BACKGROUND

Many people suffer with Osteoarthritis (OA) and subsequent morbidity. Therefore, measuring outcome associated with OA is important. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been a widely used patient reported outcome in OA. However, there is relatively little evidence to support the use of the Visual Analogue Scale (VAS) version of the scale. We aimed to explore the internal validity and responsiveness of this VAS version of the WOMAC.

METHODS

Patients with chronic hip or knee pain of mechanical origin, waiting for a hip or knee joint replacement completed the WOMAC as part of a study to investigate the effects of acupuncture and placebo controls. Validity was tested using factor analysis and Rasch analysis, and responsiveness using standardised response means.

RESULTS

Two hundred and twenty one patients (mean age 66.8, SD 8.29, 58% female) were recruited. Factor and Rasch analysis confirmed unidimensional Pain and Physical Functioning scales, capable of transformation to interval scaling and invariant over time. Some Differential Item Functioning (DIF) was observed, but this cancelled out at the test level. The Stiffness scale fitted the Rasch model but adjustments for DIF could not be made due to the shortness of the scale. Using the interval transformed data, Standardised Response Means were smaller than when using the raw, ordinal data.

CONCLUSIONS

The WOMAC Pain and Physical Functioning subscales satisfied unidimensionality and ordinal scaling tests, and the ability to transform to an interval scale. Some Differential Item Functioning was observed, but this cancelled out at the test level and, by doing so, at the same time removed the disturbance of unidimensionality. The scaling characteristics of sets of items which use VAS require further analysis, as it would appear that they can lead to spurious levels of responsiveness and scale compression because they exaggerate the distortion of the ordinal scale.

BACKGROUND

UKCRN study ID: 4881 ISRCTN78434638.

There has been some concern that participation in an intervention and exposure to a measurement instrument can change participants' interpretation of the items on a self-report questionnaire thereby distorting subsequent responses and biasing results. Differential item functioning (DIF) analysis using item response modeling can ascertain possible differences in item interpretation by testing for differences in item location between groups. The DIF for treatment versus control group differences at post-intervention assessment and the Time 1 and Time 2 differences in a control group were analyzed using data from a dietary change intervention trial for Boy Scouts. The measures included fruit and vegetable (FV) frequency of consumption, preferences and self-efficacy. Treatment-control group DIF at post-intervention assessment was detected in a higher percentage of items for FV frequency than for preference or self-efficacy. Time 1 to Time 2 differences in items for the control group were detected in one item for each of the three scales. Further research will need to clarify whether the obtained DIFs reflected true changes in frequency, preference or self-efficacy or some reinterpretation of items by participants following an intervention or merely after previous exposure to the measure.

BACKGROUND

The Geriatric Depression Scale (GDS) is widely used for screening and assessment of major depressive disorder (MDD). Screening scales are often culture-specific and should be evaluated for item response bias (synonymously differential item functioning, DIF) before use in clinical practice and research in a different population. In this study, we examined DIF associated with age, gender, ethnicity and chronic illness in a heterogeneous Asian population in Singapore.

METHODS

The GDS-15 and Structured Clinical Interview for DSM-IV diagnosis of MDD were independently administered by interviewers on 4253 non-institutionalized community living elderly subjects aged 60 years and above who were users of social service agencies. Multiple Indicator Multiple Cause latent variable modelling was used to identify DIF.

RESULTS

We found evidence of significant DIF associated with age, gender, ethnicity and chronic illness for 8 items: dropped many activities and interests, afraid something bad is going to happen, prefer staying home to going out, more problems with memory than most, think it is (not) wonderful to be alive, feel pretty worthless, feel (not) full of energy, feel that situation is hopeless.

CONCLUSIONS

The smaller number of minority Indian and Malay subjects and the self-report of chronic medical illnesses.

CONCLUSIONS

In a heterogeneous mix of respondents in Singapore, eight items of the GDS-15 showed DIF for age, gender, ethnicity and chronic illness. The awareness and identification of DIF in the GDS-15 provides a rational basis for its use in diverse population groups and guiding the derivation of abbreviated scales.

