bluuebunny/crossref_metadata_2025 huggingface dataset:
A deeper look into transcription regulatory code by preferred pair distance templates for transcription factor binding sites
Authors: Kulakovskiy I. V. , Belostotsky A. A. , Kasianov A. S. , Esipova N. G. , Medvedeva Y. A. , Eliseeva I. A. , Makeev V. J.
Published: August 2011

Motivation: Modern experimental methods provide substantial information on protein–DNA recognition. Studying arrangements of transcription factor binding sites (TFBSs) of interacting transcription factors (TFs) advances understanding of the transcription regulatory code.

Results: We constructed binding motifs for TFs forming a complex with HIF-1α at the erythropoietin 3′-enhancer. Corresponding TFBSs were predicted in the segments around transcription start sites (TSSs) of all human genes. Using the genome-wide set of regulatory regions, we observed several strongly preferred distances between hypoxia-responsive element (HRE) and binding sites of a particular cofactor protein. The set of preferred distances was called as a preferred pair distance template (PPDT). PPDT dramatically depended on the TF and orientation of its binding sites relative to HRE. PPDT evaluated from the genome-wide set of regulatory sequences was used to detect significant PPDT-consistent binding site pairs in regulatory regions of hypoxia-responsive genes. We believe PPDT can help to reveal the layout of eukaryotic regulatory segments.

Contact:  ivan.kulakovskiy@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Improved quality control processing of peptide-centric LC-MS proteomics data
Authors: Matzke Melissa M. , Waters Katrina M. , Metz Thomas O. , Jacobs Jon M. , Sims Amy C. , Baric Ralph S. , Pounds Joel G. , Webb-Robertson Bobbie-Jo M.
Published: August 2011

Motivation: In the analysis of differential peptide peak intensities (i.e. abundance measures), LC-MS analyses with poor quality peptide abundance data can bias downstream statistical analyses and hence the biological interpretation for an otherwise high-quality dataset. Although considerable effort has been placed on assuring the quality of the peptide identification with respect to spectral processing, to date quality assessment of the subsequent peptide abundance data matrix has been limited to a subjective visual inspection of run-by-run correlation or individual peptide components. Identifying statistical outliers is a critical step in the processing of proteomics data as many of the downstream statistical analyses [e.g. analysis of variance (ANOVA)] rely upon accurate estimates of sample variance, and their results are influenced by extreme values.

Results: We describe a novel multivariate statistical strategy for the identification of LC-MS runs with extreme peptide abundance distributions. Comparison with current method (run-by-run correlation) demonstrates a significantly better rate of identification of outlier runs by the multivariate strategy. Simulation studies also suggest that this strategy significantly outperforms correlation alone in the identification of statistically extreme liquid chromatography-mass spectrometry (LC-MS) runs.

Availability:  https://www.biopilot.org/docs/Software/RMD.php

Contact:  bj@pnl.gov

Supplementary information:  Supplementary material is available at Bioinformatics online.
Biochemical characterization of the tetrahydrobiopterin synthesis pathway in the oleaginous fungus Mortierella alpina
Authors: Wang Hongchao , Yang Bo , Hao Guangfei , Feng Yun , Chen Haiqin , Feng Lu , Zhao Jianxin , Zhang Hao , Chen Yong Q. , Wang Lei , Chen Wei
Published: August 2011

We characterized thede novobiosynthetic pathway of tetrahydrobiopterin (BH4) in the lipid-producing fungusMortierella alpina. The BH4cofactor is essential for various cell processes, and is probably present in every cell or tissue of higher organisms. Genes encoding two copies of GTP cyclohydrolase I (GTPCH-1 and GTPCH-2) for the conversion of GTP to dihydroneopterin triphosphate (H2-NTP), 6-pyruvoyltetrahydropterin synthase (PTPS) for the conversion of H2-NTP to 6-pyruvoyltetrahydropterin (PPH4), and sepiapterin reductase (SR) for the conversion of PPH4to BH4, were expressed heterologously inEscherichia coli. The recombinant enzymes were produced as His-tagged fusion proteins and were purified to homogeneity to investigate their enzymic activities. Enzyme products were analysed by HPLC and electrospray ionization-MS. Kinetic parameters and other properties of GTPCH, PTPS and SR were investigated. Physiological roles of BH4inM. alpinaare discussed, and comparative analyses between GTPCH, PTPS and SR proteins and other homologous proteins were performed. The presence of two functional GTPCH enzymes has, as far as we are aware, not been reported previously, reflecting the unique ability of this fungus to synthesize both BH4and folate, using the GTPCH product as a common substrate. To our knowledge, this study is the first to report the comprehensive characterization of a BH4biosynthesis pathway in a fungus.
A Francisella tularensis SCHU S4 mutant deficient in γ-glutamyltransferase activity induces protective immunity: characterization of an attenuated vaccine candidate
Authors: Ireland Philip M. , LeButt Helen , Thomas Rebecca M. , Oyston Petra C. F.
Published: August 2011

