The experimental evolution of laboratory populations of microbes provides an opportunity to observe the evolutionary dynamics of adaptation in real time. Until very recently, however, such studies have been limited by our inability to systematically find mutations in evolved organisms. We overcome this limitation by using a variety of DNA microarray-based techniques to characterize genetic changes—including point mutations, structural changes, and insertion variation—that resulted from the experimental adaptation of 24 haploid and diploid cultures of Saccharomyces cerevisiae to growth in either glucose, sulfate, or phosphate-limited chemostats for ∼200 generations. We identified frequent genomic amplifications and rearrangements as well as novel retrotransposition events associated with adaptation. Global nucleotide variation detection in ten clonal isolates identified 32 point mutations. On the basis of mutation frequencies, we infer that these mutations and the subsequent dynamics of adaptation are determined by the batch phase of growth prior to initiation of the continuous phase in the chemostat. We relate these genotypic changes to phenotypic outcomes, namely global patterns of gene expression, and to increases in fitness by 5–50%. We found that the spectrum of available mutations in glucose- or phosphate-limited environments combined with the batch phase population dynamics early in our experiments allowed several distinct genotypic and phenotypic evolutionary pathways in response to these nutrient limitations. By contrast, sulfate-limited populations were much more constrained in both genotypic and phenotypic outcomes. Thus, the reproducibility of evolution varies with specific selective pressures, reflecting the constraints inherent in the system-level organization of metabolic processes in the cell. We were able to relate some of the observed adaptive mutations (e.g., transporter gene amplifications) to known features of the relevant metabolic pathways, but many of the mutations pointed to genes not previously associated with the relevant physiology. Thus, in addition to answering basic mechanistic questions about evolutionary mechanisms, our work suggests that experimental evolution can also shed light on the function and regulation of individual metabolic pathways.

Anemia is associated with shorter survival times for patients with lung carcinoma, cervicouterine carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma, and multiple myeloma.

BackgroundThere is a lack of consistency in findings across studies on the prevalence of schizophrenia, and no recent systematic review of the literature exists. The purpose of this study is to provide an updated systematic review of population-based prevalence estimates and to understand the factors that could account for this variation in prevalence estimates.MethodsMEDLINE, Embase, and PsycInfo databases were searched for observational studies describing schizophrenia prevalence in general populations from 2003–2013 and supplemented by studies from a prior review covering 1990–2002. Studies reporting prevalence estimates from specialized populations such as institutionalized, homeless, or incarcerated persons were excluded. Prevalence estimates were compared both across and within studies by factors that might contribute to variability using descriptive statistics.ResultsSixty-five primary studies were included; thirty-one (48 %) were from Europe and 35 (54 %) were conducted in samples of ≥50,000 persons. Among 21 studies reporting 12-month prevalence, the median estimate was 0.33 % with an interquartile range (IQR) of 0.26 %–0.51 %. The median estimate of lifetime prevalence among 29 studies was 0.48 % (IQR: 0.34 %–0.85 %). Prevalence across studies appeared to vary by study design, geographic region, time of assessment, and study quality scores; associations between study sample size and prevalence were not observed. Within studies, age-adjusted estimates were higher than crude estimates by 17 %–138 %, the use of a broader definition of schizophrenia spectrum disorders compared to schizophrenia increased case identification by 18 %–90 %, identification of cases from inpatient-only settings versus any setting decreased prevalence by 60 %, and no consistent trends were noted by differing diagnostic criteria.ConclusionsThis review provides updated information on the epidemiology of schizophrenia in general populations, which is vital information for many stakeholders. Study characteristics appear to play an important role in the variation between estimates. Overall, the evidence is still sparse; for many countries no new studies were identified.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0578-7) contains supplementary material, which is available to authorized users.

OBJECTIVE -To model the lifetime costs associated with complications of type 2 diabetes. RESEARCH DESIGN AND METHODS-A cohort of 10,000 patients with diabetes was simulated using a model based on existing epidemiological studies. Complication rates were estimated for various stages of macrovascular disease, nephropathy, retinopathy, neuropathy, and hypoglycemia. At the beginning of the simulation, patients were assumed to have been treated for 5 years and have a mean HbA 1c of 8.4. From the U.K. Prospective Diabetes Study, it was estimated that on current therapies, the HbA 1c would drift upward on average 0.15% per year. Direct medical costs of managing each complication were estimated (in 2000 U.S. dollars) from all-payor databases, surveys, and literature.RESULTS -Macrovascular disease was estimated to be the largest cost component, accounting for 85% of cumulative costs of complications over the first 5 years. The costs of complications were estimated to be $47,240 per patient over 30 years, on average. The management of macrovascular disease is estimated to be the largest cost component, accounting for 52% of the costs; nephropathy accounts for 21%, neuropathy accounts for 17%, and retinopathy accounts for 10% of the costs of complications.CONCLUSIONS -The complications of diabetes account for substantial costs, with management of macrovascular disease being the largest and earliest. If improving glycemic control prevents complications, it will reduce these costs. Diabetes Care 25:476 -481, 2002

Pancreatic volume is reduced by 26% in patients with type 1 diabetes within months of diagnosis, suggesting that atrophy begins years before the onset of clinical disease. Pancreatic atrophy within individuals is therefore a potential clinical marker of disease progression.