Anything to Stay Alive: The Challenges of a Campaign for an Experimental Drug

Drug‐resistant tuberculosis (TB) has a high mortality rate. Most medicines used to treat it are poorly tested and have terrible side effects. Activists have campaigned for patients with drug‐resistant TB to have access to experimental drugs, particularly one called bedaquiline, before these have been approved by regulatory authorities such as the Food and Drug Administration (FDA) in the United States (US) and the Medicines Control Council (MCC) in South Africa. Some activists have also campaigned for bedaquiline to be approved by regulatory authorities before testing of the drug is completed. These campaigns raise ethical concerns about whether patients should be offered experimental, unapproved, medicines for the treatment of life‐threatening illnesses, and if authorities should approve drugs for life‐threatening illnesses when vital questions about safety and efficacy remain outstanding.     

Improving the Quality of Host Country Ethical Oversight of International Research: The Use of a Collaborative ‘Pre‐Review’ Mechanism for a Study of Fexinidazole for Human African Trypanosomiasis

Developing countries face numerous barriers to conducting effective and efficient ethics reviews of international collaborative research. In addition to potentially overlooking important scientific and ethical considerations, inadequate or insufficiently trained ethics committees may insist on unwarranted changes to protocols that can impair a study's scientific or ethical validity. Moreover, poorly functioning review systems can impose substantial delays on the commencement of research, which needlessly undermine the development of new interventions for urgent medical needs. In response to these concerns, the Drugs for Neglected Diseases Initiative (DNDi), an independent nonprofit organization founded by a coalition of public sector and international organizations, developed a mechanism to facilitate more effective and efficient host country ethics review for a study of the use of fexinidazole for the treatment of late stage African Trypanosomiasis (HAT). The project involved the implementation of a novel ‘pre‐review’ process of ethical oversight, conducted by an ad hoc committee of ethics committee representatives from African and European countries, in collaboration with internationally recognized scientific experts. This article examines the process and outcomes of this collaborative process.     

Projected climate impacts to South African maize and wheat production in 2055: a comparison of empirical and mechanistic modeling approaches

Crop model‐specific biases are a key uncertainty affecting our understanding of climate change impacts to agriculture. There is increasing research focus on intermodel variation, but comparisons between mechanistic (MMs) and empirical models (EMs) are rare despite both being used widely in this field. We combined MMs and EMs to project future (2055) changes in the potential distribution (suitability) and productivity of maize and spring wheat in South Africa under 18 downscaled climate scenarios (9 models run under 2 emissions scenarios). EMs projected larger yield losses or smaller gains than MMs. The EMs’ median‐projected maize and wheat yield changes were ?3.6% and 6.2%, respectively, compared to 6.5% and 15.2% for the MM. The EM projected a 10% reduction in the potential maize growing area, where the MM projected a 9% gain. Both models showed increases in the potential spring wheat production region (EM = 48%, MM = 20%), but these results were more equivocal because both models (particularly the EM) substantially overestimated the extent of current suitability. The substantial water‐use efficiency gains simulated by the MMs under elevated CO₂ accounted for much of the EM?MM difference, but EMs may have more accurately represented crop temperature sensitivities. Our results align with earlier studies showing that EMs may show larger climate change losses than MMs. Crop forecasting efforts should expand to include EM?MM comparisons to provide a fuller picture of crop–climate response uncertainties.     

Shore‐based observations of seasonality,movements, and group behavior of southern right whales in a nonnursery area on the South African west coast

The southern right whale's (Eubalaena australis) demography, occurrence, habitat use, and behavior off South Africa are known predominantly from an ongoing aerial survey data set that started in 1971. The fixed timeframes of these surveys and their geographical bias towards south coast nursery areas have constrained our knowledge about the right whale's seasonal distribution elsewhere. We present shore‐based observations and tracking of right whales at Saldanha Bay on the west coast (2001–2003) that reveal a near year‐round presence and strongly nearshore distribution. With seasonal progression from winter to summer we observed a gradual increase in sighting rate, reduction in swimming speed, less directionality of movement, an increase in group size, and more surface active groups. The area appears to be important for feeding and socializing but not as a calving or nursery area. Individual transits between the south and west coasts, bidirectional alongshore movements, and extended seasonal presence may all be indicative of reoccupation of their former range along the west coast. This is important given the increasing ship traffic at Saldanha Bay, the rapid expansion of the region's oil and gas industry, and the known vulnerability of the closely related North Atlantic right whale (E. glacialis) to ship strikes.     

