Plastic and evolutionary responses of cell size and number to larval malnutrition in Drosophila melanogaster.

Both development and evolution under chronic malnutrition lead to reduced adult size in Drosophila. We studied the contribution of changes in size vs. number of epidermal cells to plastic and evolutionary reduction of wing size in response to poor larval food. We used flies from six populations selected for tolerance to larval malnutrition and from six unselected control populations, raised either under standard conditions or under larval malnutrition. In the control populations, phenotypic plasticity of wing size was mediated by both cell size and cell number. In contrast, evolutionary change in wing size, which was only observed as a correlated response expressed on standard food, was mediated entirely by reduction in cell number. Plasticity of cell number had been lost in the selected populations, and cell number did not differ between the sexes despite males having smaller wings. Results of this and other experimental evolution studies are consistent with the hypothesis that alleles which increase body size through prolonged growth affect wing size mostly via cell number, whereas alleles which increase size through higher growth rate do so via cell size.

Sensitivity of genome-wide-association signals to phenotyping strategy: the PROP-TAS2R38 taste association as a benchmark.

Natural genetic variation can have a pronounced influence on human taste perception, which in turn may influence food preference and dietary choice. Genome-wide association studies represent a powerful tool to understand this influence. To help optimize the design of future genome-wide-association studies on human taste perception we have used the well-known TAS2R38-PROP association as a tool to determine the relative power and efficiency of different phenotyping and data-analysis strategies. The results show that the choice of both data collection and data processing schemes can have a very substantial impact on the power to detect genotypic variation that affects chemosensory perception. Based on these results we provide practical guidelines for the design of future GWAS studies on chemosensory phenotypes. Moreover, in addition to the TAS2R38 gene past studies have implicated a number of other genetic loci to affect taste sensitivity to PROP and the related bitter compound PTC. None of these other locations showed genome-wide significant associations in our study. To facilitate further, target-gene driven, studies on PROP taste perception we provide the genome-wide list of p-values for all SNPs genotyped in the current study.

Impact of a preemptive strategy after 3 months of valganciclovir cytomegalovirus prophylaxis in kidney transplant recipients.

BACKGROUND.: We assessed the impact of a preemptive strategy after discontinuation of antiviral prophylaxis in the prevention of late-onset cytomegalovirus (CMV) disease in a cohort of kidney transplant recipients. METHODS.: Patients undergoing kidney transplantation at the University Hospital of Lausanne (CHUV) between November 2003 and November 2007 were included if they were donor or recipient (D/R) seropositive for CMV. All patients received 3 months of prophylaxis with valganciclovir, followed by monitoring of CMV DNAemia by polymerase chain reaction (PCR) every 15 days during 3 additional months. Valganciclovir was restarted if CMV PCR was more than or equal to 10,000 copies/mL. The primary endpoint of the study was the incidence of late-onset CMV disease. RESULTS.: Eighty-six kidney transplant recipients were included; 30 patients were D+/R- and 56 patients were R+ for CMV. At 6 months posttransplant, CMV DNAemia had occurred in 31 of 86 (36%) patients: 13 of 30 (43%) in the D+/R- group and 18 of 56 (32%) in the R+ group (P=0.35). In the D+/R- group, among the 13 patients with CMV DNAemia, 7 (54%) patients developed late-onset CMV disease, simultaneously to the first positive viral load (n=5) or after detection of low-grade viremia (n=2). Only two patients received a preemptive treatment. In the R+ group, all positive PCR results were below the established cutoff. Thus, these 18 patients were not treated, and none of them developed late-onset CMV disease (R+ vs. D+/R-: P<0.001). CONCLUSIONS.: Within the limitations of a noncontrolled study, our data indicate that a preemptive strategy after 3 months of valganciclovir prophylaxis for CMV is not useful in R+ kidney transplant recipients. In D+/R- patients, this approach should be further evaluated.

Angiogenesehemmung in der Neuroonkologie. Eine vielversprechende Therapiestrategie gegen maligne Gliome [Angiogenesis inhibition in neurooncology. A very promising therapy strategy for malignant glioma]

The application of angiogenesis inhibitors in neurooncology is increasing. Initially, these drugs seemed to be very promising because of the surprisingly high neuroradiological response rates that were observed in first clinical trials. Meanwhile, this enthusiasm is waning, as the high response rates did not translate into substantial improvements in progression-free and overall survival. Tumor progression during or after antiangiogenic therapy is often associated with rapid clinical neurological deterioration and sometimes even with diffuse infiltrative gliomatosis-like neuroradiological phenotypes. Thus, the characterization and understanding of escape mechanisms are needed. The identification of criteria for defining the personalized use of angiogenesis inhibitors remains a challenge.