Francisella tularensis is an intracellular pathogen which causes tularaemia. There is no licensed vaccine currently available for prophylaxis. The γ-glutamyl transpeptidase (GGT) encoded by the ggt gene has been shown to be important for the intracellular survival of F. tularensis. In this study we have constructed a ggt deletion mutant in the highly virulent F. tularensis strain SCHU S4. Characterization of the mutant strain confirmed the function of ggt, and confirmed the role of GGT in cysteine acquisition. The mutant strain was highly attenuated both in vitro and in vivo using murine models of infection. Moreover, we have demonstrated that the attenuated mutant is able to induce protective immunity against an F. tularensis SCHU S4 challenge, and thus may be a candidate for the development of an attenuated vaccine.
Effects of modality on the neural correlates of encoding processes supporting recollection and familiarity
Authors: Gottlieb Lauren J. , Rugg Michael D.
Published: August 2011

Prior research has demonstrated that the neural correlates of successful encoding (“subsequent memory effects”) partially overlap with neural regions selectively engaged by the on-line demands of the study task. The primary goal of the present experiment was to determine whether this overlap is associated solely with encoding processes supporting later recollection, or whether overlapping subsequent memory and study condition effects are also evident when later memory is familiarity-based. Subjects (N = 17) underwent fMRI scanning while studying a series of visually and auditorily presented words. Memory for the words was subsequently tested with a modified Remember/Know procedure. Auditorily selective subsequent familiarity effects were evident in bilateral temporal regions that also responded preferentially to auditory items. Although other interpretations are possible, these findings suggest that overlap between study condition-selective subsequent memory effects and regions selectively sensitive to study demands is not uniquely associated with later recollection. In addition, modality-independent subsequent memory effects were identified in several cortical regions. In every case, the effects were greatest for later recollected items, and smaller for items later recognized on the basis of familiarity. The implications of this quantitative dissociation for dual-process models of recognition memory are discussed.
Green Light Induces Shade Avoidance Symptoms
Authors: Zhang Tingting , Maruhnich Stefanie A. , Folta Kevin M.
Published: August 2011

Light quality and quantity affect plant adaptation to changing light conditions. Certain wavelengths in the visible and near-visible spectrum are known to have discrete effects on plant growth and development, and the effects of red, far-red, blue, and ultraviolet light have been well described. In this report, an effect of green light on Arabidopsis (Arabidopsis thaliana) rosette architecture is demonstrated using a narrow-bandwidth light-emitting diode-based lighting system. When green light was added to a background of constant red and blue light, plants exhibited elongation of petioles and upward leaf reorientation, symptoms consistent with those observed in a shaded light environment. The same green light-induced phenotypes were also observed in phytochrome (phy) and cryptochrome (cry) mutant backgrounds. To explore the molecular mechanism underlying the green light-induced response, the accumulation of shade-induced transcripts was measured in response to enriched green light environments. Transcripts that have been demonstrated to increase in abundance under far-red-induced shade avoidance conditions either decrease or exhibit no change when green light is added. However, normal far-red light-associated transcript accumulation patterns are observed in cryptochrome mutants grown with supplemental green light, indicating that the green-absorbing form of cryptochrome is the photoreceptor active in limiting the green light induction of shade-associated transcripts. These results indicate that shade symptoms can be induced by the addition of green light and that cryptochrome receptors and an unknown light sensor participate in acclimation to the enriched green environment.
Molecular phylogenetics of the melyrid lineage (Coleoptera: Cleroidea)
Authors: Bocakova M. , Constantin R. , Bocak L.
Published: August 2011

The melyrid lineage of beetles form a distinct group of the superfamily Cleroidea with a high level of soft‐bodiedness. Here we present the first molecular phylogenetic analysis of this group. The data matrix included partial sequences of the small and large subunits of rRNA, the mitochondrial large subunit rRNA, and cytochrome oxidase subunit I of 67 melyrid and eight outgroup taxa. The concatenated sequences were analysed using maximum‐parsimony (MP), maximum‐likelihood (ML) and Bayesian analysis (BA) approach. The results strongly supported the monophyly of the melyrid lineage splitting into six major clades: Rhadalidae, Mauroniscidae, Prionoceridae, Melyridae sensu stricto, Dasytidae and Malachiidae. The rhadalids were placed in the most basal position, followed by mauroniscids and prionocerids. Three terminal lineages—the true melyrids, dasytids, and malachiids—are well supported by all analyses, but their mutual relationships remain uncertain as MP analysis proposed alternative topologies to that of the ML and BA trees, with often low node support in the latter two methods. The monophyly of the subfamily Danacaeinae (Dasytidae) with respect to the danacaeine genera of the southern hemisphere (Hylodanacaea, Listrocerus, Amecocerus) was challenged as they were found to be polyphyletic. Similarly, the monophyly of Attalus was rejected by our analyses and shown to be polyphyletic. Based on the preferred phylogenetic hypothesis, the subfamilies Rhadalinae, Dasytinae and Malachiinae are elevated to family rank.

