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The clinical and genetic associations of anti-cyclic citrullinated peptide antibodies in psoriatic arthritis.

OBJECTIVES: Antibodies recognizing a cyclic citrullinated peptide (anti-CCP) are highly specific for rheumatoid arthritis (RA) but their role in psoriatic arthritis (PsA) remains unclear. The aim of this study was therefore to investigate the prevalence of anti-CCP antibodies in PsA and assess their clinical and genetic associations. METHODS: One hundred and twenty-six patients with PsA, 40 patients with seropositive RA and 40 controls were tested for the presence of anti-CCP antibodies, rheumatoid factor (RF) and the HLA-DRB1 shared epitope. Clinical and radiological data were collected prospectively on all patients and compared between anti-CCP-positive and -negative patients. RESULTS: Seven (5.6%) patients with PsA were positive for anti-CCP antibodies compared with 0% of controls and 97% of patients with seropositive RA. The presence of anti-CCP antibodies in PsA was significantly associated with the HLA-DRB1 shared epitope (P<0.005), erosive disease (P<0.05), number of swollen joints (P<0.02) and DMARD use (P<0.05). CONCLUSIONS: Overall, the increased prevalence of anti-CCP antibodies in this PsA population failed to reach statistical significance. However, when present, they were a marker of disease severity and had RA-linked MHC class II associations. Further studies are needed in a larger population of patients with PsA and appropriate controls to confirm any true association that may be present.

Adult↗

Cafeteria factors that influence milk-drinking behaviors of elementary school children: grounded theory approach.

This study was conducted to identify factors that influenced milk-drinking behaviors of elementary school children in North Texas. Ten focus groups with a total of 41 children aged 6 to 11 years were conducted using a grounded theory approach. Based on the principles of Social Learning Theory, milk preferences and health beliefs were identified as personal factors that influenced drinking. Cafeteria rules, milk flavor, product packaging, modeling by adults, and shared experiences were environmental factors. The data suggest that school cafeterias can capitalize on their unique position to offer milk-drinking opportunities that children can share to combine nutrition education with sensory experience.

Animals↗

The effect of alternative work arrangements on women's well-being: a demand-control model.

The growth of women's participation in the labor force and evidence of the conflict they experience between job and family demands have spurred many employers to introduce alternative work arrangements such as flextime, job sharing, and telecommuting. Drawing on data gained from a sample of women (N = 998) in two large Canadian organizations, this study evaluates two mediational models of the impact of alternative work arrangements on women's stress and family role competence. Specifically, it tests and finds support for the hypotheses that (a) work arrangements involving scheduling flexibility (telecommuting and flextime) promote these aspects of women's well-being by increasing their perceived control over their time, and (b) arrangements involving reduced hours of employment (part-time employment and job sharing) promote well-being by reducing perceived job overload. Discussion of these findings centers on their implications for employed women, their employers, and future research.

Adult↗

Privatization of health care in Slovenia.

This article analyzes the results of the hitherto privatization of health care in Slovenia based on statistical indices and public opinion data. The new legislation offered much more room for quasiprivatization than for real privatization. A greater room was left for privatization of financing than for the status of health care providers and infrastructure. The statistical data on private practitioners and the share of private resources in health care costs show that the privatization is relatively slow but irreversible process. Public opinion data revealed that the population of Slovenia accepted this process but some signs of distrust in private practice and new forms of health insurance were noticed. The new legislation leaves a high degree of regulation to the state in protecting citizens' rights but there are some risks of unrestrained development of the market due to insufficient implementation of legislation.

Adult↗

Decline in HIV-1 seroprevalence and low seroconversion rate among injecting drug users at a methadone maintenance program in New York City.

To monitor the trend of HIV-1 seroprevalence, 2,194 newly admitted injecting drug users (IDUs) in a methadone maintenance program in New York City were tested from June 1988 through June 1992. This was a blinded study and unlabeled blood specimens were collected during the required physical examination. There was a significant linear trend (p = .01) toward decline in HIV-1 seropositivity by year of admission as follows: 47.0% in 1988, 43.4% in 1989, 43.2% in 1990, 39.8% in 1991, and 39.1% in 1992. From January 1988 through December 1992, admissions data that included the newly admitted IDUs showed a significant decrease (p < .0002) in self-reported current needle sharing from 11.3% to 5.4%. These two data sources suggest that a continued decline in HIV-1 seroprevalence among new admissions may be related to decreased needle sharing. A volunteer cohort of 235 HIV-1 seronegative IDUs was also enrolled from April 1990 through June 1991 in a study of HIV-1 seroconversion. Follow-up data were available on 177 patients for up to 12 months. For a total observation time of 155 person-years, there were two conversions (1.3 conversions per 100 person-years). A continued decline in HIV-1 seroprevalence among new admissions and a low HIV-1 seroconversion rate among existing patients have contributed to a lower overall HIV-1 prevalence in clinic patients of about 40%. This stands in contrast to 1985-86 estimates of HIV-1 seroprevalence that plateaued at 60%.

Adult↗

Maternal mortality in Latin American urban areas: the case of São Paulo, Brazil.

This article describes maternal mortality trends in São Paulo, Brazil, from 1960 through 1990. In so doing, it compares mortality rates derived from death certificate data with rates suggested by three independent surveys conducted in the city of São Paulo in 1962-1963, 1974-1975, and 1986. In general, these data indicate that a substantial share of all maternal deaths in the city have been ascribed to other causes on death certificates, that prevailing maternal mortality levels are far higher than those found in the urban areas of most developed countries, and that in recent years levels of maternal mortality in the city have been rising. Various measures are suggested for improving the accuracy of available data and reducing the maternal mortality they describe.

Abortion, Spontaneous↗

Analysis and interpretation of twin studies including measures of the shared environment.

Recent reports using a classical behavior genetic research design in which twin data are combined with a measured characteristic of their shared family environment have made striking claims about estimating environmental influences on behavior with genetic effects controlled. Such claims are overstated for two related reasons. First, when a variable is measured at the family level in a way that makes it necessarily equivalent for twins reared together, it is not possible to partition it into genetic and environmental components. Second, although structural equation modeling and DeFries-Fulker analysis are sound tools for the analysis of many types of twin data, they do not control for genetic or environmental confounds when estimating the effect of measured family-level variables.

Child↗

Outcome, tolerability and compliance of compassionate use interferon and ribavirin for hepatitis C infection in a shared care hospital clinic.

BACKGROUND AND AIMS: To determine response rate, side-effects and compliance in patients with chronic hepatitis C virus (HCV) infection following treatment with interferon-alpha-2b and ribavirin in a 'shared care' hospital clinic. METHODS: Data were collected prospectively on 81 patients treated with combination therapy for chronic HCV infection between 1999 and 2001. All had biochemical and virological evidence of active infection. All patients had undergone liver biopsy except haemophiliac patients. Patients infected with genotype 1 were treated for 12 months. Patients infected with genotypes 2 and 3 were treated for 6 months. Patient care was shared with the referring general practitioner. Intention to treat, end of treatment and sustained virological response (SVR) rates, side-effects and compliance were assessed. RESULTS: Eighty-one patients with chronic HCV infection were treated with combination therapy. The majority of HCV patients were genotype 1 (n = 46; 57%). There were 12 patients (15%) with cirrhosis. SVR rates were: (i) 24% for genotype 1, (ii) 58% for genotype 3 and (iii) 75% for genotype 2. SVR was achieved in three (23%) cirrhotic patients. Compliance with the treatment regimen was 98%. Seven per cent of patients were withdrawn from therapy prematurely because of side-effects. CONCLUSIONS: These 'shared care' clinic results compare well with controlled clinical trials using combination therapy for chronic HCV infection. Outcomes were poorer in genotype 1 patients and in patients with cirrhosis. Compliance with therapy was excellent because of the 'Shared Care Programme' with participation of general practitioners, psychiatrists and hepatitis C nurse practitioners in the management protocol.

Adult↗

A strategy for merging and analyzing work history data in industry-wide occupational epidemiological studies.

