Visibility graph analysis of intraspinal pressure signal predicts functional outcome in spinal cord injured patients.

To guide management of patients with acute spinal cord injuries, we developed intraspinal pressure monitoring from the injury site. Here, we examine the complex fluctuations in the intraspinal pressure signal using network theory. We analyzed 7,097 hours of intraspinal pressure data from 58 patients with severe cord injuries. Intraspinal pressure signals were split into hourly windows. Each window was mapped into a visibility graph as follows: Vertical bars were drawn at 0.1 Hz representing signal amplitudes. Each bar produced a node, thus totalling 360 nodes per graph. Two nodes were linked with an edge if the straight line through the nodes did not intersect a bar. We computed several topological metrics for each graph including diameter, modularity, eccentricity and small-worldness. Patients were followed up for 20 months on average. Our data show that the topological structure of intraspinal pressure visibility graphs is highly sensitive to pathological events at the injury site including cord compression (high intraspinal pressure), ischemia (low spinal cord perfusion pressure) and deranged autoregulation (high spinal pressure reactivity index). These pathological changes correlate with long graph diameter, high modularity, high eccentricity and reduced small-worldness. In a multivariate logistic regression model, age, neurological status on admission and average node eccentricity were independent predictors of neurological improvement. We conclude that analysis of intraspinal pressure fluctuations after spinal cord injury as graphs, rather than time series, captures clinically important information. Our novel technique may be applied to other signals recorded from injured CNS e.g intracranial pressure, tissue metabolite and oxygen levels

A general catalytic β-C-H carbonylation of aliphatic amines to β-lactams

Methods for the synthesis and functionalization of amines are intrinsically important to a variety of chemical applications. We present a general carbon-hydrogen bond activation process that combines readily available aliphatic amines and the feedstock gas carbon monoxide to form synthetically versatile value-added amide products. The operationally straightforward palladium-catalyzed process exploits a distinct reaction pathway, wherein a sterically hindered carboxylate ligand orchestrates an amine attack on a palladium anhydride to transform aliphatic amines into β-lactams. The reaction is successful with a wide range of secondary amines and can be used as a late-stage functionalization tactic to deliver advanced, highly functionalized amine products of utility for pharmaceutical research and other areas.We gratefully acknowledge funding from the European Research Council and the UK Engineering and Physical Sciences Research Council (EPSRC) (to D.W., K.F.H., A.P.S., and M.J.G.), the Herchel Smith Trust (to B.G.N.C.), the Marie Curie Foundation (to J.C.), and the Royal Society (Wolfson Merit Award to M.J.G.). Mass spectrometry data were acquired at the EPSRC UK National Mass Spectrometry Facility at Swansea University. Computational work was performed with the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell, using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England

Critical current of YBa2Cu3O7-delta low-angle grain boundaries

Transport critical current measurements have been performed on 5degrees [001]-tilt thin film YBa2Cu3O7-delta single grain boundaries with the magnetic field rotated in the plane of the film, phi. The variation of the critical current has been determined as a function of the angle between the magnetic field and the grain boundary plane. In applied fields above 1 T the critical current j(c) is found to be strongly suppressed only when the magnetic field is within an angle phi(k) of the grain boundary. Outside this angular range the behavior of the artificial grain boundary is dominated by the critical current of the grains. We show that the phi dependence of j(c) in the suppressed region is well described by a flux cutting model.EPSR

Acute spinal cord injury: monitoring the lumbar cerebrospinal fluid provides limited information about the injury site

In some centers, monitoring the lumbar cerebrospinal fluid (CSF) is used to guide management of patients with acute traumatic spinal cord injuries (TSCI) and draining lumbar CSF to improve spinal cord perfusion. Here, we investigate whether the lumbar CSF provides accurate information about the injury site and the effect of draining lumbar CSF on injury site perfusion. In 13 TSCI patients, we simultaneously monitored lumbar CSF pressure (CSFP) and intraspinal pressure (ISP) from the injury site. Using CSFP or ISP, we computed spinal cord perfusion pressure (SCPP), vascular pressure reactivity index (sPRx) and optimum SCPP (SCPPopt). We also assessed the effect on ISP of draining 10mL CSF. Metabolites at the injury site were compared with metabolites in the lumbar CSF. We found that ISP was pulsatile, but CSFP had low pulse pressure and was non-pulsatile 21% of the time. There was weak or no correlation between CSFP versus ISP (R=-0.11), SCPP(csf) versus SCPP(ISP) (R=0.39) and sPRx(csf) versus sPRx(ISP) (R=0.45). CSF drainage caused no significant change in ISP in 7/12 patients, a significant drop by <5mmHg in 4/12 patients and by ~8mmHg in 1/12 patient. Metabolite concentrations in the CSF versus injury site did not correlate for lactate (R=0.00), pyruvate (R=-0.12) or lactate-to-pyruvate ratio (R=-0.05) with weak correlations noted for glucose (R=0.31), glutamate (R=0.61) and glycerol (R=0.56). We conclude that, after a severe TSCI, monitoring from the lumbar CSF provides only limited information about the injury site and that lumbar CSF drainage does not effectively reduce ISP in most patients

