Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Variability of Sequence Surrounding the Xist Gene in Rodents Suggests Taxon-Specific Regulation of X Chromosome Inactivation

One of the two X chromosomes in female mammalian cells is subject to inactivation (XCI) initiated by the Xist gene. In this study, we examined in rodents (voles and rat) the conservation of the microsatellite region DXPas34, the Tsix gene (antisense counterpart of Xist), and enhancer Xite that have been shown to flank Xist and regulate XCI in mouse. We have found that mouse regions of the Tsix gene major promoter and minisatellite repeat DXPas34 are conserved among rodents. We have also shown that in voles and rat the region homologous to the mouse Tsix major promoter, initiates antisense to Xist transcription and terminates around the Xist gene start site as is observed with mouse Tsix. A conservation of Tsix expression pattern in voles, rat and mice suggests a crucial role of the antisense transcription in regulation of Xist and XIC in rodents. Most surprisingly, we have found that voles lack the regions homologous to the regulatory element Xite, which is instead replaced with the Slc7a3 gene that is unassociated with the X-inactivation centre in any other eutherians studied. Furthermore, we have not identified any transcription that could have the same functions as murine Xite in voles. Overall, our data show that not all the functional elements surrounding Xist in mice are well conserved even within rodents, thereby suggesting that the regulation of XCI may be at least partially taxon-specific

All different or all the same? Exploring the diversity of professional practices in Portuguese school psychology

"Published online: 29 March 2016"Studies have generally characterized school psychologists as a relative homogenous population. Understanding the differences in professional practices and related variables is important for the development of the profession. Using a sample of 446 Portuguese school psychologists, this study used cluster analysis to identify distinct profiles of professional activity, based on practitioners’ time distribution among different target audiences (i.e.,students, parents, teachers, school board members, school non-professional staff, and other professionals within the school community). Three distinct profiles emerged from the data: a group highly oriented to work with students, a group that distributes time almost equitably between adults and students, and a group that concentrates attention and professional expertise on adults. Practice setting variables, such as school-psychologists-to-student ratio, schoolpsychologists-to-school ratio, number of referrals per year, and school community level of demand for different activities, were found to be significantly related to cluster membership. No personal- or professional-background-related variables differentiated the three groups. The main implications of these findings are discussed in light of recent literature regarding the models of service delivery for school psychologists

A Dual Origin of the Xist Gene from a Protein-Coding Gene and a Set of Transposable Elements

X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC). Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA

SOSORT consensus paper: school screening for scoliosis. Where are we today?

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure

Deep-Ocean dissolved organic matter reactivity along the Mediterranea Sea: does size matter?

Original research paperDespite of the major role ascribed to marine dissolved organic matter (DOM) in the global carbon cycle, the reactivity of this pool in the dark ocean is still poorly understood. Present hypotheses, posed within the size-reactivity continuum (SRC) and the microbial carbon pump (MCP) conceptual frameworks, need further empirical support. Here, we provide field evidence of the soundness of the SRC model. We sampled the high salinity core-of-flow of the Levantine Intermediate Water along its westward route through the entire Mediterranean Sea. At selected sites, DOM was size-fractionated in apparent high (aHMW) and low (aLMW) molecular weight fractions using an efficient ultrafiltration cell. A percentage decline of the aHMW DOM from 68–76% to 40–55% was observed from the Levantine Sea to the Strait of Gibraltar in parallel with increasing apparent oxygen utilization (AOU). DOM mineralization accounted for 30±3% of the AOU, being the aHMW fraction solely responsible for this consumption, verifying the SRC model in the field. We also demonstrate that, in parallel to this aHMW DOM consumption, fluorescent humic-like substances accumulate in both fractions and protein-like substances decline in the aLMW fraction, thus indicating that not only size matters and providing field support to the MCP modelHOTMIX (grant number CTM2011–30010-C02 01-MAR and 02-MAR) and the project FERMIO (MINECO, CTM2014-57334-JIN), both co-financed with FEDER funds; (reference BES-2012- 056175) from the Spanish Ministry of Economy, Industry and Competitivenes; the project MODMED from CSIC (PIE, 201730E020) and CSIC Program “Junta para la Ampliación de Estudios” co-financed by the ESF (reference JAE DOC 040)Versión del editor2,92

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Reduction in acute filariasis morbidity during a mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea.

Background Acute painful swelling of the extremities and scrotum are debilitating clinical manifestations of Wuchereria bancrofti infection. The ongoing global program to eliminate filariasis using mass drug administration is expected to decrease this and other forms of filarial morbidity in the future by preventing establishment of new infections as a consequence of eliminating transmission by the mosquito vector. We examined whether mass treatment with anti-filarial drugs has a more immediate health benefit by monitoring acute filariasis morbidity in Papua New Guinean communities that participated in a 5-year mass drug administration trial. Methodology/Principal Findings Weekly active surveillance for acute filariasis morbidity defined by painful swelling of the extremities, scrotum and breast was performed 1 year before and each year after 4 annual mass administrations of anti-filarial drugs (16,480 person-years of observation). Acute morbidity events lasted <3 weeks in 92% of affected individuals and primarily involved the leg (74–79% of all annual events). The incidence for all communities considered together decreased from 0.39 per person-year in the pre-treatment year to 0.31, 0.15, 0.19 and 0.20 after each of 4 annual treatments (p<0.0001). Residents of communities with high pre-treatment transmission intensities (224–742 infective bites/person/year) experienced a greater reduction in acute morbidity (0.62 episodes per person-year pre-treatment vs. 0.30 in the 4th post-treatment year) than residents of communities with moderate pre-treatment transmission intensities (24–167 infective bites/person/year; 0.28 episodes per person-year pre-treatment vs. 0.16 in the 4th post-treatment year). Conclusions Mass administration of anti-filarial drugs results in immediate health benefit by decreasing the incidence of acute attacks of leg and arm swelling in people with pre-existing infection. Reduction in acute filariasis morbidity parallels decreased transmission intensity, suggesting that continuing exposure to infective mosquitoes is involved in the pathogenesis of acute filariasis morbidity

EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice

Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries