bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciding how NHS money is spent: a survey of general public and medical views
Authors: Lees Ann , Scott Nicholas , Scott Sheila N. , MacDonald Sara , Campbell Christine 
Published: March 2003

Objectives To examine the validity of the Prioritization Scoring Index (PSI) methodology by obtaining the views of our local population and clinicians regarding the criteria and weightings that should be used in deciding how NHS money is spent. Background We have used a PSI in Argyll and Clyde to allocate new money since 1996 and to determine priorities for our 1999/2000–2003/2004 Health Improvement Programme (HIP). Since the criteria and weightings for this methodology were developed subjectively, we sought to validate these by consulting local people and to change our methodology to take account of wider population views. Methods A postal questionnaire was sent to 1969 members of the general public, all 314 general practitioners and all 189 hospital consultants in Argyll and Clyde in March 1999. A reminder was sent after 4 weeks. Questions were asked about general funding and prioritization in the NHS and about specific issues relating to potential criteria for prioritization, including those used in our PSI methodology. Responses were analysed quantitatively in the Statistical Package for the Social Sciences (SPSS) and qualitatively through examination of the responses to open questions. Results The response rate was 51% for the general public and 71% for GPs and consultants. Respondents from the general public were broadly representative of the Argyll and Clyde population. The main findings were that: greater importance should be given to care that improves health, quality of life or prevents ill health rather than to cost, or to government and local health board priorities; half of the general public and most clinicians thought there should be a limit on NHS funding; extra money for the NHS should come from the national lottery (general public) or higher taxes on cigarettes and alcohol (clinicians); doctors should have the greatest influence in deciding how NHS money is spent; a higher priority should not be given to the health‐care needs of younger people rather than older people. Our public and clinicians would allocate approximately 50% of the prioritization weighting to direct patient benefits, 25% to the cost of health‐care and 25% to strategic health issues. Conclusions Consideration of public and clinician views suggests that a revised PSI should place greater weight on benefits to patients and lower weight on the cost of health‐care.
User involvement in clinical governance
Authors: Pickard Susan , Marshall Martin , Rogers Anne , Sheaff Rod , Sibbald Bonnie , Campbell Stephen , Halliwell Shirley , Roland Martin 
Published: March 2003

Objectives To investigate the involvement of users in clinical governance activities within Primary Care Groups (PCGs) and Trusts (PCTs). Drawing on policy and guidance published since 1997, the paper sets out a framework for how users are involved in this agenda, evaluates practice against this standard and suggests why current practice for user involvement in clinical governance is flawed and why this reflects a flaw in the policy design as much as its implementation. Design Qualitative data comprising semi‐structured interviews, reviews of documentary evidence and relevant literature. Setting Twelve PCGs/PCTs in England purposively selected to provide variation in size, rurality and group or trust status. Participants Key stakeholders including Lay Board members (n=12), Chief Executives (CEs) (n= 12), Clinical Governance Leads (CG leads) (n= 14), Mental Health Leads (MH leads) (n= 9), Board Chairs (n=2) and one Executive Committee Lead. Results Despite an acknowledgement of an organizational commitment to lay involvement, in practice very little has occurred. The role of lay Board members in setting priorities and implementing and monitoring clinical governance remains low. Beyond Board level, involvement of users, patients of GP practices and the general public is patchy and superficial. The PCGs/PCTs continue to rely heavily on Community Health Councils (CHCs) as a conduit or substitute for user involvement; although their abolition is planned, their role to be fulfilled by new organizations called Voices, which will have an expanded remit in addition to replacing CHCs. Conclusions Clarity is required about the role of lay members in the committees and subcommittees of PCGs and PCTs. Involvement of the wider public should spring naturally from the questions under consideration, rather than be regarded as an end in itself.
Resource allocation, social values and the QALY: a review of the debate and empirical evidence
Authors: Schwappach David L. B. 
Published: March 2003

