bluuebunny/crossref_metadata_2025_split huggingface dataset:
An independent evaluation of the modernization of NHS endoscopy services in England: data poverty and no improvement
Authors: Thorne Kymberley , Hutchings Hayley A. , Elwyn Glyn 
Published: June 2010

AbstractRationale, aims and objectives  The Modernising Endoscopy Services (MES) programme introduced a focussed modernization drive and data collection regime to English NHS endoscopy services. We independently evaluated the MES programme by comparing routinely collected, service‐related endoscopy data from sites that participated in the MES programme and sites that did not.Methods  A random selection of 10 endoscopy units who had participated in the MES programme (intervention sites) were compared with a random selection of 10 endoscopy units who redesigned their services independently (control sites). Data on demand, numbers waiting, activity and cancellations were collected for eight time points between January 2003 and April 2006. Data were aggregated into intervention and control groups for statistical analysis using a two‐way analysis of variance. Activity data were validated using an equivalent Hospital Episode Statistics dataset.Results  Data were not routinely collected by 11 of 19 endoscopy units. Trust‐held datasets were subsequently included to address problems with data availability. The accuracy of the Activity data was successfully validated. Statistical analysis of the data showed that neither the intervention group nor the control group were able to significantly improve their services over time. There was also no significant difference between the intervention group and the control group in the improvement of their endoscopy services at any point time.Conclusions  Based on the data collected, the intervention programme did not significantly improve NHS endoscopy services in England over and above what could have been achieved independently with only the intention to redesign.
Effects of two educational programmes aimed at improving the utilization of non‐opioid analgesics in family medicine clinics in Mexico
Authors: Doubova (Dubova Svetlana Vladislavovna , Mino‐León Dolores , Reyes‐Morales Hortensia , Flores‐Hernandez Sergio , Torres‐Arreola Laura del Pilar , Pérez‐Cuevas Ricardo 
Published: June 2010

AbstractObjectives  To develop and test two educational programmes (interactive and passive) aimed at improving family doctors' (FD) prescribing practices and patient's knowledge and use of non‐opioid analgesics (NOA).Methods  The educational programmes were conducted in two family medicine clinics by using a three‐stage approach: baseline evaluation, design, and implementation of educational activities, and post‐programme evaluation. An interactive educational programme (IEP) was compared with a passive educational programme (PEP); both were participated by FDs and patients. The IEP for FDs comprised of workshops, discussion groups, in‐service training and guidelines, while for patients the IEP consisted of an interactive session with a video, leaflets and a discussion. The PEP consisted in delivering the guidelines to the FDs and the leaflets to patients. The effect of the programmes on the FDs was measured through the appropriateness of prescriptions and analysed using the differences‐in‐differences estimator (D‐in‐D), and on patients through changes in self‐medication and in their knowledge about the proper use and adverse events by analysing the inter‐ and intra‐group differences before and after the programmes.Results  The IEP obtained better results to improve appropriate FDs prescription of NOA than PEP (D‐in‐D = 15%). Regarding the patients, the PEP group reached higher reduction of self‐medication than the IEP group (13.4% vs. 9.1%); the knowledge of proper NOA use increased by 8.5% in both groups, whereas knowledge of NOA‐related adverse events was better in the IEP (39.6%) than in the PEP group (9.2%).Conclusions  The IEP was better to improve the doctors' abilities to prescribe NOAs, and both programmes improved patients' knowledge.
Computerized physician order entry (CPOE) system: expectations and experiences of users
Authors: Van Doormaal Jasperien E. , Mol Peter G. M. , Zaal Rianne J. , Van Den Bemt Patricia M. L. A. , Kosterink Jos G. W. , Vermeulen Karin M. , Haaijer‐Ruskamp Flora M. 
Published: June 2010

