This study tested for the presence of differential item functioning (DIF) in DSM-IV Pathological Gambling Disorder (PGD) criteria based on gender, race/ethnicity and age. Using a nationally representative sample of adults from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), indicating current gambling (n = 10,899), Multiple Indicator-Multiple Cause (MIMIC) models tested for DIF, controlling for income, education, and marital status. Compared to the reference groups (i.e., Male, Caucasian, and ages 25-59 years), women (OR = 0.62; P < .001) and Asian Americans (OR = 0.33; P < .001) were less likely to endorse preoccupation (Criterion 1). Women were more likely to endorse gambling to escape (Criterion 5) (OR = 2.22; P < .001) but young adults (OR = 0.62; P < .05) were less likely to endorse it. African Americans (OR = 2.50; P < .001) and Hispanics were more likely to endorse trying to cut back (Criterion 3) (OR = 2.01; P < .01). African Americans were more likely to endorse the suffering losses (OR = 2.27; P < .01) criterion. Young adults were more likely to endorse chasing losses (Criterion 9) (OR = 1.81; P < .01) while older adults were less likely to endorse this criterion (OR = 0.76; P < .05). Further research is needed to identify factors contributing to DIF, address criteria level bias, and examine differential test functioning.

Prespore and prestalk cells can be distinguished within aggregates of Dictyostelium by the expression of well-characterized cell type-specific genes. Fusion of the tagB regulatory region to Escherichia coli beta-galactosidase revealed that this prestalk specific gene marks the differentiation of the initial prestalk cell population, PST-1. The reporter gene was expressed normally in tagB- mutant cells despite the fact that they do not accumulate measurable levels of DIF-I, a morphogen that was previously implicated in prestalk differentiation. In an independent experimental system, wild-type cells respond to the addition of DIF-I by induction of the prestalk marker ecmA and repression of the prespore marker cotB. We found that DIF-1 did not affect the expression of the tagB or carB genes, both of which are prestalk specific and essential for PST-A cell differentiation. We conclude that the initiation of prestalk development is not dependent on DIF-1 and suggest that the morphogen participates mainly at later stages.

Myxococcus xanthus fibril exopolysaccharide (EPS), essential for the social gliding motility and development of this bacterium, is regulated by the Dif chemotaxis-like pathway. DifA, an MCP homolog, is proposed to mediate signal input to the Dif pathway. However, DifA lacks a prominent periplasmic domain, which in classical chemoreceptors is responsible for signal perception and for initiating transmembrane signaling. To investigate the signaling properties of DifA, we constructed a NarX-DifA (NafA) chimera from the sensory module of Escherichia coli NarX and the signaling module of M. xanthus DifA. We report here the first functional chimeric signal transducer constructed using genes from organisms in two different phylogenetic subdivisions. When expressed in M. xanthus, NafA restored fruiting body formation, EPS production, and S-motility to difA mutants in the presence of nitrate. Studies with various double mutants indicate that NafA requires the downstream Dif proteins to function. We propose that signal inputs to the Dif pathway and transmembrane signaling by DifA are essential for the regulation of EPS production in M. xanthus. Despite the apparent structural differences, DifA appears to share similar transmembrane signaling mechanisms with enteric sensor kinases and chemoreceptors.

During Dictyostelium stalk cell differentiation, cells vacuolate, synthesize a cellulose cell wall and die. This process of programmed cell death is accompanied by expression of the prestalk gene ecmB and induced by the differentiation inducing factor DIF. Using cell lines expressing the recombinant Ca2+-sensitive photoprotein apoaequorin, we found that 100 nM DIF increases cytosolic Ca2+ ([Ca2+]i) levels from approximately 50 to 150 nM over a period of 8 h. The Ca2+-ATPase inhibitor 2,5-di(tert-butyl)-1,4-hydroquinone (BHQ) induced a similar increase in [Ca2+]i levels and induced expression of the prestalk gene ecmB to the same level as DIF. The [Ca2+]i increases induced by DIF and BHQ showed similar kinetics and preceded ecmB gene expression by approximately 1-2 h. The Ca2+ chelator 1,2-bis(o-aminophenoxy)-ethane-N,N,N'N'-tetra-acetic acid (BAPTA) efficiently inhibited the BHQ-induced [Ca2+]i increase and blocked DIF-induced expression of the ecmB gene. These data indicate that the effects of DIF on stalk gene expression are mediated by a sustained increase in [Ca2-]i. Sustained [Ca2+]i elevation mediates many forms of programmed cell death in vertebrates. The Dictyostelium system may be the earliest example of how this mechanism developed during early eukaryote evolution.