Comparison of male reproductive success in malaria-refractory and susceptible strains of Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>In female mosquitoes that transmit malaria, the benefits of being refractory to the <it>Plasmodium </it>parasite are balanced by the immunity costs in the absence of infection. Male mosquitoes, however, gain no advantage from being refractory to blood-transmitted parasites, so that any costs associated with an enhanced immune system in the males limit the evolution of female refractoriness and has practical implications for the release of transgenic males.</p> <p>Methods</p> <p>Aspects of the male cost of carrying <it>Plasmodium</it>-refractory genes were estimated by comparing the males' immune response and reproductive success among strains of <it>Anopheles gambiae </it>that had been selected for refractoriness or extreme susceptibility to the rodent malaria parasite, <it>Plasmodium yoelii nigeriensis</it>. The refractory males had a stronger melanization response than males from the susceptible line. Four traits were used as correlates of a male's reproductive success: the proportion of females that were inseminated by a fixed number of males in a cage within a fixed time frame, the proportion of females with motile sperm in their spermathecae, the proportion of ovipositing females, and the mean number of eggs per batch.</p> <p>Results</p> <p>Although there were significant differences among groups of males in sperm motility and oviposition success, these differences in male reproductive success were not associated with the refractory or susceptible male genotypes. Contrary to expectation, females mated to early emerging refractory males laid significantly more eggs per batch than females mated to later emerging susceptible males. Sperm motility and oviposition success were strongly correlated suggesting that variation in sperm motility influences female oviposition and ultimately male reproductive success.</p> <p>Conclusion</p> <p>An increased melanization response in male <it>A. gambiae </it>does not diminish male reproductive success under the experimental protocol used in this study. That refractory males induced ovipositing females to lay more eggs than susceptible males is an interesting result for any strategy considering the release of transgenic males. That sperm motility influences female oviposition is also important for the release of transgenic males.</p

Which patients with heart failure should receive specialist palliative care?

AIMS: We investigated which patients with heart failure (HF) should receive specialist palliative care (SPC) by first creating a definition of need for SPC in patients hospitalised with HF using patient-reported outcome measures (PROMs) and then testing this definition using the outcome of days alive and out of hospital (DAOH). We also evaluated which baseline variables predicted need for SPC and whether those with this need received SPC. METHODS AND RESULTS: PROMs assessing quality of life (QoL), symptoms, and mood were administered at baseline and every 4 months. SPC need was defined as persistently severe impairment of any PROM without improvement (or severe impairment immediately preceding death). We then tested whether need for SPC, so defined, was reflected in DAOH, a measure which combines length of stay, days of hospital re-admission, and days lost due to death. Of 272 patients recruited, 74 (27%) met the definition of SPC needs. These patients lived one third fewer DAOH than those without SPC need (and less than a quarter of QoL-adjusted DAOH). A Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score of <29 identified patients who subsequently had SPC needs (area under receiver operating characteristic curve 0.78). Twenty-four per cent of patients with SPC needs actually received SPC (n = 18). CONCLUSIONS: A quarter of patients hospitalised with HF had a need for SPC and were identified by a low KCCQ score on admission. Those with SPC need spent many fewer DAOH and their DAOH were of significantly worse quality. Very few patients with SPC needs accessed SPC services

The formation of professional identity in medical students: considerations for educators

&lt;b&gt;Context&lt;/b&gt; Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objectives&lt;/b&gt; This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Implications&lt;/b&gt; A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education

A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616]

BACKGROUND: IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity. OBJECTIVE OF THE STUDY: The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACE(i )and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF. DESIGN: After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor(®), 100 (2 × 50) patients with IgAN and a urinary P/C ratio ≥ 0.6 (males) and ≥ 0.8 (females) and an estGFR ≥ 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor(® )for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two

The impact of low erythrocyte density in human blood on the fitness and energetic reserves of the African malaria vector Anopheles gambiae

Background Anaemia is a common health problem in the developing world. This condition is characterized by a reduction in erythrocyte density, primarily from malnutrition and/or infectious diseases such as malaria. As red blood cells are the primary source of protein for haematophagous mosquitoes, any reduction could impede the ability of mosquito vectors to transmit malaria by influencing their fitness or that of the parasites they transmit. The aim of this study was to determine the impact of differences in the density of red blood cells in human blood on malaria vector (Anopheles gambiae sensu stricto) fitness. The hypotheses tested are that mosquito vector energetic reserves and fitness are negatively influenced by reductions in the red cell density of host human blood meals commensurate with those expected from severe anaemia. Methods Mosquitoes (An. gambiae s.s.) were offered blood meals of different packed cell volume(PCV) of human blood consistent with those arising from severe anaemia (15%) and normalPCV (50%). Associations between mosquito energetic reserves (lipid, glucose and glycogen)and fitness measures (reproduction and survival) and blood meal PCV were investigated. Results The amount of protein that malaria vectors acquired from blood feeding (indexed by haematin excretion) was significantly reduced at low blood PCV. However, mosquitoes feeding on blood of low PCV had the same oviposition rates as those feeding on blood of normal PCV, and showed an increase in egg production of around 15%. The long-term survival of An. gambiae s.s was reduced after feeding on low PCV blood, but PCV had no significant impact on the proportion of mosquitoes surviving through the minimal period required to develop and transmit malaria parasites (estimated as 14 days post-blood feeding). The impact of blood PCV on the energetic reserves of mosquitoes was relatively minor. Conclusions These results suggest that feeding on human hosts whose PCV has been depleted due to severe anaemia does not significantly reduce the fitness or transmission potential of malaria vectors, and indicates that mosquitoes may be able exploit resources for reproduction more efficiently from blood of low rather than normal PCV

Clues from nearby galaxies to a better theory of cosmic evolution

The great advances in the network of cosmological tests show that the relativistic Big Bang theory is a good description of our expanding universe. But the properties of nearby galaxies that can be observed in greatest detail suggest a still better theory would more rapidly gather matter into galaxies and groups of galaxies. This happens in theoretical ideas now under discussion.Comment: published in Natur