A test of general relativity from the three-dimensional orbital geometry of a binary pulsar

Binary pulsars provide an excellent system for testing general relativity because of their intrinsic rotational stability and the precision with which radio observations can be used to determine their orbital dynamics. Measurements of the rate of orbital decay of two pulsars have been shown to be consistent with the emission of gravitational waves as predicted by general relativity, providing the most convincing evidence for the self-consistency of the theory to date. However, independent verification of the orbital geometry in these systems was not possible. Such verification may be obtained by determining the orientation of a binary pulsar system using only classical geometric constraints, permitting an independent prediction of general relativistic effects. Here we report high-precision timing of the nearby binary millisecond pulsar PSR J0437-4715, which establish the three-dimensional structure of its orbit. We see the expected retardation of the pulse signal arising from the curvature of space-time in the vicinity of the companion object (the `Shapiro delay'), and we determine the mass of the pulsar and its white dwarf companion. Such mass determinations contribute to our understanding of the origin and evolution of neutron stars.Comment: 5 pages, 2 figure

The influence of the coroner's inquisition on the common law and the medico legal system.

Inquisitions held by various authoritative bodies from the Crown in the eleventh century to the Board of Trade or the local Borough Council in the twentieth, have existed for many and different reasons. In contemporary society any commission of inquiry can be termed an inquisition, whether its purpose is a retrospective assessment or a prospective modification of established policy. The inquisitorial theory is the searching out and correcting of error on the basis that there is safety in the truth. As a legal principle it is the demarcation line between the ancient prophetic laws of the oracles and the scientific legal systems of modern civilisations. William the Conqueror introduced the "Inquisitio" into England as one of the measures of facilitating the integration of local administration with the centralisation of Royal Justice. Initially, its main function was of a fiscal and political nature but the institution was not allowed to suffer the corruption and misuse of its process, as was its continental counterpart following the Lateran and Toulouse Councils in the thirteenth century. Given expression in the Coroner's inquest it was used mýin1y in the investigation of unnatural death or c-m y matter ordered by the King's writ. From the onset it acquired a significant role in the developing common law when inquisition records were used by the Justices in Eyre for the conducting their business. The Coroner's inquiry exists in all parts of the world where the common law took root, but its purpose has changed; although on occasion an inquest may bring to light a secret homicide or contribute to the preferment of a criminal charge; its duty is to provide a forensic forum for the sifting of medical, legal and scientific issues in the prevention of untimely death and the promotion of a better quality of life

Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV-infected children in Zimbabwe.

BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing. RESULTS: Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9-12] years. Median time on ART was 4.6 years (IQR 2.4-6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2-32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1-32.3) higher in those recently hospitalized for a chest infection. CONCLUSION: We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available

The effectiveness of neuromuscular warm-up strategies, that require no additional equipment, for preventing lower limb injuries during sports participation: a systematic review

PMCID: PMC3408383The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/75. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Static stretching of the hamstring muscle for injury prevention in football codes: a systematic review

Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes. Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool. Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs. Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future

Over-Selectivity is Related to Autism Quotient and Empathizing, But not to Systematizing

The relationships of autism quotient (AQ), systematizing (SQ), and empathizing (EQ), with over-selectivity were explored to assess whether over-selectivity is implicated in complex social skills, which has been assumed, but not experimentally examined. Eighty participants (aged 18–60) were trained on a simultaneous discrimination task (AB+CD−), and tested in extinction on the degree to which they had learned about both elements of the reinforced (AB) compound. Higher AQ and lower EQ scorers demonstrated greater over-selectivity, but there was no relationship between SQ and over-selectivity. These results imply that high AQ scorers perform similarly to individuals with ASD on this cognitive task, and that over-selectivity may be related to some complex social skills, like empathy

Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons

Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer’s disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ₄₂ activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ₄₂-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1. Aβ₄₂-induced neurotoxicity was also inhibited by treatment with TPEN used as a Zn²⁺-specific chelator. Cell imaging revealed that Aβ₄₂-induced lysosomal dysfunction, cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS. These effects were suppressed by TRPM2-KO, inhibition of TRPM2 or PARP-1, or treatment with TPEN. Bafilomycin-induced lysosomal dysfunction also resulted in TRPM2-dependent cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, and mitochondrial generation of ROS, supporting that lysosomal dysfunction and accompanying Zn²⁺ release trigger mitochondrial Zn²⁺ accumulation and generation of ROS. Aβ₄₂-induced effects on lysosomal and mitochondrial functions besides neurotoxicity were also suppressed by inhibition of PKC and NOX. Furthermore, Aβ₄₂-induced neurotoxicity was prevented by inhibition of MEK/ERK. Therefore, our study reveals multiple molecular mechanisms, including PKC/NOX-mediated generation of ROS, activation of MEK/ERK and PARP-1, lysosomal dysfunction and Zn²⁺ release, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS, are critically engaged in forming a positive feedback loop that drives Aβ₄₂-induced activation of the TRPM2 channel and neurotoxicity in hippocampal neurons. These findings shed novel and mechanistic insights into AD pathogenesis

Influence of a montmorency cherry juice blend on indices of exercise-induced stress and upper respiratory tract symptoms following marathon running—a pilot investigation

Background: Prolonged exercise, such as marathon running, has been associated with an increase in respiratory mucosal inflammation. The aim of this pilot study was to examine the effects of Montmorency cherry juice on markers of stress, immunity and inflammation following a Marathon. Methods: Twenty recreational Marathon runners consumed either cherry juice (CJ) or placebo (PL) before and after a Marathon race. Markers of mucosal immunity secretory immunoglobulin A (sIgA), immunoglobulin G (IgG), salivary cortisol, inflammation (CRP) and self-reported incidence and severity of upper respiratory tract symptoms (URTS) were measured before and following the race. Results: All variables except secretory IgA and IgG concentrations in saliva showed a significant time effect (P < 0.01). Serum CRP showed a significant interaction and treatment effect (P < 0.01). The CRP increase at 24 and 48 h post-Marathon was lower (P < 0.01) in the CJ group compared to PL group. Mucosal immunity and salivary cortisol showed no interaction effect or treatment effect. The incidence and severity of URTS was significantly greater than baseline at 24 h and 48 h following the race in the PL group and was also greater than the CJ group (P < 0.05). No URTS were reported in the CJ group whereas 50 % of runners in the PL group reported URTS at 24 h and 48 h post-Marathon. Conclusions: This is the first study that provides encouraging evidence of the potential role of Montmorency cherries in reducing the development of URTS post-Marathon possibly caused by exercise-induced hyperventilation trauma, and/or other infectious and non-infectious factors

Hippocampal - diencephalic - cingulate networks for memory and emotion: An anatomical guide

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus