Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that ...urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
Two novel Ru(II)-Rh(III) polypyridine dyads, containing carboxylic functions at the Rh(III) unit, RhIII(dcb)2-(BL)-RuII(dmp)2 and RhIII(dcb)2-(BL)-RuII(bpy)2 (bpy = 2,2‘-bipyridine; dcb = ...4,4‘-dicarboxy-2,2‘-bipyridine; dmp = 4,7-dimethyl-1,10-phenanthroline; BL = 1,2-bis4-(4‘-methyl-2,2‘-bipyridyl)ethane), have been synthesized. Their photophysical behavior in solution, compared with that of the mononuclear RuII(dcb)2(dmb) model (dmb = 4,4‘-dimethyl-2,2‘-bipyridine), indicates the occurrence of fast (108−109 s-1) and efficient (>95%) Rh(III)-*Ru(II) → Rh(II)-Ru(III) photoinduced electron transfer. These species adsorb firmly on nanoporous TiO2 films, via the dcb ligands of the Rh(III) units. The behavior of the adsorbed species has been studied by means of nanosecond time-resolved emission and absorption measurements, as well as by photocurrent measurements. Photocurrent action spectra demonstrate that light absorption by the Ru(II) chromophore leads to electron injection into the semiconductor. A detailed analysis of the transient behavior of the TiO2-RhIII(dcb)2-(BL)-RuII(bpy)2 system indicates that about one-third of the adsorbed dyads (probably because of different orientation at the surface or accidental contacts in small cavities) undergo direct electron injection from the excited state of the Ru(II) chromophore. The remaining dyads display stepwise charge injection processes, i.e., intramolecular electron transfer, TiO2-Rh(III)-*Ru(II) → TiO2-Rh(II)-Ru(III), followed by charge separation by electron injection,TiO2-Rh(II)-Ru(III) → TiO2(e-)-Rh(III)-Ru(III). The first process has comparable rates and efficiencies as for the free dyads in solution. The second step is 40% efficient, because of competing primary recombination, TiO2-Rh(II)-Ru(III) → TiO2-Rh(III)-Ru(II). When the final recombination between injected electrons and oxidized Ru(III) centers is studied, a remarkable slowing down is obtained for the supramolecular systems, e.g., TiO2-RhIII(dcb)2-(BL)-RuII(bpy)2, relative to analogous systems containing simple mononuclear sensitizers, e.g., TiO2-RuII(dcb)2(dmb). Stepwise charge separation and slow recombination between remote sites are distinctive features that suggest the labeling of these systems as “heterotriads”.
^sup 18^F-Fluoroethylcholine (^sup 18^F-FECh) is excreted via the urinary system with high activity accumulation in the urinary bladder. Furosemide and oral hydration can be administered ...concomitantly to reduce urinary activity to provide better detectability of retroperitoneal and pelvic lesions. Currently it is unknown if there is any effect of furosemide on ^sup 18^F-FECh uptake in organs, tissues and tumour lesions and the extent to which image quality along the urinary tract may be improved by furosemide. We retrospectively analysed 217 ^sup 18^F-FECh PET/CT examinations from 213 patients with known prostate cancer (PCa), performed either with oral hydration (109) or furosemide 20 mg together with oral hydration (108). Maximum ^sup 18^F-FECh uptake in different organs, tissues, lymph nodes and osseous metastases was quantified in terms of standardized uptake value (SUV) in a volume of interest and compared between the two groups. To characterize the impact of furosemide on lesion detectability a three-point rating scale was used to assess the presence of focal activity spots in the ureters and of perivesicular artefacts. Patient characteristics and distribution of tumour lesions were well balanced between the two groups. Overall, SUVmax values from normal organs were increased after furosemide compared to the values in patients scanned without furosemide. Significant changes were observed in the salivary glands, liver, spleen, pancreas, kidneys, gluteus muscle and perirenal fat. SUVmax values were significantly decreased after furosemide in lymph node metastases (SUVmax 4.81±2.68 vs. 6.48±4.22, p=0.0006), but not in osseous metastases. Evaluation of image quality along the urinary tract revealed significantly better depiction of the perivesicular space and significantly less focal tracer accumulation in the ureters in patients receiving furosemide, but the number of detected lymph nodes was not significantly different. Furosemide administration reduced choline uptake in tumour lesions, especially significant in pelvic lymph node metastases. Although furosemide administration improved image quality, optimal image quality may also be obtained by adequate hydration without the risk of diminishing choline uptake in PCa lesions. Therefore a controlled hydration protocol seems more appropriate than administration of furosemide.PUBLICATION ABSTRACT
Decisions to stop randomized trials are often based on traditional P value thresholds and are often unconvincing to clinicians. To familiarize clinical investigators with the application and ...advantages of Bayesian monitoring methods, we illustrate the steps of Bayesian interim analysis using a recent major trial that was stopped based on frequentist analysis of safety and futility.