AbstractMost health economists agree that public preferences should play a major role in setting criteria for distributing scarce resources. The quality‐adjusted life year (QALY) is used as a preference‐based measure for the outcome of health‐care activities in health economic evaluative studies. Traditionally, health economists proposed maximizing the additional health gain in terms of QALYs so as to maximize social welfare. Evidence has grown however, that neither potential health gain as a single relevant determinant of value, nor the rule of maximizing this health gain are sufficient. Concerns about fairness and equity are also important to the public in distributional decisions. This paper reviews the debate on the role and limitations of the QALY in health‐care priority setting and the empirical evidence surrounding it. A framework is used to systematically explore the available data on factors considered to be important to the public in health‐care resource allocation, and to investigate how these fit with the implicit value judgements inherent in the original QALY formulation. Potential sources of social value are classified into (1) factors that relate to the characteristics of patients and (2) factors related to the characteristics of the intervention's effect on patients' health. As well as these main categories, the article considers preferences for distributional rules. Recent approaches that aim to capture public preferences more comprehensively and to better reflect the value attributed to different health‐care programmes in economic evaluation methods are outlined briefly.
Medical tests: women's reported and preferred decision‐making roles and preferences for information on benefits, side‐effects and false results
Authors: Davey Heather M. , Barratt Alexandra L. , Davey Elizabeth , Butow Phyllis N. , Redman Sally , Houssami Nehmat , Salkeld Glenn P. 
Published: March 2003

AbstractObjective  To determine women's preferences for and reported experience with medical test decision‐making.Design  Computer‐assisted telephone survey.Setting and participants  Six hundred and fifty‐two women resident in households randomly selected from the New South Wales electronic white pages.Main outcome measures  Reported and preferred test and treatment (for comparison) decision‐making, satisfaction with and anxiety about information on false results and side‐effects; and effect of anxiety on desire for such information.Results  Overall most women preferred to share test (94.6%) and treatment (91.2%) decision‐making equally with their doctor, or to take a more active role, with only 5.4–8.9% reporting they wanted the doctor to make these decisions on their behalf. This pattern was consistent across all age groups. In general, women reported experiencing a decision‐making role that was consistent with their preference. Women who had a usual doctor were more likely to report experiencing an active role in decision‐making. More women reported receiving as much information as they wanted about the benefits of tests and treatment than about the side‐effects of tests and treatment. Most women wanted information about the possibility of false test results (91.5%) and test side‐effects (95.6%), but many reported the doctor never provided this information (false results = 40.0% and side‐effects = 31.3%). A substantial proportion said this information would make them anxious (false results = 56.6% and side‐effects = 43.1%), but reported they wanted the information anyway (false results = 77.6% and side‐effects = 88.1%).Conclusions  Women prefer an active role in test and treatment decision‐making. Many women reported receiving inadequate information. If so, this may jeopardize informed decision‐making.
Acceptability of willingness to pay techniques to consumers
Authors: Taylor Susan J. , Armour Carol L. 
Published: March 2003

AbstractObjective The purpose of this study was to assess and compare the proportion of usable responses and protest votes obtained with two willingness to pay (WTP) techniques, contingent valuation (CV) and discrete choice experiment (DCE) and to assess the acceptability of the techniques to respondents.Setting and participants Pregnant women attending the public antenatal clinics of a Sydney teaching hospital were surveyed.Main variables studied Preference for either Treatment A (artificial rupture of the membranes followed by intravenous oxytocin) or Treatment B (prostaglandin E2 gel followed by oxytocin if necessary) was assessed. Then WTP for the preferred treatments was assessed using CV and WTP for specific attributes of the treatments in the DCE. In addition, the acceptability of the two techniques was compared in terms of responses deemed to be valid according to defined criteria, protest votes and comments recorded by consumers.Results With the CV, 74% of respondents chose gel and their maximum WTP was Aus$178 compared with $133 for the alternative. A total of 68% of responses were deemed to be valid including 5% who may have been expressing a protest vote. With the DCE, respondents were WTP $55 for every 1 h reduction in the length of time from induction to delivery. A total of 72% of responses were deemed valid and only two of these 258 women were considered to have expressed a protest vote.Conclusions Only a small number of women expressed objections to the use of WTP questions in health‐care and the majority of women completed both questions successfully.
ORF6 from the clavulanic acid gene cluster of Streptomyces clavuligerus has ornithine acetyltransferase activity
Authors: Kershaw Nadia J. , McNaughton Heather J. , Hewitson Kirsty S. , Hernández Helena , Griffin John , Hughes Claire , Greaves Philip , Barton Barry , Robinson Carol V. , Schofield Christopher J. 
Published: March 2003

