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Biomedical subjects

Stephen Martin

Publications and source records attributed to Stephen Martin.

At least 19 recordsLinked to original sources
PubMed2007

The effects of expanding patient choice of provider on waiting times: evidence from a policy experiment.

Long waiting times for inpatient treatment in the UK National Health Service have been a source of popular and political concern, and therefore a target for policy initiatives. In the London Patient Choice Project, patients at risk of breaching inpatient waiting time targets were offered the choice of an alternative hospital with a guaranteed shorter wait. This paper develops a simple theoretical model of the effect of greater patient choice on waiting times. It then uses a difference in difference econometric methodology to estimate the impact of the London choice project on ophthalmology waiting times. In line with the model predictions, the project led to shorter average waiting times in the London region and a convergence in waiting times amongst London hospitals.

Choice Behavior↗
PubMed2006

The market for elective surgery: joint estimation of supply and demand.

This paper develops models of the demand for and supply of elective (non-emergency) surgery using a panel of quarterly data for 200 English hospitals over the period 1995-2002. Unusually, distinct measures of supply (outpatients seen and inpatient admissions) and demand (outpatient referrals and decisions to admit) are available for each observation. These offer the opportunity to estimate separate empirical models of supply and demand using ordinary least squares (OLS) regression methods. However, the strong correlation between the residuals of these models suggests some merit in the deployment of seemingly unrelated regression (SUR) methods. Although both static and dynamic SUR estimations leave the results largely qualitatively unchanged, SUR estimation can have a considerable quantitative effect relative to the OLS results. For example, SUR estimation generates a lower elasticity of inpatient demand with respect to waiting time than that obtained via OLS. The results offer an important justification for more careful econometric modelling of hospital behaviour than has traditionally been employed in the health economics literature.

Elective Surgical Procedures↗
PubMed2006

YfhJ, a molecular adaptor in iron-sulfur cluster formation or a frataxin-like protein?

The yfhJ gene is part of the isc operon, which encodes the machinery devoted to assemble iron-sulfur clusters in prokaryotes. Its transcript is a small acidic protein that binds the desulfurase IscS, which is essential in iron-specific metabolic pathways. To understand its cellular role, we have characterized the structure of YfhJ in solution and its interactions with potential cellular partners. It contains a modified winged helix motif, usually present in DNA binding proteins, and is able to bind iron cations. The IscS interaction surface is the same as that involved in iron binding. This observation and the pattern of conservation through species strongly suggest that YfhJ is a molecular adaptor that is able to modulate the function of IscS in iron-sulfur cluster formation. The remarkable similarity between the in vitro behavior of YfhJ and that of the protein frataxin also suggests new hypotheses regarding the functional role of both proteins.

Amino Acid Sequence↗
PubMed2006

Powered, air-purifying particulate respirator filter penetration by a DOP aerosol.

In 1995, new certification requirements for all nonpowered, air-purifying particulate filter respirators were put in place when 42 CFR 84 replaced 30 CFR 11. However, the certification requirements for all other classes of respirators, including powered air-purifying respirators (PAPRs), were transferred to 42 CFR 84 from 30 CFR 11 without major changes. Since the inception of 42 CFR 84, researchers have learned that the efficiency of electrostatic filter media, in contrast with mechanical filter media, can be rapidly degraded by oil aerosols. Further, confusion may exist among respirator users, since electrostatic PAPR filters have the same magenta color assigned to high-efficiency filters for nonpowered particulate respirators that have been tested and certified for use against oil aerosols (i.e., P100 filters). Users may expect that the magenta color of certified PAPR filters indicates suitability for use against oil aerosols. This may not be the case. To illustrate the potential degradation of electrostatic PAPR filters, new filters certified under 42 CFR 84 were tested using a TSI model 8122 Automated Respirator Tester against charged and neutralized DOP aerosols with intermittent loading schedules. The performance of a magenta-colored electrostatic PAPR filter--one for which the manufacturer's user instructions appropriately indicates is not suitable for use in oily environments--was compared with the performance of several mechanical PAPR filters. In tests against both DOP aerosols, the electrostatic PAPR filter showed a significant decrease in performance at DOP loadings exceeding 400 mg, whereas mechanical filters showed no significant change in the performance except at extremely high loadings. The decreased performance of the electrostatic PAPR filter was found to be significantly greater when tested against a neutralized DOP aerosol when compared with a charged DOP aerosol. While laboratory tests show that the filtration efficiency of this electrostatic PAPR filter degrades with exposure to DOP aerosol, the observed laboratory degradation may or may not affect workplace performance, as similar degradation has not been verified in workplace studies. Based on these laboratory results, a proposed method for evaluating high-efficiency PAPR filters is presented. This proposed method would ensure that high-efficiency PAPR filters (> or = 99.97% efficient and magenta in color) meet critical performance criteria when loaded.

