Travellers' malaria - 'one shoe does not fit all'

Travellers' malaria is an exciting topic. It is a field in flux with evolving options for chemoprophylaxis, self-diagnosis, self-treatment, risk/strategy analyses and surveillance. Ideologies vary and experts differ but debate is needed and can bring change. The launch of a new thematic series in the Malaria Journal -- " Travellers' malaria " -- creates an ideal forum to bring together research papers, reviews, opinion papers and commentaries, and will hopefully stimulate debate.     

Genetic Characterization of a Novel Rhizobial Plasmid Conjugation System in Rhizobium leguminosarum bv. viciae Strain VF39SM

Rhizobium leguminosarum strain VF39SM contains two plasmids that have previously been shown to be self-transmissible by conjugation. One of these plasmids, pRleVF39b, is shown in this study to carry a set of plasmid transfer genes that differs significantly from conjugation systems previously studied in the rhizobia but is similar to an uncharacterized set of genes found in R. leguminosarum bv. trifolii strain WSM2304. The entire sequence of the transfer region on pRleVF39b was determined as part of a genome sequencing project, and the roles of the various genes were examined by mutagenesis. The transfer region contains a complete set of mating pair formation (Mpf) genes, a traG gene, and a relaxase gene, traA, all of which appear to be necessary for plasmid transfer. Experimental evidence suggested the presence of two putative origins of transfer within the gene cluster. A regulatory gene, trbR, was identified in the region between traA and traG and was mutated. TrbR was shown to function as a repressor of both trb gene expression and plasmid transfer.     

Maritime Boundary Delimitation: United States Practice

China's recent claims to a large “U-shaped” area in the South China Sea, involving the disputed Spratly and Paracel Islands, has given rise to a number of serious criticisms not only from neighboring states, but also some states beyond the region. The claim also raises a number of theoretical questions, including whether historic title claims without hard evidence have validity under international law. This article explores this and other issues raised by China's U-shaped claim.     

The Irish DAFNE Study Protocol: A cluster randomised trial of group versus individual follow-up after structured education for Type 1 diabetes

Background

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.

Methods

We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.

Discussion

A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.     

Active sexual reproduction but no sign of genetic diversity in range-edge populations of Vanilla roscheri Rchb. f. (Orchidaceae) in South Africa

In South Africa, the wild leafless Vanilla roscheri Rchb. f. (Orchidaceae) is distributed only on the banks of the Lake Sibaya in KwaZulu-Natal Coastal Forest in the iSimangaliso Wetland Park. It is the southernmost vanilloid orchid on the African continent and a species of high conservation priority with little understanding of its reproductive biology and levels of genetic diversity. Mating systems and pollination ecology of the species were assessed by in situ experiments, in addition to genotyping plants at 16 microsatellite markers. Allogamous but self-compatible, V. roscheri depends on pollinators to achieve sexual reproduction. Its natural fruit set (26.3 %) is the highest reported for a non-spontaneously self-pollinating Vanilla species. It was associated with numerous flower visitors including two female allodapine bees (Allodapula variegata and Allodape rufogastra, Xylocopinae), captured with pollinia stored on the hind legs, and one female anthophorine bee. On the other hand, we report an absence of genetic diversity and homozygosity of the South-African populations of V. roscheri for all the genetic markers. Given the preferential outbreeding, the high natural fruit set and the pollinator/visitor richness of V. roscheri in Sibaya, a high level of genetic diversity was expected, but this was not the case. We detected a counterintuitive situation between the results of reproductive biology and genetics, making sense once the population situation on the margins of the species distribution is included. The null diversity expressed through the homozygous monomorphic markers is a consequence of the range-edge localization of the populations, which may have been subjected to severe bottlenecks (due to long distance colonization or fragmentation) along with inbreeding, in the past. The analysis highlights the complementarity of the approaches for which the implications in terms of conservation of the species in South Africa are discussed.     

Genes and generalizations: Darden's strategies and the question of context

In her recent book Lindley Darden has endeavored to reclaim for philosophy an active role in the elaboration of good science. She has done this, not by holding up some set of rational standards derived from outside of scientific practice, but rather by delving into the history of science and coming out with a set of scientific strategies. Unconcerned about whether any particular strategy wasin fact employed in a given historical case her project depends upon two claims, first that these strategiescould have been successfully deployed in the particular cases from which they were construed, and second and more importantly, that these strategies can be generalized beyond any particular context and be put to future use. It will be argued that Darden's conception of the possible context independence of scientific strategies is based upon an overly cognitivist misconstrual. An alternative account of the relationship of context dependent and context independent aspects of scientific theory formation will be offered as well as its implications for philosophy.     