The clinically used beta‐lactamase inhibitor clavulanic acid is produced by fermentation of Streptomyces clavuligerus. The orf6 gene of the clavulanic acid biosynthetic gene cluster in S. clavuligerus encodes a protein that shows sequence homology to ornithine acetyltransferase (OAT), the fifth enzyme of the arginine biosynthetic pathway. Orf6 was overexpressed in Escherichia coli (at ≈ 15% of total soluble protein by SDS/PAGE analysis) indicating it was not toxic to the host cells. The recombinant protein was purified (to > 95% purity) by a one‐step technique. Like other OATs it was synthesized as a precursor protein which underwent autocatalytic internal cleavage in E. coli to generate α and β subunits. Cleavage was shown to occur between the alanine and threonine residues in a KGXGMXXPX‐‐(M/L)AT	(M/L)L motif conserved within all identified OAT sequences. Gel filtration and native electrophoresis analyses implied that the ORF6 protein was an α2β2 heterotetramer and direct evidence for this came from mass spectrometric analyses. Although anomalous migration of the β subunit was observed by standard SDS/PAGE analysis, which indicated the presence of two bands (as previously observed for other OATs), mass spectrometric analyses did not reveal any evidence for post‐translational modification of the β subunit. Extended denaturation with SDS before PAGE resulted in observation of a single major β subunit band. Purified ORF6 was able to catalyse the reversible transfer of an acetyl group from N‐acetylornithine to glutamate, but not the formation of N‐acetylglutamate from glutamate and acetyl‐coenzyme A, nor (detectably) the hydrolysis of N‐acetylornithine. Mass spectrometry also revealed the reaction proceeds via acetylation of the β subunit.
BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro
Authors: Schmitt‐Bernard Clair‐Florent , Chavanieu Alain , Herrada Gudrun , Subra Guy , Arnaud Bernard , Demaille Jacques G. , Calas Bernard , Argilés Ángel 
Published: March 2003

Amyloid deposits with Arg124 mutated TGFBI protein have been identified in autosomal dominant blinding corneal dystrophies. We assessed in vitro the mechanisms determining TGFBI protein amyloid transformation involving mutations of Arg124. Eight peptides synthesized following the TGFBI protein sequence, centered on codon Arg124 holding the previously reported amyloidogenic mutations and the respective controls were studied. Cys124 and His124 mutated peptide preparations contained significantly higher amounts of amyloid than the native peptide. Blocking the SH group of Cys124 and deleting the first four NH2‐terminal amino acids including Val112‐Val113 resulted in a decrease in amyloid fibril formation while deletion of the nine CONH2‐terminal residues increased amyloid fibril concentration. Fourrier transformed‐infrared spectroscopy analysis of the different peptide solutions showed an increase in β‐pleated sheet structures in those with enhanced amyloid yielding. We designed a peptide (BB1) likely to counteract the role of Val112‐Val113 in amyloid fibril formation. Incubation of Cys124 peptide with BB1 indeed resulted in a 35% inhibition of amyloid fibril formation.Our results are in keeping with the clinical observations of Arg124 mutation‐linked amyloidosis and show the importance of Val112–Val113, disulfide and hydrogen bonding in increasing the β‐pleated conformation and amyloid formation. These findings shed new light on the molecular mechanisms of TGFBI protein amyloidogenesis and encourage further research on the use of specifically designed peptides as putative therapeutic agents for these disabling diseases.
Structure of the O polysaccharides and serological classification of Pseudomonas syringae pv. porri from genomospecies 4
Authors: Zdorovenko Evelina L. , Zatonskii George V. , Kocharova Nina A. , Shashkov Aleksander S. , Knirel Yuriy A. , Ovod Vladimir V. 
Published: March 2003