We have shown previously that developing amoebae of Dictyostelium discoideum release one or more low-Mr factors, which can induce isolated cells to differentiate into stalk cells in the presence of cyclic AMP [Town, C. D., Gross, J. D. and Kay, R. R. (1976) Nature (Lond.) 262, 717-719; Town, C. D. and Stanford, E. (1979) Proc. Natl Acad. Sci. USA, 76, 308-312]. These differentiation-inducing factors (DIF) have now been purified by a procedure involving binding to and elution from XAD-2 resin, extraction into hexane and two steps of reverse-phase high-pressure liquid chromatography (HPLC). Our results show the following. HPLC resolves a major stalk-cell-inducing activity (DIF-1) and at least four minor and more polar activities (DIFs 2-5). DIF-1 has been purified at least 3000-fold over the starting dialysed medium with a recovery of about 2%. This low recovery of DIF-1 can be explained in part by the loss of non-specific stimulatory ('helper') factors during the purification. A few micrograms purified DIF-1 were obtained from 10(12) cells. This material could induce stalk cell differentiation in the standard assay at less than 0.2 nM. The biological activity of DIFs 1, 2 and 3 was sensitive to borohydride reduction, suggesting the presence of an essential carbonyl group. DIF-5 was partially sensitive and DIF-4 resistant. Other properties of DIF-1 suggest that it is a non-polar molecule of Mr less than 500, which becomes charged in alkaline solution, and that it is neither a peptide nor has essential sugar moieties. The purification of DIF should make possible its eventual identification by sensitive physical techniques, such as mass spectroscopy, and will allow further investigation of its biological effects.

Early during Dictyostelium development a fundamental cell-fate decision establishes the anteroposterior (prestalk/prespore) axis. Signaling via the 7-transmembrane cAMP receptor CAR4 is essential for creating and maintaining a normal pattern; car4-null alleles have decreased levels of prestalk-specific mRNAs but enhanced expression of prespore genes. car4- cells produce all of the signals required for prestalk differentiation but lack an extracellular factor necessary for prespore differentiation of wild-type cells. This secreted factor decreases the sensitivity of prespore cells to inhibition by the prestalk morphogen DIF-1. At the cell autonomous level, CAR4 is linked to intracellular circuits that activate prestalk but inhibit prespore differentiation. The autonomous action of CAR4 is antagonistic to the positive intracellular signals mediated by another cAMP receptor, CAR1 and/or CAR3. Additional data indicate that these CAR-mediated pathways converge at the serine/threonine protein kinase GSK3, suggesting that the anterior (prestalk)/posterior (prespore) axis of Dictyostelium is regulated by an ancient mechanism that is shared by the Wnt/Fz circuits for dorsoventral patterning during early Xenopus development and establishing Drosophila segment polarity.

Cbl proteins downregulate metazoan signalling pathways by ubiquitylating receptor tyrosine kinases, thereby targeting them for degradation. They contain a phosphotyrosine-binding region, comprising an EF-hand and an SH2 domain, linked to an E3 ubiquitin-ligase domain. CblA, a Dictyostelium homologue of the Cbl proteins, contains all three conserved domains. In a cblA(-) strain early development occurs normally but migrating cblA(-) slugs frequently fragment and the basal disc of the culminants that are formed are absent or much reduced. These are characteristic features of mutants in signalling by DIF-1, the low-molecular-mass prestalk and stalk cell inducer. Tyrosine phosphorylation of STATc is induced by DIF-1 but in the cblA(-) strain this response is attenuated relative to parental cells. We present evidence that CblA fulfils this function, as a positive regulator of STATc tyrosine phosphorylation, by downregulating PTP3, the protein tyrosine phosphatase responsible for dephosphorylating STATc. Thus Cbl proteins have an ancient origin but, whereas metazoan Cbl proteins regulate tyrosine kinases, the Dictyostelium Cbl regulates via a tyrosine phosphatase.

