Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting

Background: An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. Methods: Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. Results: The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P 3.36). Conclusion: An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.Peer reviewedAuthor versio

TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons

<p>Abstract</p> <p>Background</p> <p>Familial amyloidotic polyneuropathy (FAP) is a peripheral neuropathy caused by the extracellular accumulation and deposition of insoluble transthyretin (TTR) aggregates. However the molecular mechanism that underlies TTR toxicity in peripheral nerves is unclear. Previous studies have suggested that amyloidogenic proteins can aggregate into oligomers which disrupt intracellular calcium homeostasis by increasing the permeability of the plasma membrane to extracellular calcium. The aim of the present study was to examine the effect of TTR on calcium influx in dorsal root ganglion neurons.</p> <p>Results</p> <p>Levels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Na_v1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.</p> <p>Conclusions</p> <p>These data suggest that activation of TRPM8 channels triggers the activation of Na_v1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of Alzheimer's disease.</p

Binary Quasars in the Sloan Digital Sky Survey: Evidence for Excess Clustering on Small Scales

We present a sample of 218 new quasar pairs with proper transverse separations R_prop < 1 Mpc/h over the redshift range 0.5 < z < 3.0, discovered from an extensive follow up campaign to find companions around the Sloan Digital Sky Survey and 2dF Quasar Redshift Survey quasars. This sample includes 26 new binary quasars with separations R_prop < 50 kpc/h (theta < 10 arcseconds), more than doubling the number of such systems known. We define a statistical sample of binaries selected with homogeneous criteria and compute its selection function, taking into account sources of incompleteness. The first measurement of the quasar correlation function on scales 10 kpc/h < R_prop < 400 kpc/h is presented. For R_prop < 40 kpc/h, we detect an order of magnitude excess clustering over the expectation from the large scale R_prop > 3 Mpc/h quasar correlation function, extrapolated down as a power law to the separations probed by our binaries. The excess grows to ~ 30 at R_prop ~ 10 kpc/h, and provides compelling evidence that the quasar autocorrelation function gets progressively steeper on sub-Mpc scales. This small scale excess can likely be attributed to dissipative interaction events which trigger quasar activity in rich environments. Recent small scale measurements of galaxy clustering and quasar-galaxy clustering are reviewed and discussed in relation to our measurement of small scale quasar clustering.Comment: 25 pages, 12 figures, 9 tables. Submitted to the Astronomical Journa

Retracing Micro-Epidemics of Chagas Disease Using Epicenter Regression

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population\u27s infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission

Use of Individual-Level Covariates to Improve Latent Class Analysis of Trypanosoma Cruzi Diagnostic Tests

Statistical methods such as latent class analysis can estimate the sensitivity and specificity of diagnostic tests when no perfect reference test exists. Traditional latent class methods assume a constant disease prevalence in one or more tested populations. When the risk of disease varies in a known way, these models fail to take advantage of additional information that can be obtained by measuring risk factors at the level of the individual. We show that by incorporating complex field-based epidemiologic data, in which the disease prevalence varies as a continuous function of individual-level covariates, our model produces more accurate sensitivity and specificity estimates than previous methods. We apply this technique to several simulated populations and to actual Chagas disease test data from a community near Arequipa, Peru. Results from our model estimate that the first-line enzyme-linked immunosorbent assay has a sensitivity of 78% (95% CI: 62-100%) and a specificity of 100% (95% CI: 99-100%). The confirmatory immunofluorescence assay is estimated to be 73% sensitive (95% CI: 65-81%) and 99% specific (95% CI: 96-100%)

The Freshman, vol. 1, no. 14

The Freshman was a weekly, student newsletter issued on Mondays throughout the academic year. The newsletter included calendar notices, coverage of campus social events, lectures, and athletic teams. The intent of the publication was to create unity, a sense of community, and class spirit among first year students. Campus coverage in this issue includes changes in rules governing the Senior Skulls in an effort to create a better spirit among the entire student body, by prohibiting the wearing of knickers, prep school insignia, and sports shoes

