Background Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs. Methods The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study. Results Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested. Conclusions These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.

Joanne Baker plunges into an exhibition on visionaries who break all the rules.

Joanne Baker enjoys a biography of the doughty French inventor of the bull's-eye lens, the secret of the modern lighthouse.

The safety and tolerability of primaquine (PQ) administered as a short higher-dose (30 mg twice daily for 7 days) regimen in 203 Australian Defence Force personnel was evaluated in an open-label presumptive anti-relapse therapy study. No clinically significant differences were measured in the subjects' haematological and biochemical indices before and after PQ treatment. The most common adverse events were nausea, abdominal pain, headache and insomnia, many of which were mild in severity (30%; 60/203) and transient; 19% of subjects (39/203) experienced moderate (with some interference with daily duties requiring no or minimal medical therapy) adverse events. Two subjects (1%) had severe gastrointestinal adverse events requiring cessation of medication, but neither was seriously ill. Ten subjects (5%) had peripheral cyanosis (blueness of the lips), but none reported any respiratory compromise. These findings suggest that the short higher-dose PQ regimen is safe and well tolerated, which could improve PQ compliance and effectiveness.

Background Malaria rapid diagnostic tests (RDTs) are now widely used for prompt on-site diagnosis in remote endemic areas where reliable microscopy is absent. Aberrant results, whereby negative test results occur at high parasite densities, have been variously reported for over a decade and have led to questions regarding the reliability of the tests in clinical use. Methods In the first trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2-detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium falciparum parasites were tested against three HRP2-detecting RDTs. Results A prozone-like effect occurred in RDTs at a high concentration of the target antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds to more than 312000 parasites per μL. Similar results were noted on three RDT products using dilutions of cultured parasites up to a parasite density of 25%. While reduced line intensity was observed, no false negative results occurred. Conclusions These results suggest that false-negative malaria RDT results will rarely occur due to a prozone-like effect in high-density infections, and other causes are more likely. However, RDT line intensity is poorly indicative of parasite density in high-density infections and RDTs should, therefore, not be considered quantitative. Immediate management of suspected severe malaria should rely on clinical assessment or microscopy. Evaluation against high concentrations of antigen should be considered in malaria RDT product development and lot-release testing, to ensure that very weak or false negative results will not occur at antigen concentrations that might be seen clinically.

Background Although rapid diagnostic tests (RDTs) for Plasmodium falciparum infection that target histidine rich protein 2 (PfHRP2) are generally sensitive, their performance has been reported to be variable. One possible explanation for variable test performance is differences in expression level of PfHRP in different parasite isolates. Methods Total RNA and protein were extracted from synchronised cultures of 7 P. falciparum lines over 5 time points of the life cycle, and from synchronised ring stages of 10 falciparum lines. Using quantitative real-time polymerase chain reaction, Western blot analysis and ELISA we investigated variations in the transcription and protein levels of pfhrp2, pfhrp3 and PfHRP respectively in the different parasite lines, over the parasite intraerythrocytic life cycle. Results Transcription of pfhrp2 and pfhrp3 in different parasite lines over the parasite life cycle was observed to vary relative to the control parasite K1. In some parasite lines very low transcription of these genes was observed. The peak transcription was observed in ring-stage parasites. Pfhrp2 transcription was observed to be consistently higher than pfhrp3 transcription within parasite lines. The intraerythrocytic lifecycle stage at which the peak level of protein was present varied across strains. Total protein levels were more constant relative to total mRNA transcription, however a maximum 24 fold difference in expression at ring-stage parasites relative to the K1 strain was observed. Conclusions The levels of transcription of pfhrp2 and pfhrp3, and protein expression of PfHRP varied between different P. falciparum strains. This variation may impact on the detection sensitivity of PfHRP2-detecting RDTs.

Some of our biggest decisions are made without conscious awareness, argues Washington Post columnist Shankar Vedantam in The Hidden Brain (Spiegel & Grau, 2010). Using powerful case studies, Vedantam examines with a light touch unconscious bias and sexism; why we seem to care more about animal welfare than genocide; and how decisions taken by those on the 88th and 89th floors of the World Trade Center's South Tower on 11 September 2001 determined whether they lived or died.

The prevalence of the discourse of 'successful girls' (and failing boys) in Australia and internationally has been widely documented. Against the much-vaunted lifting of barriers to opportunity for girls and women, it might reasonably be expected that their educational experiences and career paths are expressive of wider opportunities, greater confidence and autonomy. This article draws on qualitative research with young women in regional Australia to argue that supposedly outmoded but evidently durable patterns of educational and occupational experience remain and are accompanied by new burdens and anxieties. Importantly, young women are now obliged to account for these unfashionable arrangements, using the ubiquitous belief in choice and the possibility of self-actualisation to demonstrate the volition and agency deemed appropriate to a post-feminist ethos. Thus, techniques of reflective selfhood and neoliberal accountability are mobilised to justify social reproduction, while at the same time showcasing invigorated notions of meritocracy and social mobility.

BACKGROUND:Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region.METHODS:The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs.RESULTS:Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified.CONCLUSIONS:The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

In this paper, the experiences of young mothers are examined in the contemporary context of a heightened emphasis on individuated personhood and suggestions of a vastly changed modern femininity. Sociological preoccupation with the features of post-industrial society has emphasized the declining influence of preordained and institutionalized structures. The declining influence of such structures in turn ushers in new requirements for personal agency and decision-making. Under the influence of such posited de-traditionalization, the family is widely conceived to be constituted less through obligation and more through negotiation. Understandings of the regulatory dimensions of neo-liberalism and the post-feminist sensibility are drawn on to consider how young women are implicated in this landscape of de-traditionalization and individualism. This paper reports on Australian empirical research with young women who are mothers that reveals the continuation of supposedly outmoded but evidently enduring features of traditional motherhood. Significantly, though, these supposedly superseded gendered features of family life are now encountered amidst the requirements of reflexive modernity, and it is argued that they are responded to in ways that reflect transformations in the experience of the personal; particularly the construction of individualized biographies of reinvention through motherhood.

An edited extract fromScience and Governmentby C. P. Snow, with an introduction by Joanne Baker.

The theory of evolution challenges artists and philosophers as much as scientists. Joanne Baker rounds up the many forthcoming events worldwide that examine Darwin's life, his work and reactions to it. February 2009 sees the 200th anniversary of the birth of Charles Robert Darwin and November 2009 the 150th anniversary of the publication of his great work, On the Origin of Species. In the intervening two centuries, no single scientist has matched Darwin's impact on the sciences, politics, religion, philosophy and art. This issue of Nature brings together news, research and analysis of Darwin, his life, his science and his legacy. Darwin saw the eye — so complex and seemingly useless with any of its components part-formed — as an obstacle to the acceptance of natural selection. Today we know it as one of evolution's crowning glories — celebrated with a fold-out pictorial feature and current research that refers right back to the 'protoeyes' hypothesized by Darwin. In later writings (Descent of Man, 1871), Darwin touched on a topic that still divides evolutionary biologists — group selection. Does natural selection work for individuals against the interests of the group? Or is such thinking a historical mistake? We report on the debate and why it is important, and review a 'landmark book' on the superorgansims of the insect world, where the group looms large. Extinction comes with the evolutionary territory. But is it for ever? With the publication of the genome sequence of the long-gone woolly mammoth, some researchers are even claiming that mammoths will one day be recreated. Biologists tend to see evolved living systems as finely tuned machines, prone to failure if one component is faulty. But, as Tanguy Chouard reveals, this is not what happens in the real world. Plenty for biologists to celebrate and plenty of places to do it: we have trawled the world for events commemorating Darwin's life and works and trawled the publishers' lists for books doing the same. Not quite everybody will be in celebratory mood. The scientists we spoke to mostly are, but past celebrations have had to tread carefully. The Darwin-related content from this issue — and extra online-only material — can be accessed via: http://www.nature.com/darwin .

The editor of this second anthology of the best scientific communiqués from the blogosphere thinks blogs offer new ways to discuss science.The Open Laboratory 2007: the Best Science Writing on Blogs (Lulu.com,2008) takes the curious approach of using dead tree format to highlight the diversity of scientific ideas, opinions and voices flowing across the Internet.Every year a different guest editorhere Reed Cartwright, a blogger and genetics and bioinformatics postdoc from North Carolina State University -picks the best posts to coincide with the Science Blogging Conference (in North Carolina on 19 January).First-hand accounts bring to life the stresses of a graduate student, a mother returning to the bench and an archaeologist's joy at unearthing mammoth fossils.Topics tackled are as varied as the writers, from Viagra and tapeworms to trepanning.Explanations are often offered with a personal twist, such as a father's tale of his child's Asperger's syndrome.The measured voices of trustworthy academics make medical research easy to swallow.If you are overwhelmed by the surge in science-related blogging and don't know where to start, then this compilation may help you steer a course through the sea of perspectives on offer -or inspire you to start a blog yourself.

Whether to build the International Linear Collider is an open question, but R&D on it should be supported.

This paper outlines a research project which seeks to centre the voices of parents who have been involved with Child Protection services. The need for a study which focuses on the experiences of service users who have 'complicated lives' is discussed with reference to some literature about the intersection of child protection with multiple difficulties relating to violence, disability and problematic substance use.

s Natural History Museum, delivered a public lecture at the Royal Institution of Great Britain.In a strident discourse that set the stage for Charles Darwin's account of evolution, Owen revealed similarities in biological forms from species to species that suggested some underlying ideal plan or archetype.He sought to debunk the prevailing view that anatomical pattern could be explained as a consequence of biological function.With example after example, Owen hammered home the point that structural correspondences between species, or even between parts of the same individual, cannot be explained simply by adaptation.The echoes of his words still reverberate.Owen's ideas contributed directly to Darwin's synthesis of evidence for evolution a decade later.Where Owen saw an archetype -an abstracted common pattern -Darwin glimpsed an ancestor or ancestral condition."Nothing, " Darwin wrote in On the Origin of Species, "can be more hopeless than to attempt to explain this similarity of pattern in members of the same class, by utility or by the doctrine of final causes."My first reaction to re-reading Owen's tour de force was that it must have been a slow evening.In long-winded prose, Owen pores over the minutiae of vertebrate limb bones, the mistakes of lesser scientists and the relationship between observed anatomy and his theoretical template for vertebrate-kind.Many readers might be tempted to skip the text and turn to the pictures, especially the classic plate