Alveolar macrophage-fibroblast interaction may be involved in the pathogenesis of interstitial lung diseases (ILD). Herein, we compared IL-6 secretion from alveolar macrophages (AM) and alveolar fibroblasts (AFb) recovered from patients with sarcoidosis (SA) and with diffuse interstitial fibrosis (DIF). Moreover, we evaluated the effect of IL-6 on the in vitro AFb proliferation in both diseases. AM and AFb from SA patients showed increased spontaneous secretion of IL-6 compared with cells from DIF subjects. Tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1) enhanced IL-6 secretion and IL-6 mRNA transcription in AFb of SA patients. Addition of anti-IL-6 MoAbs increased AFb proliferation capacity in SA, but suppressed it in DIF. These results show that only SA AM and AFb secrete high levels of IL-6 which have suppressive effect on AFb proliferation. This may indicate a potential role of IL-6 in the fibrogenesis of ILD.

OBJECTIVE

Limited studies consider the effect of differential item functioning (DIF) on health-related quality of life (HRQOL) comparisons between ill and health children. The objective is to assess DIF and compare HRQOL between children with special health-care needs (CSHCN) and children without needs.

METHODS

Data were collected from 1195 families of children enrolled in Florida's public insurance programs. HRQOL was measured using physical, emotional, social, and school functioning of the Pediatric Quality of Life Inventory (PedsQL). We identified CSHCN using the CSHCN Screener and assessed DIF related to CSHCN using a multiple group-multiple indicators-multiple causes method (MG-MIMIC). We assessed the impact of DIF by examining expected item/test scores and item/test information function. We tested the discrepancy between underlying HRQOL scores of both groups before and after DIF calibration (allowing parameters of DIF items to be different and DIF-free items to be the same across both groups).

RESULTS

Two (25%) and three items (60%) of physical and school functioning, respectively, were identified with nonuniform DIF, and two items (40%) of social functioning were identified with uniform DIF. Expected item/test scores and item/test information function suggest that the impact of DIF is minimal. Before DIF calibration, HRQOL in CSHCN was more impaired than in children without needs (effect sizes -1.04, -0.74, -0.96, and -0.98 for physical, emotional, social, and school functioning, respectively). After DIF calibration, the discrepancy was increased slightly.

CONCLUSIONS

Although 30% of items on the PedsQL were identified with DIF related to CSHCN status, the impact of DIF is minimal.

OBJECTIVE

To investigate the psychometric properties of the Visual Function (VF) and Quality of Life (QOL) questionnaires, using the Rasch measurement model.

METHODS

Four hundred eighty-nine patients with cataract awaiting surgery, drawn from the surgical waiting list of the Flinders Medical Centre, Adelaide, South Australia, were mailed the VF and QOL questionnaires for self-administration. Rasch analysis was undertaken to assess the following properties: measurement of a single construct (i.e., unidimensionality by fit statistics and principal components analysis), discrimination between strata of participant ability (person separation, recommended minimum value 2.0), targeting of item difficulty to participant ability, and differential item functioning (DIF, whether items function similarly for different subgroups and notable DIF defined as >1.0 logit).

RESULTS

The VF questionnaire fit the Rasch model showing good metric properties, including unidimensionality, and was free of notable DIF. The QOL questionnaire showed inadequate person separation, two misfitting items and significant multidimensionality (Eigenvalue of 2.3 for the first contrast), suggesting the presence of a separate subscale, self-care, but this was not valid because of inadequate person separation. Deleting these contrasting items from the QOL questionnaire removed multidimensionality and item misfit but did not improve person separation, indicating that it could not effectively discriminate between the participant's QOL. Both VF and QOL questionnaires demonstrated poor targeting (-2.22 and -3.26 logits, respectively), indicating that items were too easy and participants had higher QOL than that the items allowed for. Three items in the QOL questionnaire demonstrated notable DIF by age and systemic comorbidity. None of the subscales functioned optimally.

