Primary structure and sexual stage-specific expression of a LAMMER protein kinase of Plasmodium falciparum.

We have isolated a LAMMER-like gene from Plasmodium falciparum by vectorette technique. The gene consists of 3316 bp encoding a protein 881 amino acids with a predicted molecular mass of approximately 106.7 kDa. The encoded protein, termed PfLAMMER, is composed of two distinct domains. The N-terminal domain is not related to any previously described protein kinases and has several interesting features including multiple consensus phosphorylation sites for a range of protein kinases, a number of RS/SR dipeptides, a large proportion of charged amino acids, two putative nuclear localisation signals and 14 copies of a tetramer DKYD repeats. The C-terminal domain is characteristic of a kinase in the LAMMER family with the highest homology to the Arabidopsis thaliana AFC3 kinase. Genomic restriction analysis showed that PfLAMMER is encoded by a single copy gene in the parasite genome. A single transcript of approximately 3800 nucleotides is expressed specifically in the sexual stage, indicating that PfLAMMER may be important in regulating the processes of sexual differentiation of the parasite

Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies

There is growing concern that poor experimental design and lack of transparent reporting contribute to the frequent failure of pre-clinical animal studies to translate into treatments for human disease. In 2010, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were introduced to help improve reporting standards. They were published in PLOS Biology and endorsed by funding agencies and publishers and their journals, including PLOS, Nature research journals, and other top-tier journals. Yet our analysis of papers published in PLOS and Nature journals indicates that there has been very little improvement in reporting standards since then. This suggests that authors, referees, and editors generally are ignoring guidelines, and the editorial endorsement is yet to be effectively implemented

A solver combining reduced basis and convergence acceleration with applications to non-linear elasticity

International audienceAn iterative solver is proposed to solve the family of linear equations arising from the numerical computation of non‐linear problems. This solver relies on two quantities coming from previous steps of the computations: the preconditioning matrix is a matrix that has been factorized at an earlier step and previously computed vectors yield a reduced basis. The principle is to define an increment in two sub‐steps. In the first sub‐step, only the projection of the unknown on a reduced subspace is incremented and the projection of the equation on the reduced subspace is satisfied exactly. In the second sub‐step, the full equation is solved approximately with the help of the preconditioner. Last, the convergence of the sequences is accelerated by a well‐known method, the modified minimal polynomial extrapolation. This algorithm assessed by classical benchmarks coming from shell buckling analysis. Finally, its insertion in path following techniques is discussed. This leads to non‐linear solvers with few matrix factorizations and few iterations

Does cueing training improve physical activity in patients with Parkinson's disease?

Patients with Parkinson’s disease (PD) are encouraged to stay active to maintain their mobility. Ambulatory activity monitoring (AM) provides an objective way to determine type and amount of gait-related daily activities. Objective To investigate the effects of a home cueing training program on functional walking activity in PD. Methods In a single-blind, randomized crossover trial, PD patients allocated to early intervention received cueing training for 3 weeks, whereas the late intervention group received training in the following 3 weeks. Training was applied at home, using a prototype cueing device. AM was applied at baseline, 3, 6, and 12 weeks in the patient’s home, to record body movements. Postures and motions were classified as percentage of total time spent on (a) static activity, further specified as % sitting and % standing, and (b) % dynamic activity, further specified as % walking, % walking periods exceeding 5 seconds (W>5s) and 10 seconds (W>10s). Random coefficient analysis was applied. Results A total of 153 patients participated in this trial. Significant improvements were found for dynamic activity ( = 4.46; P 5s ( = 2.63; P 10s ( = 2.90; P < .01). All intervention effects declined significantly at 6 weeks follow-up. Conclusion Cueing training in PD patients’ own home significantly improves the amount of walking as recorded by AM. Treatment effects reduced after the intervention period, pointing to the need for permanent cueing devices and follow-up cueing training

A prickly problem: developing a volunteer-friendly tool for monitoring populations of a terrestrial urban mammal, the West European hedgehog (Erinaceus europaeus)

Across Europe, hedgehogs (Erinaceus europaeus) appear to be in decline in both urban and rural landscapes. Current methods used to monitor urban populations are, however, associated with several potential limitations. In this study, we conducted hedgehog footprint-tunnel surveys in 219 residential gardens across Reading, UK between May–September in 2013 and/or 2014; gardens were surveyed for five continuous days. Single-species occupancy models were used to investigate factors influencing hedgehog occupancy and two-species occupancy models were used to estimate a species interaction factor (SIF) between hedgehogs and (a) badgers (Meles meles), (b) foxes (Vulpes vulpes) and (c) dogs (Canis familiaris). The five-day survey protocol was associated with a false-absence error rate of 0.1–0.4%, indicating that it was a reliable method for determining hedgehog presence; conversely, 34.7% of householders were not able to correctly predict hedgehog presence or absence. Hedgehogs were widely distributed across Reading, but detected in only 32–40% of gardens. None of the within-garden or outside-garden factors investigated significantly affected hedgehog occupancy in the single-species models, but the two-species models indicated that badgers (SIF = 0.471 ± 0.188), but not foxes (SIF = 0.954 ± 0.048) or dogs (SIF = 0.780 ± 0.228), negatively affected the presence of hedgehogs in gardens, although not significantly. Overall, footprint-tunnels represent a viable field method for monitoring urban hedgehog populations, however, other approaches are required to identify factors that make gardens "hedgehog friendly"

Comparing breast cancer mortality rates before-and-after a change in availability of screening in different regions: Extension of the paired availability design

BACKGROUND: In recent years there has been increased interest in evaluating breast cancer screening using data from before-and-after studies in multiple geographic regions. One approach, not previously mentioned, is the paired availability design. The paired availability design was developed to evaluate the effect of medical interventions by comparing changes in outcomes before and after a change in the availability of an intervention in various locations. A simple potential outcomes model yields estimates of efficacy, the effect of receiving the intervention, as opposed to effectiveness, the effect of changing the availability of the intervention. By combining estimates of efficacy rather than effectiveness, the paired availability design avoids confounding due to different fractions of subjects receiving the interventions at different locations. The original formulation involved short-term outcomes; the challenge here is accommodating long-term outcomes. METHODS: The outcome is incident breast cancer deaths in a time period, which are breast cancer deaths that were diagnosed in the same time period. We considered the plausibility of the basic five assumptions of the paired availability design and propose a novel analysis to accommodate likely violations of the assumption of stable screening effects. RESULTS: We applied the paired availability design to data on breast cancer screening from six counties in Sweden. The estimated yearly change in incident breast cancer deaths per 100,000 persons ages 40–69 (in most counties) due to receipt of screening (among the relevant type of subject in the potential outcomes model) was -9 with 95% confidence interval (-14, -4) or (-14, -5), depending on the sensitivity analysis. CONCLUSION: In a realistic application, the extended paired availability design yielded reasonably precise confidence intervals for the effect of receiving screening on the rate of incident breast cancer death. Although the assumption of stable preferences may be questionable, its impact will be small if there is little screening in the first time period. However, estimates may be substantially confounded by improvements in systemic therapy over time. Therefore the results should be interpreted with care

Changing the culture of care for children and adolescents with functional neurological disorder.

As members of a multidisciplinary team of professionals who treat children and adolescents with functional neurological (conversion) disorder (FND), we highlight the pressing need to develop an FND-informed culture of care that takes into account recent advances in our understanding of this group of patients. Stories of clinical encounters in health care settings from around the world-told by children and adolescents with FND, their parents, and health professionals-portray an outdated culture of care characterized by iatrogenic stigma, erosion of empathy and compassion within the clinician-patient relationship, and a lack of understanding of FND and its complex neurobiology. After a brief exploration of the outdated culture, we share our counterstories: how we and our colleagues have worked, and continue to work, to create an FND-informed culture in the health systems where we practice. We discuss the therapeutic use of child-friendly language. We also discuss a range of structural, educational, and process interventions that can be used to promote FND-informed beliefs and attitudes, FND-informed clinician-patient encounters, and FND-informed referral processes, treatment pathways, and therapeutic interventions