AbstractObjectives  To explore physicians' and nurses' expectations before and experiences after the implementation of a computerized physician order entry (CPOE) system in order to give suggestions for future optimization of the system as well as the implementation process.Method  On four internal medicine wards of two Dutch hospitals, 18 physicians and 42 nurses were interviewed to measure expectations and experiences with the CPOE system. Using semi‐structured questionnaires, expectations and experiences of physicians and nurses with the CPOE system were measured with statements on a 5‐point Likert scale (1 = completely disagree, 5 = completely agree). The percentage respondents agreeing (score of 4 or 5) was calculated. Chi‐squared tests were used to compare the expectations versus experiences of physicians and nurses and to assess the differences between physicians and nurses.Results  In general, both physicians and nurses were positive about CPOE before and after the implementation of this system. Physicians and nurses did not differ in their views towards CPOE except for the overview of patients' medication use that was not clear according to the nurses. Both professions were satisfied with the implementation process. CPOE could be improved especially with respect to technical aspects (including the medication overview) and decision support on drug–drug interactions.Conclusion  Overall we conclude that physicians and nurses are positive about CPOE and the process of its implementation and do accept these systems. However, these systems should be further improved to fit into clinical practice.
The UK National Chronic Obstructive Pulmonary Disease Resources and Outcomes Project – a feasibility study of large‐scale clinical service peer review
Authors: Roberts Christopher M. , Buckingham Rhona J. , Stone Robert A. , Lowe Derek , Pearson Michael G. 
Published: June 2010

AbstractRationale, aims and objectives Service provision and clinical outcomes for patients admitted with chronic obstructive pulmonary disease remain unacceptably variable despite guidelines and performance feedback of national audit, data. This study aims to assess the impact of mutual peer review on service improvement. The initial phase of this study was to assess the feasibility and determine the practicalities of delivering such a peer review programme on a large scale.Methods All UK acute hospitals were invited to participate in a reciprocal peer review programme administered by a central team from three UK health organizations. Hospitals with the most resources were paired with those with the least (as defined in a baseline survey) and pairs randomized on a 3:2 basis into intervention or control groups. A number of key quality indicators were derived to measure service levels at the beginning and end of the study. Peer review teams included clinicians and managers from acute and primary care organizations and when possible a patient representative. Visits were focussed on four key areas of chronic obstructive pulmonary disease service. Teams were to agree service improvements and submit plans signed off by participants. Monthly change diaries were to be used to record progress towards agreed goals.Results A total of 100 hospitals participated in the programme. Overall, 52 of 54 peer review visits took place within a 4‐week time frame and all units submitted service improvement plans within an agreed time frame. Secondary care representatives participated in all visits, primary care in 30 but patients in only 17. The mean number of diaries returned was 2, but 94% of units returned initial and final versions.Conclusions It is possible to deliver successful large‐scale mutual peer review using a limited but focussed programme. Participation of patients and use of change diaries requires further evaluation.
Maternity of emergency queens in the Cape honey bee, Apis mellifera capensis
Authors: HOLMES MICHAEL J. , OLDROYD BENJAMIN P. , ALLSOPP MICHAEL H. , LIM JULIANNE , WOSSLER THERESA C. , BEEKMAN MADELEINE 
Published: June 2010

AbstractDuring reproductive swarming, some workers of the Cape honey bee, Apis mellifera capensis, lay eggs in queen cells, many of which are reared to maturity. However, it is unknown if workers are able to lay in queen cells immediately after queen loss during an episode of emergency queen rearing. In this study we experimentally de‐queened colonies and determined the maternity of larvae and pupae that were reared as queens. This allowed us to determine how soon after queen loss workers contribute to the production of new queens. We were further interested to see if workers would preferentially raise new queens from queen‐laid brood if this was introduced later. We performed our manipulations in two different settings: an apiary setting where colonies were situated close together and a more natural situation in which the colonies were well separated. This allowed us to determine how the vicinity of other colonies affects the presence of parasites. We found that workers do indeed contribute to queen cell production immediately after the loss of their queen, thus demonstrating that some workers either have activated ovaries even when their colony has a queen or are able to activate their ovaries extremely rapidly. Queen‐laid brood introduced days after queen loss was ignored, showing that workers do not prefer to raise new queens from queen brood when given a choice. We also detected non‐natal parasitism of queen cells in both settings. We therefore conclude that some A. m. capensis genotypes specialize in parasitizing queen cells.
The β‐subunits of the Snf1 kinase in Saccharomyces cerevisiae, Gal83 and Sip2, but not Sip1, are redundant in glucose derepression and regulation of sterol biosynthesis
Authors: Zhang Jie , Olsson Lisbeth , Nielsen Jens 
Published: June 2010