CONCLUSIONS

The QOL questionnaire is not a valid measure of QOL. However, the VF questionnaire is a reliable and valid measure of visual disability in patients with cataract, and although targeting was suboptimal in a developed country, it may be optimal in a developing country as was originally intended.

OBJECTIVE

The Hospital Anxiety and Depression Scale (HADS) is often used to screen for cancer caregivers' anxiety and depression, despite few studies examining the tool's psychometric performance within this population. The purpose of this article is to use Rasch analysis to assess the psychometric properties of the HADS in a sample of cancer caregivers.

METHODS

HADS was administered to 541 caregivers of a population-based sample of patients diagnosed with one of the eight most incident cancers in Australia. Rasch analysis was conducted using RUMM2020.

RESULTS

More than two-thirds of caregivers were women and most participants were married (95.9%) and caring for their spouse/partner with cancer (89.8%). The HADS-Anxiety (HADS-A) subscale showed good fit to the model, with appropriate internal consistency after removal of item 11. There were no disordered thresholds and no differential item functioning (DIF) for sex or age. To achieve satisfactory model fit for the HADS-Depression (HADS-D) subscale item 8 was removed due to DIF for sex and item 14 was rescored to resolve disordered thresholds. Analyses supported the unidimensionality of the individual subscales; however, there was no support for the combination of subscales to form a HADS-Total.

CONCLUSIONS

The results of Rasch analysis support the use of a modified version of the HADS-A and HADS-D among cancer caregivers. Further research is needed to confirm these findings and identify revised clinical cut-points. Findings reinforce the need for clinicians and researchers to formally test the psychometric properties of the instruments that they intend to use with different samples. Copyright © 2010 John Wiley & Sons, Ltd.

OBJECTIVE

Fear of cancer recurrence (FCR) is prevalent amongst survivors, and breast cancer survivors are particularly vulnerable. Currently, there are few well-validated brief measures of FCR and none specific to breast cancer. This manuscript describes the development and initial validation of a new measure of FCR for breast cancer survivors, the Concerns about Recurrence Questionnaire (CARQ), and reports its initial validation in an Australian and Danish population-based sample of breast cancer survivors.

METHODS

CTT analyses explored scale reliability and validity; Rasch analyses explored model fit statistics, item bias (DIF) and local dependency. Three-item, four-item and five-item versions were considered.

RESULTS

Two hundred eighteen Australian women aged 28-45 years diagnosed with early-stage breast cancer (stages 0-2) and 2001 Danish women diagnosed with breast cancer (stages 1-3) aged 26-70 completed the CARQ. Based on the results of both CTT and IRT analyses, the four-item English version of the scale performed best. Although the CTT analyses suggested that the CARQ-4 was reliable and valid in both samples, Rasch analyses identified item bias relative to age, and local dependence which may be remedied by further scale development.

CONCLUSIONS

The CARQ-4 English version is currently one of the most rigorously tested brief scales of FCR available.

CONCLUSIONS

The availability of more valid and reliable brief measures of FCR will help to promote research and screening of FCR amongst cancer survivors.

BACKGROUND

Medical research increasingly utilizes patient-reported outcome measures administered and scored in different languages. In order to pool or compare outcomes from different language versions, instruments should be measurement equivalent across linguistic groups. The objective of this study was to examine the cross-language measurement equivalence of the Patient Health Questionnaire-9 (PHQ-9) between English- and French-speaking Canadian patients with systemic sclerosis (SSc).

METHODS

The sample consisted of 739 English- and 221 French-speaking SSc patients. Multiple-Indicator Multiple-Cause (MIMIC) modeling was used to identify items displaying possible differential item functioning (DIF).

RESULTS

A one-factor model for the PHQ-9 fit the data well in both English- and French-speaking samples. Statistically significant DIF was found for 3 of 9 items on the PHQ-9. However, the overall estimate in depression latent scores between English- and French-speaking respondents was not influenced substantively by DIF.

CONCLUSIONS

Although there were several PHQ-9 items with evidence of minor DIF, there was no evidence that these differences influenced overall scores meaningfully. The PHQ-9 can reasonably be used without adjustment in Canadian English- and French-speaking samples. Analyses assessing measurement equivalence should be routinely conducted prior to pooling data from English and French versions of patient-reported outcome measures.