The Mediator complex is the major multiprotein transcriptional coactivator complex in Drosophila melanogaster. Mediator components interact with diverse sets of transcriptional activator proteins to elicit the sophisticated regulation of gene expression. The distinct phenotypes associated with certain mutations in some of the Mediator genes and the specific in vitro interactions of Mediator gene products with transcriptional activator proteins suggest the presence of activator-specific binding subunits within the Mediator complex. However, the physiological relevance of these selective in vitro interactions has not been addressed. Therefore, we analyzed dTRAP80, one of the putative activator-binding subunits of the Mediator, for specificity of binding to a number of natural transcriptional activators from Drosophila. Among the group of activator proteins that requires the Mediator complex for transcriptional activation, only a subset of these proteins interacted with dTRAP80 in vitro and only these dTRAP80-interacting activators were defective for activation under dTRAP80-deficient in vivo conditions. In particular, activation of Drosophila antimicrobial peptide drosomycin gene expression by the NF-kappa B-like transcription factor Dif during induction of the Toll signaling pathway was dependent on the dTRAP80 module. These results, and the indirect support from the dTRAP80 artificial recruitment assay, indicate that dTRAP80 serves as a genuine activator-binding target responsible for a distinct group of activators.

BACKGROUND

The Headache Impact Test (HIT)-6 was developed and has been validated in patients with various types of headache. The objective of this study was to report the psychometric properties of the HIT-6 among patients with chronic migraine.

METHODS

Data came from two international, multicenter, randomized, double-blind, placebo-controlled clinical trials of chronic migraine patients (N = 1,384) undergoing prophylaxis therapy. Confirmatory factor analysis and differential item functioning (DIF) analysis were used to test the latent structure and cross-cultural comparability of the HIT-6. Reliability, construct validity, and responsiveness were assessed. Two sets of criterion groups were used: (1) 28-day headache frequency: <10, 10-14, and ≥15 days; (2) sample quartiles of the total cumulative hours of headache: <140, 140 to <280, 280 to <420, and ≥420 hours. Two sets of responsiveness categories were defined as reduction of <30%, 30% to <50%, or ≥50% in (1) number of headache days and (2) cumulative hours of headache.

RESULTS

Measurement invariance tests supported the stability of the HIT-6 latent structure across studies. DIF analysis supported cross-cultural comparability. Good reliability was observed across studies (Cronbach's α: 0.75-0.92; intraclass correlation coefficient: 0.76-0.80). HIT-6 scores correlated strongly (-0.86 to -0.59) with scores of the Migraine-Specific Quality-of-Life Questionnaire. Analysis of variance indicated that HIT-6 scores discriminated across both types of criterion groups (P<0.001), across studies and time points. HIT-6 change scores were significantly higher in magnitude in groups experiencing greater improvement (P<0.001).

CONCLUSIONS

All measurement properties were consistently verified across the two studies, supporting the validity of the HIT-6 among chronic migraine patients.

BACKGROUND

NCT00156910 and NCT00168428 on www.ClinicalTrials.gov.

A variety of statistical methods have been suggested for detecting differential item functioning (DIF) in the Rasch model. Most of these methods are designed for the comparison of pre-specified focal and reference groups, such as males and females. Latent class approaches, on the other hand, allow the detection of previously unknown groups exhibiting DIF. However, this approach provides no straightforward interpretation of the groups with respect to person characteristics. Here, we propose a new method for DIF detection based on model-based recursive partitioning that can be considered as a compromise between those two extremes. With this approach it is possible to detect groups of subjects exhibiting DIF, which are not pre-specified, but result from combinations of observed covariates. These groups are directly interpretable and can thus help generate hypotheses about the psychological sources of DIF. The statistical background and construction of the new method are introduced by means of an instructive example, and extensive simulation studies are presented to support and illustrate the statistical properties of the method, which is then applied to empirical data from a general knowledge quiz. A software implementation of the method is freely available in the R system for statistical computing.

BACKGROUND

The main morbidity associated with Henoch-Schonlein purpura (HSP) results from glomerulonephritis and associated renal symptoms; thus early and accurate diagnosis would have follow-up implications.

OBJECTIVE

To determine the strength of association of IgA vascular deposition with HSP in a mostly adult and hospital-based population.

METHODS

We retrospectively analyzed patients with a histologic diagnosis of cutaneous leukocytoclastic vasculitis (LCV) and corresponding direct immunofluorescence (DIF) studies between 2000 and 2010. European League Against Rheumatism criteria were used to diagnose HSP cases clinically. They are purpura or petechiae with lower limb predominance plus at least one of the following: abdominal pain, LCV or proliferative glomerulonephritis with predominant IgA deposit, arthritis/arthralgia, or proteinuria or hematuria.

RESULTS

IgA positivity was significantly associated with HSP (P = .0001), and yielded sensitivity of 81% and specificity of 83%. Positive predictive value of IgA staining for HSP was 84%, and negative predictive value was 81%. No other histologic features were significantly associated with HSP.

CONCLUSIONS

Our sample size was relatively small and mostly an inpatient population (79%). We may have missed cases of HSP and a subset of IgA+ LCV patients who did not have clinical findings of HSP by limiting our series to only cases with DIF studies done. Certain clinical data may be incomplete since they were collected retrospectively.

CONCLUSIONS

Our study confirms a strong association between IgA deposits on DIF and HSP, but also highlights a subset of HSP cases in which vascular IgA deposition in the skin appears to be negative.

Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptoms, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome, and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed several interesting suggestive associations. For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10^-5). SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10^-4), an association that is significantly stronger in females (p _{dif f} = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10^-4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants could play a role in diseases such as thrombocytopenia, hypertension, and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.

Keywords: ACE2; ARBs (angiotensin II receptor blockers); COVID-19; NSAIDs (non-steroidal anti-inflammatory drugs); PheWAS; SARS-CoV-2; TMPRSS2.

Item response theory methods were used to study differential item functioning (DIF) between gender groups on a measure of stress reaction. Results revealed that women were more likely to endorse items describing emotional vulnerability and sensitivity, whereas men were more likely to endorse items describing tension, irritability, and being easily upset. Item factor analysis yielded 5 correlated factors, and the DIF analysis, in turn, revealed differential gender mean differences on these factors. This finding illustrates how even in an essentially unidimensional scale, comparison of group mean differences can be affected by multidimensionality caused by item clusters that share similar content. Results do not support arguments that measures of negative affective dispositions "artificially" produce gender mean differences by focusing on specific selected content areas.

OBJECTIVE

To establish reference values for the 6-min walk test in healthy children and adolescents aged 6-12 years.

METHODS

This cross-sectional, prospective study selected healthy children and adolescents aged 6-12 years, at three elementary schools in Porto Alegre. The anthropometric data of all the individuals were evaluated and two 6-min walk tests were performed. Based on this, a reference equation was generated, and the test reproducibility was evaluated.

RESULTS

One hundred eighty-eight children (92 boys) performed the test. Pearson correlation showed that age (r = 0.51), height (r = 0.49), difference in heart rate before and after the test (dif. HR) (r = 0.30), and weight (r = 0.29) were significantly correlated with the distance covered in 6 min. The best multiple regression model included these four variables resulting in the following equation: 145.343 + [11.78 x age (years)] + [292.22 x height (m)] + [0.611 x dif. HR (bpm)] - [2.684 x body weight (kg)]. The intraclass correlation coefficient confirmed the reproducibility among tests.

CONCLUSIONS

The reference equation for the 6-min walk test was generated and the distance covered is influenced by age, height, difference in heart rate before and after the test, and body weight.

The Dermatology Life Quality Index (DLQI) is a widely used health-related quality of life measure. However, little research has been conducted on its dimensionality. The objectives of the current study were to apply Rasch analysis to DLQI data to determine whether the scale is unidimensional, to assess its measurement properties, test the response format, and determine whether the measure exhibits differential item functioning (DIF) by disease (atopic dermatitis versus psoriasis), gender, or age group. The results show that there were several problems with the scale, including misfitting items, DIF by disease, age, and gender, disordered response thresholds, and inadequate measurement of patients with mild illness. As the DLQI did not benefit from the application of Rasch analysis in its development, it is argued that a new measure of disability related to dermatological disease is required. Such a measure should use a coherent measurement model and ensure that items are relevant to all potential respondents. The current use of the DLQI as a guide to treatment selection is of concern, given its inadequate measurement properties.