SummaryThe conserved Snf1/AMP‐activated protein kinase family is one of the central components in the nutrient sensing and regulation of the carbon metabolism in eukaryotes. It is also involved in several other processes such as stress resistance, invasive growth and ageing. Snf1 kinase is composed of a catalytic α‐subunit Snf1, a regulatory γ‐subunit Snf4 and one of three possible β‐subunits, Sip1, Sip2 or Gal83. We used a systematic approach to study the role of the three β‐subunits by analysing all seven possible combinations of β‐subunit deletions together with the reference strain. Previous studies showed that the three β‐subunits are redundant for growth on alternative carbon sources. Here we report that the mutant strain with only SIP1 expressed (sip2Δgal83Δ) could utilize acetate, but neither ethanol nor glycerol, as alternative carbon source. We also showed that Gal83 is the most important isoform not only for the growth on non‐fermentable carbon sources, but also for regulation of ergosterol biosynthetic genes, under glucose‐limited condition. Furthermore, we found that Sip2, but not Sip1, can take over when Gal83 is deleted, but to a lesser extent. However, Sip1 may be sufficient for some other processes such as regulation of the nitrogen metabolism and meiosis.
Chromobacterium pathogenicity island 1 type III secretion system is a major virulence determinant for Chromobacterium violaceum‐induced cell death in hepatocytes
Authors: Miki Tsuyoshi , Iguchi Mirei , Akiba Kinari , Hosono Masato , Sobue Tomoyoshi , Danbara Hirofumi , Okada Nobuhiko 
Published: June 2010

Summary Chromobacterium violaceum is a Gram‐negative bacterium that causes fatal septicaemia in humans and animals. C. violaceum ATCC 12472 possesses genes associated with two distinct type III secretion systems (T3SSs). One of these systems is encoded by Chromobacterium pathogenicity islands 1 and 1a (Cpi‐1/‐1a), another is encoded by Chromobacterium pathogenicity island 2 (Cpi‐2). Here we show that C. violaceum causes fulminant hepatitis in a mouse infection model, and Cpi‐1/‐1a‐encoded T3SS is required for its virulence. In addition, using C. violaceum strains with defined mutations in the genes that encode the Cpi‐1/‐1a or Cpi‐2 locus in combination with cultured mammalian cell lines, we found that C. violaceum is able to induce cytotoxicity in a Cpi‐1/‐1a‐dependent manner. Characterization of Chromobacterium‐induced cytotoxicity revealed that cell lysis by C. violaceum infection involves the formation of pore structures on the host cell membrane, as demonstrated by protection by cytotoxicity in the presence of osmoprotectants. Finally, we demonstrated that CipB, a Cpi‐1/‐1a effector, is implicated in translocator‐mediated pore formation and the ability of CipB to form a pore is essential for Chromobacterium‐induced cytotoxicity. These results strongly suggest that Cpi‐1/‐1a‐encoded T3SS is a virulence determinant that causes fatal infection by the induction of cell death in hepatocytes.
Interleukin‐10 Promotes NK Cell Killing of Autologous Macrophages by Stimulating Expression of NKG2D Ligands
Authors: Schulz U. , Kreutz M. , Multhoff G. , Stoelcker B. , Köhler M. , Andreesen R. , Holler E. 
Published: June 2010

AbstractUnder inflammatory conditions, the pleiotropic cytokine interleukin‐10 (IL‐10) is released in many tissues. It mediates anti‐inflammatory effects in particular by inhibiting the release of T helper type 1 (Th1) cytokines. In contrast, we show here that NK cell cytotoxicity against autologous macrophages is elevated if both cell types are cultured with IL‐10. The expression of most activatory NK receptors is increased after culture in the presence of IL‐10. On the other hand, macrophages cultured in the presence of IL‐10 show elevated expression of the NKG2D ligands major histocompatibility complex (MHC) class 1‐like molecules (MIC) – A and – B, as well as UL‐16 binding proteins (ULBP) – ULBP‐1, ULBP‐2 and ULBP‐3. By masking the interaction of NK cells with macrophages through interruption of the NKG2D receptor with its ligands, we could reverse the IL‐10‐induced lysis of macrophages. Our data therefore reveal that IL‐10 may exert a novel immunomodulatory role by stimulating NKG2D ligand expression on macrophages, thereby rendering them susceptible to NK cell elimination. This suggests that NK cells would delete macrophages and potentially other immature antigen‐presenting cells (APC) or their precursors under inflammatory conditions as a feedback mechanism to shut off uncontrolled immune responses.
Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use
Authors: Byrd J. B. , Woodard‐Grice A. , Stone E. , Lucisano A. , Schaefer H. , Yu C. , Eyler A. E. , Salloum N. E. , Brown N. J. 
Published: June 2010

