content.

Results:  Greater methionine‐enkephalin content was measured in the right ventricles of the patients suffering from recent cyanotic spells compared with those with no recent spells (cyanotic spells: 2418 ± 844 pg/g wet weight tissue, n= 6; no spells: 1175 ± 189 pg/g wet weight tissue, n= 14, P= 0.04). An inverse correlation was evident between the arterial oxygen saturation and myocardial methionine‐enkephalin content.

Conclusion:  Myocardial methionine‐enkephalin levels increase with the severity of hypoxic stress in congenital cardiac disease and may play an important adaptive role in countering adrenergic over‐activity and related excess demand on myocardial metabolic capacity.
Quantitative ultrasonometry of the calcaneus in children with osteogenesis imperfecta
Authors: Kutilek Stepan , Bayer Milan
Published: July 2010

Aims:  Osteogenesis imperfecta (OI) is characterised by low bone density and increased bone fragility. The aim was to evaluate calcaneal quantitative ultrasonometry (QUS) parameters in children with OI and to look for relationship with the number of prevalent fractures.

Methods:  Eighteen children (12 boys and six girls; mean age 9.8 ± 3.5 years) with OI (type I, n= 15; type IV, n= 3; mean fracture prevalence 3.7 per patient) had the velocity of sound (VOS) and broadband ultrasound attenuation (BUA) measured on both heels with a Cuba Clinical (McCue Ultrasonics, Winchester, UK) dry ultrasound portable device. Both BUA and VOS were expressed as either age‐dependent or height‐related values. The obtained values of VOS and BUA were correlated to number of prevalent fractures.

Results:  The patients were of short stature (Z‐score –1.73 ± 1.20 SD; P < 0.001). Both age‐related BUA and VOS were low in comparison to reference values (P < 0.0001), same as height‐adjusted BUA and VOS (P < 0.0001). We found no correlations between number of prevalent fractures and BUA or VOS (age‐related or height‐adjusted) (r= 0.02, r= 0.017, r=–0.13, r= 0.015, respectively).

Conclusions:  Children with OI have low QUS parameters with no relationship to number of prevalent fractures.
The safety of long‐acting beta‐agonists: More evidence is needed
Authors: KAZANI Shamsah , WARE James H. , DRAZEN Jeffrey M. , TAYLOR D. Robin , SEARS Malcolm R.
Published: July 2010

There is controversy regarding the possibility that long‐acting beta‐agonists (LABA) may paradoxically contribute adversely to asthma mortality. While studies and meta‐analyses indicate increased risk, epidemiological data indicate a slow fall in asthma mortality since the introduction of LABA. Advocates for LABA propose that mandatory simultaneous use of inhaled corticosteroids satisfactorily reduce any potential risk. In the face of lingering doubts, others propose that LABA should be withdrawn from use. In this pro–con article, Kazaniet al. provide the rationale for a modified randomized controlled trial that would define the level of risk more clearly, and provide the basis for a clear judgment to be made. Sears argues that current knowledge about the risks associated with LABA, especially when prescribed as monotherapy, provides sufficient evidence for clinicians and licensing authorities alike, and that the logistics and likely outcomes for a large prospective study are unjustified.
Perinatal development of inhibitory synapses in the nucleus tractus solitarii of the rat
Authors: Dufour Amandine , Tell Fabien , Baude Agnès
Published: July 2010

The nucleus tractus solitarii (NTS) plays a key role in the central control of the autonomic nervous system. In adult rats, both GABA and glycine are used as inhibitory neurotransmitter in the NTS. Using a quantitative morphological approach, we have investigated the perinatal development of inhibitory synapses in the NTS. The density of both inhibitory axon terminals and synapses increased from embryonic day 20 until the end of the second postnatal week (postnatal day 14). Before birth, only GABAergic axon terminals developed and their number increased during the first postnatal week. Mixed GABA/glycine axon terminals appeared at birth and their number increased during the first postnatal week. This suggests the development of a mixed GABA/glycine inhibition in parallel to pure GABA inhibition. However, whereas GABAergic axon terminals were distributed throughout the NTS, mixed GABA/glycine axon terminals were strictly located in the lateral part of the NTS. Established at birth, this specific topography remained in the adult rat. From birth, GABAA receptors, glycine receptors and gephyrin were clustered in inhibitory synapses throughout the NTS, revealing a neurotransmitter–receptor mismatch within the medial part of the NTS. Together these results suggest that NTS inhibitory networks develop and mature until postnatal day 14. Developmental changes in NTS synaptic inhibition may play an important role in shaping neural network activity during a time of maturation of autonomic functions. The first two postnatal weeks could represent a critical period where the impact of the environment influences the physiological phenotypes of adult rats.
Ecology of arthritis
Authors: Peterson Rolf O. , Vucetich John A. , Fenton Gus , Drummer Thomas D. , Larsen Clark Spencer
Published: July 2010