Study populations examined in epidemiologic investigations of occupational disease risks often are assembled by the pooling of employee data from several workplaces that share common exposure factors. The primary objectives of this approach are to enhance the representativeness of the overall study population and to obtain sufficient employee sample sizes in exposure subgroups of interest. Among the many epidemiologic aspects that must be considered carefully in such industry-wide studies is the inter- and intra-company or plant comparability of employee work history data. Currently, the literature is void of articles that specifically address the fundamental data reduction and statistical analysis issues related to merging work history data from several distinct cohorts. This paper describes the basic methodologic problems associated with the pooling of work history data and proposes a joint job title/job exposure-based uniform coding scheme (UCS) that facilitates the aggregation of data from similar or diverse cohorts in a variety of epidemiologic study settings. The utility of the UCS as both an efficient data coding structure and a flexible basis for statistical analysis is described within the context of a popular computer software program for analyzing occupational cohort data. The fundamental features of the UCS are illustrated using data from a recent industry-wide study of copper and zinc smelter workers.

Data Collection↗

Association rule mining in peer-to-peer systems.

We extend the problem of association rule mining--a key data mining problem--to systems in which the database is partitioned among a very large number of computers that are dispersed over a wide area. Such computing systems include grid computing platforms, federated database systems, and peer-to-peer computing environments. The scale of these systems poses several difficulties, such as the impracticality of global communications and global synchronization, dynamic topology changes of the network, on-the-fly data updates, the need to share resources with other applications, and the frequent failure and recovery of resources. We present an algorithm by which every node in the system can reach the exact solution, as if it were given the combined database. The algorithm is entirely asynchronous, imposes very little communication overhead, transparently tolerates network topology changes and node failures, and quickly adjusts to changes in the data as they occur. Simulation of up to 10,000 nodes show that the algorithm is local: all rules, except for those whose confidence is about equal to the confidence threshold, are discovered using information gathered from a very small vicinity, whose size is independent of the size of the system.

Algorithms↗

WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy.

WD-repeat proteins are regulatory beta-propeller platforms that enable the assembly of multiprotein complexes. Here, we report the functional and bioinformatic analysis of human WD-repeat protein Interacting with PhosphoInosides (WIPI)-1alpha (WIPI49/Atg18), a member of a novel WD-repeat protein family with autophagic capacity in Saccharomyces cerevisiae and Caenorhabditis elegans, recently identified as phospholipid-binding effectors. Our phylogenetic analysis divides the WIPI protein family into two paralogous groups that fold into 7-bladed beta-propellers. Structural modeling identified two evolutionary conserved interaction sites in WIPI propellers, one of which may bind phospholipids. Human WIPI-1alpha has LXXLL signature motifs for nuclear receptor interactions and binds androgen and estrogen receptors in vitro. Strikingly, human WIPI genes were found aberrantly expressed in a variety of matched tumor tissues including kidney, pancreatic and skin cancer. We found that endogenous hWIPI-1 protein colocalizes in part with the autophagosomal marker LC3 at punctate cytoplasmic structures in human melanoma cells. In addition, hWIPI-1 accumulated in large vesicular and cup-shaped structures in the cytoplasm when autophagy was induced by amino-acid deprivation. These cytoplasmic formations were blocked by wortmannin, a classic inhibitor of PI-3 kinase-mediated autophagy. Our data suggest that WIPI proteins share an evolutionary conserved function in autophagy and that autophagic capacity may be compromised in human cancers.

Amino Acid Sequence↗

immX immunity region of rhizobium phage 16-3: two overlapping cistrons of repressor function.

16-3 is a temperate phage of the symbiotic nitrogen-fixing bacterium Rhizobium meliloti 41. Its prophage state and immunity against superinfection by homoimmune phages are governed by a complex set of controls: the immC and immX repressor systems and the avirT element are all located in well-separated, distinct regions which span 25 kb on the bacteriophage chromosome. The anatomy and function of the immC region are well documented; however, fewer analyses have addressed the immX and avirT regions. We focused in this paper on the immX region and dissected it into two major parts: X(U/L) and X(V). The X(U/L) part (0.6 kb) contained two overlapping cistrons, X(U) and X(L), coding for proteins pXU and pXL, respectively. Inactivation of either gene inactivated the repressor function of the immX region. Loss-of-function mutants of X(U) and X(L) complemented each other in trans in double lysogens. The X(V) part (1 kb) contained a target for X(U/L) repressor action. Mutations at three sites in X(V) led to various degree of ImmX insensitivity in a hierarchic manner. Two sites (X(V1) and X(V3)) exhibited the inverted-repeat structures characteristic of many repressor binding sites. However, X(V1) could also be folded into a transcription terminator. Of the two immunity regions of 16-3, immX seems to be unique both in its complex genetic anatomy and in its sequence. To date, no DNA or peptide sequence homologous to that of ImmX has been found in the data banks. In contrast, immC shares properties of a number of immunity systems commonly found in temperate phages.

