A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity

A teleofunctional account of evolutionary mismatch.

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10539-016-9527-1When the environment in which an organism lives deviates in some essential way from that to which it is adapted, this is described as "evolutionary mismatch," or "evolutionary novelty." The notion of mismatch plays an important role, explicitly or implicitly, in evolution-informed cognitive psychology, clinical psychology, and medicine. The evolutionary novelty of our contemporary environment is thought to have significant implications for our health and well-being. However, scientists have generally been working without a clear definition of mismatch. This paper defines mismatch as deviations in the environment that render biological traits unable, or impaired in their ability, to produce their selected effects (i.e., to perform their proper functions in Neander's sense). The machinery developed by Millikan in connection with her account of proper function, and with her related teleosemantic account of representation, is used to identify four major types, and several subtypes, of evolutionary mismatch. While the taxonomy offered here does not in itself resolve any scientific debates, the hope is that it can be used to better formulate empirical hypotheses concerning the effects of mismatch. To illustrate, it is used to show that the controversial hypothesis that general intelligence evolved as an adaptation to handle evolutionary novelty can, contra some critics, be formulated in a conceptually coherent way

Evaluation of a multifaceted "Resident-as-Teacher" educational intervention to improve morning report

BACKGROUND: Resident-led morning report is an integral part of most residency programs and is ranked among the most valuable of educational experiences. The objectives of this study were to evaluate the effect of a resident-as-teacher educational intervention on the educational and teaching experience of morning report. METHODS: All senior internal medicine residents were invited to participate in this study as teaching participants. All internal medicine residents and clerks were invited to participate as audience participants. The educational intervention included reading material, a small group session and feedback after teaching sessions. The educational and teaching experiences were rated prior to and three months after the intervention using questionnaires. RESULTS: Forty-six audience participants and 18 teaching participants completed the questionnaires. The degree to which morning report met the educational needs of the audience was higher after the educational intervention (effect size, d = 0.26, p = 0.01). The perceptions of the audience were that delivery had improved and that the sessions were less intimidating and more interactive. The perception of the teaching participants was that delivery was less stressful, but this group now reported greater difficulty in engaging the audience and less confidence in their medical knowledge. CONCLUSION: Following the educational intervention the audience's perception was that the educational experience had improved although there were mixed results for the teaching experience. When evaluating such interventions it is important to evaluate the impact on both the educational and teaching experiences as results may differ

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Cost-effectiveness of problem-solving treatment in comparison with usual care for primary care patients with menthal health problems: a randomized trial

BACKGROUND: Mental health problems are common and are associated with increased disability and health care costs. Problem-Solving Treatment (PST) delivered to these patients by nurses in primary care might be efficient. The aim of this study was to evaluate the cost-effectiveness of PST by mental health nurses compared with usual care (UC) by the general practitioner for primary care patients with mental health problems. METHODS: An economic evaluation from a societal perspective was performed alongside a randomized clinical trial. Patients with a positive General Health Questionnaire score (score ≥ 4) and who visited their general practitioner at least three times during the past 6 months were eligible. Outcome measures were improvement on the Hospital Anxiety and Depression Scale and QALYs based on the EQ-5D. Resource use was measured using a validated questionnaire. Missing cost and effect data were imputed using multiple imputation techniques. Bootstrapping was used to analyze costs and cost-effectiveness of PST compared with UC. RESULTS: There were no statistically significant differences in clinical outcomes at 9 months. Mean total costs were €4795 in the PST group and €6857 in the UC group. Costs were not statistically significantly different between the two groups (95% CI -4698;359). The cost-effectiveness analysis showed that PST was cost-effective in comparison with UC. Sensitivity analyses confirmed these findings. CONCLUSIONS: PST delivered by nurses seems cost-effective in comparison with UC. However, these results should be interpreted with caution, since the difference in total costs was mainly caused by 3 outliers with extremely high indirect costs in the UC group. TRIAL REGISTRATION: Nederlands Trial Register ISRCTN5102101

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role ofpecific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, β-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case–control study in Greece. Eight hundrednd twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collectedhrough a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment forotal energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Amongost-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Amongremenopausal women, β-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but afterutual adjustment among the three nutrients only β-carotene remained significant; the odds ratio (OR) for a one-quintilencrease in β-carotene intake was 0.84 (95% confidence interval 0.73–0.97). The inverse association observed with β-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data,aising the possibility that the observed β-carotene effect is accounted for by another component of vegetables. ©1999 Cancer Research Campaig