To cite this article:Byrd JB, Woodard‐Grice A, Stone E, Lucisano A, Schaefer H, Yu C, Eyler AE, Salloum NE, Brown NJ. Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use.Allergy2010;65: 1381–1387.AbstractBackground: Immunosuppressants decrease circulating dipeptidyl peptidase IV (DPPIV) activity in transplant patients, and decreased DPPIV activity has been associated with angiotensin‐converting enzyme (ACE) inhibitor‐associated angioedema. One study has reported an increased incidence of ACE inhibitor‐associated angioedema among transplant patients compared to published rates, while several case series report angioedema in patients taking specific immunosuppressant agents.Objective: To test the hypothesis that transplant patients are at increased risk of ACE inhibitor‐associated angioedema.Methods: We assessed the proportion of transplant patients in 145 cases with ACE inhibitor‐associated angioedema and 280 ACE inhibitor‐exposed controls. We measured the relationship between case–control status, transplant status, and immunosuppressant use and circulating DPPIV activity. We also assessed the incidence of angioedema among consecutive patients who underwent renal or cardiac transplant and were treated with an ACE inhibitor.Results: Transplant patients were significantly overrepresented among ACE inhibitor‐associated angioedema cases compared to controls (odds ratio 18.5, 95% CI 2.3–147.2,P = 0.0004). Immunosuppressant use, chronic renal failure, seasonal allergies and smoking were also associated with ACE inhibitor‐associated angioedema in univariate analysis. The association of transplant status with ACE inhibitor‐associated angioedema was no longer significant after inclusion of immunosuppressant therapy in a multivariate analysis. Dipeptidyl peptidase IV activity was significantly decreased in sera from cases compared to ACE inhibitor‐exposed controls, as well as in individuals taking immunosuppressants. Two of 47 ACE inhibitor‐treated renal transplant patients and one of 36 ACE inhibitor‐treated cardiac transplant patients developed angioedema.Conclusion: Transplant patients are at increased risk of ACE inhibitor‐associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.
Hippocampal–anterior thalamic pathways for memory: uncovering a network of direct and indirect actions
Authors: Aggleton John P. , O’Mara Shane M. , Vann Seralynne D. , Wright Nick F. , Tsanov Marian , Erichsen Jonathan T. 
Published: June 2010

AbstractThis review charts recent advances from a variety of disciplines that create a new perspective on why the multiple hippocampal–anterior thalamic interconnections are together vital for human episodic memory and rodent event memory. Evidence has emerged for the existence of a series of parallel temporal–diencephalic pathways that function in a reciprocal manner, both directly and indirectly, between the hippocampal formation and the anterior thalamic nuclei. These extended pathways also involve the mammillary bodies, the retrosplenial cortex and parts of the prefrontal cortex. Recent neuropsychological findings reveal the disproportionate importance of these hippocampal–anterior thalamic systems for recollective rather than familiarity‐based recognition, while anatomical studies highlight the precise manner in which information streams are kept separate but can also converge at key points within these pathways. These latter findings are developed further by electrophysiological stimulation studies showing how the properties of the direct hippocampal–anterior thalamic projections are often opposed by the indirect hippocampal projections via the mammillary bodies to the thalamus. Just as these hippocampal–anterior thalamic interactions reflect an interdependent system, so it is also the case that pathology in one of the component sites within this system can induce dysfunctional changes to distal sites both directly and indirectly across the system. Such distal effects challenge more traditional views of neuropathology as they reveal how extensive covert pathology might accompany localised overt pathology, and so impair memory.
A thermophilic bacterial origin and subsequent constraints by redox, light and salinity on the evolution of the microbial mercuric reductase
Authors: Barkay Tamar , Kritee K. , Boyd Eric , Geesey Gill 
Published: June 2010

