bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing practice as a quality indicator for primary care: analysis of data on voluntary disenrollment from the English GP Patient Survey
Authors: Nagraj Shobhana , Abel Gary , Paddison Charlotte , Payne Rupert , Elliott Marc , Campbell John , Roland Martin 
Published: June 2013

Abstract

Background
Changing family practice (voluntary disenrollment) without changing address may indicate dissatisfaction with care. We investigate the potential to use voluntary disenrollment as a quality indicator for primary care.

Methods
Data from the English national GP Patient Survey (2,169,718 respondents), the number of voluntary disenrollments without change of address, data relating to practice characteristics (ethnicity, deprivation, gender of patients, practice size and practice density) and doctor characteristics were obtained for all family practices in England (n = 8450). Poisson regression analyses examined associations between rates of voluntary disenrollment, patient experience, and practice and doctor characteristics.

Results
Mean and median rates of annual voluntary disenrollment were 11.2 and 7.3 per 1000 patients respectively. Strongest associations with high rates of disenrollment were low practice scores for doctor-patient communication and confidence and trust in the doctor (rate ratios 4.63 and 4.85). In a fully adjusted model, overall satisfaction encompassed other measures of patient experience (rate ratio 3.46). Patients were more likely to move from small practices (single-handed doctors had 2.75 times the disenrollment rate of practices with 6–9 doctors) and where there were other local practices. After allowing for these, substantial unexplained variation remained in practice rates of voluntary disenrollment.

Conclusion
Family practices with low levels of patient satisfaction, especially for doctor patient communication, are more likely to experience high rates of disenrollment. However substantial variation in disenrollment rates remains among practices with similar levels of patient satisfaction, limiting the utility of voluntary disenrollment as a performance indicator for primary care in England.
Macromolecular juggling by ubiquitylation enzymes
Authors: Lorenz Sonja , Cantor Aaron J , Rape Michael , Kuriyan John 
Published: June 2013

Abstract
The posttranslational modification of target proteins with ubiquitin and ubiquitin-like proteins is accomplished by the sequential action of E1, E2, and E3 enzymes. Members of the E1 and E3 enzyme families can undergo particularly large conformational changes during their catalytic cycles, involving the remodeling of domain interfaces. This enables the efficient, directed and regulated handover of ubiquitin from one carrier to the next one. We review some of these conformational transformations, as revealed by crystallographic studies.
Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis
Authors: Tricco Andrea C , Chit Ayman , Soobiah Charlene , Hallett David , Meier Genevieve , Chen Maggie H , Tashkandi Mariam , Bauch Chris T , Loeb Mark 
Published: June 2013

Abstract

Background
Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.

Methods
We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).

Results
We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).

Conclusions
The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.
Body mass index in relation to truncal asymmetry of healthy adolescents, a physiopathogenetic concept in common with idiopathic scoliosis: summary of an electronic focus group debate of the IBSE
Authors: Grivas Theodoros B , Burwell R Geoffrey , Dangerfield Peter H 
Published: June 2013

Abstract
There is no generally accepted scientific theory for the cause of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE).introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr TB Grivas. It is based on published research from Athens, Greece evaluating schoolchildren age 11–17 years for the relation of body mass index (BMI) to each of truncal asymmetry (TA) and menarcheal status. Girls with relatively lower BMI were found to have a significant excess of severe TAs and significantly later menarche confirming the well-known relation of BMI to menarche. Together with other evidence linking nutritional status to skeletal growth, the observations suggest energy balance via the hypothalamus is related to trunk asymmetry. As with a recent speculative hypothesis for the pathogenesis of AIS in girls, Grivas et al. suggest that the severe TAs involve a genetically-determined selectively increased sensitivity (up-regulation) of the hypothalamus to circulating leptin with asymmetry as an adverse response to stress (hormesis). The TA is expressed bilaterally via the sympathetic nervous system to produce left-right asymmetry in ribs and/or vertebrae leading to severe TAs when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion in the trunk. This EFG discusses the findings and interpretations of the paper by Grivas and colleagues as research at the borderland between the genesis of TA (physiogenesis) and AIS (pathogenesis). It is suggested that TAs, here regarded in common with AIS, result from the combination of secondary sexual development affecting body composition, adolescent skeletal growth velocity, and an asymmetry process. The possible involvement of epigenetic factors is not considered.
Functional characterisation of the non-essential protein kinases and phosphatases regulating Aspergillus nidulans hydrolytic enzyme production
Authors: Brown Neil Andrew , de Gouvea Paula Fagundes , Krohn Nádia Graciele , Savoldi Marcela , Goldman Gustavo Henrique 
Published: June 2013