Although it is well known that mating increases the risk of infection, we do not know how females mitigate the fitness costs of sexually transmitted infections (STIs). It has recently been shown that female fruitflies, Drosophila melanogaster, specifically upregulate two members of the Turandot family of immune and stress response genes, Turandot M and Turandot C (TotM and TotC), when they hear male courtship song. Here, we use the Gal4/UAS RNAi gene knockdown system to test whether the expression of these genes provides fitness benefits for females infected with the entomopathogenic fungus, Metarhizium robertsii under sexual transmission. As a control, we also examined the immunity conferred by Dorsal-related immunity factor (Dif), a central component of the Toll signalling pathway thought to provide immunity against fungal infections. We show that TotM, but not TotC or Dif, provides survival benefits to females following STIs, but not after direct topical infections. We also show that though the expression of TotM provides fecundity benefits for healthy females, it comes at a cost to their survival, which helps to explain why TotM is not constitutively expressed. Together, these results show that the anticipatory expression of TotM promotes specific immunity against fungal STIs and suggest that immune anticipation is more common than currently appreciated.

Alveolar macrophages isolated by bronchoalveolar lavage from nonsmoking patients with sarcoidosis, interstitial pulmonary fibrosis (DIF), and normal volunteers were examined for surface expression of Ia-like (DR) antigen using a monoclonal antibody technique. We found increased percentages of alveolar macrophages expressing DR antigen in the 8 patients with sarcoidosis (77 +/- 3%) and the 7 patients with DIF (78 +/- 3%) over that in the 9 healthy, nonsmoking volunteers (21 +/- 5%, p less than 0.05). Four patients, 2 with DIF and 2 with sarcoidosis, were studied before and 3 months after initiation of therapy. A decrease in DR antigen expression was found to be associated with clinical improvement. Alveolar macrophages from 3 patients were studied serially in culture, with a steady decrease in DR antigen expression with time. We conclude (1) that alveolar macrophages from patients with sarcoidosis and DIF are in a state of heightened activity, and (2) that DR antigen expression may be an indicator of disease activity.

BACKGROUND

In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2) were originally identified as the factors (chlorinated alkylphenones) that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions.

RESULTS

To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase) and a decrease in the intracellular cGMP concentration ([cGMP](i)). DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase) and an increase in [cGMP](i). Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part.

CONCLUSIONS

Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules) for chemotaxis having differentiation-inducing activity.

Dictyostelium atg1- mutant cells provide an experimentally and genetically favorable model to study necrotic cell death (NCD) with no interference from apoptosis or autophagy. In such cells subjected to starvation and cAMP, induction by the differentiation-inducing factor DIF or by classical uncouplers led within minutes to mitochondrial uncoupling, which causally initiated NCD. We now report that (1) in this model, NCD included a mitochondrial-lysosomal cascade of events, (2) mitochondrial uncoupling and therefore initial stages of death showed reversibility for a surprisingly long time, (3) subsequent lysosomal permeabilization could be demonstrated using Lysosensor blue, acridin orange, Texas red-dextran and cathepsin B substrate, (4) this lysosomal permeabilization was irreversible, and (5) the presence of the uncoupler was required to maintain mitochondrial lesions but also to induce lysosomal lesions, suggesting that signaling from mitochondria to lysosomes must be sustained by the continuous presence of the uncoupler. These results further characterized the NCD pathway in this priviledged model, contributed to a definition of NCD at the lysosomal level, and suggested that in mammalian NCD even late reversibility attempts by removal of the inducer may be of therapeutic interest.

DIF-1 is a novel chlorinated alkyl phenone which induces differentiation of prestalk cells in Dictyostelium discoideum. It is broken down and inactivated by a cytoplasmic enzyme, DIF-1 3(5)-dechlorinase (hereafter referred to as DIF-1 dechlorinase), which is found only in prestalk cells. We show that DIF-1 dechlorinase levels are induced at least 50-fold when cells are treated with DIF-1. This response is rapid--enzyme activity doubles within 15 min and is fully induced within an hour--and occurs early in development, before other prestalk markers can be induced by DIF-1. Maximum inducibility is seen towards the end of aggregation, when DIF-1 dechlorinase is barely detectable in uninduced cells. The dose-dependence reveals a threshold concentration of DIF-1 (15 nM) below which almost no response is seen. Cyclic AMP, which is the chemoattractant during aggregation and plays a key role in later development, suppresses the induction of DIF-1 dechlorinase by DIF-1. We conclude that induction of DIF-1 dechlorinase is one of the first steps on the developmental pathway which leads to prestalk cell differentiation, and suggest that the resulting negative feedback on DIF-1 levels is an important part of the mechanism by which cells decide whether to become prestalk or prespore cells.

A total of 15 mixtures involving 9 different stocks attributed to the 19/20, 32 and 39 major clonal genotypes of Trypanosoma cruzi were used to infect third-instar nymphs of Triatoma infestans via an artificial feeding device. Three biological parameters were considered: (1) the percentage of infected insects (%II), (2) the number of flagellates per insect (NFI), and (3) the percentage of trypomastigotes per insect (%DIF). Genetic characterization by both multilocus enzyme electrophoresis (MLEE) and random amplification of polymorphic DNA (RAPD) indicated that in almost all cases (87%), mixtures remained present after completion of the whole cycle in the insect vector. Two lines of comparison were performed: (1) pure clonal genotypes versus corresponding mixed clonal genotypes and (2) the actual behavior of mixed clonal genotypes versus the expected behavior of the theoretical mixture (i.e. the arithmetic mean of the results observed for each of the two clonal genotypes taken separately). Statistical analyses of the variables were made difficult because of the presence of large standard deviations. Nevertheless, in several cases, mixtures differed significantly from pure clonal genotypes, and in one case the actual mixture differed significantly from the theoretical mixture. In some cases, interaction (either potentialization or reciprocal inhibition) could be suspected.

OBJECTIVE

Evaluation of the internal construct validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index adapted for use in patients with femoro-acetabular impingement (FAI) and osteoarthritis (OA) of the hip.

METHODS

Distribution of a German version of WOMAC to patients upon first consultation. Patients with FAI [n=100, mean age 31.7 years, standard deviation (SD) 9.7] and OA (n=57, mean age 60.3 years, SD 11.7) and without comorbidities or prior hip surgery were included and compared to age- and gender-matched control population to FAI (n=200, mean age 32.6 years, SD 5.6). WOMAC data of 157 questionnaires were evaluated by Rasch analysis using RUMM2020 software.

RESULTS

Summation of total WOMAC shows misfit to the Rasch model as well as multidimensionality. While the pain subset shows adequate fit and is unidimensional, item reduction is required to fit a unidimensional subset of functional items to the Rasch model. Summating the two fitting subsets yields again slight model misfit and multidimensionality requiring further item reduction. Finally, a 12-item version of the total WOMAC shows good model fit and unidimensionality, i.e., internal construct validity, for assessment of patients with FAI and OA without differential item functioning (DIF). A person separation index (PSI)=0.93 indicates a high internal consistency reliability for the 12-item subscale. Scores for FAI are significantly higher than control (P<0.001, effect size 0.71) and lower than OA group (P<0.001, effect size 0.45). Adequate statistical power is shown discriminating the three groups, therefore indicating some evidence also for external construct validity.

CONCLUSIONS

The WOMAC as a total construct is multidimensional and summating the subsets into a total score is not valid. The reduced 12-item WOMAC is demonstrated to have internal construct validity for assessing patients with FAI and OA on the same scale and high internal consistency reliability. Discrimination of the groups with adequate statistical power also indicates external construct validity.

In Drosophila embryos, dorsal-ventral polarity is defined by a signal transduction pathway that regulates nuclear import of the Dorsal protein. Dorsal protein's ability to act as a transcriptional activator of some zygotic genes and a repressor of others defines structure along the dorsal-ventral axis. Dorsal is a member of a group of proteins, the Rel-homologous proteins, whose activity is regulated at the level of nuclear localization. Dif, a more recently identified Drosophila Rel-homologue, has been proposed to act as a mediator of the immune response in Drosophila. In an effort to understand the function and regulation of Rel-homologous proteins in Drosophila, we have expressed Dif protein in Drosophila embryos derived from dorsal mutant mothers. We found that the Dif protein was capable of restoring embryonic dorsal-ventral pattern elements and was able to define polarity correctly with respect to the orientation of the egg shell. This, together with the observation that the ability of Dif to restore a dorsal-ventral axis depended on the signal transduction pathway that normally regulates Dorsal, suggests that Dif protein formed a nuclear concentration gradient similar to that seen for Dorsal. By studying the expression of Dorsal target genes we found that Dif could activate the zygotic genes that Dorsal activates and repress the genes repressed by Dorsal. Differences in the expression of these target genes, as well as the results from interaction studies carried out in yeast, suggest that Dif is not capable of synergizing with the basic helix-loop-helix transcription factors with which Dorsal normally interacts, and thereby lacks an important component of Dorsal-mediated pattern formation.

OBJECTIVE

Differential item functioning (DIF) is present when respondents of unique subgroups endorse certain items differently given the respondents have the same underlying ability. This study investigates the presence of DIF regarding chronic illnesses among items of the physical functioning (PF) and mental health (MH) domains of the SF-36 health survey.

METHODS

Multiple indicators multiple causes (MIMIC) model was applied to data extracted from the Kaiser Permanente database for members who completed the SF-36 during 1994-1995 (N = 7538). DIF effects were evaluated for sociodemographic variables and for indicators of 5 chronic conditions: hypertension, rheumatic conditions, diabetes, respiratory diseases, and depression. An iterative strategy with backward selection was applied to build DIF models, which were estimated by weighted least squares. The Hochberg procedure was applied to P values for multiple tests.

RESULTS

After controlling for the selected covariates and the latent ability, DIF was present in 3 items for hypertension, one for respiratory diseases, and one for diabetes. Adjusting for DIF did not modify the overall pattern of exogenous variables' effects on PF or MH, except Hispanic and other ethnicity on PF, education on MH became insignificant; and black ethnicity on PF, old ages and other ethnicity on MH became significant.

CONCLUSIONS

Considering the number of items and disease subgroups compared, the presence of DIF was minimal among items of the PF and MH domains of the SF-36. DIF had little effect on comparisons of sociodemographic or disease groups.

Model-based roentgen stereophotogrammetric analysis (RSA) uses a three-dimensional surface model of an implant in order to estimate accurately the pose of that implant from a stereo pair of roentgen images. The technique is based on minimization of the difference between the actually projected contour of an implant and the virtually projected contour of a model of that same implant. The advantage of model-based RSA over conventional marker-based RSA is that it is not necessary to attach markers to the implant. In this paper, three pose estimation algorithms for model-based RSA are evaluated. The algorithms were assessed on the basis of their sensitivities to noise in the actual contour, to the amount of drop-outs in the actual contour, to the number of points in the actual contour and to shrinkage or expansion of the actual contour. The algorithms that were studied are the iterative inverse perspective matching (IIPM) algorithm, an algorithm based on minimization of the difference (DIF) between the actual contour and the virtual contour, and an algorithm based on minimization of the non-overlapping area (NOA) between the actual and virtual contour. The results of the simulation and phantom experiments show that the NOA algorithm does not fulfil the high accuracy that is necessary for model-based RSA. The IIPM and DIF algorithms are robust to the different distortions, making model-based RSA a possible replacement for marker-based RSA.