Ecology Letters (2010) 13: 1124–1128

Osteoarthritis (OA) is a widespread degenerative disease of skeletal joints and is often associated with senescence in vertebrates. OA commonly results from excessive or abnormal mechanical loading of weight‐bearing joints (‘wear‐and‐tear’), arising from heavy long‐term use or specific injuries; yet, in the absence of injury, the aetiology of OA remains obscure. We show that poor nutritional conditions experienced by moose (Alces alces) early in life are linked to greater prevalence of OA during senescence as well as reduced life expectancy. Moreover, we also found a negative relationship between kill rate by wolves (Canis lupus) and prevalence of OA, suggesting a potential connection between senescence of prey and the population ecology of predator–prey systems. This association between OA and early malnutrition also provides a basis for explaining the observation in anthropology that OA became more prevalent in native Americans as their diet become poorer – the result of relying more on corn and agriculture and less on hunting and gathering.
Host physiological phenotype explains pathogen reservoir potential
Authors: Cronin James Patrick , Welsh Miranda E. , Dekkers Martin G. , Abercrombie Samuel T. , Mitchell Charles E.
Published: July 2010

Control of emerging infectious diseases often hinges on identifying a pathogen reservoir, the source of disease transmission. The potential to function as a pathogen reservoir can be influenced by host lifespan, geographic provenance and phylogeny. Yet, no study has identified factors that causally determine the reservoir potential of diverse host species. We propose the host physiological phenotype hypothesis, which predicts that hosts with short‐lived, poorly defended, nutrient rich and high metabolism tissue have greater values for three epidemiological parameters that determine reservoir potential: host susceptibility to infection, competence to infect vectors and ability to support vector populations. We experimentally tested these predictions using a generalist vectored virus and six wild grass species. Host physiological phenotype explained why hosts differed in all three epidemiological parameters while host lifespan, provenance and phylogeny could not explain host competence. Thus, a single, general axis describing variation in host physiological phenotype may explain reservoir potential.
Radiation, chemotherapy and biological therapy in the curative treatment of locally advanced rectal cancer
Authors: Gollins S.
Published: July 2010

Objective  To review the published evidence relating to the use of radiotherapy (RT), chemotherapy and biological therapy as adjuncts to surgery in the curative treatment of rectal cancer.

Methods  Searches were carried out of the MEDLINE and CANCERLIT databases together with conference abstracts from key meetings including the American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancers Symposium and the ECCO/ESMO Multidisciplinary Congress.

Results  RT reduces local pelvic recurrence when used as an adjunct to surgery, even when this is performed optimally by total mesorectal excision (TME). RT is usually given as short‐course preoperative radiotherapy (SCPRT) followed by immediate surgery which produces no or very little downstaging or long‐course concurrent chemoradiation (CRT) followed by a 6‐8 week gap prior to surgery which produces significant downstaging. The prognostic importance of achieving a clear histological circumferential resection margin is now well recognised and pathological assessment of the quality of surgery can predict long‐term outcomes. Internationally there is considerable heterogeneity in the staging modalities and criteria used in deciding which approach might be used, in the reporting of histological results and in RT parameters (time/dose/fractionation/volume). Attempts to increase the potency of CRT have included the addition of concurrent chemotherapeutic and biological agents to the standard fluoropyrimidine although there is little randomised data and none with regard to long‐term survival outcomes. Neither SCPRT nor downstaging CRT have been shown to reduce the rate of subsequent distant metastatic relapse which remains a significant clinical problem. The potential additional benefit of neoadjuvant or adjuvant chemotherapy in addition to SCPRT or long‐course CRT remains ill‐defined. Late morbidity can include bowel and sexual dysfunction, pelvic fractures and second malignancies with considerably more being known in relation to SCPRT than long‐course CRT.