© The Willi Hennig Society 2011.
Potato virus X movement in Nicotiana benthamiana: new details revealed by chimeric coat protein variants
Authors: BETTI CAMILLA , LICO CHIARA , MAFFI DARIO , D'ANGELI SIMONE , ALTAMURA MARIA MADDALENA , BENVENUTO EUGENIO , FAORO FRANCO , BASCHIERI SELENE
Published: August 2011

Potato virus X coat protein is necessary for both cell‐to‐cell and phloem transfer, but it has not been clarified definitively whether it is needed in both movement phases solely as a component of the assembled particles or also of differently structured ribonucleoprotein complexes. To clarify this issue, we studied the infection progression of a mutant carrying an N‐terminal deletion of the coat protein, which was used to construct chimeric virus particles displaying peptides selectively affecting phloem transfer or cell‐to‐cell movement. Nicotiana benthamiana plants inoculated with expression vectors encoding the wild‐type, mutant and chimeric viral genomes were examined by microscopy techniques. These experiments showed that coat protein–peptide fusions promoting cell‐to‐cell transfer only were not competent for virion assembly, whereas long‐distance movement was possible only for coat proteins compatible with virus particle formation. Moreover, the ability of the assembled PVX to enter and persist into developing xylem elements was revealed here for the first time.
The effect of frugivory on postdispersal seed removal and germination in the pantropical forest tree Antiaris toxicaria Leschenault
Authors: Kankam Bright O. , Oduro William
Published: August 2011

The quality of seed treatment by frugivores has an effect on seed removal after dispersal, seed germination and tree recruitment. We provide information on postdispersal seed removal, germination and subsequent recruitment in tropical forest tree species Antiaris toxicaria in Ghana. We tested whether postdispersal seed removal and germination rates were differentially affected by the following seed treatments: seeds that were spat out by monkeys with all fruit pulp removed and spitting seeds with fruit pulp partially removed as observed in some birds and bats. We used seeds of intact ripened fruits as control. Frugivore seed treatment and distance from bole affected seed removal patterns, whereas intact seeds were significantly removed from all seed stations. The germination success was greater for seeds that were spat out by monkeys and poor for seeds with fruit pulp partially removed and intact fruits. More recruits were recorded at the edge of the adult A. toxicaria canopy radius. There was weak relationship (r2 = 0.042) between the number of recruits and distance away from the adult tree. Results suggest that the subsequent recruitment in tropical forest tree species may be enhanced by some frugivore fruit‐handling behaviour where fruit pulp is removed from the seeds without destroying the seeds.
Impact of paediatric human immunodeficiency virus infection on children's and caregivers' daily functioning and well‐being: a qualitative study
Authors: Punpanich W. , Gorbach P. M. , Detels R.
Published: August 2011

Background  Human immunodeficiency virus (HIV) infection impacts not only upon the physical health of affected children, but also their psychosocial functions, family relationships and economical status. Caregivers are confronted with complex challenges related to the physical, emotional and financial demands of raising these children. The purpose of this study was to enhance our understanding of the impact of HIV disease on both children's and caregivers' well‐being, using a qualitative inquiry approach.

Methods  A total of 35 primary caregivers of HIV‐infected children participated in in‐depth interviews. The issues discussed included the major negative impacts on children's daily functioning and well‐being, and the perceived caregiver/parental burden. Participants included parents (40%), grandparents (22.8%), other relatives (e.g. uncles, aunts) (34.3%) and one foster parent (2.8%).

Results  Qualitative analysis revealed that the major negative impacts of HIV/AIDS included physical symptoms, school performance and relationship changes. The major negative impacts on caregivers' well‐being included acceptance of the diagnosis, dealing with the financial burden and keeping the diagnosis private.

Conclusions  Approaches are needed to address these challenges by enhancing families' coping skills and building supportive networks.
Total and free testosterone concentrations are strongly influenced by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and diabetes‐related quality of life
Authors: Biswas Mousumi , Hampton David , Newcombe Robert G. , Rees D. Aled
Published: August 2011

Objective  Testosterone levels are commonly lowered in men with diabetes, but it is unclear how these relate to symptoms of hypogonadism and quality of life. We sought to investigate the relationship between testosterone levels, symptoms of androgen deficiency, erectile function and quality of life in men with type 1 and type 2 diabetes.

Design and subjects  Cross‐sectional study of 115 men with type 2 diabetes, 93 men with type 1 diabetes and 121 healthy controls.

Measurements  Total, bioavailable and free testosterone levels were measured or calculated by Vermuelen’s formula. Quality of life and symptom scores were assessed by the Audit of Diabetes Dependent Quality of Life (ADDQoL), androgen deficiency in the aging male (ADAM) and International Index of Erectile Function (IIEF) questionnaires.

Results  Forty‐five and sixty‐one per cent of men with type 2 diabetes had low total and calculated free testosterone (CFT) levels, respectively. Total testosterone (TT) levels were not lowered in men with type 1 diabetes, but 32% had low CFT. After adjustment for age and waist circumference, only CFT in men with type 2 diabetes (−0·037 nm, 95% CI −0·075 to −0·0003, P = 0.048) remained lowered compared with controls. CFT correlated weakly with ADAM (r = −0·26, 95% CI −0.42 to −0·08, P = 0·006), IIEF (r = 0.19, 95% CI 0.01–0.37, P = 0.042) and ADDQoL (r = 0.21, 95% CI 0·03 to 0·38, P = 0·022) scores in men with type 2, but not type 1 diabetes. Age exerted the predominant effect on erectile function in both groups, in a model incorporating age, testosterone level and complications.

Conclusions  Testosterone levels are strongly affected by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and erectile function. Testosterone levels do not appear to be a major determinant of quality of life in patients with diabetes.
Development of hypothyroidism during long‐term follow‐up of patients with toxic nodular goitre after radioiodine therapy
Authors: Kahraman Deniz , Keller Christian , Schneider Christina , Eschner Wolfgang , Sudbrock Ferdinand , Schmidt Matthias , Schicha Harald , Dietlein Markus , Kobe Carsten
Published: August 2011

Objective  To investigate the cure rate and incidence of hypothyroidism of radioiodine treatment with a calculated dose regimen and an intended thyroid dose of 150 Gy in patients with toxic nodular goitre during long‐term follow‐up.