Abstract

Background
Despite recent advances in the understanding of lignocellulolytic enzyme regulation, less is known about how different carbon sources are sensed and the signaling cascades that result in the adaptation of cellular metabolism and hydrolase secretion. Therefore, the role played by non-essential protein kinases (NPK) and phosphatases (NPP) in the sensing of carbon and/or energetic status was investigated in the model filamentous fungus Aspergillus nidulans.

Results
Eleven NPKs and seven NPPs were identified as being involved in cellulase, and in some cases also hemicellulase, production in A. nidulans. The regulation of CreA-mediated carbon catabolite repression (CCR) in the parental strain was determined by fluorescence microscopy, utilising a CreA::GFP fusion protein. The sensing of phosphorylated glucose, via the RAS signalling pathway induced CreA repression, while carbon starvation resulted in derepression. Growth on cellulose represented carbon starvation and derepressing conditions. The involvement of the identified NPKs in the regulation of cellulose-induced responses and CreA derepression was assessed by genome-wide transcriptomics (GEO accession 47810). CreA::GFP localisation and the restoration of endocellulase activity via the introduction of the ∆creA mutation, was assessed in the NPK-deficient backgrounds. The absence of either the schA or snfA kinase dramatically reduced cellulose-induced transcriptional responses, including the expression of hydrolytic enzymes and transporters. The mechanism by which these two NPKs controlled gene transcription was identified, as the NPK-deficient mutants were not able to unlock CreA-mediated carbon catabolite repression under derepressing conditions, such as carbon starvation or growth on cellulose.

Conclusions
Collectively, this study identified multiple kinases and phosphatases involved in the sensing of carbon and/or energetic status, while demonstrating the overlapping, synergistic roles of schA and snfA in the regulation of CreA derepression and hydrolytic enzyme production in A. nidulans. The importance of a carbon starvation-induced signal for CreA derepression, permitting transcriptional activator binding, appeared paramount for hydrolase secretion.
Chromosomal Abnormalities Are Major Prognostic Factors in Elderly Patients With Multiple Myeloma: The Intergroupe Francophone du Myélome Experience
Authors: Avet-Loiseau Hervé , Hulin Cyrille , Campion Loic , Rodon Philippe , Marit Gerald , Attal Michel , Royer Bruno , Dib Mamoun , Voillat Laurent , Bouscary Didier , Caillot Denis , Wetterwald Marc , Pegourie Brigitte , Lepeu Gerard , Corront Bernadette , Karlin Lionel , Stoppa Anne-Marie , Fuzibet Jean-Gabriel , Delbrel Xavier , Guilhot Francois , Kolb Brigitte , Decaux Olivier , Lamy Thierry , Garderet Laurent , Allangba Olivier , Lifermann Francois , Anglaret Bruno , Moreau Philippe , Harousseau Jean-Luc , Facon Thierry 
Published: June 2013