SummaryMercuric reductase (MerA) is central to the mercury (Hg) resistance (mer) system, catalyzing the reduction of ionic Hg to volatile Hg(0). A total of 213merAhomologues were identified in sequence databases, the majority of which belonged to microbial lineages that occupy oxic environments.merAwas absent among phototrophs and in lineages that inhabit anoxic environments. Phylogenetic reconstructions of MerA indicate that (i)merAoriginated in a thermophilic bacterium following the divergence of the Archaea and Bacteria with a subsequent acquisition in Archaea via horizontal gene transfer (HGT), (ii) HGT ofmerAwas rare across phylum boundaries and (iii) MerA from marine bacteria formed distinct and strongly supported lineages. Collectively, these observations suggest that a combination of redox, light and salinity conditions constrain MerA to microbial lineages that occupy environments where the most oxidized and toxic form of Hg, Hg(II), predominates. Further, the taxon‐specific distribution of MerA with and without a 70 amino acid N‐terminal extension may reflect intracellular levels of thiols. In conclusion, MerA likely evolved following the widespread oxygenation of the biosphere in a thermal environment and its subsequent evolution has been modulated by the interactions of Hg with the intra‐ and extracellular environment of the organism.
DNA hypermethylation in papillary renal cell carcinoma
Authors: Ellinger Jörg , Holl Daniel , Nuhn Philipp , Kahl Philip , Haseke Nicolas , Staehler Michael , Siegert Sabine , Hauser Stefan , Stief Christian G. , Müller Stefan C. , Bastian Patrick J. 
Published: June 2010

What’s known on the subject? and What does the study add? Epigenetic alterations play an essential role during carcinogenesis, and earlier studies suggested that global histone modification levels are predictive for patients’ outcome in various tumour entities (e.g. prostate, lung, breast and kidney cancer). So far, only smaller studies on histone H3K9 acetylation in patients with papillary urothelial neoplasm of low malignant potential (PUNLMP) and histone H2AX phosphorylation in non‐muscle invasive bladder cancer exist; both studies indicate prognostic relevance for bladder cancer.We demonstrate that histone methylation levels (H3K4, H4K20) decrease from normal tissue over non‐muscle invasive and muscle invasive bladder cancer to bladder cancer metastases. Histone modifications are correlated to advanced pathological stage in non‐muscle and muscle invasive bladder cancer. Furthermore, H4K20me3 appeared to be predictive for bladder cancer specific survival in patients with muscle‐invasive bladder cancer undergoing radical cystectomy.OBJECTIVETo investigate the pattern of DNA CpG island hypermethylation in papillary renal cell carcinoma (pRCC).MATERIAL AND METHODSDNA from pRCC (n= 32) and adjacent normal tissue (n= 15) was isolated. A quantitative methylation‐specific PCR was performed to analyse the methylation pattern at APC (actin beta), CDH1 (E‐cadherin), GSTP1 (glutathione S‐transferase pi 1), RASSF1A (Ras association domain family member 1A) and TIMP3 (TIMP metallopeptidase inhibitor 3); a sequence of ACTB without CpG was used to normalize for DNA input and to calculate the relative amount of methylated DNA (normalized index of methylation, NIM).RESULTS RASSF1A hypermethylation was observed in most pRCC and normal samples (100 vs 94.4%), but the median NIM was significantly higher in pRCC samples (2.11 vs 0.61; P < 0.001). RASSF1A hypermethylation allowed discrimination of pRCC and normal tissue with a sensitivity of 87.5% and a specificity of 73.3% as determined via receiver operator characteristic analysis (area under curve = 0.814). Hypermethylation at APC (3.0 vs 6.7%), CDH1 (15.6 vs 0%), GSTP1 (21.9 vs 6.7%) and TIMP3 (6.3 vs 0%) was infrequent in pRCC and normal tissue. CDH1 was significantly correlated with pathological stage (P= 0.015), and patients with methylated CDH1 methylation showed a trend towards shorter recurrence‐free survival (log‐rank P= 0.057). The number of methylated gene sites was correlated with pathological stage (P= 0.007) and lymph node metastasis (P= 0.008).CONCLUSIONSDNA hypermethylation at RASSF1A is common in pRCC tissue irrespective of the histological subtype, but also frequently seen at lower levels in normal adjacent tissue. Aberrant hypermethylation could be a prognostic marker for pRCC.