Hypoglycémie et traitement du diabète de type 2. Le retour à une normoglycémie n'est pas nécessairement la meilleure stratégie thérapeutique [Hypoglycemia and diabetes treatment: the return to normal glucose level is not always the best therapeutic strategy].

Recent clinical trials with type 2 diabetic patients and the quest of normal glyceamic values, have revealed difficulties and limitations. These too normal glyceamic targets corresponding to the physiological standards are associated with very high rate of hypoglycemia and an increase of mortality. A too simplistic view of treatment: "the lowest, the better is in the diabetes" is no longer defensible. The knowledge from complex systems behavior invites us to search targets adapted to a new state of equilibrium due to loss of self-regulation. These targets should not aim the physiological standards but to be adapted to patient's situation. Shared decision-making and consensus are the two pillars of this new strategy supported by the new ADA-EASD guidelines.

Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests in returning travellers and migrants: a retrospective study.

BACKGROUND: Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis and prompt treatment. Validation of their usefulness in travellers with fever was needed. The safety of a strategy to diagnose falciparum malaria based on RDT followed by immediate or delayed microscopy reading at first attendance was evaluated in one referral hospital in Switzerland. METHODS: A retrospective study was conducted in the outpatient clinic and emergency ward of University Hospital, covering a period of eight years (1999-2007). The study was conducted in the outpatient clinic and emergency ward of University Hospital. All adults suspected of malaria with a diagnostic test performed were included. RDT and microscopy as immediate tests were performed during working hours, and RDT as immediate test and delayed microscopy reading out of laboratory working hours. The main outcome measure was occurrence of specific complications in RDT negative and RDT positive adults. RESULTS: 2,139 patients were recruited. 1987 had both initial RDT and blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed uncomplicated malaria with both RDT and BS positive on day 1 and day 6 respectively. Among the 152 patients initially malaria positive, 137 had both RDT and BS positive, four only BS positive and five only RDT positive (PCR confirmed) (six had only one test performed). None of the four initially RDT negative/BS positive and none of the five initially BS negative/RDT positive developed severe malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a reduction of a median of 2.1 hours to get a first malaria test result. CONCLUSIONS: A malaria diagnostic strategy based on RDTs and a delayed BS is safe in non-immune populations, and shortens the time to first malaria test result.

An alternative socio-ecological strategy? International Trade Unions' engagement with climate change

In the context of a global ecological crisis, it is an important move when trade unions turn to environmentalism. Yet, the form that this environmentalism takes is often overlooked. This is especially the case with international trade unions. Based on an empirical study of international trade unions' engagement with the climate change issue, this article argues that international trade unions follow three different (and partially conflicting) strategies. I label these strategies as 'deliberative', 'collaborative growth' and 'socialist', and I examine each in turn. I argue that such analysis is important if we want to identify the potential for transforming the social relations of production that are at the root of the current climate crisis, and for identifying an alternative socio-ecological strategy.

Life-history consequences of adaptation to larval nutritional stress in Drosophila.

Many animal species face periods of chronic nutritional stress during which the individuals must continue to develop, grow, and/or reproduce despite low quantity or quality of food. Here, we use experimental evolution to study adaptation to such chronic nutritional stress in six replicate Drosophila melanogaster populations selected for the ability to survive and develop within a limited time on a very poor larval food. In unselected control populations, this poor food resulted in 20% lower egg-to-adult viability, 70% longer egg-to-adult development, and 50% lower adult body weight (compared to the standard food on which the flies were normally maintained). The evolutionary changes associated with adaptation to the poor food were assayed by comparing the selected and control lines in a common environment for different traits after 29-64 generations of selection. The selected populations evolved improved egg-to-adult viability and faster development on poor food. Even though the adult dry weight of selected flies when raised on the poor food was lower than that of controls, their average larval growth rate was higher. No differences in proportional pupal lipid content were observed. When raised on the standard food, the selected flies showed the same egg-to-adult viability and the same resistance to larval heat and cold shock as the controls and a slightly shorter developmental time. However, despite only 4% shorter development time, the adults of selected populations raised on the standard food were 13% smaller and showed 20% lower early-life fecundity than the controls, with no differences in life span. The selected flies also turned out less tolerant to adult malnutrition. Thus, fruit flies have the genetic potential to adapt to poor larval food, with no detectable loss of larval performance on the standard food. However, adaptation to larval nutritional stress is associated with trade-offs with adult fitness components, including adult tolerance to nutritional stress.