This work studied the mechanisms of interaction between Eudragit RS100 (RS) and RL100 (RL) polymers with 3 nonsteroidal anti-inflammatory drugs: diflunisal (DIF), flurbiprofen (FLU), and piroxicam (PIR). Solid dispersions of polymers and drugs at different weight ratios were prepared by coevaporation of their ethanol solutions. The resulting coevaporates were characterized in the solid state (Fourier-transformed infrared spectroscopy (FT-IR) IR, differential scanning calorimetry, powder-x-ray diffractometry) as well as by studying the in vitro drug release in a gastroenteric environment. Absorption tests from drug solutions to the solid polymers were also performed to better explain the mechanism of interactions between them. The preparative conditions did not induce changes in the crystalline state of the drugs (amorphization or polymorphic change). Drugs strongly interacted with the ammonium groups present in polymers, giving an electrostatic interaction that reinforced the mere physical dispersion of drug molecules within polymer networks. Such interactions are related to the chemical structure of the drugs and to their dissociated or undissociated state. The dispersion of drugs in the polymer matrices strongly influenced their dissolution rate, which appeared slower and more gradual than those of the pure drugs, when polymer ratios were increased. RL coevaporates usually displayed higher dissolution rates. The kinetic evaluation of the dissolution profile, however, suggested that both the drug solubility in the external medium and its diffusion capacity within the polymer network are involved. In the sorption experiments, RL showed a greater adsorptive capacity than RS, in relation to the greater number of quaternary ammonium functions, which behave as activity sites for the electrostatic interactions. In the presence of Tris-HCl buffer (pH 7.4), drug adsorption was reduced, as a consequence of the competition of the chloride ions with drug anions for the polymer binding sites. In general, DIF and FLU displayed a similar interaction with RS and RL active sites; PIR's was different. The different molecular structures of these agents can justify such findings. The presence of a carboxyl group (instead of another dissociable acidic moiety, like the hydroxy-enolic one in the PIR molecule) could help explain the strong interaction with RS and RL polymers' quaternary ammonium centers. Preliminary studies like ours are important in helping develop better forecasting and increasing the understanding of the incorporation/release behavior of drugs from particulate delivery systems that can be made from these polymers.

The Short Inventory of Problems-Alcohol and Drugs (SIP-AD) is a 15-item measure that assesses concurrently negative consequences associated with alcohol and illicit drug use. Current psychometric evaluation has been limited to classical test theory (CTT) statistics, and it has not been validated among non-treatment seeking men-who-have-sex-with-men (MSM). Methods from Item Response Theory (IRT) can improve upon CTT by providing an in-depth analysis of how each item performs across the underlying latent trait that it is purported to measure. The present study examined the psychometric properties of the SIP-AD using methods from both IRT and CTT among a non-treatment seeking MSM sample (N=469). Participants were recruited from the New York City area and were asked to participate in a series of studies examining club drug use. Results indicated that five items on the SIP-AD demonstrated poor item misfit or significant differential item functioning (DIF) across race/ethnicity and HIV status. These five items were dropped and two-parameter IRT analyses were conducted on the remaining 10 items, which indicated a restricted range of item location parameters (-.15 to -.99) plotted at the lower end of the latent negative consequences severity continuum, and reasonably high discrimination parameters (1.30 to 2.22). Additional CTT statistics were compared between the original 15-item SIP-AD and the refined 10-item SIP-AD and suggest that the differences were negligible with the refined 10-item SIP-AD indicating a high degree of reliability and validity. Findings suggest the SIP-AD can be shortened to 10 items and appears to be a non-biased reliable and valid measure among non-treatment seeking MSM.

The Myxococcus xanthus dif locus encodes several bacterial chemotaxis homologues that are crucial for fibril exopolysaccharide (EPS) production, social gliding motility, and fruiting body development. In primary sequence, DifA is homologous to methyl-accepting chemotaxis protein, DifC to CheW, DifD to CheY, DifE to CheA, and DifG to CheC. In this study, the interactions among the Dif chemotaxis-like proteins were investigated using the yeast two-hybrid (Y2H) system. DifC was found to interact with both DifA and DifE. Using a modified Y2H or a "three-hybrid" system, it was demonstrated that DifC is capable of mediating the formation of DifA, DifC, and DifE ternary protein complexes. The conserved domains of DifE, based on sequence analysis, likely reflect functional conservations of CheA-type kinases, because its P2 domain interacts with DifD, P5 with DifC, and the P3 domain appears to dimerize. Similarly, C-terminal regions of DifA appear to dimerize as well. In addition, DifG was found to interact with DifD, which is consistent with the hypothesis that DifG is a phosphatase of DifD-phosphate. These findings support the models in which Dif proteins constitute a unique chemotaxis-like signal transduction pathway with central functions in regulating EPS production in M. xanthus.