Aerosols↗
PubMed2006

Integrated unit performance testing of powered, air-purifying particulate respirators using a DOP challenge aerosol.

Although workplace protection factor (WPF) and simulated workplace protection factor (SWPF) studies provide useful information regarding the performance capabilities of powered air-purifying respirators (PAPRs) under certain workplace or simulated workplace conditions, some fail to address the issue of total PAPR unit performance over extended time. PAPR unit performance over time is of paramount importance in protecting worker health over the course of a work shift or at least for the recommended service lifetime of the PAPR battery pack, whichever is shorter. The need for PAPR unit performance testing has become even more important with the inception of 42 CFR 84 and the recent introduction of electrostatic respirator filter media into the PAPR market. This study was conducted to learn how current PAPRs certified by the National Institute for Occupational Safety and Health would perform under an 8-hour unit performance test similar to the dioctyl phthalate (DOP) loading test described in 42 CFR 84 for R- and P-series filters for nonpowered, air-purifying particulate respirators. In this study, entire PAPR units, four with mechanical filters and one with an electrostatic filter, were tested using a TSI Model 8122 Automated Respirator Tester, with and without the built-in breathing machine. The two, tight-fitting PAPRs, both with mechanical filters, showed little effect on performance resulting from the breathing machine. The two loose-fitting helmet PAPRs indicate that unit performance testing without the breathing machine is a more stringent test than testing with the breathing machine under the conditions used. The PAPR with a loose-fitting hood gave inconclusive results as to which testing condition is more stringent. The PAPR unit equipped with electrostatic filters gave the highest maximum penetration values during unit performance testing.

Aerosols↗
PubMed2006

Evaluation of flavorings-related lung disease risk at six microwave popcorn plants.

OBJECTIVE: After investigating fixed airways obstruction in butter flavoring-exposed workers at a microwave popcorn plant, we sought to further characterize lung disease risk from airborne butter-flavoring chemicals. METHODS: We analyzed data from medical and environmental surveys at six microwave popcorn plants (including the index plant). RESULTS: Respiratory symptom and airways obstruction prevalences were higher in oil and flavorings mixers with longer work histories and in packaging-area workers near nonisolated tanks of oil and flavorings. Workers were affected at five plants, one with mixing-area exposure to diacetyl (a butter-flavoring chemical with known respiratory toxicity potential) as low as 0.02 ppm. CONCLUSIONS: Microwave popcorn workers at many plants are at risk for flavoring-related lung disease. Peak exposures may be hazardous even when ventilation maintains low average exposures. Respiratory protection and engineering controls are necessary to protect workers.

Adolescent↗
PubMed2006

The effects of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea: a multicenter, placebo-controlled, parallel group trial in subjects with chronic pancreatitis.

OBJECTIVES: Creon 10 Minimicrospheres is an enteric-coated, delayed-release pancrelipase preparation designed to deliver active pancreatic enzymes to the small intestine. The primary objective of this study was to compare the effect of Creon 10 with placebo in the control of steatorrhea in chronic pancreatitis patients. Secondary objectives included evaluation of stool parameters and global improvement of symptoms scales. METHODS: The study was a randomized, double-blind, placebo-controlled, 2-week trial. After a placebo run-in ("washout") phase, the effect on coefficient of fat absorption (%), daily fat excretion before and after treatment, and stool frequency and consistency were assessed. RESULTS: In Creon 10-treated subjects, the change in mean coefficient of fat absorption (%) from run-in to double-blind phase was significantly higher compared with placebo-treated subjects (+36.7 vs. +12.1, P = 0.0185). Stool consistency improved significantly more with Creon 10 than with placebo (P = 0.0102) resulting in more subjects with formed stool; stool frequency decreased significantly more with Creon 10 than with placebo (P = 0.0015) from 10.8 during placebo run-in to 5.2 stools per day during double-blind treatment; and daily mean fat excretion in stool decreased significantly more (-56.5 vs. -11.4 g/d, P = 0.0181) in Creon 10-treated subjects compared with placebo-treated subjects. Global disease symptom scores showed greater improvement for both physicians and subjects in the Creon 10 group relative to those receiving placebo. Between treatment difference reached statistical significance for Creon 10 (P = 0.0435) for physician score and showed a trend (P = 0.0634) favoring Creon for subject score. CONCLUSIONS: This randomized, placebo-controlled trial found that Creon 10 treatment controlled steatorrhea, as reflected in reduced fat excretion, decreased stool frequency and improved stool consistency. Creon 10 treatment was safe and well tolerated.