Bacteriophages↗

An evaluation of structural models for the photosynthetic water-oxidizing complex derived from spectroscopic and X-ray diffraction signatures.

Four of the five intermediate oxidation states (S-states) in the catalytic cycle of water oxidation used by O2-evolving photoautotrophs have been previously characterized by EPR and/or ENDOR spectroscopy, with the first reports for the S0, S1, and S3 states available in just the last three years. The first electron density map of the Mn cluster derived from X-ray diffraction measurements of single crystals of photosystem II at 3.8-4.2 A resolution has also appeared this year. This wealth of new information has provided significant insight into the structure of the inorganic core (Mn4OxCa1Cl1-2), the Mn oxidation states, and the location and function of the essential Ca2+ cofactor within the water-oxidizing complex (WOC). We summarize these advances and provide a unified interpretation of debated structural proposals and Mn oxidation states, based on an integrated analysis of the published data, particularly from Mn X-ray absorption spectroscopy (XAS) and EPR/ENDOR data. Only three magnetic spin-exchange models for the inter-manganese interactions are possible from consideration of the EPR data for the S0, S1, S2 and S(-N) (NO-reduced) states. These models fall into one of three types denoted butterfly, funnel, or tetrahedron. A revised set of eight allowed chemical structures for the Mn4Ox core can be deduced that are shown to be consistent with both EPR and XAS. The popular "dimer-of-dimers" structural model is not compatible with the possible structural candidates. EPR data have identified two inter-manganese couplings that are sensitive to the S-state, suggesting two possible bridging sites for substrate water molecules. Spin densities derived from 55Mn hyperfine data together with Mn K-edge energies from Ca-depleted samples provide an internally consistent assignment for the Mn oxidation states of Mn4(3III,IV) for the S2 state. EPR and XAS data also provide a consistent picture, locating Ca2+ as an integral part of the inorganic core, probably via shared bridging ligands with Mn (aqua/hydroxo/carboxylato/chloro). XAS data reveal that the Ca2+ cofactor increases the Mn(1s-->4p) transition energy by 0.6-1 eV with minimal structural perturbation versus the Ca-depleted WOC. Thus, calcium binding appears to increase the Mn-ligand covalency by increasing electron transfer from shared ligands to Mn, suggesting a direct role for Ca2+ in substrate water oxidation. Consideration of both the XAS and the EPR data, together with reactivity studies on two model complexes that evolve O2, suggest two favored structure types as feasible models for the reactive S4 state that is precursor to the O2 evolution step. These are a calcium-capped "cuboidal" core and a calcium-capped "funnel" core.

Electron Spin Resonance Spectroscopy↗

Data storage and knowledge representation for clinical workstations.

The representation of patient information for use in clinical workstations is a complex problem. Ideally, it should be addressed in a way that allows multiple uses of the data, including simple manual review, sharing and pooling across institutions, and as input to knowledge-based decision support systems. To a great extent, this means coding information with controlled medical vocabularies, but it does not mean that all information must be codable before workstations are feasible. This paper defines some of the choices, both current and future, that are available to address the needs of controlled medical vocabularies for representing data and knowledge in clinical workstations and explores some of the implications of those choices.

Computer Communication Networks↗

Alternative professional roles in health care delivery: leadership patterns in self-help groups.

The increasing professionalization of health care delivery systems, improved client awareness, funding cutbacks, and an emphasis on voluntarism have led recipients of health services to turn increasingly to self-help groups. This article examines the leadership and organizational pattern of such groups, using a study of 43 self-help groups from around the U.S. whose members are parents of children with cancer. Three leadership patterns emerged: groups were independent and parent-led, were led by professionals, or had a shared leadership of parents and professionals. Data indicate that the professionally led groups were the smallest, least formal, and had the narrowest range of activities. The groups with shared leadership had the greatest longevity, tended most often to retain as members parents of deceased children. The authors conclude that such coalitions of clients and professionals are vital for ensuring proper service delivery at a time when health care systems will likely remain bureaucratic and public resources for professional care are being reduced.