Strains of Pseudomonas syringae pv. porri are characterized by a number of pathovar‐specific phenotypic and genomic characters and constitute a highly homogeneous group. Using monoclonal antibodies, they all were classified in a novel P. syringae serogroup O9. The O polysaccharides (OPS) isolated from the lipopolysaccharides (LPS) of P. syringae pv. porri NCPPB 3365 and NCPPB 3364T possess multiple oligosaccharide O repeats, some of which are linear and composed of l‐rhamnose (l‐Rha), whereas the major O repeats are branched with l‐rhamnose in the main chain and GlcNAc in side chains (structures 1 and 2). Both branched O repeats, which differ in the position of substitution of one of the Rha residues and in the site of attachment of GlcNAc, were found in the two strains studied, O repeat 1 being major in strain NCPPB 3365 and 2 in strain NCPPB 3364T. The relationship between OPS chemotype and serotype on one hand and the genomic characters of P. syringae pv. porri and other pathovars delineated in genomospecies 4 on the other hand is fdiscussed.
Bioenergetics of the formyl‐methanofuran dehydrogenase and heterodisulfide reductase reactions in Methanothermobacter thermautotrophicus
Authors: de Poorter Linda M. I. , Geerts Wim G. , Theuvenet Alexander P. R. , Keltjens Jan T. 
Published: March 2003

The synthesis of formyl‐methanofuran and the reduction of the heterodisulfide (CoM‐S‐S‐CoB) of coenzyme M (HS‐CoM) and coenzyme B (HS‐CoB) are two crucial, H2‐dependent reactions in the energy metabolism of methanogenic archaea. The bioenergetics of the reactions in vivo were studied in chemostat cultures and in cell suspensions of Methanothermobacter thermautotrophicus metabolizing at defined dissolved hydrogen partial pressures ( pH2). Formyl‐methanofuran synthesis is an endergonic reaction (ΔG°′ = +16 kJ·mol−1). By analyzing the concentration ratios between formyl‐methanofuran and methanofuran in the cells, free energy changes under experimental conditions (ΔG′) were found to range between +10 and +35 kJ·mol−1 depending on the pH2 applied. The comparison with the sodium motive force indicated that the reaction should be driven by the import of a variable number of two to four sodium ions.Heterodisulfide reduction (ΔG°′ = −40 kJ·mol−1) was associated with free energy changes as high as −55 to −80 kJ·mol−1. The values were determined by analyzing the concentrations of CoM‐S‐S‐CoB, HS‐CoM and HS‐CoB in methane‐forming cells operating under a variety of hydrogen partial pressures. Free energy changes were in equilibrium with the proton motive force to the extent that three to four protons could be translocated out of the cells per reaction. Remarkably, an apparent proton translocation stoichiometry of three held for cells that had been grown at pH2<0.12 bar, whilst the number was four for cells grown above that concentration. The shift occurred within a narrow pH2 span around 0.12 bar. The findings suggest that the methanogens regulate the bioenergetic machinery involved in CoM‐S‐S‐CoB reduction and proton pumping in response to the environmental hydrogen concentrations.
The 3′‐UTR of the mRNA coding for the major protein kinase C substrate MARCKS contains a novel CU‐rich element interacting with the mRNA stabilizing factors HuD and HuR
Authors: Wein Georg , Rössler Marek , Klug Roland , Herget Thomas 
Published: March 2003

The expression of the major protein kinase C substrate MARCKS (myristoylated alanine‐rich C kinase substrate) is controlled by the stability of its mRNA. While the MARCKS mRNA is long living in quiescent fibroblasts (t1/2 = 14 h), its half‐life time is drastically reduced (t1/2 = 2 h) in cells treated with phorbol esters to activate protein kinase C (PKC) or treated with growth factors. In a first step to study the underlying mechanism we identified both a cis‐element on the MARCKS mRNA and the corresponding trans‐acting factors. Fusing the complete 3′‐UTR or specific regions of the 3′‐UTR of the MARCKS gene to a luciferase reporter gene caused a drastic decrease in luciferase expression to as low as 5–10% of controls. This down‐regulation was a result of destabilization of the chimeric transcript as shown by RNA run‐off and Northern blot‐assays. By RNase/EMSA and UV‐cross‐linking experiments, we identified a stretch of 52 nucleotides [(CUUU)11(U)8] in the 3′‐UTR of the MARCKS mRNA specifically recognized by two RNA‐binding proteins, HuD and HuR. These trans‐acting factors are members of the ELAV gene family and bind the MARCKS CU‐rich sequence with high affinity. Overexpression of HuD and HuR in murine fibroblasts caused a striking stabilization of the endogenous MARCKS mRNA even under conditions when the MARCKS mRNA is normally actively degraded, i.e. after treating cells with phorbol ester.These data imply, that the identified CU‐rich cis‐element of the MARCKS 3′‐UTR is involved in conferring instability to mRNAs and that members of the ELAV gene family oppose this effect. Based on its structural and functional properties, the (CUUU)11(U)8 sequence described here can be grouped into class III of AU‐rich elements.
Identification and characterization of B′′‐subunits of protein phosphatase 2 A in Xenopus laevis oocytes and adult tissues
Authors: Stevens Ilse , Janssens Veerle , Martens Ellen , Dilworth Stephen , Goris Jozef , Van Hoof Christine 
Published: March 2003