Administration, Oral↗
PubMed2006

Exploring the determinants of NHS performance ratings: lessons for performance assessment systems.

OBJECTIVES: A basic tenet of effective performance management is that decision makers should be held responsible only for aspects of performance over which they have control. We examine the degree to which variations in the performance of health care organizations are explained by a range of factors that are subject to differing degrees of managerial control. METHODS: We use multiple regression methods and data on 304 National Health Service (NHS) Primary Care Trusts (PCTs) in England for 2002/03 to analyse the relationship between their performance, as measured by 'star ratings' and nine key performance targets, and a large number of explanatory variables. We classify the explanatory variables into five groups along a spectrum from 'no managerial control' to 'total managerial control'. We also analyse the relationship between PCTs that are service purchasers and their main providers to assess the degree to which their performance is linked. RESULTS: For all of the key performance targets, most of the variation in performance is unexplained, although variables in groups 1, 2 and 3 (less managerial control) explain the largest proportion of variation. We find some evidence that socioeconomic and geographic factors have an impact on performance. We also find a positive relationship between the performances of purchaser and provider organizations. CONCLUSIONS: The star ratings did not allow for the different environmental circumstances within which PCTs operate and which affect their performance. Policy-makers should exercise caution in using such performance indicators to regulate health care organizations.

England↗
PubMed2006

A case-cohort study to investigate concomitant waterborne outbreaks of Campylobacter and gastroenteritis in Söderhamn, Sweden, 2002-3.

Increased domestic, laboratory confirmed, Campylobacter notifications were reported in Siderhamn municipality, December 2002 and January 2003. Concurrently, during preliminary investigations a large outbreak of acute gastroenteritis was detected. Simultaneously, two studies were completed to identify risk factors for infection with Campylobacter and acute gastrointestinal infection (AGI): (1) a case-cohort study using Campylobacter cases (N = 101) with a large random sample from the municipal population as referents (N = 1000) and (2) a retrospective cohort study for the outcome AGI using the same sample. A postal questionnaire was used to collect demographic, clinical, water and food consumption data. Measures of association (risk ratio (RR), odds ratio (OR)) and 95% confidence intervals (CI) were calculated. Stool, environmental and water samples were tested by standard methods at Gävle Hospital and SMI laboratories respectively. In the case-cohort study, Camplylobacter cases were more likely than referents to consume communal water (OR = 12.6 (95% CI 1.7-92.3)). In the cohort study, risk of gastroenteritis was 2.3 times higher in those who consumed water (AR = 27.3%) than others (AR = 12%). Risk of illness was associated with the amount of water consumed in both studies. Campylobacter was detected in stools and Escherichia coli (E. coli) from routine communal water (CW) samples. Results suggest both Söderhamn outbreaks of Campylobacter and AGI were associated with consumption of CW. The method used strengthened epidemiological evidence and was efficient in the use of time and resources.

Adolescent↗
PubMed2005

Identification of Amadori-modified plasma proteins in type 2 diabetes and the effect of short-term intensive insulin treatment.