We conducted Bayesian reanalysis of a factorial trial in newborn infants with hypoxic-ischemic encephalopathy that was designed to investigate whether outcomes would be improved by deeper (32 °C) or longer cooling (120 h), as compared with those achieved by standard whole body cooling (33.5 °C for 72 h). Using prior trial data, we developed neutral and enthusiastic prior probabilities for the effect on predischarge mortality, defined stopping guidelines for a clinically meaningful effect, and derived posterior probabilities for predischarge mortality.
Bayesian relative risk estimates for predischarge mortality were closer to 1.0 than were frequentist estimates. Posterior probabilities suggested increased predischarge mortality (relative risk > 1.0) for the three intervention groups; two crossed the Bayesian futility threshold.
Bayesian analysis incorporating previous trial results and different pre-existing opinions can help interpret accruing data and facilitate informed stopping decisions that are likely to be meaningful and convincing to clinicians, meta-analysts, and guideline developers.
ClinicalTrials.gov NCT01192776 . Registered on 31 August 2010.
PURPOSEThe exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68Ga-HBED-CC-PSMA PET/CT with ...multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material.METHODOLOGYSeven patients with histopathologically proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion.RESULTSPSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max).CONCLUSIONIn a slice by slice analysis with histopathology, 68Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.
Rationale
Methamphetamine (MA) is an addictive psychostimulant associated with neurocognitive impairment, including inhibitory deficits characterized by a reduced ability to control responses to ...stimuli. While various domains of inhibition such as exaggerated novelty seeking and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar models have not been utilized in human substance abusers. We recently developed a cross-species translational human open-field paradigm, the human behavior pattern monitor (hBPM), consisting of an unfamiliar room containing novel and engaging objects. Previous work demonstrated that manic bipolar subjects exhibit a disinhibited pattern of behavior in the hBPM characterized by increased object interactions.
Objectives
In the current study, we examined the effect of MA dependence on inhibitory deficits using this paradigm. hBPM activity and object interactions were quantified in 16 abstinent MA-dependent individuals and 18 matched drug-free comparison subjects. The Wisconsin card sorting task (WCST) and the positive and negative syndrome scale (PANSS) were administered to assess executive function and psychopathology.
Results
MA-dependent participants exhibited a significant increase in total object interactions, time spent with objects, and perseverative object interactions relative to comparison subjects. Greater object interaction was associated with impaired performance on the WCST, higher PANSS scores, and more frequent MA use in the past year.
Conclusions
Abstinent MA-dependent individuals exhibited impaired inhibition in the hBPM, displaying increased interaction with novel stimuli. Utilization of this measure may enable assessment of inhibitory deficits relevant to drug-seeking behavior and facilitate development of intervention methods to reduce high-risk conduct in this population.
To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and ...virologic outcomes.
Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration.
HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the "intention-to-treat" effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates.
A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: -0.7%, 0.8%) and the AIDS-free survival difference was -0.3% (-1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens.
Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival.
The magnitude of genetic and environmental factors and the influence of contrast effects on attention-deficit hyperactivity disorder (ADHD) symptomatology were examined on a sample of 900 twin pairs, ...aged 7-13, participating in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). In addition, the genetic and environmental correlations between ADHD and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatology were estimated. A series of structural models was applied to maternal ratings from a telephone survey, designed to screen for the three dimensions of ADHD symptomatology (hyperactivity, impulsivity, and inattention) and ODD/CD symptomatology. Model-fitting results suggested that ADHD symptomatology is highly heritable and influenced mostly by additive genetic, specific environmental, and contrast effects. However, this analysis could not exclude with statistical significance additional effects from dominance. The results of the best-fitting bivariate model suggested that the genetic correlation between the two traits is 50% and replicated previous findings of a common genetic factor influencing the comorbidity of ADHD and ODD/CD symptomatologies.
Despite the availability of highly effective vaccines, Bordetella pertussis incidence has been rapidly rising in highly vaccinated populations. Recent outbreaks have received media attention, feeding ...concerns about the emergence of dangerous new strains with increased virulence or that escape vaccine-induced immunity. To accelerate the study of this reemerging pathogen, we sequenced the genomes of 28 B. pertussis strains isolated during outbreaks from 2010 through 2012, making both strains and sequence data available to the scientific community.
PDF