Adult↗

Stilbene and chalcone synthases: related enzymes with key functions in plant-specific pathways.

Several years of extensive research using the new powerful techniques of molecular biology have enabled the direct comparison of functionally or evolutionarily related genes and their products at the nucleotide and amino acid sequence levels. Two types of synthase with similar functions are discussed as an interesting example. Stilbene synthases, e.g. resveratrol synthase, produce the stilbene backbone as a key reaction in the biosynthesis of stilbene-type phytoalexins. Chalcone synthase is a key enzyme in the biosynthesis of flavonoids, including certain phytoalexins derived from a 6'-deoxychalcone which is synthesized by cooperation of chalcone synthase with a reductase. Resveratrol and chalcone synthases utilize the same substrates (4-coumaroyl-CoA and 3 molecules of malonyl-CoA) and catalyze the same condensing type of enzyme reaction (resulting in sequential addition of acetate units via malonyl-CoA), but the products differ in the newly formed ring systems (resveratrol and naringenin chalcone). A comparative analysis of cloned DNA sequences and of the reaction mechanisms indicates that the two enzymes are closely related. It seems likely that the proteins possess a common scaffold for substrate recognition and for the condensing reaction, and that the different folding of an enzyme-bound intermediate prior to closure of the new aromatic ring is responsible for the formation of the different products. The same type of condensing reaction is utilized by the 2-ketoacyl-ACP synthases of fatty-acid biosynthesis. However, the available data indicate that these enzymes share little overall homology with either resveratrol or chalcone synthase. One exception may be a short amino acid sequence which corresponds to the active center of the condensing reaction in 2-ketoacyl-ACP synthases.

Acyltransferases↗

Semi-supervised discovery of differential genes.

BACKGROUND: Various statistical scores have been proposed for evaluating the significance of genes that may exhibit differential expression between two or more controlled conditions. However, in many clinical studies to detect clinical marker genes for example, the conditions have not necessarily been controlled well, thus condition labels are sometimes hard to obtain due to physical, financial, and time costs. In such a situation, we can consider an unsupervised case where labels are not available or a semi-supervised case where labels are available for a part of the whole sample set, rather than a well-studied supervised case where all samples have their labels. RESULTS: We assume a latent variable model for the expression of active genes and apply the optimal discovery procedure (ODP) proposed by Storey (2005) to the model. Our latent variable model allows gene significance scores to be applied to unsupervised and semi-supervised cases. The ODP framework improves detectability by sharing the estimated parameters of null and alternative models of multiple tests over multiple genes. A theoretical consideration leads to two different interpretations of the latent variable, i.e., it only implicitly affects the alternative model through the model parameters, or it is explicitly included in the alternative model, so that the interpretations correspond to two different implementations of ODP. By comparing the two implementations through experiments with simulation data, we have found that sharing the latent variable estimation is effective for increasing the detectability of truly active genes. We also show that the unsupervised and semi-supervised rating of genes, which takes into account the samples without condition labels, can improve detection of active genes in real gene discovery problems. CONCLUSION: The experimental results indicate that the ODP framework is effective for hypotheses including latent variables and is further improved by sharing the estimations of hidden variables over multiple tests.

Algorithms↗

Tower of London procedure: a standard method and developmental data.

The Tower of London procedure (TOL) is being utilized increasingly in clinical and experimental contexts, although there is considerable variation in how it is administered and scored. The procedure detailed here was developed using Shallice's original problems and, along with the Porteus Maze Test (PMT), was administered to 205 elementary school students and 74 young adults. TOL scores increased with age in a linear fashion, and the performance of the sixth, seventh, and eighth grade subjects were not statistically different from the young adults. The TOL was moderately correlated with the PMT suggesting that these procedures share a planning component. These data provide initial developmental standards, and the materials, administration, and scoring procedures documented here provide a standard method for utilization of this instrument.

Adolescent↗