OBJECTIVE: Growing evidence supports that nonenzymatic glycation products may cause hyperglycemia-induced diabetes complications. Amadori-modified proteins are the intermediate products of nonenzymatic glycation and constitute the forms of glycated proteins in diabetes. The objective of the current study was to utilize two-dimensional gel electrophoresis, Western blot, and mass spectrometry to identify Amadori-modified plasma proteins in type 2 diabetic patients with poor glycemic control and assess the impact of short-term insulin treatment on the glycation of these proteins. RESEARCH DESIGN AND METHODS: We compared eight type 2 diabetic subjects (aged 56 +/- 3 years and BMI 29.7 +/- 0.9 kg/m(2)) with an average diabetes duration of 8.5 years (range 3-19) with equal numbers of weight-matched (aged 56 +/- 2 years and BMI 30.1 +/- 10.0 kg/m(2)) and lean (aged 58 +/- 2 years and BMI 25 +/- 00.5 kg/m(2)) nondiabetic subjects who have no first-degree relatives with diabetes. Two separate blood samples were collected from the type 2 diabetic subjects, one following 2 weeks of withdrawal of all antidiabetic medications (T(2)D-; plasma glucose 12.6 +/- 1.0 mmol/l) and another following 10 days of intensive insulin treatment (T(2)D+; plasma glucose 5.5 +/- 0.2 mmol/l). Plasma proteins were separated using single and two-dimensional gel electrophoresis. Western blot analysis was performed, and several proteins, which reacted with the Amadori-antibody (1-deoxyfructosyl lysine), were identified by tandem mass spectrometry. RESULTS: No significant differences in the glycation of proteins between the obese and lean groups were noted, but type 2 diabetic patients had several proteins with higher glycation than the control groups. We identified 12 plasma proteins with reduced reaction to the anti-Amadori antibody upon intensive insulin treatment. A significant (P < 0.03) difference in Amadori modification was observed between the T(2)D- and control subjects for all these proteins except the Ig light chain. Insulin treatment reduced Amadori modification of albumin (23.2%, P < 0.02), fibrin (34.6%, P < 0.001), Ig heavy chain constant region (20.7%, P < 0.05), transferrin (25.4%, P < 0.04), and Ig light chain (13%, P < 0.02). In addition, Western blot analysis of two-dimensional gel electrophoresis identified alpha-fibrinogen precursor, beta-fibrinogen precursor, fibrinogen gamma-B chain precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor as proteins with a reduced reaction to anti-Amadori antibody upon intensive insulin treatment. CONCLUSIONS: The current approach offers the opportunity to identify Amadori modification of many proteins that may cause functional alterations and offers the potential for monitoring short-term glycemic control in diabetic patients.

Blood Glucose↗
PubMed2004

Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents.

We describe here a multiplexed protein quantitation strategy that provides relative and absolute measurements of proteins in complex mixtures. At the core of this methodology is a multiplexed set of isobaric reagents that yield amine-derivatized peptides. The derivatized peptides are indistinguishable in MS, but exhibit intense low-mass MS/MS signature ions that support quantitation. In this study, we have examined the global protein expression of a wild-type yeast strain and the isogenic upf1Delta and xrn1Delta mutant strains that are defective in the nonsense-mediated mRNA decay and the general 5' to 3' decay pathways, respectively. We also demonstrate the use of 4-fold multiplexing to enable relative protein measurements simultaneously with determination of absolute levels of a target protein using synthetic isobaric peptide standards. We find that inactivation of Upf1p and Xrn1p causes common as well as unique effects on protein expression.

Cations↗
PubMed2004

Cutting edge: distinct roles for T help and CD40/CD40 ligand in regulating differentiation of proliferation-competent memory CD8+ T cells.

Murine primary antiviral cytotoxic T cell (CTL) responses are often induced in the absence of Th cells. In this study, we show that virus-like particles, if combined with DNA rich in CpG motifs, efficiently trigger primary CTL responses and comparable frequencies of memory CTLs in the presence or absence of T help. However, memory CTLs primed in the absence of T help failed to proliferate upon viral challenge. Nevertheless, they were efficiently recruited to sites of inflammation, indicating that T help may regulate the balance between proliferation-competent and migration-competent memory CTLs. Surprisingly, generation of proliferation-competent memory CTLs was completely independent of CD40 or CD40L, molecules commonly assumed to be central for mediating the beneficial effects of Th cells on CTL development. Thus, Th cells but not CD40/CD40L are key for the differentiation of proliferation-competent central memory CD8(+) T cells.

Animals↗
PubMed2004

The factors governing the thermal stability of frataxin orthologues: how to increase a protein's stability.

Understanding the factors governing the thermal stability of proteins and correlating them to the sequence and structure is a complex and multiple problem that can nevertheless provide important information on the molecular forces involved in protein folding. Here, we have carried out a comparative genomic study to analyze the effects that different intrinsic and environmental factors have on the thermal stability of frataxins, a family of small mitochondrial iron-binding proteins found in organisms ranging from bacteria to humans. Low expression of frataxin in humans causes Friedreich's ataxia, an autosomal recessive neurodegenerative disease. The human, yeast, and bacterial orthologues were selected as representatives of different evolutionary steps. Although sharing high sequence homology and the same three-dimensional fold, the three proteins have a large variability in their thermal stabilities. Whereas bacterial and human frataxins are thermally stable, well-behaved proteins, under the same conditions yeast frataxin exists in solution as an unstable species with apprechable tracts in a conformational exchange. By designing suitable mutants, we show and justify structurally that the length of the C-terminus is an important intrinsic factor that directly correlates with the thermal stabilities of the three proteins. Thermal stability is also gained by the addition of Fe(2+). This effect, however, is not uniform for the three orthologues nor highly specific for iron: a similar albeit weaker stabilization is observed with other mono- and divalent cations. We discuss the implications that our findings have for the role of frataxins as iron-binding proteins.

Amino Acid Sequence↗
PubMed2004

Depth of proteome issues: a yeast isotope-coded affinity tag reagent study.

As a test case for optimizing how to perform proteomics experiments, we chose a yeast model system in which the UPF1 gene, a protein involved in nonsense-mediated mRNA decay, was knocked out by homologous recombination. The results from five complete isotope-coded affinity tag (ICAT) experiments were combined, two using matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry (MS/MS) and three using electrospray MS/MS. We sought to assess the reproducibility of peptide identification and to develop an informatics structure that characterizes the identification process as well as possible, especially with regard to tenuous identifications. The cleavable form of the ICAT reagent system was used for quantification. Most proteins did not change significantly in expression as a consequence of the upf1 knockout. As expected, the Upf1 protein itself was down-regulated, and there were reproducible increases in expression of proteins involved in arginine biosynthesis. Initially, it seemed that about 10% of the proteins had changed in expression level, but after more thorough examination of the data it turned out that most of these apparent changes could be explained by artifacts of quantification caused by overlapping heavy/light pairs. About 700 proteins altogether were identified with high confidence and quantified. Many peptides with chemical modifications were identified, as well as peptides with noncanonical tryptic termini. Nearly all of these modified peptides corresponded to the most abundant yeast proteins, and some would otherwise have been attributed to "single hit" proteins at low confidence. To improve our confidence in the identifications, in MALDI experiments, the parent masses for the peptides were calibrated against nearby components. In addition, five novel parameters reflecting different aspects of identification were collected for each spectrum in addition to the Mascot score that was originally used. The interrelationship between these scoring parameters and confidence in protein identification is discussed.

Amino Acid Sequence↗
PubMed2004

A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.

Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.

Acute Disease↗
PubMed2004

A short peptide at the amino terminus of the Sendai virus C protein acts as an independent element that induces STAT1 instability.

The Sendai virus C protein acts to dismantle the interferon-induced cellular antiviral state in an MG132-sensitive manner, in part by inducing STAT1 instability. This activity of C maps to the first 23 amino acids (C(1-23)) of the 204-amino-acid (aa)-long protein (C(1-204)). C(1-23) was found to act as an independent viral element that induces STAT1 instability, since this peptide fused to green fluorescent protein (C(1-23)/GFP) is at least as active as C(1-204) in this respect. This peptide also induces the degradation of C(1-23)/GFP and other proteins to which it is fused. Most of C(1-204), and particularly its amino-terminal half, is predicted to be structurally disordered. C(1-23) as a peptide was found to be disordered by circular dichroism, and the first 11 aa have a strong potential to form an amphipathic alpha-helix in low concentrations of trifluoroethanol, which is thought to mimic protein-protein interaction. The critical degradation-determining sequence of C(1-23) was mapped by mutation to eight residues near its N terminus: (4)FLKKILKL(11). All the large hydrophobic residues of (4)FLKKILKL(11), plus its ability to form an amphipathic alpha-helix, were found to be critical for STAT1 degradation. In contrast, C(1-23)/GFP self-degradation did not require (8)ILKL(11), nor the ability to form an alpha-helix throughout this region. Remarkably, C(1-23)/GFP also stimulated C(1-204) degradation, and this degradation in trans required the same peptide determinants as for STAT1. Our results suggest that C(1-204) coordinates its dual activities of regulating viral RNA synthesis and counteracting the host innate antiviral response by sensing both its own intracellular concentration and that of STAT1.

Amino Acid Sequence↗
PubMed2003

Observation of a smecticlike crystalline structure in polydisperse colloids.

We present the results of crystallographic measurements on samples of two latexes: one with a relatively symmetric particle size distribution, and another with a highly skewed pseudobimodal distribution. For the skewed latex, crystallites are clearly visible, but they exhibit only a single Bragg reflection, indicating long-range order in only one direction. We propose a schematic model that explains this result in terms of stacks of planes, which are unregistered due to a high incidence of stacking faults caused by the incorporation of a large number of small particles.

Journal Article↗