Protein phosphatase 2A is a phosphoserine/threonine phosphatase implicated in many cellular processes. The core enzyme comprises a catalytic and a PR65/A‐subunit. The substrate specificity and subcellular localization are determined by a third regulatory B‐subunit (PR55/B, PR61/B′ and PR72/130/B′′).To identify the proteins of the B′′ family in Xenopus laevis oocytes, a prophase Xenopus oocyte cDNA library was screened using human PR130 cDNA as a probe. Three different classes of cDNAs were isolated. One class is very similar to human PR130 and is probably the Xenopus orthologue of PR130 (XPR130). A second class of clones (XN73) is identical to the N‐terminal part of XPR130 but ends a few amino acids downstream of the putative splicing site of PR130. To investigate how this occurs, the genomic structure of the human PR130 gene was determined. This novel protein does not act as a PP2A subunit but might compete with the function of PR130. The third set of clones (XPR70) is very similar to human PR48 but has an N‐terminal extension. Further analysis of the human EST‐database and the human PR48 gene structure, revealed that the human PR48 clone published is incomplete. The Xenopus orthologue of PR48 encodes a protein of 70 kDa which like the XPR130, interacts with the A‐subunit in GST pull‐down assays. XPR70 is ubiquitously expressed in adult tissues and oocytes whereas expression of XPR130 is very low in brain and oocytes. Expression of XN73 mainly parallels XPR130 with the exception of the brain.
Mutational analysis of residues forming hydrogen bonds in the Rieske [2Fe‐2S] cluster of the cytochrome bc1 complex in Paracoccus denitrificans
Authors: Schröter Thomas , Hatzfeld Oliver M. , Gemeinhardt Sabine , Korn Marcus , Friedrich Thorsten , Ludwig Bernd , Link Thomas A. 
Published: March 2003

Two mutations (S157A and Y159F) in the Rieske iron‐sulfur subunit of the ubihydroquinone‐cytochrome c oxidoreductase from Paracoccus denitrificans have been characterized with respect to the protein and [2Fe‐2S] cluster stability, the enzyme activity and the redox potential of the [2Fe‐2S] cluster.In the structure of the water‐soluble fragment of the Rieske iron‐sulfur protein of the bovine heart mitochondrial bc1 complex, both residues (S163 and Y165 in the bovine sequence) form the following hydrogen bonds to sulfur atoms in the [2Fe‐2S] cluster : Ser163 Oγ‐S‐1 and Tyr165 Oη‐Cys139 Sγ [Iwata, S., Saynovits, M., Link, T. A. & Michel, H. (1996) Structure 4, 567−579]. They are conserved in all known Rieske iron‐sulfur proteins from bc1 complexes including that from P. denitrificans.Both amino acid exchanges, introduced as separate point mutations on plasmids containing the fbc operon, lead to a fully assembled three‐subunit complex in P. denitrificans, with a metal and heme content as well as subunit composition indistinguishable from the parental strain.The purified complexes show decreased turnover numbers and redox potentials of the Rieske cluster. Whereas the turnover number of the bc1 complex isolated from the parental strain was 145 s−1, the turnover numbers for the mutants S157A and Y159F were 10 s−1 and 52 s−1, respectively, corresponding to 7 % and 36 % activity, respectively. The midpoint potential Em of the Rieske cluster at pH 6 and 5 +C was +360 mV for the bc1 complex from the parental strain; the values in the mutant complexes were +316 mV (Y159F) and +265 mV (S157A). Shifts of the g values in the electron paramagnetic resonance spectra indicate an altered electron distribution in the mutants compared to in the wild‐type protein.