A Closed-Form Solution for the Optimal Time Evolution of an Exponentially Decaying Signal with Thermal Noise

The signal-to-noise ratio of a monoexponentially decaying signal exhibits a maximum at an evolution time of approximately 1.26 T-2. It has previously been thought that there is no closed-form solution to express this maximum. We report in this note that this maximum can be represented in a specific, analytical closed form in terms of the negative real branch of an inverse function known as the Lambert W function. The Lambert function is finding increasing use in the solution of problems in a variety of areas in the physical sciences. (C) 2014 Wiley Periodicals, Inc.

Selection and recombination drive the evolution of MHC class II DRB diversity in ungulates

Major histocompatibility complex (MHC) antigen-presenting genes are the most variable loci in vertebrate genomes. Host-parasite co-evolution is assumed to maintain the excessive polymorphism in the MHC loci. However, the molecular mechanisms underlying the striking diversity in the MHC remain contentious. The extent to which recombination contributes to the diversity at MHC loci in natural populations is still controversial, and there have been only few comparative studies that make quantitative estimates of recombination rates. In this study, we performed a comparative analysis for 15 different ungulates species to estimate the population recombination rate, and to quantify levels of selection. As expected for all species, we observed signatures of strong positive selection, and identified individual residues experiencing selection that were congruent with those constituting the peptide-binding region of the human DRB gene. However, in addition for each species, we also observed recombination rates that were significantly different from zero on the basis of likelihood-permutation tests, and in other non-quantitative analyses. Patterns of synonymous and non-synonymous sequence diversity were consistent with differing demographic histories between species, but recent simulation studies by other authors suggest inference of selection and recombination is likely to be robust to such deviations from standard models. If high rates of recombination are common in MHC genes of other taxa, re-evaluation of many inference-based phylogenetic analyses of MHC loci, such as estimates of the divergence time of alleles and trans-specific polymorphism, may be required.

The performance of computer-aided detection when analyzing prior mammograms of newly detected breast cancers with special focus on the time interval from initial imaging to detection

PURPOSE: The clinical role of CAD systems to detect breast cancer, which have not been on cancer containing mammograms not detected by the radiologist was proven retrospectively. METHODS: All patients from 1992 to 2005 with a histologically verified malignant breast lesion and a mammogram at our department, were analyzed in retrospect focussing on the time of detection of the malignant lesion. All prior mammograms were analyzed by CAD (CADx, USA). The resulting CAD printout was matched with the cancer containing images yielding to the radiological diagnosis of breast cancer. CAD performance, sensitivity as well as the association of CAD and radiological features were analyzed. RESULTS: 278 mammograms fulfilled the inclusion criteria. 111 cases showed a retrospectively visible lesion (71 masses, 23 single microcalcification clusters, 16 masses with microcalcifications, in one case two microcalcification clusters). 54/87 masses and 34/41 microcalcifications were detected by CAD. Detection rates varied from 9/20 (ACR 1) to 5/7 (ACR 4) (45% vs. 71%). The detection of microcalcifications was not influenced by breast tissue density. CONCLUSION: CAD might be useful in an earlier detection of subtle breast cancer cases, which might remain otherwise undetected.

Radiation metabolomics. 2. Dose- and time-dependent urinary excretion of deaminated purines and pyrimidines after sublethal gamma-radiation exposure in mice

Gamma-radiation exposure of humans is a major public health concern as the threat of terrorism and potential hostile use of radiological devices increases worldwide. We report here the effects of sublethal gamma-radiation exposure on the mouse urinary metabolome determined using ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry-based metabolomics. Five urinary biomarkers of sublethal radiation exposure that were statistically significantly elevated during the first 24 h after exposure to doses ranging from 1 to 3 Gy were unequivocally identified by tandem mass spectrometry. These are deaminated purine and pyrimidine derivatives, namely, thymidine, 2'-deoxyuridine, 2'-deoxyxanthosine, xanthine and xanthosine. Furthermore, the aminopyrimidine 2'-deoxycytidine appeared to display reduced urinary excretion at 2 and 3 Gy. The elevated biomarkers displayed a time-dependent excretion, peaking in urine at 8-12 h but returning to baseline by 36 h after exposure. It is proposed that 2'-deoxyuridine and 2'-deoxyxanthosine arise as a result of gamma irradiation by nitrosative deamination of 2'-deoxycytidine and 2'-deoxyguanosine, respectively, and that this further leads to increased synthesis of thymidine, xanthine and xanthosine. The urinary excretion of deaminated purines and pyrimidines, at the expense of aminopurines and aminopyrimidines, appears to form the core of the urinary radiation metabolomic signature of mice exposed to sublethal doses of ionizing radiation.

Parametric estimation of pulse arrival time: a robust approach to pulse wave velocity

Pulse wave velocity (PWV) is a surrogate of arterial stiffness and represents a non-invasive marker of cardiovascular risk. The non-invasive measurement of PWV requires tracking the arrival time of pressure pulses recorded in vivo, commonly referred to as pulse arrival time (PAT). In the state of the art, PAT is estimated by identifying a characteristic point of the pressure pulse waveform. This paper demonstrates that for ambulatory scenarios, where signal-to-noise ratios are below 10 dB, the performance in terms of repeatability of PAT measurements through characteristic points identification degrades drastically. Hence, we introduce a novel family of PAT estimators based on the parametric modeling of the anacrotic phase of a pressure pulse. In particular, we propose a parametric PAT estimator (TANH) that depicts high correlation with the Complior(R) characteristic point D1 (CC = 0.99), increases noise robustness and reduces by a five-fold factor the number of heartbeats required to obtain reliable PAT measurements.

Is perioperative point-of-care prothrombin time testing accurate compared to the standard laboratory test?

There is no accepted way of measuring prothrombin time without time loss for patients undergoing major surgery who are at risk of intraoperative dilution and consumption coagulopathy due to bleeding and volume replacement with crystalloids or colloids. Decisions to transfuse fresh frozen plasma and procoagulatory drugs have to rely on clinical judgment in these situations. Point-of-care devices are considerably faster than the standard laboratory methods. In this study we assessed the accuracy of a Point-of-care (PoC) device measuring prothrombin time compared to the standard laboratory method. Patients undergoing major surgery and intensive care unit patients were included. PoC prothrombin time was measured by CoaguChek XS Plus (Roche Diagnostics, Switzerland). PoC and reference tests were performed independently and interpreted under blinded conditions. Using a cut-off prothrombin time of 50%, we calculated diagnostic accuracy measures, plotted a receiver operating characteristic (ROC) curve and tested for equivalence between the two methods. PoC sensitivity and specificity were 95% (95% CI 77%, 100%) and 95% (95% CI 91%, 98%) respectively. The negative likelihood ratio was 0.05 (95% CI 0.01, 0.32). The positive likelihood ratio was 19.57 (95% CI 10.62, 36.06). The area under the ROC curve was 0.988. Equivalence between the two methods was confirmed. CoaguChek XS Plus is a rapid and highly accurate test compared with the reference test. These findings suggest that PoC testing will be useful for monitoring intraoperative prothrombin time when coagulopathy is suspected. It could lead to a more rational use of expensive and limited blood bank resources.

The Use of a Vaginal Conductivity Probe to Influence Calf Sex Ratio via Altered Insemination Time

One hundred eighty-nine mixed breed beef heifers from 13 consignors enrolled in the MACEP heifer development project were utilized in this study. Heifers were synchronized by feeding 0.5 mg melengestrol acetate (MGA) per head per day for 14 days followed by an injection of prostaglandin F2a (PGF2a; 25 mg Lutalyse®) 17 days after the last MGA feeding. Each heifer was fitted with a Heatwatch® transmitter on the morning of PGF2a administration to facilitate detection of estrus. Vaginal conductivity measurements were taken using an Ovatec® probe every 12 hours for 96 hours beginning at the time of PGF2a injection. Heifers randomly assigned to produce a female calf were inseminated near the onset of estrus (as indicated by probe values of £ 55 on the decline). Heifers randomly assigned to produce a male calf were inseminated approximately 24 hours after the onset of estrus (as indicated by probe values of ³ 60 on the incline). All heifers not inseminated by 96 hours after PGF2a were mass inseminated in an attempt to impregnate as many heifers as possible. Heifers that were diagnosed as pregnant as a result of the artificial insemination were subjected to ultrasonography for fetal sex determination. Only 70 of the 189 heifers (37.0%) exhibited estrus according to Heatwatch® and incidence of estrus was influenced by heifer average daily gain, reproductive tract score, and disposition score. Heifers receiving a disposition score of 3 (78.7) had a higher (P<.05) probe reading at AI than those receiving a disposition score of 1 or 2 (70.8 and 72.5, respectively). Heifers with probe readings at insemination of 80 - 84 and > 84 had lower (P<.05) pregnancy rates to AI (13.6 and 0.0%, respectively) than heifers with probe readings in the ranges of < 60, 60 - 64, 65 - 69, 70 - 74, and 75 - 79 (35.7, 40.9, 31.4, 35.3, and 26.9% respectively). Heifers that were bred when probe values were increasing had a lower (P<.05) percentage of male fetuses (34.4%) than those bred during a period of decreasing probe values (69.2% male fetuses). These results demonstrate that a vaginal conductivity probe may be a useful tool to determine an insemination time that could potentially alter calf sex ratio.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner

BACKGROUND & AIMS Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

Is there good simulation basic training for end-to-side vascular microanastomoses?

BACKGROUND Microvascular anastomosis is the cornerstone of free tissue transfers. Irrespective of the microsurgical technique that one seeks to integrate or improve, the time commitment in the laboratory is significant. After extensive previous training on several animal models, we sought to identify an animal model that circumvents the following issues: ethical rules, cost, time-consuming and expensive anesthesia, and surgical preparation of tissues required to access vessels before performing the microsurgical training, not to mention that laboratories are closed on weekends. METHODS Between January 2012 and April 2012, a total of 91 earthworms were used for 150 microsurgical training exercises to simulate vascular end-to-side microanastomosis. The training sessions were divided into ten periods of 7 days. Each training session included 15 simulations of end-to-side vascular microanastomoses: larger than 1.5 mm (n=5), between 1.0 and 1.5 mm (n=5), and smaller than 1.0 mm (n=5). A linear model with the main variables being the number of weeks (as a numerical covariate) and the size of the animal (as a factor) was used to determine the trend in time of anastomosis over subsequent weeks as well as the differences between the different size groups. RESULTS The linear model shows a significant trend (p<0.001) in time of anastomosis in the course of the training, as well as significant differences (p<0.001) between the groups of animals of different sizes. For microanastomoses larger than 1.5 mm, the mean anastomosis time decreased from 19.3±1.0 to 11.1±0.4 min between the first and last week of training (decrease of 42.5%). For training with smaller diameters, the results showed a decrease in execution time of 43.2% (diameter between 1.0 and 1.5 mm) and 40.9% (diameter<1.0 mm) between the first and last periods. The study demonstrates an improvement in the dexterity and speed of nodes execution. CONCLUSION The earthworm appears to be a reliable experimental model for microsurgical training of end-to-side microanastomoses. Its numerous advantages are discussed here and we predict training on earthworms will significantly grow and develop in the near future. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The risk of early mortality of polytrauma patients associated to ISS, NISS, APACHE II values and prothrombin time

BACKGROUND: The early hemodynamic normalization of polytrauma patients may lead to better survival outcomes. The aim of this study was to assess the diagnostic quality of trauma and physiological scores from widely used scoring systems in polytrauma patients. METHODS: In total, 770 patients with ISS > 16 who were admitted to a trauma center within the first 24 hours after injury were included in this retrospective study. The patients were subdivided into three groups: those who died on the day of admission, those who died within the first three days, and those who survived for longer than three days. ISS, NISS, APACHE II score, and prothrombin time were recorded at admission. RESULTS: The descriptive statistics for early death in polytrauma patients who died on the day of admission, 1--3 days after admission, and > 3 days after admission were: ISS of 41.0, 34.0, and 29.0, respectively; NISS of 50.0, 50.0, and 41.0, respectively; APACHE II score of 30.0, 25.0, and 15.0, respectively; and prothrombin time of 37.0%, 56.0%, and 84%, respectively. These data indicate that prothrombin time (AUC: 0.89) and APACHE II (AUC: 0.88) have the greatest prognostic utility for early death. CONCLUSION: The estimated densities of the scores may suggest a direction for resuscitative procedures in polytrauma patients.Trial registration: "Retrospektive Analysen in der Chirurgischen Intensivmedizin" StV01-2008.http://www.kek.zh.ch/internet/gesundheitsdirektion/kek/de/home.html.

Penetrating or stricturing diseases are the major determinants of time to first and repeat resection surgery in Crohn's disease

BACKGROUND About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS. METHODS Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS. RESULTS Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05). CONCLUSION The risk of RS was confirmed to be very high for CD in our cohort. Smoking status at diagnosis, but mostly penetrating and stricturing diseases increase the risk of RS.

Neurogranin controls the spatiotemporal pattern of postsynaptic Ca2+/CaM signaling.

Neurogranin (Ng) is a postsynaptic IQ-motif containing protein that accelerates Ca(2+) dissociation from calmodulin (CaM), a key regulator of long-term potentiation and long-term depression in CA1 pyramidal neurons. The exact physiological role of Ng, however, remains controversial. Two genetic knockout studies of Ng showed opposite outcomes in terms of the induction of synaptic plasticity. To understand its function, we test the hypothesis that Ng could regulate the spatial range of action of Ca(2+)/CaM based on its ability to accelerate the dissociation of Ca(2+) from CaM. Using a mathematical model constructed on the known biochemistry of Ng, we calculate the cycle time that CaM molecules alternate between the fully Ca(2+) saturated state and the Ca(2+) unbound state. We then use these results and include diffusion of CaM to illustrate the impact that Ng has on modulating the spatial profile of Ca(2+)-saturated CaM within a model spine compartment. Finally, the first-passage time of CaM to transition from the Ca(2+)-free state to the Ca(2+)-saturated state was calculated with or without Ng present. These analyses suggest that Ng regulates the encounter rate between Ca(2+) saturated CaM and its downstream targets during postsynaptic Ca(2+) transients.

Sea surface temperature and sea ice variability in the subpolar North Atlantic from explosive volcanism of the late thirteenth century

In this study, we use IP and alkenone biomarker proxies to document the subdecadal variations of sea ice and sea surface temperature in the subpolar North Atlantic induced by the decadally paced explosive tropical volcanic eruptions of the second half of the thirteenth century. The short- and long-term evolutions of both variables were investigated by cross analysis with a simulation of the IPSL-CM5A LR model. Our results show short-term ocean cooling and sea ice expansion in response to each volcanic eruption. They also highlight that the long response time of the ocean leads to cumulative surface cooling and subsurface heat buildup due to sea ice capping. As volcanic forcing relaxes, the surface ocean rapidly warms, likely amplified by subsurface heat, and remains almost ice free for several decades

The spatial distribution of water in the inner coma of Comet 9P/Tempel 1: Comparison between models and observations

The near nucleus coma of Comet 9P/Tempel 1 has been simulated with the 3D Direct Simulation Monte Carlo (DSMC) code PDSC++ (Su, C.-C. [2013]. Parallel Direct Simulation Monte Carlo (DSMC) Methods for Modeling Rarefied Gas Dynamics. PhD Thesis, National Chiao Tung University, Taiwan) and the derived column densities have been compared to observations of the water vapour distribution found by using infrared imaging spectrometer on the Deep Impact spacecraft (Feaga, L.M., A’Hearn, M.F., Sunshine, J.M., Groussin, O., Farnham, T.L. [2007]. Icarus 191(2), 134–145. http://dx.doi.org/10.1016/j.icarus.2007.04.038). Modelled total production rates are also compared to various observations made at the time of the Deep Impact encounter. Three different models were tested. For all models, the shape model constructed from the Deep Impact observations by Thomas et al. (Thomas, P.C., Veverka, J., Belton, M.J.S., Hidy, A., A’Hearn, M.F., Farnham, T.L., et al. [2007]. Icarus, 187(1), 4–15. http://dx.doi.org/10.1016/j.icarus.2006.12.013) was used. Outgassing depending only on the cosine of the solar insolation angle on each shape model facet is shown to provide an unsatisfactory model. Models constructed on the basis of active areas suggested by Kossacki and Szutowicz (Kossacki, K., Szutowicz, S. [2008]. Icarus, 195(2), 705–724. http://dx.doi.org/10.1016/j.icarus.2007.12.014) are shown to be superior. The Kossacki and Szutowicz model, however, also shows deficits which we have sought to improve upon. For the best model we investigate the properties of the outflow.

Bond Strength of Resin Composite to Dentin with Different Adhesive Systems: Influence of Relative Humidity and Application Time.

PURPOSE To investigate the influence of relative humidity and application time on bond strength to dentin of different classes of adhesive systems. MATERIALS AND METHODS A total of 360 extracted human molars were ground to mid-coronal dentin. The dentin specimens were treated with one of six adhesive systems (Syntac Classic, OptiBond FL, Clearfil SE Bond, AdheSE, Xeno Select, or Scotchbond Universal), and resin composite (Filtek Z250) was applied to the treated dentin surface under four experimental conditions (45% relative humidity/application time according to manufacturers' instructions; 45% relative humidity/reduced application time; 85% relative humidity/application time according to manufacturers' instructions; 85% relative humidity/reduced application time). After storage (37°C, 100% humidity, 24 h), shear bond strength (SBS) was measured and data analyzed with nonparametric ANOVA followed by Kruskal-Wallis tests and Mann-Whitney U-tests with Bonferroni-Holm correction for multiple testing (level of significance: α = 0.05). RESULTS Increased relative humidity and reduced application time had no effect on SBS for Clearfil SE Bond and Scotchbond Universal (p = 1.00). For Syntac Classic, OptiBond FL, AdheSE, and Xeno Select there was no effect on SBS of reduced application time of the adhesive system (p ≥ 0.403). However, increased relative humidity significantly reduced SBS for Syntac Classic, OptiBond FL, and Xeno Select irrespective of application time (p ≤ 0.003), whereas for AdheSE, increased relative humidity significantly reduced SBS at recommended application time only (p = 0.002). CONCLUSION Generally, increased relative humidity had a detrimental effect on SBS to dentin, but reduced application time had no effect.