Purpose Chromosomal abnormalities, especially t(4;14) and del(17p), are major prognostic factors in patients with multiple myeloma (MM). However, this has been especially demonstrated in patients age < 66 years treated with intensive approaches. The goal of this study was to address this issue in elderly patients treated with conventional-dose chemotherapy. Patients and Methods To answer this important question, we retrospectively analyzed a series of 1,890 patients (median age, 72 years; range, 66 to 94 years), including 1,095 with updated data on treatment modalities and survival. Results This large study first showed that the incidence of t(4;14) was not uniform over age, with a marked decrease in the oldest patients. Second, it showed that both t(4;14) and del(17p) retained their prognostic value in elderly patients treated with melphalan and prednisone–based chemotherapy. Conclusion t(4;14) and del(17p) are major prognostic factors in elderly patients with MM, both for progression-free and overall survival, indicating that these two abnormalities should be investigated at diagnosis of MM, regardless of age.
Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem-Cell Transplantation in Older Patients With De Novo Myelodysplastic Syndromes: An International Collaborative Decision Analysis
Authors: Koreth John , Pidala Joseph , Perez Waleska S. , Deeg H. Joachim , Garcia-Manero Guillermo , Malcovati Luca , Cazzola Mario , Park Sophie , Itzykson Raphael , Ades Lionel , Fenaux Pierre , Jadersten Martin , Hellstrom-Lindberg Eva , Gale Robert Peter , Beach C.L. , Lee Stephanie J. , Horowitz Mary M. , Greenberg Peter L. , Tallman Martin S. , DiPersio John F. , Bunjes Donald , Weisdorf Daniel J. , Cutler Corey 
Published: June 2013

Purpose Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk. Patients and Methods A Markov decision model with quality-of-life utility estimates for different MDS and transplantation states was assessed. Outcomes were life expectancy (LE) and quality-adjusted life expectancy (QALE). A total of 514 patients with de novo MDS aged 60 to 70 years were evaluated. Chronic myelomonocytic leukemia, isolated 5q– syndrome, unclassifiable, and therapy-related MDS were excluded. Transplantation using T-cell depletion or HLA-mismatched or umbilical cord donors was also excluded. RIC transplantation (n = 132) stratified by IPSS risk was compared with best supportive care for patients with nonanemic low/intermediate-1 IPSS (n = 123), hematopoietic growth factors for patients with anemic low/intermediate-1 IPSS (n = 94), and hypomethylating agents for patients with intermediate-2/high IPSS (n = 165). Results For patients with low/intermediate-1 IPSS MDS, RIC transplantation LE was 38 months versus 77 months with nontransplantation approaches. QALE and sensitivity analysis did not favor RIC transplantation across plausible utility estimates. For intermediate-2/high IPSS MDS, RIC transplantation LE was 36 months versus 28 months for nontransplantation therapies. QALE and sensitivity analysis favored RIC transplantation across plausible utility estimates. Conclusion For patients with de novo MDS aged 60 to 70 years, favored treatments vary with IPSS risk. For low/intermediate-1 IPSS, nontransplantation approaches are preferred. For intermediate-2/high IPSS, RIC transplantation offers overall and quality-adjusted survival benefit.
Treatment-Related Mortality in Patients With Advanced-Stage Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group
Authors: Wongso Diana , Fuchs Michael , Plütschow Annette , Klimm Beate , Sasse Stephanie , Hertenstein Bernd , Maschmeyer Georg , Vieler Tom , Dührsen Ulrich , Lindemann Walter , Aulitzky Walter , Diehl Volker , Borchmann Peter , Engert Andreas 
Published: June 2013

Purpose The introduction of BEACOPPescalated (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPPescalated. Patients and Methods In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPPescalated-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Results Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPPescalated (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. Conclusion The individual risk of TRM associated with BEACOPPescalated can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.
Central Hypothyroidism and Its Replacement Have a Significant Influence on Cardiovascular Risk Factors in Adult Hypopituitary Patients
Authors: Klose M. , Marina D. , Hartoft-Nielsen M.-L. , Klefter O. , Gavan V. , Hilsted L. , Rasmussen Å. K. , Feldt-Rasmussen U. 
Published: June 2013

