Comparison of the NEO-FFI, the NEO-FFI-R and an alternative short version of the NEO-PI-R (NEO-60) in Swiss and Spanish samples

Three different short versions of the NEO-PI-R were compared: The NEO-FFI, the NEO-FFI-R, and a new short version developed in the current study (NEO-60). This new version is intended to improve the psychometric characteristics of the original NEO-FFI, specially in regard to the factor structure at the item-level. A French version of the NEO-PI-R was given to 1090 Swiss subjects, whereas the Spanish (Castilian) version of the NEO-PI-R was administered to 1006 Spanish subjects. Results replicate the limitations of the NEO-FFI already found in other countries. Compared to the NEO-FFI, reliability coefficients and factor structure was enhanced by the NEO-FFI-R and the NEO-60 in both samples, although substantial differences were not found. The factor structure of the NEO-60 shows the best fit since only three items do not load mainly on their own factor in both samples. Besides, correlations between items and NEO-PI-R domain scores are also higher for the items included in the NEO-60 version. On the other hand, convergent correlations with the NEO-PI-R dimensions were satisfactory irrespective of the version, and confirmatory factor analyses show slight differences among the different models generated after the three short versions.

High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

OBJECTIVE-We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.RESEARCH DESIGN AND METHODS-Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Testa scanner and correlated with the corresponding (immuno)histological sections.RESULTS-In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of beta-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.CONCLUSIONS-Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo. Diabetes 60:2853-2860, 2011

Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR) and reverse transcriptase (RT) inhibitors may display impaired infectivity and replication capacity. The individual contributions of mutated HIV-1 PR and RT to infectivity, replication, RT activity, and protein maturation (herein referred to as "fitness") in recombinant viruses were investigated by separately cloning PR, RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild-type NL4-3 background. Both mutant PR and RT contributed to measurable deficits in fitness of viral constructs. In peripheral blood mononuclear cells, replication rates (means +/- standard deviations) of RT recombinants were 72.5% +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3 replication rates. Cloning of the cognate RT improved fitness of some PR mutant clones. For a multidrug-resistant virus transmitted through sexual contact, RT constructs displayed a marked infectivity and replication deficit and diminished packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%, and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a decreased-fitness phenotype. Despite the identified impairment of recombinant clones, fitness of two of the three drug-resistant isolates was comparable to that of wild-type, susceptible viruses, suggestive of extensive compensation by genomic regions away from PR and RT. Only limited reversion of mutated positions to wild-type amino acids was observed for the native isolates over 100 viral replication cycles in the absence of drug selective pressure. These data underscore the complex relationship between PR and RT adaptive changes and viral evolution in antiretroviral drug-resistant HIV-1.

Long-Lasting Protection of Activity of Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors (PIs) by Boosted PI Containing Regimens.

BACKGROUND: The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments. METHODS: We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3-6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression. RESULTS: Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3-6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3-6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1-42.8), p<0.001). CONCLUSIONS: The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.

The 16PF5 and the NEO-PI-R in Spanish and Swiss samples: A cross-cultural comparison

This study compared the Spanish (Castilian) and French versions of the 16PF5 and of the NEO-PI-R in Spanish and Swiss samples. The five-factor solution for the 16PF5 only seems clear for the Castilian version, but not for the French version. Indeed, the congruence coefficients for the Tough-Mindedness and the Self-Control dimensions are low. On the other hand, the five-factor solutions are highly similar for both countries concerning the NEO-PI-R, and the congruence coefficients are above .95 for all five dimensions. The low cross-cultural replicability for the 16PF5 makes it difficult to analyze the differences at the mean level for this inventory. For the NEO-PI-R, the differences are generally very small and globally account for 2.6% of the total variance. Spaniards seem to have slightly lower scores on Actions and slightly higher scores on Dutifulness. These differences could either be due to translation problems, sample selection, or cultural differences.

Individual reproductive success and effective population size in the greater white-toothed shrew Crocidura russula.

In order to investigate the determinants of effective population size in the socially monogamous Crocidura russula, the reproductive output of 44 individuals was estimated through genetic assignment methods. The individual variance in breeding success turned out to be surprisingly high, mostly because the males were markedly less monogamous than expected from previous behavioural data. Males paired simultaneously with up to four females and polygynous males had significantly more offspring than monogamous ones. The variance in female reproductive success also exceeded that of a Poisson distribution (though to a lesser extent), partly because females paired with multiply mated males weaned significantly more offspring. Polyandry also occurred occasionally, but only sequentially (i.e. without multiple paternity of litters). Estimates of the effective to census size ratio were ca. 0.60, which excluded the mating system as a potential explanation for the high genetic variance found in this shrew's populations. Our data suggest that gene flow from the neighbourhood (up to one-third of the total recruitment) is the most likely cause of the high levels of genetic diversity observed in this shrew's subpopulations.