Patients  A total of 265 consecutive patients with toxic nodular goitre were treated between March 2003 and August 2004 at our institute and followed up for a maximum of 8 years. Preliminary radioiodine testing with volumetric measurement of the thyroid by ultrasound as well as individual thyroidal radioiodine uptake and half‐life measurements were performed before radioiodine therapy. The estimated radiation dose to the thyroid was 150 Gy.

Measurements  Follow‐up controls with respect to success of therapy and development of hypothyroidism were performed 3 months, 1 and up to 8 years after radioiodine treatment. The relation of the achieved thyroid dose to the success rate of treatment and to the incidence of hypothyroidism was analysed.

Results  The cure rates were 85% at 3 months, 98% at 1 year and 98% at the end of follow‐up. Above an achieved thyroid dose of more than 120 Gy, there was no significant association between the dose achieved in the thyroid and the cure rate on follow‐up. The incidences of hypothyroidism at 3 months, at 1 year and at the end of follow‐up were 32%, 55% and 73%, respectively.

Conclusions  Radioiodine treatment with a calculated dose regimen is a highly effective treatment option in patients with toxic goitre with an overall success rate of 98%. However, radioiodine treatment with an intended thyroid dose of 150 Gy leads to a high incidence of hypothyroidism on long‐term follow‐up. This finding supports the suggestion that in future intended thyroid doses could be lowered in patients treated with a calculated dose regimen for toxic nodular goitre.
Glucose fluctuations in subjects with normal glucose tolerance, impaired glucose regulation and newly diagnosed type 2 diabetes mellitus
Authors: Wang Chun , Lv Lifang , Yang Yanzhi , Chen Dawei , Liu Guanjian , Chen Lihong , Song Yuanxia , He Liping , Li Xiujun , Tian Haoming , Jia Weiping , Ran Xingwu
Published: August 2011

Objective  Glycemic variability is poorly studied in the nondiabetic individuals and newly diagnosed patients with type 2 diabetes. The aim of the study is to investigate the characteristics of glucose fluctuations in subjects with normal glucose tolerance (NGT), impaired glucose regulation (IGR) and newly diagnosed, drug‐naïve type 2 diabetes mellitus (DM‐2).

Design and patients  This is a cross‐sectional study of three groups including 53 subjects with IGR, 56 DM‐2 patients and 53 NGT individuals. Monitoring by a continuous glucose monitoring system (CGMS® System Gold™) was performed for three consecutive days.

Measurements  Mean blood glucose (MBG), standard deviation of MBG (SDBG), largest amplitude of glycemic excursions (LAGE) and mean amplitude of glycemic excursions (MAGE) were calculated to estimate intraday blood glucose variability. Interday variability of glucose was evaluated by absolute means of daily differences (MODD). Postprandial glucose excursion (PPGE) was calculated to assess the influence of meals on glucose fluctuation.

Results  Twenty‐two percentage of NGT and 33·9% of IGR individuals experienced blood glucose ≥11·1 mmol/l; 49·1% of NGT, 50·9% of IGR and 30·8% of DM‐2 participants had hypoglycemic episodes (CGM values <3·9 mmol/l). The IGR and DM‐2 groups had greater SDBG (P = 0·010 and P < 0·001), LAGE (P = 0·014 and P < 0·001) and MAGE (P = 0·044 and P < 0·001) compared with the NGT group. Significantly greater MODD and PPGEs were found in the DM‐2 groups than in the IGR and NGT groups (P < 0·001). The DM‐2 patients had higher 72‐MBG and glucose levels overnight than the NGT and IGR subjects (P < 0·001). In the patients with diabetes, MAGE was positively associated with MODD (r = 0·558, P < 0·001) and PPGEs (r = 0·738–0·843, P < 0·001).

Conclusions  Glucose variability is present to an increasing degree from NGT to IGR and IGR to DM‐2. Compared with the NGT individuals, the IGR and DM‐2 subjects show more predominant intraday glucose fluctuations. The DM‐2 patients demonstrate increased PPGEs, higher glucose levels overnight and greater interday fluctuations.
Clinical relevance of cardiac structure and function abnormalities in patients with Cushing’s syndrome before and after cure
Authors: Toja Paola M. , Branzi Giovanna , Ciambellotti Francesca , Radaelli Piero , De Martin Martina , Lonati Laura Maria , Scacchi Massimo , Parati Gianfranco , Cavagnini Francesco , Pecori Giraldi Francesca
Published: August 2011

Objectives  Sustained hypercortisolism impacts cardiac function, and, indeed, cardiac disease is one of the major determinants of mortality in patients with Cushing’s syndrome. The aim of this study was to assess the clinical relevance of cardiac structure and function alterations by echocardiography in patients with active Cushing’s syndrome and after disease remission.

Study design  Seventy‐one patients (61 women, 10 men) with Cushing’s syndrome and 70 age‐, sex‐ and blood pressure‐matched controls were enrolled. Echocardiography was performed in 49 patients with active disease and at several time points after remission in 44 patients (median follow‐up 46·4 months), and prevalence of abnormal left ventricular mass measurements and systolic and diastolic functions indices was compared between patients with active disease, after remission and controls. Twenty‐two patients were evaluated both before and after remission.