Context:Thyroid dysfunction may have detrimental effects on patient outcomes. Few studies have assessed this issue in patients with secondary hypothyroidism.Objective:Our objective was to test the hypothesis that thyroid hormone status has an impact on cardiovascular risk factors in adult patients with hypopituitarism.Design and Setting:This was a retrospective observational study (1993–2012) at a tertiary referral university hospital.Patients:All GH-deficient patients starting GH replacement (1993–2009) with measured free T4 (fT4) (n = 208). Baseline fT4 defined patients as TSH-sufficient and TSH-deficient (further divided into tertiles according to baseline fT4; first tertile had lowest fT4).Main Outcome Measures:Anthropometric (body mass index [BMI], waist circumference, total fat (fat mass) and lean body mass [LBM]) and biochemical (lipids and fasting plasma glucose) data were collected at baseline and a median 4.1 years after commencement of GH.Results:At baseline, fT4 was negatively associated with BMI and waist circumference, but positively with high-density lipoprotein, independent of age, gender, and IGF-I (SD score). Only first-tertile TSH-deficient patients had higher BMI (P = .02), fat mass (P = .03), total cholesterol (P = .05), triglycerides (P &lt; .01), and waist circumference (P = .01), and lower high-density lipoprotein cholesterol (P = .03) as compared with TSH-sufficient patients. At follow-up, IGF-I, LBM, and plasma glucose had increased in all subgroups (P &lt; .01). The change in fT4 (ΔfT4) (follow-up − baseline) was negatively correlated to ΔBMI, ΔLBM, Δtotal cholesterol, and Δlow-density lipoprotein cholesterol (all P &lt; .05, adjusted for ΔIGF-I and ΔGH and hydrocortisone dose). The negative correlation to Δtotal cholesterol and Δlow-density lipoprotein cholesterol persisted only in first-tertile TSH-deficient patients.Conclusion:This single-center study over a 20-year period has strengthened the importance of improved awareness of thyroid status and optimal thyroid replacement of hypopituitary patients to reduce cardiovascular risks in hypopituitary patients.
Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons
Authors: Barraud Perrine , St John James A. , Stolt C. Claus , Wegner Michael , Baker Clare V. H. 
Published: June 2013

Summary
Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH) neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs). Here, we demonstrate that in homozygous Sox10lacZ/lacZ mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting). Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.
Fluoreszenz-Lymphographie
Authors: Schingale F.-J. 
Published: June 2013

ZusammenfassungDer fluoreszierenden Farbstoff Indocyaningrün ermöglicht es uns, in Verbindung mit einer Infrarotkamera den Lymphabfluss zu beurteilen, den Sentinel-Lymphknoten zu entdecken, in neuen Operationstechniken die Funktionsfähigkeit der Lymphgefäße zu beurteilen, sowie die Wirksamkeit alter und neuer Behandlungsmethoden zu erkennen.
Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients
Authors: Meintker Lisa , Haimerl Maria , Ringwald Jürgen , Krause Stefan W. 
Published: June 2013

AbstractBackground:Measurement of immature platelets was introduced into routine diagnostics by Sysmex as immature platelet fraction (IPF) some years ago and recently by Abbott as reticulated platelet fraction (rPT). Here, we compare both methods.Methods:We evaluated the precision and agreement of these parameters between Sysmex XE-5000 and Abbott CD-Sapphire in three distinct thrombocytopaenic cohorts: 30 patients with beginning thrombocytopaenia and 64 patients with recovering platelets (PLT) after chemotherapy, 16 patients with immune thrombocytopaenia (ITP) or heparin-induced thrombocytopaenia type 2 (HIT) and 110 additional normal controls. Furthermore, we analysed, how IPF/rPT differed between these thrombocytopaenic cohorts and controls.Results:Both analysers demonstrated acceptable overall precision (repeatability) of IPF/rPT with lower precision at low PLT counts. IPF/rPT artificially increased during storage of blood samples overnight. Inter-instrument comparison showed a moderate correlation (Pearson r²=0.38) and a systematic bias of 1.04 towards higher IPF-values with the XE-5000. IPF/rPT was highest in recovering thrombopoesis after chemotherapy and moderately increased in ITP/HIT. The normal range deduced from control samples was much narrower with CD-Sapphire (1.0%–3.8%, established here for the first time) in comparison to XE-5000 (0.8%–7.9%) leading to a smaller overlap of samples with increased PLT turnover and normal controls.Conclusions:IPF and rPT both give useful information on PLT turnover, although the two analysers only show a moderate inter-instrument correlation and have different reference ranges. A better separation of patient groups with high PLT turnover like ITP/HIT from normal controls is obtained by CD-Sapphire.