Conclusions  Improvements in imaging, pathology and surgical technique combined with multimodality treatment using RT and chemotherapy are leading to continuing improvements in the long term outcome for patients with rectal cancer although much remains to be learnt regarding the optimum strategy for use of these in different clinical contexts and their relationship to long‐term morbidity.
Association between alcohol consumption and diabetic retinopathy and visual acuity—the AdRem Study
Authors: Lee C. C. , Stolk R. P. , Adler A. I. , Patel A. , Chalmers J. , Neal B. , Poulter N. , Harrap S. , Woodward M. , Marre M. , Grobbee D. E. , Beulens J. W. ,   on behalf of the AdRem project team and ADVANCE management committee
Published: July 2010

Diabet. Med. 27, 1130–1137 (2010)

Aims  We investigated the association between alcohol consumption and diabetic retinopathy and deterioration of visual acuity in individuals with Type 2 diabetes.

Methods  We conducted a cohort analysis of 1239 participants with Type 2 diabetes aged 55–81 years enrolled in the AdRem study, a sub‐study of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Current and past consumption of wine, spirits and beer was measured by self‐report. Moderate and heavy alcohol consumption was defined as 1–14 and > 14 drinks/week, respectively. Diabetic retinopathy, measured by mydriatic stereoscopic seven‐field retinal photography, was defined by a 2‐step progression in the Early Treatment of Diabetic Retinopathy Study (ETDRS) score or the presence of any retinal vascular lesions. Deterioration of visual acuity was defined by a decrease of two lines in best vision in either eye, measured corrected, or through a pinhole using a Snellen chart.

Results  In a mean follow‐up of 5.5 years, we identified 182 participants with a 2‐step progression in the ETDRS score, 640 participants with the presence of any retinal vascular lesions and 693 participants with a deterioration of visual acuity. Current moderate consumption of alcohol, compared with no current consumption, was not associated with presence or progression of diabetic retinopathy; however, it was associated with higher risk of deterioration of visual acuity (multivariable‐adjusted OR 1.83; 95% CI 1.34–2.48; P < 0.001).

Conclusions  Alcohol consumption is associated with increased risk of deterioration of visual acuity, but not with retinopathy in individuals with Type 2 diabetes.
Estimated costs of acute hospital care for people with diabetes in the United Kingdom: a routine record linkage study in a large region*
Authors: Morgan C. Ll. , Peters J. R. , Dixon S. , Currie C. J.
Published: July 2010

Diabet. Med. 27, 1066–1073 (2010)

Aims  Diabetes represents a notable burden to health payers. The purpose of this study was to estimate acute hospital care costs of treating people with diabetes with reference to the costs of treating those without.

Methods  This was a retrospective study. Data from routine hospital practice were available from a large health region (439 000 people), with an estimated prevalence of diabetes of 3.4%. Common records were identified using probabilistic record linkage. Cost estimates were attributed to admissions using healthcare resource group software. Outpatient costs were attributed using published values. Data described are for 2004, and prices in pounds sterling for 2005. Standardised cost ratios were estimated to compare the costs observed in the diabetes population with those expected from the non‐diabetic reference population.

Results  The total annual cost of admissions was £28 944 811 per 100 000 people, of which £3 650 869 per 100 000 (12.6%) was diabetes related. The standardised cost rate of inpatient treatment was 2.9. The total cost of outpatient attendances was £6 589 971 per 100 000, of which £711 431 per 100 000 (10.8%) was diabetes related. The standardised cost ratio for outpatient care was 4.1. The total cost of hospital care for patients with diabetes was £11 206 986 per 100 000, or 12.3% of acute hospital expenditure. The combined standardised cost ratio was 3.1. Costs of care for inpatient treatment increased from 8.7% of revenue in 1994 to 12.3% in 2004.