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.     

The easy road to genome‐wide medium density SNP screening in a non‐model species: development and application of a 10 K SNP‐chip for the house sparrow (Passer domesticus)

With the advent of next generation sequencing, new avenues have opened to study genomics in wild populations of non‐model species. Here, we describe a successful approach to a genome‐wide medium density Single Nucleotide Polymorphism (SNP) panel in a non‐model species, the house sparrow (Passer domesticus), through the development of a 10 K Illumina iSelect HD BeadChip. Genomic DNA and cDNA derived from six individuals were sequenced on a 454 GS FLX system and generated a total of 1.2 million sequences, in which SNPs were detected. As no reference genome exists for the house sparrow, we used the zebra finch (Taeniopygia guttata) reference genome to determine the most likely position of each SNP. The 10 000 SNPs on the SNP‐chip were selected to be distributed evenly across 31 chromosomes, giving on average one SNP per 100 000 bp. The SNP‐chip was screened across 1968 individual house sparrows from four island populations. Of the original 10 000 SNPs, 7413 were found to be variable, and 99% of these SNPs were successfully called in at least 93% of all individuals. We used the SNP‐chip to demonstrate the ability of such genome‐wide marker data to detect population sub‐division, and compared these results to similar analyses using microsatellites. The SNP‐chip will be used to map Quantitative Trait Loci (QTL) for fitness‐related phenotypic traits in natural populations.     

The response of life‐history traits to a new species in the community: a story of Drosophila parasitoids from the Rhône and Saône valleys

In the present study, we investigated the evolution of life‐history traits in the main species of a community, after the arrival of a new competitor. Two parasitoid species, Leptopilina heterotoma and Asobara tabida, are present throughout the Rhône and Saône valleys, whereas a third species, Leptopilina boulardi, is slowly extending its distribution northwards. In the presence of L. boulardi, competing parasitoids experience a higher mortality and lower host availability. Resources should thus be re‐allocated between traits according to these new factors. We compared life‐history traits of populations of L. heterotoma and A. tabida in areas with and without L. boulardi. As predicted by both Price's balanced mortality hypothesis and the theory of life‐history traits, we found that investment in reproduction is higher in southern populations for both native species, coupled with higher travelling abilities. However, only A. tabida paid their higher fecundity by a lower longevity. The absence of a clear trade‐off between these traits in L. heterotoma may be explained by a lower metabolic rate in southern populations. These results highlight the importance of the community change over climate in the evolution of life‐history traits in this parasitoid community. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ?? , ??–??.     

The influence of feeding on the evolution of sensory signals: a comparative test of an evolutionary trade‐off between masticatory and sensory functions of skulls in southern African Horseshoe bats (Rhinolophidae)

The skulls of animals have to perform many functions. Optimization for one function may mean another function is less optimized, resulting in evolutionary trade‐offs. Here, we investigate whether a trade‐off exists between the masticatory and sensory functions of animal skulls using echolocating bats as model species. Several species of rhinolophid bats deviate from the allometric relationship between body size and echolocation frequency. Such deviation may be the result of selection for increased bite force, resulting in a decrease in snout length which could in turn lead to higher echolocation frequencies. If so, there should be a positive relationship between bite force and echolocation frequency. We investigated this relationship in several species of southern African rhinolophids using phylogenetically informed analyses of the allometry of their bite force and echolocation frequency and of the three‐dimensional shape of their skulls. As predicted, echolocation frequency was positively correlated with bite force, suggesting that its evolution is influenced by a trade‐off between the masticatory and sensory functions of the skull. In support of this, variation in skull shape was explained by both echolocation frequency (80%) and bite force (20%). Furthermore, it appears that selection has acted on the nasal capsules, which have a frequency‐specific impedance matching function during vocalization. There was a negative correlation between echolocation frequency and capsule volume across species. Optimization of the masticatory function of the skull may have been achieved through changes in the shape of the mandible and associated musculature, elements not considered in this study.