Loneliness is experienced in many cultures. To properly assess cross-cultural differences, attention should be paid to the level, determinants, and measurement of loneliness. However, cross-cultural studies have rarely taken into account more than one of these. Differences in the level of loneliness were hypothesized on the basis of national differences in partnership, kinship, and friendship, which were assumed to be related to cultural standards within a society. Differences were examined among married and widowed older adults aged 70 to 89 years living independently in The Netherlands (N = 1,847), Tuscany, Italy (N = 562), and Manitoba, Canada (N = 1,134). Loneliness was measured with an 11-item scale. The Manitobans were high on emotional loneliness and the Tuscans were high on social loneliness. Partner status excepted, the determinants were nearly the same across the three locations. Differential item functioning (DIF) related to the three locations was observed for most items. Interactions with gender and the availability of a partner relationship were observed.

BACKGROUND

Instruments to measure mental health and well-being are largely developed and often used within Western populations and this compromises their validity in other cultures. A previous qualitative study in Singapore demonstrated the relevance of spiritual and religious practices to mental health, a dimension currently not included in exiting multi-dimensional measures. The objective of this study was to develop a self-administered measure that covers all key and culturally appropriate domains of mental health, which can be applied to compare levels of mental health across different age, gender and ethnic groups. We present the item reduction and validation of the Positive Mental Health (PMH) instrument in a community-based adult sample in Singapore.

METHODS

Surveys were conducted among adult (21-65 years) residents belonging to Chinese, Malay and Indian ethnicities. Exploratory and confirmatory factor analysis (EFA, CFA) were conducted and items were reduced using item response theory tests (IRT). The final version of the PMH instrument was tested for internal consistency and criterion validity. Items were tested for differential item functioning (DIF) to check if items functioned in the same way across all subgroups.

RESULTS

EFA and CFA identified six first-order factor structure (General coping, Personal growth and autonomy, Spirituality, Interpersonal skills, Emotional support, and Global affect) under one higher-order dimension of Positive Mental Health (RMSEA=0.05, CFI=0.96, TLI=0.96). A 47-item self-administered multi-dimensional instrument with a six-point Likert response scale was constructed. The slope estimates and strength of the relation to the theta for all items in each six PMH subscales were high (range:1.39 to 5.69), suggesting good discrimination properties. The threshold estimates for the instrument ranged from -3.45 to 1.61 indicating that the instrument covers entire spectrums for the six dimensions. The instrument demonstrated high internal consistency and had significant and expected correlations with other well-being measures. Results confirmed absence of DIF.

CONCLUSIONS

The PMH instrument is a reliable and valid instrument that can be used to measure and compare level of mental health across different age, gender and ethnic groups in Singapore.

BACKGROUND

The presence of disseminated tumor cells (DTCs) in bone marrow (BM) is an independent prognostic factor in early breast cancer but does not uniformly predict outcome. Tumor cells can persist in a quiescent state over time, but clinical studies of markers predicting the awakening potential of DTCs are lacking. Recently, experiments have shown that NR2F1 (COUP-TF1) plays a key role in dormancy signaling.

METHODS

We analyzed the NR2F1 expression in DTCs by double immunofluorescence (DIF) staining of extra cytospins prepared from 114 BM samples from 86 selected DTC-positive breast cancer patients. Samples collected at two or more time points were available for 24 patients. Fifteen samples were also analyzed for the proliferation marker Ki67.

RESULTS

Of the patients with detectable DTCs by DIF, 27% had ≥ 50% NR2F1high DTCs, chosen a priori as the cut-off for "dormant profile" classification. All patients with systemic relapse within 12 months after BM aspiration carried ≤ 1% NR2F1high DTCs, including patients who transitioned from having NR2F1high-expressing DTCs in previous BM samples. Of the patients with serial samples, half of those with no relapse at follow-up had ≥ 50% NR2F1high DTCs in the last BM aspiration analyzed. Among the 18 relapse-free patients at the time of the last DTC-positive BM aspiration with no subsequent BM analysis performed, distant disease-free intervals were favorable for patients carrying ≥ 50% NR2F1high DTCs compared with those with predominantly NR2F1low DTCs (p = 0.007, log-rank). No survival difference was observed by classification according to Ki67-expressing DTCs (p = 0.520).

