Investigation of Protease Activity in Early Postmortem MuscleSubjected to Alternative Chilling Conditions

The objective of this study was two-fold: 1) determine the conditions (temperature, pH) that exist in early postmortem muscle of normally-chilled and delay-chilled beef carcasses to provide a model for in vitro work, and 2) determine the mechanism by which specific early postmortem temperature/pH conditions found in normally-chilled and delay-chilled muscle influence the enzymes that regulate the aging process in vitro. For objective 1, seven market-ready calves (HCW 848 ± 17.5 lb) were harvested with the right sides subjected to normal chilling (2.3°C) and the left sides subjected to ambient temperature (delay chilling; 22.6°C) for an additional 4.75 h and then allowed to normally chill. Carcasses were monitored for longissimus dorsi muscle temperature, pH, postmortem proteolysis, and sarcomere length. Steaks aged for 1, 7 and 14 d were evaluated for tenderness using Warner-Bratzler shear force (WBSF) and carcasses were swabbed over the rump, flank, and brisket for total aerobic plate counts. Delay-chilled carcasses had a faster pH decline and a slower rate of carcass cooling (P\u3c0.05). No differences were seen in sarcomere length, total plate counts, or in postmortem proteolysis of troponin T (TnT)(P\u3e0.05). WBSF was not different at 1 and 7 d (P\u3e0.05), but was less in steaks from normally-chilled carcasses at 14 d (P=0.0144). Further data analysis indicated a strong, negative correlation between 14 d WBSF and the change in pH from 6 to 12 hr postmortem (Figure 3, r = -0.8105, P=0.0004). These results were utilized to design the methodology for objective 2, where isolated myofibrils were subjected to μ-calpain digestion at 4 or 22°C with either a fast or slow initial pH decline. Digests were evaluated for pH, μ-calpain activity, and intact TnT degradation. Digestions with a fast initial pH decline had lower pH values in the early time points of the incubation (P\u3c0.05). No differences were detected in μ-calpain activity or in the degradation of intact TnT (P\u3e0.05) between the fast and slow pH decline treatments. Meanwhile, a temperature x time interaction was revealed in μ-calpain activity and in the degradation of intact TnT (P\u3c0.05). Additionally, intact TnT and μ-calpain activity decreased over time (P\u3c0.05) while warmer digestions resulted in a tendency for reduced μ-calpain activity (P=0.0854) and a significant reduction in intact TnT (P=0.0105)

Birth rates after radioactive iodine treatment for differentiated thyroid cancer

Treatment with radioactive iodine (RAI) for differentiated thyroid cancer has been associated with alterations in gonadal function in women, including changes in menstrual function and an earlier age at menopause. Our objective was to evaluate associations between RAI and postdiagnosis live birth rates among thyroid cancer survivors diagnosed at ages 15–39 years. We identified women diagnosed with differentiated thyroid cancer between January 2000 and December 2013 in the North Carolina Central Cancer Registry (CCR). CCR records were linked to state birth certificate files to identify livebirths to thyroid cancer survivors through December 2014. Person-years of follow-up were accrued from 6 months after diagnosis to first birth, 46th birthday, death, or December 31, 2014, whichever came first. Cox proportional hazards regression was used to estimate hazards ratios (HR) and 95% confidence intervals (CI) for first livebirth. Among 2,360 women with a differentiated thyroid cancer diagnosis, 53% received RAI. The cumulative incidence of birth at the end of follow-up (maximum 14.5 years) was 30.0 and 29.3% among those who were and were not treated with RAI, respectively. Overall, first birth rates did not significantly differ between groups (HR = 1.00; 95% CI: 0.82, 1.23). In our observational cohort, treatment with RAI was not associated with a reduced birth rate. Our findings add to the evidence available for counseling thyroid cancer patients with concerns about future fertility

An integrated approach to emergency triage assessment and treatment in Uganda

Background: Reducing mortality among patients who present to primary referral facilities in need of emergency care requires efficient triage and immediate correct management known more commonly as Emergency Triage, Assessment and Treatment (ETAT). Integrated Management of Infectious Disease (IMID) training and on-site support (OSS) have been the tools used to build capacity among mid-level practitioners who have been found to be lacking in ETAT skills in the region.Objective: To investigate the use of Integrated Management of Infectious Disease (IMID) training and on-site support (OSS) tools to improve ETAT in health care facilities in rural Uganda.Design: Randomized mixed methods evaluation.Setting: Thirty-six facilities in Uganda were randomized 1:1 to arm A (IMID and OSS) and arm B (IMID alone).Subjects: Two mid-level practitioners, (clinical officers or senior nurses), from each facility participated in offsite IMID training. Staff at 18 facilities in arm A participated in OSS (two days each month of outreach and quality improvement for nine months).Results: Time series data on facility performance of three ETAT indicators were compared over 14 months and data on mortality among pediatric inpatients were compared across arms. Improvements differed across facilities and indicators, but steady improvement in triage occurred in arm A, with convergence across arms in the management of emergency patients. Analysis of baseline indicators and improvements demonstrated that facilities could improve their performance regardless of their starting point.Conclusion: IMID and OSS both improved the management of patients with an acute illness presenting to rural health facilities

Green functions for generalized point interactions in 1D: A scattering approach

Recently, general point interactions in one dimension has been used to model a large number of different phenomena in quantum mechanics. Such potentials, however, requires some sort of regularization to lead to meaningful results. The usual ways to do so rely on technicalities which may hide important physical aspects of the problem. In this work we present a new method to calculate the exact Green functions for general point interactions in 1D. Our approach differs from previous ones because it is based only on physical quantities, namely, the scattering coefficients, $R$ and $T$, to construct $G$. Renormalization or particular mathematical prescriptions are not invoked. The simple formulation of the method makes it easy to extend to more general contexts, such as for lattices of $N$ general point interactions; on a line; on a half-line; under periodic boundary conditions; and confined in a box.Comment: Revtex, 9 pages, 3 EPS figures. To be published in PR

p53 convergently activates Dux/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models

p53 activates Dux in mouse embryos and embryonic stem cells, as well as DUX4 in human facioscapulohumeral muscular dystrophy cell models.In mammalian embryos, proper zygotic genome activation (ZGA) underlies totipotent development. Double homeobox (DUX)-family factors participate in ZGA, and mouse Dux is required for forming cultured two-cell (2C)-like cells. Remarkably, in mouse embryonic stem cells, Dux is activated by the tumor suppressor p53, and Dux expression promotes differentiation into expanded-fate cell types. Long-read sequencing and assembly of the mouse Dux locus reveals its complex chromatin regulation including putative positive and negative feedback loops. We show that the p53-DUX/DUX4 regulatory axis is conserved in humans. Furthermore, we demonstrate that cells derived from patients with facioscapulohumeral muscular dystrophy (FSHD) activate human DUX4 during p53 signaling via a p53-binding site in a primate-specific subtelomeric long terminal repeat (LTR)10C element. In summary, our work shows that p53 activation convergently evolved to couple p53 to Dux/DUX4 activation in embryonic stem cells, embryos and cells from patients with FSHD, potentially uniting the developmental and disease regulation of DUX-family factors and identifying evidence-based therapeutic opportunities for FSHD.Molecular Technology and Informatics for Personalised Medicine and HealthFunctional Genomics of Muscle, Nerve and Brain Disorder

An improved method for measuring muon energy using the truncated mean of dE/dx

The measurement of muon energy is critical for many analyses in large Cherenkov detectors, particularly those that involve separating extraterrestrial neutrinos from the atmospheric neutrino background. Muon energy has traditionally been determined by measuring the specific energy loss (dE/dx) along the muon's path and relating the dE/dx to the muon energy. Because high-energy muons (E_mu > 1 TeV) lose energy randomly, the spread in dE/dx values is quite large, leading to a typical energy resolution of 0.29 in log10(E_mu) for a muon observed over a 1 km path length in the IceCube detector. In this paper, we present an improved method that uses a truncated mean and other techniques to determine the muon energy. The muon track is divided into separate segments with individual dE/dx values. The elimination of segments with the highest dE/dx results in an overall dE/dx that is more closely correlated to the muon energy. This method results in an energy resolution of 0.22 in log10(E_mu), which gives a 26% improvement. This technique is applicable to any large water or ice detector and potentially to large scintillator or liquid argon detectors.Comment: 12 pages, 16 figure

All-particle cosmic ray energy spectrum measured with 26 IceTop stations

We report on a measurement of the cosmic ray energy spectrum with the IceTop air shower array, the surface component of the IceCube Neutrino Observatory at the South Pole. The data used in this analysis were taken between June and October, 2007, with 26 surface stations operational at that time, corresponding to about one third of the final array. The fiducial area used in this analysis was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV measured for three different zenith angle ranges between 0{\deg} and 46{\deg}. Because of the isotropy of cosmic rays in this energy range the spectra from all zenith angle intervals have to agree. The cosmic-ray energy spectrum was determined under different assumptions on the primary mass composition. Good agreement of spectra in the three zenith angle ranges was found for the assumption of pure proton and a simple two-component model. For zenith angles {\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on composition assumption. Spectral indices above the knee range from -3.08 to -3.11 depending on primary mass composition assumption. Moreover, an indication of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change