Intra-individual stability of neuromotor tasks from 6 to 18 years: a longitudinal study.

This study investigates the intra-individual stability of the speed of several motor tasks and the intensity of associated movements in 256 children (131 girls, 125 boys) from the Zurich generational study using the Zurich neuromotor assessment battery (ZNA) over a 12-year period from the age of 6 to 18 years. The stability was assessed by correlograms of standard deviation scores calculated from age- and gender-adjusted normative values and compared with standing height and full scale intelligence quotient (IQ). While motor tasks of hand, finger and foot (HFT) and contralateral associated movements (CAM) exhibited a moderate stability (summary measure as correlation coefficients between two measurements made 4 years apart: .61 and .60), other tasks (dynamic balance, static balance and pegboard) were only weakly stable (.46, .47 and .49). IQ and height were more stable than neuromotor components (.72 and .86). We conclude that the moderately stable HFT and CAM may reflect "motor traits", while the stability of the pegboard and balance tasks is weaker because these skills are more experience related and state-dependent.

Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.

Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes. The present study used a double-blind crossover design to compare the effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on several skills required for safe driving. Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas chromatography-mass spectrometry-negative ion chemical ionization. Compared to smoking studies, relatively low concentrations were measured in blood. The highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL) 2.5-5.5 h after intake. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, (e.g., driving a friend to a party). Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction. Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the molar ratio of main active to inactive cannabinoids, greater than 10 was found to correlate with a strong feeling of intoxication. It also matched with a significant decrease in the willingness to drive, and it matched also with a significant impairment in tracking performances. The mathematic model II proposed by Huestis et al. (1992) provided at best a rough estimate of the time of oral administration with 27% of actual values being out of range of the 95% confidence interval. The sum of THC and 11-OH-THC blood concentrations provided a better estimate of impairment than THC alone. This controlled clinical study points out the negative influence on fitness to drive after medium or high dose oral THC or dronabinol.

Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries.

BACKGROUND: Among the many definitions of frailty, the frailty phenotype defined by Fried et al. is one of few constructs that has been repeatedly validated: first in the Cardiovascular Health Study (CHS) and subsequently in other large cohorts in the North America. In Europe, the Survey of Health, Aging and Retirement in Europe (SHARE) is a gold mine of individual, economic and health information that can provide insight into better understanding of frailty across diverse population settings. A recent adaptation of the original five CHS-frailty criteria was proposed to make use of SHARE data and measure frailty in the European population. To test the validity of the SHARE operationalized frailty phenotype, this study aims to evaluate its prospective association with adverse health outcomes. METHODS: Data are from 11,015 community-dwelling men and women aged 60+ participating in wave 1 and 2 of the Survey of Health, Aging and Retirement in Europe, a population-based survey. Multivariate logistic regression analyses were used to assess the 2-year follow up effect of SHARE-operationalized frailty phenotype on the incidence of disability (disability-free at baseline) and on worsening disability and morbidity, adjusting for age, sex, income and baseline morbidity and disability. RESULTS: At 2-year follow up, frail individuals were at increased risk for: developing mobility (OR 3.07, 95% CI, 1.02-9.36), IADL (OR 5.52, 95% CI, 3.76-8.10) and BADL (OR 5.13, 95% CI, 3.53-7.44) disability; worsening mobility (OR 2.94, 95% CI, 2.19- 3.93) IADL (OR 4.43, 95% CI, 3.19-6.15) and BADL disability (OR 4.53, 95% CI, 3.14-6.54); and worsening morbidity (OR 1.77, 95% CI, 1.35-2.32). These associations were significant even among the prefrail, but with a lower magnitude of effect. CONCLUSIONS: The SHARE-operationalized frailty phenotype is significantly associated with all tested health outcomes independent of baseline morbidity and disability in community-dwelling men and women aged 60 and older living in Europe. The robustness of results validate the use of this phenotype in the SHARE survey for future research on frailty in Europe.

Global surveillance of cancer survival 1995-2009 : analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data.

BACKGROUND: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. METHODS: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. FINDINGS: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). INTERPRETATION: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. FUNDING: Bill & Melinda Gates Foundation.

Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis.

UNLABELLED: The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. INTRODUCTION: The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. METHODS: In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. RESULTS: Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS (p < 0.001). The predictive value of QUS was the same for men and women and for all ages (p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time (p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). CONCLUSIONS: Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values.