CONCLUSIONS

Our study translates findings from basic biological analysis of DTC dormancy to the clinical situation and supports further clinical studies of NR2F1 as a marker of dormancy.

BACKGROUND

For people to be able to access, understand, and benefit from the increasing digitalization of health services, it is critical that services are provided in a way that meets the user's needs, resources, and competence.

OBJECTIVE

The objective of the study was to develop a questionnaire that captures the 7-dimensional eHealth Literacy Framework (eHLF).

METHODS

Draft items were created in parallel in English and Danish. The items were generated from 450 statements collected during the conceptual development of eHLF. In all, 57 items (7 to 9 items per scale) were generated and adjusted after cognitive testing. Items were tested in 475 people recruited from settings in which the scale was intended to be used (community and health care settings) and including people with a range of chronic conditions. Measurement properties were assessed using approaches from item response theory (IRT) and classical test theory (CTT) such as confirmatory factor analysis (CFA) and reliability using composite scale reliability (CSR); potential bias due to age and sex was evaluated using differential item functioning (DIF).

RESULTS

CFA confirmed the presence of the 7 a priori dimensions of eHLF. Following item analysis, a 35-item 7-scale questionnaire was constructed, covering (1) using technology to process health information (5 items, CSR=.84), (2) understanding of health concepts and language (5 items, CSR=.75), (3) ability to actively engage with digital services (5 items, CSR=.86), (4) feel safe and in control (5 items, CSR=.87), (5) motivated to engage with digital services (5 items, CSR=.84), (6) access to digital services that work (6 items, CSR=.77), and (7) digital services that suit individual needs (4 items, CSR=.85). A 7-factor CFA model, using small-variance priors for cross-loadings and residual correlations, had a satisfactory fit (posterior productive P value: .27, 95% CI for the difference between the observed and replicated chi-square values: -63.7 to 133.8). The CFA showed that all items loaded strongly on their respective factors. The IRT analysis showed that no items were found to have disordered thresholds. For most scales, discriminant validity was acceptable; however, 2 pairs of dimensions were highly correlated; dimensions 1 and 5 (r=.95), and dimensions 6 and 7 (r=.96). All dimensions were retained because of strong content differentiation and potential causal relationships between these dimensions. There is no evidence of DIF.

CONCLUSIONS

The eHealth Literacy Questionnaire (eHLQ) is a multidimensional tool based on a well-defined a priori eHLF framework with robust properties. It has satisfactory evidence of construct validity and reliable measurement across a broad range of concepts (using both CTT and IRT traditions) in various groups. It is designed to be used to understand and evaluate people's interaction with digital health services.

The Rasch model prescribes procedures to ensure that a scale constructed from multiple items conforms to fundamental requirements of interval scales of measurement.

To test the Rasch properties of the domains of the World Health Organization Quality of Life Instrument-abbreviated version (WHOQOL-BREF) in depressed patients from primary care settings.

Cross-sectional, cross-national study.

Primary care.

The sample consisted of 1193 patients having a confirmed diagnosis of depression from 6 countries (Australia, Brazil, Israel, Russia, Spain, and the United States) involved in the Longitudinal Investigation of Depression Outcomes (LIDO) study.

The Composite International Diagnostic Interview (CIDI) diagnosed depression, whereas the Center for Epidemiological Studies Depression Scale (CES-D) assessed severity of depression. The WHOQOL-BREF measured generic quality of life (QOL).

Three of the 4 WHOQOL-BREF domains (physical, psychological, and environment) conform to the Rasch model expectations, following adjustments required mainly because of individual item misfit or differential item functioning (DIF) due to age or country. The social domain showed relatively poor psychometric properties, as observed in previous studies.

The Rasch analysis demonstrated that, with some modifications, all domains of the WHOQOL-BREF, except for the social domain, provide an interval scale measure of generic subjective QOL in the context of depressed primary care patients in 6 countries worldwide.