Conclusions  The costs of acute hospital care for treating people with diabetes increased markedly over a decade, and now exceed 12% of revenue.
Smoking cessation during pregnancy: A systematic literature review
Authors: SCHNEIDER SVEN , HUY CHRISTINA , SCHÜTZ JESSICA , DIEHL KATHARINA
Published: July 2010

Issues. Second‐hand smoke presents a health risk for a large group of entirely helpless nonsmokers: unborn children. Reliable data on women continuing to smoke during pregnancy are essential for effective preventive and interventional programs. The aim of this review is therefore to identify this risk group compared with spontaneous quitters of smoking. Approach. This systematic literature review is based solely on empirical original papers derived from samples of pregnant women smoking at the beginning of pregnancy. In accordance with the QUOROM Statement all population or clinic‐based samples were included. Collectives from intervention studies were not included. All studies were from developed nations and published between January 1997 and March 2008. Key Findings. A total of 19 studies were identified. The rate of quitters was between 4.0% and 69.7% for population‐based studies, and 26.5% and 47.0% for clinic‐based studies. A smoking partner, a large number of children, a high rate of tobacco consumption, as well as deficiencies in prenatal care were predictors of smoking during pregnancy. Implications. This study identifies risk factors and correlates and indicates common obstacles for women to quit smoking during pregnancy. Conclusion. The risk groups that can be defined based on our results are a key target population for preventive measures.[Schneider S, Huy C, Schütz J, Diehl K. Smoking cessation during pregnancy: A systematic literature review. Drug Alcohol Rev 2009]
Doing good, but looking bad? Local perceptions of two humanitarian organisations in eastern Democratic Republic of the Congo
Authors: Dijkzeul Dennis , Wakenge Claude Iguma
Published: July 2010

This paper examines local perceptions of two international humanitarian organisations, the International Rescue Committee (IRC) and Malteser International, in the eastern Democratic Republic of the Congo (DRC) (formerly known as Zaire). At times, the self‐perception of these organisations differs considerably from the perceptions of local beneficiaries and stakeholders. This study begins by reviewing the current status of research on local perceptions of externally‐introduced humanitarian action. It goes on to discuss the local perceptions of the IRC and Malteser International, as well as the origins of these perceptions, and to show that three different narratives are used by local actors to explain their different perceptions. The paper ends with an examination of the factors that help to account for the differences in perceptions and of the implications of this type of research for humanitarian principles and management, as well as for the study of local perceptions.
Welfare Policy in the Presence of Unionised Labour and Internationally Mobile Firms*
Authors: Rocha‐Akis Silvia , Schöb Ronnie
Published: July 2010

To what extent does the welfare state exacerbate the loss of jobs due to offshoring? We consider a model with oligopolistic sectors that are exposed to offshoring, as well as a unionised labour force that is entitled to unemployment benefits. We find that deeper economic integration induces wage moderation to the point that wages become independent of workers' outside options. Because the entire incidence of redistribution falls on net wages, the unions' willingness to moderate wages is constrained by the level of redistribution. Beyond an upper limit of redistribution, extending the welfare state compels unions to oppose wage moderation at the cost of losing jobs to offshoring. Below that upper limit, however, redistribution becomes less rather than more distortive.
Stability Selection
Authors: Meinshausen Nicolai , Bühlmann Peter
Published: July 2010

Estimation of structure, such as in variable selection, graphical modelling or cluster analysis, is notoriously difficult, especially for high dimensional data. We introduce stability selection. It is based on subsampling in combination with (high dimensional) selection algorithms. As such, the method is extremely general and has a very wide range of applicability. Stability selection provides finite sample control for some error rates of false discoveries and hence a transparent principle to choose a proper amount of regularization for structure estimation. Variable selection and structure estimation improve markedly for a range of selection methods if stability selection is applied. We prove for the randomized lasso that stability selection will be variable selection consistent even if the necessary conditions for consistency of the original lasso method are violated. We demonstrate stability selection for variable selection and Gaussian graphical modelling, using real and simulated data.
Explicit Estimating Equations for Semiparametric Generalized Linear Latent Variable Models
Authors: Ma Yanyuan , Genton Marc G.
Published: July 2010

We study generalized linear latent variable models without requiring a distributional assumption of the latent variables. Using a geometric approach, we derive consistent semiparametric estimators. We demonstrate that these models have a property which is similar to that of a sufficient complete statistic, which enables us to simplify the estimating procedure and explicitly to formulate the semiparametric estimating equations. We further show that the explicit estimators have the usual root n consistency and asymptotic normality. We explain the computational implementation of our method and illustrate the numerical performance of the estimators in finite sample situations via extensive simulation studies. The advantage of our estimators over the existing likelihood approach is also shown via numerical comparison. We employ the method to analyse a real data example from economics.