Results  Up to 70% of patients with active Cushing’s syndrome presented abnormal left ventricular mass parameters; 42% presented concentric hypertrophy and 23% concentric remodelling. Major indices of systolic and diastolic functions, i.e. ejection fraction and E/A ratio, respectively, were normal. Upon remission of hypercortisolism, left ventricular mass parameters ameliorated considerably, although abnormal values were still more frequent than in controls. Both cortisol excess and hypertension contribute to cardiac mass alterations and increase the prevalence of target organ damage.

Conclusions  Cushing’s syndrome is associated with an increased risk for abnormalities of cardiac mass, which ameliorates, but does not fully disappear after remission. Systolic and diastolic functions are largely within the normal range in these patients.
Use of management strategy comparison scatterplots to identify clusters of high‐performing strategies
Authors: McGARVEY R. , BURCH P. , FEENSTRA J. E.
Published: August 2011

Abstract  A management simulation model was developed to test quota, trip limits and reduced longline hook numbers as alternatives to yearly seasonal (November) closure in South Australian snapper fisheries. Population dynamics equations and maximum‐likelihood parameter estimates were supplied by an age‐ and length‐based stock assessment model. The relative performance of tested management strategies was quantified by comparing change in egg production vs change in average catch, to optimise the trade‐off between reproductive sustainability and catch foregone. Clusters of better‐performing strategies were visually identifiable in management strategy scatterplots. These scatterplots display percentage change from the status quo in egg‐production‐per‐female‐recruit (y‐axis) vs percentage change in catch‐per‐recruit (x‐axis). Evaluated strategies fell into three distinct performance clusters. The best performing strategy extended November closure by 2 weeks. Strategies that retained the November closure performed uniformly better than those that removed it. Further simulation showed this resulted from non‐closure strategies regulating only the commercial sector.
Using sprint swimming performance to predict upstream passage of the endangered Macquarie perch in a highly regulated river
Authors: STARRS D. , EBNER B. C. , LINTERMANS M. , FULTON C. J.
Published: August 2011

Abstract  Barriers to migration are a major threat to freshwater fish populations. A novel measurement of swimming speed performance and an analytical model were used to calculate the probability that endangered Macquarie perch, Macquaria australasica Cuvier, can swim through instream structures. Over the range of river discharges (2.7–166 ML day−1) and temperatures (10–22 °C) examined, M. australasica could successfully pass through a rock‐ramp fishway and nearby natural riffles under most river discharges, whilst pipe culverts were passable only to large individuals (>17.7 cm total length) under a high river discharge. Cold water temperatures (below 16 °C) significantly reduced the likelihood of passage in each case. It was concluded that both the volume and thermal characteristics of environmental flow releases should be considered when assessing and remediating potential instream barriers to fish passage in regulated river systems.
Accuracy of snorkelling counts in assessing spawning stock of Atlantic salmon, Salmo salar, verified by radio‐tagging and underwater video monitoring
Authors: ORELL P. , ERKINARO J. , KARPPINEN P.
Published: August 2011

Abstract  The accuracy of underwater snorkel counts of adult Atlantic salmon, Salmo salar L., was analysed in a small tributary of the River Teno before and during the spawning period using two independent verification methods (video counts and radio‐tagged fish) with known numbers of fish. The observation efficiency of snorkelling crews was generally high, but that of an inexperienced crew (65–72%) was significantly lower than an experienced crew (81–82%). Habitat type affected the accuracy of snorkelers, especially those of the inexperienced crew. The efficiency of snorkelers was high in pool‐type habitats (75–100%) but decreased considerably in faster flowing turbulent habitats (43–82%), where the inexperienced crew provided the lowest estimates. Thus, snorkel counting is a valid method for estimating Atlantic salmon spawning population densities in small rivers with adequate underwater visibility and with a sufficiently experienced snorkelling crew.
Risk of inhibitor development in mild haemophilia A increases with age
Authors: MAUSER‐BUNSCHOTEN E. P. , DEN UIJL I. E. M , SCHUTGENS R. E. G , ROOSENDAAL G. , FISCHER K.
Published: August 2011

Summary.  Mild haemophilia A is a rare disease with a relatively mild phenotype. Treatment with factor VIII (FVIII) is indicated after trauma or for surgery only. FVIII infusion may result in the development of inhibiting antibodies against FVIII. This study describes the relation between age and other risk factors for inhibitor development in mild haemophilia. A retrospective cohort study was conducted among all patients with mild haemophilia (FVIII 0.05–0.40 IU mL−1) registered at the van Creveldkliniek, University Medical Centre Utrecht, The Netherlands. Data on peak treatment with FVIII, gene mutation and history of inhibitor development were obtained from patient files from the period between 1st January 1970 and 31st December 2009. A total of 231 out of 297 (78%) patients had at least one exposure to FVIII, of whom 14 (6.1%) developed an inhibitor to FVIII at a median age of 66 years after a median of 50 exposure days (ED). Age at first exposure, age at peak treatment, number of peak treatments and Arg593Cys mutation were significantly associated with the development of an inhibitor, while continuous infusion with FVIII was not. Although the incidence of inhibitors in mild haemophilia is low, it increases with age and peak treatments. With increasing age patients with mild haemophilia will suffer from co‐morbidity more frequently, requiring surgical interventions and exposing them to an increased risk of inhibitor development. Especially patients with a change of arginine in cysteine at 593 are at risk for inhibitor development.
Liver transplantation in the haemophilia patient
Authors: LAMBING A. , KURIAKOSE P. , KACHALSKY E.
Published: August 2011