Dictyostelium discoideum has been very useful for elucidating principles of development over the last 50 years, but a key attribute means there is a lot to be learned from a very different intellectual tradition: social evolution. Because Dictyostelium arrives at multicellularity by aggregation instead of through a single-cell bottleneck, the multicellular body could be made up of genetically distinct cells. If they are genetically distinct, natural selection will result in conflict over which cells become fertile spores and which become dead stalk cells. Evidence for this conflict includes unequal representation of two genetically different clones in spores of a chimera, the poison-like differentiation inducing factor (DIF) system that appears to involve some cells forcing others to become stalk, and reduced functionality in migrating chimeras. Understanding how selection operates on chimeras of genetically distinct clones is crucial for a comprehensive view of Dictyostelium multicellularity. In nature, Dictyostelium fruiting bodies are often clonal, or nearly so, meaning development will often be very cooperative. Relatedness levels tell us what benefits must be present for sociality to evolve. Therefore it is important to measure relatedness in nature, show that it has an impact on cooperation in the laboratory, and investigate genes that Dictyostelium uses to discriminate between relatives and non-relatives. Clearly, there is a promising future for research at the interface of development and social evolution in this fascinating group.

BACKGROUND

The Cognitive Abilities Screening Instrument (CASI) was designed for use in cross-cultural studies of Japanese and Japanese-American elderly in Japan and the U.S.A. The measurement equivalence in Japanese and English had not been confirmed in prior studies.

METHODS

We analyzed the 40 CASI items for differential item functioning (DIF) related to test language, as well as self-reported proficiency with written Japanese, age, and educational attainment in two large epidemiologic studies of Japanese-American elderly: the Kame Project (n=1708) and the Honolulu-Asia Aging Study (HAAS; n = 3148). DIF was present if the demographic groups differed in the probability of success on an item, after controlling for their underlying cognitive functioning ability.

RESULTS

While seven CASI items had DIF related to language of testing in Kame (registration of one item; recall of one item; similes; judgment; repeating a phrase; reading and performing a command; and following a three-step instruction), the impact of DIF on participants' scores was minimal. Mean scores for Japanese and English speakers in Kame changed by <0.1 SD after accounting for DIF related to test language. In HAAS, insufficient numbers of participants were tested in Japanese to assess DIF related to test language. In both studies, DIF related to written Japanese proficiency, age, and educational attainment had minimal impact.

CONCLUSIONS

To the extent that DIF could be assessed, the CASI appeared to meet the goal of measuring cognitive function equivalently in Japanese and English. Stratified data collection would be needed to confirm this conclusion. DIF assessment should be used in other studies with multiple language groups to confirm that measures function equivalently or, if not, form scores that account for DIF.

A new PCR kit (AMPLICOR CT/NG; Roche Diagnostic Systems, Inc., Branchburg, N.J.) was used as a screening tool for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in first-void urine (FVU) specimens from 3,340 asymptomatic women attending European health care units for contraceptive advice or pregnancy termination. All samples were kept frozen (-20 degrees C) prior to testing. Chlamydia-positive samples were retested once by the plasmid-based PCR kit and also by a major outer membrane protein (MOMP) primer-based PCR. Discrepancies were resolved by using the direct immunofluorescence test (DIF) with the centrifuged sediment of the FVU specimens. Samples positive for N. gonorrhoeae were retested by chromosomal primer-based PCR and verified by a 16S RNA PCR. Of the samples tested, 1.8% were considered inhibitory by using the internal amplification control. Of 81 samples positive for C. trachomatis, 74 samples were positive by both plasmid- and MOMP-based PCRs, 6 samples were positive by plasmid-based PCR and DIF, and one sample was positive by both MOMP-based PCR and DIF. Nine samples (0.3%) were positive for N. gonorrhoeae by the chromosomal primer-based PCR; however, none of the results could be confirmed. The test offers the unique ability to identify inhibition of amplification with the optional internal control.

BACKGROUND

The Patient Activation Measure (PAM) consists of 13 items and assesses patient (or consumer) self-reported knowledge, skills, and confidence for self-management of one's health or chronic condition. The aim of this study was to translate the original American version of the PAM13 into German and to test the psychometric properties of the German version in an elderly, multimorbid population with various chronic conditions.