Retracing Micro-Epidemics of Chagas Disease Using Epicenter Regression

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S

The Freshman, vol. 1, no. 10 [issue misnumbered]

The Freshman was a weekly, student newsletter issued on Mondays throughout the academic year. The newsletter included calendar notices, coverage of campus social events, lectures, and athletic teams. The intent of the publication was to create unity, a sense of community, and class spirit among first year students. This issue includes an editorial exploring how to maintain self-identity in the face of academic stereotypes

The On-Orbit Performance of the Galaxy Evolution Explorer

We report the first year on-orbit performance results for the Galaxy Evolution Explorer (GALEX), a NASA Small Explorer that is performing a survey of the sky in two ultraviolet bands. The instrument comprises a 50 cm diameter modified Ritchey-Chretien telescope with a 1.25 degree field of view, selectable imaging and objective grism spectroscopic modes, and an innovative optical system with a thin-film multilayer dichroic beam splitter that enables simultaneous imaging by a pair of photon counting, microchannel plate, delay line readout detectors. Initial measurements demonstrate that GALEX is performing well, meeting its requirements for resolution, efficiency, astrometry, bandpass definition and survey sensitivity.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issu

Ringed, Bearded, and Ribbon Seal Vocalizations North of Barrow, Alaska: Seasonal Presence and Relationship with Sea Ice

The acoustic repertoires of ringed, bearded, and ribbon seals are described, along with their seasonal occurrence and relationship to sea ice concentration. Acoustic recordings were made between September and June over three years (2006 – 09) along the continental slope break in the Chukchi Sea, 120 km north-northwest of Barrow, Alaska. Vocalizations of ringed and bearded seals occurred in winter and during periods of 80% – 100% ice cover but were mostly absent during open water periods. The presence of ringed and bearded seal calls throughout winter and spring suggests that some portion of their population is overwintering. Analysis of the repertoire of ringed and bearded seal calls shows seasonal variation. Ringed seal calls are primarily barks in winter and yelps in spring, while bearded seal moans increase during spring. Ribbon seal calls were detected only in the fall of 2008 during the open water period. The repertoire of known ribbon seal vocalizations was expanded to include three additional calls, and two stereotyped call sequences were common. Retrospective analyses of ringed seal recordings from 1982 and ribbon seal recordings from 1967 showed a high degree of stability in call repertoire across large spatial and temporal scales.Le répertoire acoustique des phoques annelés, des phoques barbus et des phoques à bandes sont décrits, de même que leur présence saisonnière et leur rapport avec la concentration de glace de mer. Des enregistrements acoustiques ont été effectués entre septembre et juin sur une période de trois ans (2006 – 2009), le long de la rupture de la pente continentale, dans la mer des Tchouktches, à 120 km au nord-nord-ouest de Barrow, en Alaska. Les vocalisations de phoques annelés et de phoques barbus étaient présentes pendant l’hiver et pendant les périodes où la concentration de glace était de 80 % à 100 %, mais elles se faisaient rares pendant les périodes d’eau libre. La présence des cris de phoques annelés et de phoques barbus tout au long de l’hiver et du printemps suggère qu’une partie de leur population hiverne. L’analyse du répertoire de cris de phoques annelés et de phoques barbus indique une variation saisonnière. L’hiver, le cri du phoque annelé prend principalement la forme d’aboiements, tandis que le printemps, il prend la forme de glapissements. Les gémissements du phoque barbu s’intensifient au printemps. Le cri des phoques à bandes n’a été capté qu’à l’automne 2008, pendant la période des eaux libres. Le répertoire des vocalisations connues du phoque à bandes a été élargi pour inclure trois autres cris, bien que deux séquences de cris stéréotypées étaient courantes. L’analyse rétrospective des enregistrements de cris de phoques annelés de 1982 et de phoques à bandes de 1967 a laissé entrevoir une grande stabilité du point de vue du répertoire des cris, et ce, sur de vastes échelles spatiales et temporelles