Summary.  Hepatitis C is a chronic condition that many persons with haemophilia contracted in the 1980s due to the infusion of factor concentrates that did not have viral inactivation processes in place. Many patients with haemophilia are now living longer lives, well into their eighties due to the improvement of their care. The effects of the hepatitis C virus on the liver over time are now being realized as this population ages. Although the new treatments for hepatitis C have a prolonged response, as demonstrated by a persistent negative viral load, many haemophilia patients have either not responded to the therapy or had significant side effects to treatment, which prevented continued therapy. Of these infected haemophiliacs with liver disease, many have demonstrated a slow progressive decline resulting in liver failure, cirrhosis or liver cancer. Liver transplant then becomes their only option. This article will review liver transplantation in the haemophilia patient highlighting three case studies demonstrating the effectiveness of specific short‐term factor infusions and other haemostatic support to minimize bleeding during the surgical period. These cases confirm the opportunity for successful liver transplantation for haemophilia patients utilizing specific factor recommendations with minimal bleeding risk.
A Steinian approach to an empathic understanding of hope among patients and clinicians in the culture of palliative care
Authors: Richardson Kate , MacLeod Rod , Kent Bridie
Published: August 2011

richardson k., macleod r.. & kent b.
(2012) A Steinian approach to an empathic understanding of hope among patients and clinicians in the culture of palliative care. Journal of Advanced Nursing68(3), 686–694.

Aim.  This article presents a discussion of empathy in the context of human person, reason and hopes in the clinical setting.

Background.  Empathy was introduced to nursing as part of an ethical and philosophical foundation for caring. It helped to solve the tension and meet the demands that empathy placed upon nursing practice.

Data sources.  This article is based on two studies undertaken between 2008 and 2010 to understand the concept of hope and empathy among people with terminal cancer and doctors who care for them. Doctoral dissertations and theses of Edith Stein (1916–1917), Marianne Sawicki [Body, Text and Science. The Literary of Investigative Practices and the Phenomenology of Edith Stein (1997) Kluwer Academic Publisher, Dordrecht], and Sister M. Judith Parsons (2005) have been used to examine: ‘the essence of acts of empathy’, ‘the constitution of the psycho‐physical individual’ and ‘empathy as understanding of intellectual persons’. CINAHL, MEDLINE and PROQUEST have provided further supporting data.

Discussion.  Steinian empathy requires that we use affective resonance, cognitive understanding and distance, as we grasp another person’s emotional and situational reality while in the caring role as nurses.

Implications for current nursing.  Steinian empathy is about recognizing a lived experience and standing side‐by‐side with that person. Nurses can transmit this knowledge to enable and support courage and wisdom to reduce feelings of helplessness when caring for people with terminal illness.

Conclusion.  Not only is empathy a safe and permissible emotion, it is the linchpin to a caring patient–nurse relationship and we must embrace this.
Pain descriptors for critically ill patients unable to self‐report
Authors: Haslam Lynn , Dale Craig , Knechtel Leasa , Rose Louise
Published: August 2011

haslam l., dale c., knechtel l. & rose l. (2011) Pain descriptors for critically ill patients unable to self‐report. Journal of Advanced Nursing 68(5), 1082–1089.

Aim.  To examine descriptors used by nurses in two Canadian intensive care units to document pain presence for critically ill patients unable to self‐report.

Background.  Systematic documentation of pain assessment is essential for communication and continuity of pain management, thereby enabling better pain control, maximizing recovery and reducing physical and psychological sequelae.

Method.  A retrospective, mixed method, having observational design in two Level‐III intensive care units of a quaternary academic centre in Toronto, Canada. During 2008–2009, data were abstracted via chart review guided by a reference compendium of potential behavioural descriptors compiled from existing behavioural pain assessment tools.

Results.  A total of 679 narrative descriptions were extracted. Behavioural descriptors (232, 34%), physiological descriptors (93, 14%), and descriptors indicating the patient was pain free (117, 17%) were used to describe pain presence or absence. Narratives also described analgesia administered without descriptors of pain assessment (117, 17%) and assessment and analgesic administration prior to a known painful procedure (30, 4%). Emerging themes included life‐threatening treatment interference, decisional uncertainty and a wakefulness continuum.

Conclusion.  Inconsistent or ambiguous documentation was problematic in this sample. This may reflect confounding behaviours and concomitant safety priorities. Developing a lexicon of pain assessment descriptors of critically ill patients unable to self‐report for use in combination with valid and reliable measures may improve documentation facilitating appropriate analgesic management. Protocols or unit guidelines that prioritize a trial of analgesia before administration of sedatives may decrease decisional uncertainty when patients exhibit ambiguous behaviours such as agitation or restlessness.
The consequences of unsafe abortion : a qualitative study
Authors: Shahbazi Shirin
Published: August 2011

shahbazi s. (2012) The consequences of unsafe abortion : a qualitative study. Journal of Advanced Nursing68(6), 1247–1255.

Aim.  This paper is a report of a study of the consequences of illegal abortions experienced by Iranian women.

Background.  Despite the increase in effective and safe methods of contraception and the distribution of information about these methods, unwanted pregnancy is still a problem in some societies. Induced abortion is a common procedure throughout the world and at least half of more than 45 million induced abortions which happen in a year are performed under unsafe circumstances. Unsafe abortions carry a high risk of maternal mortality and morbidity, accounting for more than 80,000 maternal deaths per year.

Method.  In this qualitative study, 27 participants were interviewed in 2006. Some participants were women who had illegal abortions and others were people who had contact with those women. Content analysis was used to identify and categorize participants’ responses to the interview questions.

Findings.  Four consequences of women’s experiences of illegal abortion were identified: physical, psychological, socio‐political and judicial.

Conclusion.  In Iran, as in some other developing countries intentional abortion, except for some special cases, is illegal because of social and religious beliefs. In these countries, offering services and support to women with unwanted pregnancies seems to be the best solution for reducing or preventing illegal abortion.
Medical humanities' challenge to medicine
Authors: Macnaughton Jane
Published: August 2011

Medicine is predicated on a view of human nature that is highly positivist and atomistic. This is apparent in the way in which its students are taught, clinical consultations are structured and medical evidence is generated. The field of medical humanities originally emerged as a challenge to this overly narrow view, but it has rarely progressed beyond tinkering around the edges of medical education. This is partly because its practitioners have largely been working from within a pervasive medical culture from which it is difficult to break free, and partly because the field has been insufficiently armed with scholarly thinking from the humanities. This is beginning to change and there is a sign that research in medical humanities has the potential to mount a persuasive challenge to medicine's ways of teaching, working and finding out. This article problematizes medicine's narrow viewpoint, grounding its critique in philosophical ideas from phenomenology and pragmatism. I will reflect upon the historical context within which medical humanities has emerged and briefly examine specific examples of how its interdisciplinary approach, involving humanities scholars with clinicians and medical scientists, may develop new research directions in medicine.
Comparison of screening methods to evaluate the response of St. Augustine grass to Magnaporthe oryzae
Authors: Metz S. P. , Chandra A. , Genovesi A. D. , Campos C. F.
Published: August 2011

The objective of this study was to develop a reliable and high throughput screening method to evaluate the response of St. Augustine grass (Stenotaphrum secundatum) genotypes to the grey leaf spot (GLS) caused by Magnaporthe oryzae infection. Whole plant, detached stolon and detached leaf assays under growth chamber conditions were compared to field conditions on eight commercial and nine advanced breeding lines of St. Augustine grass. Disease was assessed using two variables, lesion size (LS) and overall plant disease severity (SEV). LS and SEV were highly correlated for field and growth chamber screening methods using the whole plant assay (LS r2 = 0·79; SEV r2 = 0·83; P ≤ 0·001), the detached stolon assay (LS r2 = 0·75; SEV r2 = 0·72; P ≤ 0·001), and the detached leaf assay (LS r2 = 0·46; SEV r2 = 0·60; P ≤ 0·001). Genotypic variation for resistance in 17 St. Augustine grass genotypes was identified using all screening methods for LS (P < 0·05) and SEV (P < 0·05). The rank‐sum method was used to classify St. Augustine grass genotypes into highly resistant (HR), resistant (R), moderately resistant (MR), moderately susceptible (MS), susceptible (S) and highly susceptible (HS) classes based on the rank‐sum values of LS and SEV. Two introduced African polyploids used as parents, and two F1 interploid progeny obtained using an in vitro embryo rescue technique, were classified as highly resistant (HR), or resistant (R), across all screening methods.
Y chromosome genetic diversity in the Lidia bovine breed: a highly fragmented population
Authors: Cortes O. , Tupac‐Yupanqui I. , Dunner S. , Fernández J. , Cañón J.
Published: August 2011

To assess the paternal gene pool in the Lidia bovine breed (or fighting bull), a total of 603 animals belonging to 81 herds classified in 33 lineages were genotyped for six Y chromosome microsatellites, one single nucleotide polymorphism and one indel. A total of 10 haplotypes were determined with a high level of frequency variation between them, ranging from 0.2 to 74%. All the haplotypes identified belong to two previously defined major haplogroups (Y1 and Y2). Two major paternal influences were identified, corresponding to the two most common haplotypes (H1Y1 and H3Y2) with frequencies of 74 and 18%, respectively. The detection of the INRA189‐104 allele evidenced an African influence in the Lidia bovine breed. Low levels of haplotype diversity have been achieved and only eight lineages showed more than one haplotype. Analysis of molecular variance showed a high level of interlineage variance (FST = 86%). Network results evidenced two main clusters made for those haplotypes belonging to Y1 and Y2 haplogroups, respectively. The findings support a high level of genetic structure together with a low level of genetic diversity in the Lidia bovine breed.
Patterns of spatial variation of nutrient content, epiphyte load and shoot size of Posidonia oceanica seagrass meadows (Mediterranean Sea)
Authors: Castejón‐Silvo Inés , Terrados Jorge
Published: August 2011