Associations between Intimate Partner Violence and Termination of Pregnancy: A Systematic Review and Meta-Analysis

Background

Intimate partner violence (IPV) and termination of pregnancy (TOP) are global health concerns, but their interaction is undetermined. The aim of this study was to determine whether there is an association between IPV and TOP.

Methods and Findings

A systematic review based on a search of Medline, Embase, PsycINFO, and Ovid Maternity and Infant Care from each database''s inception to 21 September 2013 for peer-reviewed articles of any design and language found 74 studies regarding women who had undergone TOP and had experienced at least one domain (physical, sexual, or emotional) of IPV. Prevalence of IPV and association between IPV and TOP were meta-analysed. Sample sizes ranged from eight to 33,385 participants. Worldwide, rates of IPV in the preceding year in women undergoing TOP ranged from 2.5% to 30%. Lifetime prevalence by meta-analysis was shown to be 24.9% (95% CI 19.9% to 30.6%); heterogeneity was high (I ²>90%), and variation was not explained by study design, quality, or size, or country gross national income per capita. IPV, including history of rape, sexual assault, contraceptive sabotage, and coerced decision-making, was associated with TOP, and with repeat TOPs. By meta-analysis, partner not knowing about the TOP was shown to be significantly associated with IPV (pooled odds ratio 2.97, 95% CI 2.39 to 3.69). Women in violent relationships were more likely to have concealed the TOP from their partner than those who were not. Demographic factors including age, ethnicity, education, marital status, income, employment, and drug and alcohol use showed no strong or consistent mediating effect. Few long-term outcomes were studied. Women welcomed the opportunity to disclose IPV and be offered help. Limitations include study heterogeneity, potential underreporting of both IPV and TOP in primary data sources, and inherent difficulties in validation.

Conclusions

IPV is associated with TOP. Novel public health approaches are required to prevent IPV. TOP services provide an opportune health-based setting to design and test interventions. Please see later in the article for the Editors'' Summary     

Ethnography,Advocacy and Feminism: A Volatile Mix. A View from a Reading of Diane Bell's Ngarrindjeri Wurruwarrin

Ethnography may lie at the heart of anthropological methodology but its claims are contested. Feminist anthropologists in particular have debated the challenges a critical academic discipline poses for a consciously politicised positioning of the ethnographer, examining the constraints this might impose on the ethnographic project. Such dilemmas are compounded in the context of advocacy work. This critique of a feminist ethnography (Diane Bell's Ngarrindjeri Wurruwarrin), which emerged from advocacy work in a litigious Australian context, suggests that the truth demands of advocacy work sit uneasily with both the partiality of critical ethnography and the politics of the feminist project.     

An MRI-derived definition of MCI-to-AD conversion for long-term, automatic prognosis of MCI patients

Alzheimer''s disease (AD) and mild cognitive impairment (MCI) are of great current research interest. While there is no consensus on whether MCIs actually “convert” to AD, this concept is widely applied. Thus, the more important question is not whether MCIs convert, but what is the best such definition. We focus on automatic prognostication, nominally using only a baseline brain image, of whether an MCI will convert within a multi-year period following the initial clinical visit. This is not a traditional supervised learning problem since, in ADNI, there are no definitive labeled conversion examples. It is not unsupervised, either, since there are (labeled) ADs and Controls, as well as cognitive scores for MCIs. Prior works have defined MCI subclasses based on whether or not clinical scores significantly change from baseline. There are concerns with these definitions, however, since, e.g., most MCIs (and ADs) do not change from a baseline CDR = 0.5 at any subsequent visit in ADNI, even while physiological changes may be occurring. These works ignore rich phenotypical information in an MCI patient''s brain scan and labeled AD and Control examples, in defining conversion. We propose an innovative definition, wherein an MCI is a converter if any of the patient''s brain scans are classified “AD” by a Control-AD classifier. This definition bootstraps design of a second classifier, specifically trained to predict whether or not MCIs will convert. We thus predict whether an AD-Control classifier will predict that a patient has AD. Our results demonstrate that this definition leads not only to much higher prognostic accuracy than by-CDR conversion, but also to subpopulations more consistent with known AD biomarkers (including CSF markers). We also identify key prognostic brain region biomarkers.     

Linguistic Traces of a Scientific Fraud: The Case of Diederik Stapel

When scientists report false data, does their writing style reflect their deception? In this study, we investigated the linguistic patterns of fraudulent (N  =  24; 170,008 words) and genuine publications (N  =  25; 189,705 words) first-authored by social psychologist Diederik Stapel. The analysis revealed that Stapel''s fraudulent papers contained linguistic changes in science-related discourse dimensions, including more terms pertaining to methods, investigation, and certainty than his genuine papers. His writing style also matched patterns in other deceptive language, including fewer adjectives in fraudulent publications relative to genuine publications. Using differences in language dimensions we were able to classify Stapel''s publications with above chance accuracy. Beyond these discourse dimensions, Stapel included fewer co-authors when reporting fake data than genuine data, although other evidentiary claims (e.g., number of references and experiments) did not differ across the two article types. This research supports recent findings that language cues vary systematically with deception, and that deception can be revealed in fraudulent scientific discourse.     

Measuring the health of nations: analysis of mortality amenable to health care

Objective To assess whether and how the rankings of the world''s health systems based on disability adjusted life expectancy as done in the 2000 World Health Report change when using the narrower concept of mortality amenable to health care, an outcome more closely linked to health system performance.Design Analysis of mortality amenable to health care (including and excluding ischaemic heart disease).Main outcome measure Age standardised mortality from causes amenable to health careSetting 19 countries belonging to the Organisation for Economic Cooperation and Development.Results Rankings based on mortality amenable to health care (excluding ischaemic heart disease) differed substantially from rankings of health attainment given in the 2000 World Health Report. No country retained the same position. Rankings for southern European countries and Japan, which had performed well in the report, fell sharply, whereas those of the Nordic countries improved. Some middle ranking countries (United Kingdom, Netherlands) also fell considerably; New Zealand improved its position. Rankings changed when ischaemic heart disease was included as amenable to health care.Conclusion The 2000 World Health Report has been cited widely to support claims for the merits of otherwise different health systems. High levels of health attainment in well performing countries may be a consequence of good fortune in geography, and thus dietary habits, and success in the health effects of policies in other sectors. When assessed in terms of achievements that are more explicitly linked to health care, their performance may not be as good.     

Formal Darwinism

Two questions are raised for Grafen’s formal darwinism project of aligning evolutionary dynamics under natural selection with the optimization of phenotypes for individuals of a population. The first question concerns mean fitness maximization during frequency-dependent selection; in such selection regimes, not only is mean fitness typically not maximized but it is implausible that any parameter closely related to fitness is being maximized. The second question concerns whether natural selection on inclusive fitness differences can be regarded as individual selection or whether it leads to a departure from the central motivation that led to the formal darwinism project, viz., to show that “Darwinian” evolution through individual selection leads to “good design” or phenotypic adaptation through trait optimization.     

The Viscoelastic Properties of Passive Eye Muscle in Primates. II: Testing the Quasi-Linear Theory

We have extensively investigated the mechanical properties of passive eye muscles, in vivo, in anesthetized and paralyzed monkeys. The complexity inherent in rheological measurements makes it desirable to present the results in terms of a mathematical model. Because Fung''s quasi-linear viscoelastic (QLV) model has been particularly successful in capturing the viscoelastic properties of passive biological tissues, here we analyze this dataset within the framework of Fung''s theory.We found that the basic properties assumed under the QLV theory (separability and superposition) are not typical of passive eye muscles. We show that some recent extensions of Fung''s model can deal successfully with the lack of separability, but fail to reproduce the deviation from superposition.While appealing for their elegance, the QLV model and its descendants are not able to capture the complex mechanical properties of passive eye muscles. In particular, our measurements suggest that in a passive extraocular muscle the force does not depend on the entire length history, but to a great extent is only a function of the last elongation to which it has been subjected. It is currently unknown whether other passive biological tissues behave similarly.     

Breaking up fights between others: a model of intervention behaviour

To examine when and why animals break up fights between others in their group, I modelled whether ''winner'' and ''loser'' effects might be one element driving the evolution of intervention behaviour. I considered one particular type of intervention: when the intervener simply breaks up fights between two others, but does not favour either party in so doing. When victories at time T + 1 are more likely given a victory at time T (i.e. winner effects), intervention is often favoured. Intervention is favoured in these circumstances because the intervening party in essence stops others from ''getting on a roll'' and climbing up any hierarchy that exists. However, when loser effects alone are at work (defeats at time T + 1 are more likely given a defeat at time T), breaking up fights between others is never selected. If both winner and loser effects are operating simultaneously, then the likelihood of intervention behaviour evolving is a function of the relative strength of these two effects. The greater the winner effect relative to the loser effect, the more likely intervention behaviour is to evolve.     

The formal darwinism project in outline

The formal darwinism project aims to provide a mathematical framework within which important fundamental ideas in large parts of biology can be articulated, including Darwin's central argument in The Origin (that mechanical processes of inheritance and reproduction can give rise to the appearance of design), modern extensions of evolutionary theory including ESS theory and inclusive fitness, and Dawkins' synthesis of them into a single structure. A new kind of argument is required to link equations of motion on the one hand to optimisation programs on the other, and a major point is that the biologist's concept of fitness maximisation is not represented by concepts from dynamical systems such as Lyapunov functions and gradient functions. The progress of the project so far is reviewed, though with only a brief glance at the rather complicated mathematics itself, and the centrality of fitness maximisation ideas to many areas of biology is emphasised.     

Pollination biology of Canna indica (Cannaceae) with particular reference to the functional morphology of the style

The anatomy of the bizarre style of Canna indica is analyzed functionally and comparatively within Zingiberales, particularly in relation to the presence of two stigma-like areas, one apical and the other lateral and subapical. We asked whether these areas have separate receptive or adhesive functions and whether they are derived from a single stigma that previously had both functions. We expected that the mechanism of pollen transference would be highly effective at the flower level, i.e., that pollen limitation would affect fruit set rather than seed set. Both areas produce a sticky carbohydrate- and mucilage-positive exudate but only the apical one leads to pollen tube growth into the stylar canal. The subapical and lateral area is regarded here as being homologous to the viscidium of Lowiaceae and Marantaceae. High pollen limitation through fruit set is attributable to the low visitation rate of the single long-billed hummingbird pollinator (Heliomaster furcifer) and to pollen loss caused by nectar robbers, while low limitation through seed set suggests that the efficiency of a few visits of pollen-carrying hummingbirds is high. Recordings of the pollination process indicate that the viscidium is touched before the pollen presenter, when hummingbirds are flying out of the flowers.     

Do seasonal microbiome changes affect infection susceptibility,contributing to seasonal disease outbreaks?

The aim of the present paper is to explore whether seasonal outbreaks of infectious diseases may be linked to changes in host microbiomes. This is a very important issue, because one way to have more control over seasonal outbreaks is to understand the factors that underlie them. In this paper, I will evaluate the relevance of the microbiome as one of such factors. The paper is based on two pillars of reasoning. Firstly, on the idea that microbiomes play an important role in their hosts’ defence against infectious diseases. Secondly, on the idea that microbiomes are not stable, but change seasonally. These two ideas are combined in order to argue that seasonal changes in a given microbiome may influence the functionality of the host's immune system and consequently make it easier for infectious agents to infect the host at certain times of year. I will argue that, while this is only a theoretical possibility, certain studies may back up such claims. Furthermore, I will show that this does not necessarily contradict other hypotheses aimed at explaining seasonal outbreaks; in fact, it may even enhance them.     

Relationships of the purple-fringed orchids Platanthera Psycodes and P. grandiflora

The vegetative and floral differences between two frequently confused species are discussed in terms of function.Platanthera psycodes is a widespread species with flowers adapted to visits by short-tongued lepidoptera, especially skippers of the genusPolites; the pollinaria are attached to the base of the proboscis.Platanthera grandiflora is a geographically more limited species with flowers adapted to visits by longer-tongued lepidoptera; the pollinaria are probably attached to compound eyes. The species overlap geographically and phenologically. Chromosome numbers are 2n = 42 in each species. Cultivated plants of each are partially self-incompatible but produce apparently normal embryos when intercrossed. Mechanical, seasonal, ethological, and distributional differences isolate the species.Habenaria andPlatanthera are considered distinct but closely related genera.Platanthera psycodes is based upon a type at L,P. grandiflora on a type at AMES.Platanthera grandiflora andP. psycodes have affinities with three other eastern North American species characterized by tripartite, fringed, or erose labella. Species pairs within this group, based on column structure, includegrandifloraperamoena andpsycodeslacera. The column ofP. leucophaea is morphologically intermediate in form.