METHODS

Translation was performed by a standardized forward-backward translation process. The PAM13 was sent to 9.075 participants enrolled in a randomized controlled study. 4.306 participants responded to the questionnaire. Descriptive and reliability analyses were carried out. To examine scale properties, Andrich's Rasch Rating Scale Model was fitted.

RESULTS

The internal consistency is good (α = 0.88) and the item-rest-correlations were found as strong to moderate. The unidimensionality of the construct was confirmed, with a variance explanation of 40.9% and good model-fits for the Rasch model. However, the lowest response options were very rarely used across all items (below 5%) and ranking order of items according to their difficulty was substantially different from that of the American version. Differential item functioning (DIF) was found in subgroups (sex, age, health status), but differences were small.

CONCLUSIONS

The German version of the PAM13 showed acceptable reliability and the model-fit statistics confirmed the Rasch model. The different ranking order of the items and the unfair distribution of the response options suggest further research on validation and revision of the construct.

Dif and Frz, two Myxococcus xanthus chemosensory pathways, are required in phosphatidylethanolamine (PE) chemotaxis for excitation and adaptation respectively. DifA and FrzCD, the homologues of methyl-accepting chemoreceptors in the two pathways, were examined for methylation in the context of chemotaxis and inter-pathway interactions. Evidence indicates that DifA may not undergo methylation, but signals transmitting through DifA do modulate FrzCD methylation. Results also revealed that M. xanthus possesses Dif-dependent and Dif-independent PE-sensing mechanisms. Previous studies showed that FrzCD methylation is decreased by negative chemostimuli but increased by attractants such as PE. Results here demonstrate that the Dif-dependent sensory mechanism suppresses the increase in FrzCD methylation in attractant response and elevates FrzCD methylation upon negative stimulation. In other words, FrzCD methylation is governed by opposing forces from Dif-dependent and Dif-independent sensing mechanisms. We propose that the Dif-independent but Frz-dependent PE sensing leads to increases in FrzCD methylation and subsequent adaptation, while the Dif-dependent PE signalling suppresses or diminishes the increase in FrzCD methylation to decelerate or delay adaptation. We contend that these antagonistic interactions are crucial for effective chemotaxis in this gliding bacterium to ensure that adaptation does not occur too quickly relative to the slow speed of M. xanthus movement.

Rapid transcriptional induction of genes in response to gamma interferon (IFN-gamma) is mediated by the IFN-gamma activation site (GAS) and its cognate protein, the IFN-gamma activation factor (GAF). We describe a GAS-associated, differentiation-induced factor (DIF) as a potential molecular link between the activities of IFN-gamma and of growth and differentiation factors. DIF DNA binding was activated by colony-stimulating factor 1 in murine macrophages and also during tetradecanoyl phorbol acetate-induced differentiation or IFN-gamma treatment in myeloid U937 cells. IFN-gamma activation of DIF decreased significantly upon monocytic differentiation. DIF binding to DNA was inhibited by antiphosphotyrosine antibodies and could be induced by treatment of U937 cells with vanadate. Unlike GAF, DIF-DNA complexes did not contain the 91-kDa protein (p91) from ISGF-3. DIF bound with high affinity to GAS from the promoters of the IFP 53/tryptophanyl-tRNA synthetase and Fc gamma RI genes, intermediate affinity to the Ly6A/E GAS, and low affinity to the guanylate-binding protein GAS. DIF may belong to a family of cytokine- or growth factor-induced factors binding with variable affinities to GAS-related elements: the interleukin-6-responsive acute-phase response factor associated with GAS from different IFN-inducible promoters but with a different preference of binding compared with DIF. The sis-inducible element of the c-fos promoter bound GAF but not DIF. However, the sis-inducible element could be changed by point mutation to compete for GAF and DIF binding. Our data show DIF to be a novel DNA-binding protein which is activated in response to differentiating signals. Moreover, they suggest that a family of cytokine- or growth factor-regulated proteins integrates and coordinates the responses to cytokines and to growth and differentiation factors by binding to GAS-related elements.