Knowledge of patterns of spatial variability of vegetative development, epiphyte load and nutrient availability in seagrass meadows is essential for the adequate design of research and environmental monitoring programmes. Differences in shoot size, epiphyte load and nutrient content of leaves and epiphytes of the Mediterranean endemic seagrass Posidonia oceanica at spatial scales ranging from metres to hundreds of metres are evaluated using a hierarchical nested sampling design. The size and epiphyte load of P. oceanica shoots and the nitrogen and phosphorus content of leaves and epiphytes were different in most of the spatial scales considered. Sampling efforts concentrated at the metre scale incorporated most of the variability in size, epiphyte load and nutrient content of the leaves and epiphytes of P. oceanica shoots. Epiphyte load showed no correlation with nutrient content in the epiphytes or in the leaves. However, epiphyte load and shoot size were negatively correlated, which suggests that light penetration in the canopy may be a main determinant of epiphyte load.
Genome content of uncultivated marine Roseobacters in the surface ocean
Authors: Luo Haiwei , Löytynoja Ari , Moran Mary Ann
Published: August 2011

Understanding of the ecological roles and evolutionary histories of marine bacterial taxa can be complicated by mismatches in genome content between wild populations and their better‐studied cultured relatives. We used computed patterns of non‐synonymous (amino acid‐altering) nucleotide diversity in marine metagenomic data to provide high‐confidence identification of DNA fragments from uncultivated members of the Roseobacter clade, an abundant taxon of heterotrophic marine bacterioplankton in the world's oceans. Differences in gene stoichiometry in the Global Ocean Survey metagenomic data set compared with 39 sequenced isolates indicated that natural Roseobacter populations differ systematically in several genomic attributes from their cultured representatives, including fewer genes for signal transduction and cell surface modifications but more genes for Sec‐like protein secretion systems, anaplerotic CO2 incorporation, and phosphorus and sulfate uptake. Several of these trends match well with characteristics previously identified as distinguishing r‐ versus K‐selected ecological strategies in bacteria, suggesting that the r‐strategist model assigned to cultured roseobacters may be less applicable to their free‐living oceanic counterparts. The metagenomic Roseobacter DNA fragments revealed several traits with evolutionary histories suggestive of horizontal gene transfer from other marine bacterioplankton taxa or viruses, including pyrophosphatases and glycosylation proteins.
EXCHANGE RATE TARGET ZONES: A SURVEY OF THE LITERATURE
Authors: Portugal Duarte António , Sousa Andrade João , Duarte Adelaide
Published: August 2011

This work selectively reviews the literature on exchange rate target zones and their theoretical and empirical methodologies and examines whether they can be used to clarify to what extent this type of exchange rate regime could contribute to greater exchange rate stability. We discuss the main contributions of the first and second generations of exchange rate target zone models. In an attempt to reconcile the poor empirical performance of the Krugman model with the reality of exchange rate target zone regimes, this line of research integrates target zones with alternative underlying economic models, such as imperfect credibility, intra‐marginal interventions and sticky price models. It was thus possible to understand the correlations observed between the exchange rate, its fundamentals determinants and the interest rate differential, and to explain the fact that the statistical distribution of the exchange rate is hump shaped rather than U shaped. This implies that the initial emphasis of target zone models on nonlinearities, ‘honeymoon effect’, ‘smooth pasting’ and marginal interventions has vanished. Exchange rate target zones are better described as similar to managed floating regimes with intra‐marginal interventions, with some marginal interventions when the exchange rate reaches the edges of the floating band.
A note on mean squared prediction error under the unit root model with deterministic trend
Authors: Yu Shu‐Hui , Lin Chien‐Chih , Cheng Hung‐Wen
Published: August 2011

Assume that observations are generated from the first‐order autoregressive (AR) model with linear time trend and the unknown model coefficients are estimated by least squares. This article develops an asymptotic expression for the mean squared prediction error (MSPE) of the least squares predictor in the presence of a unit root. As a by‐product, we also obtain a connection between the MSPE and the growth rate of the Fisher information. The key technical tool used to derive these results is the negative moment bound for the minimum eigenvalue of the normalized Fisher information matrix.
Clinical characteristics of well women seeking labial reduction surgery: a prospective study
Authors: Crouch NS , Deans R , Michala L , Liao L‐M , Creighton SM
Published: August 2011

Please cite this paper as: Crouch N, Deans R, Michala L‐M, Liao L, Creighton S. Clinical characteristics of well women seeking labial reduction surgery: a prospective study. BJOG 2011;118:1507–1510.

Objective  To assess clinical characteristics and expectations in well women requesting elective labial reduction surgery.

Design  Prospective study of women attending an outpatient gynaecology clinic.

Setting  General gynaecology clinic at a Central London teaching hospital.

Sample  Women requesting labial reduction surgery and referred by their general practitioner.

Methods  The labia minora width and length were measured for all participants for comparison with published normal values. The presenting complaint was recorded, along with demographic details, expectations of surgery and sources of information regarding appearance of the labia.

Main outcome measures  Labial measurements, reported symptoms and expectations of surgery.

Results  The labia of all participants were within normal published limits, with a mean (SD) of 26.9 (12.8) mm (right labia), and 24.8 (13.1) mm (left labia). The majority of complaints were regarding appearance or discomfort. Expectations were to alter the appearance with surgery.

Conclusions  All women seeking surgery had normal‐sized labia minora. Clear guidance is needed for clinicians on how best to care for the worried well woman seeking surgery.