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CSL112 (apolipoprotein A-I, apo AI [human]) is an investigational drug in Phase 3 development for risk reduction of early recurrent cardiovascular events following an acute myocardial infarction (AMI). Although CSL112 is known to be well tolerated with a regimen of four weekly 6 g intravenous infusions after AMI, high doses of reconstituted apo AI preparations can transiently elevate liver enzymes in rats, raising the possibility of additive liver toxicity and toxicokinetic (TK) effects upon co-administration with cholesterol-lowering drugs, i.e., HMG-CoA reductase and proprotein convertase subtilisin/kexin type 9 inhibitors. We performed a toxicity and TK study in CD rats assigned to eleven treatment groups, including two dose levels of intravenous (IV) CSL112 (140 mg/kg, low-dose; 600 mg/kg, high-dose) administered as a single dose, alone or with intravenous alirocumab 50 mg/kg/week and/or oral atorvastatin 10 mg/kg/day. In addition, control groups of atorvastatin and alirocumab alone and in combination were investigated. Results showed some liver enzyme elevations (remaining <2-fold of baseline) related to administration of CSL112 alone. There was limited evidence of an additive effect of CSL112 on liver enzymes when combined, at either dose level, with alirocumab and/or atorvastatin, and histology revealed no evidence of an increased incidence or severity of hepatocyte vacuolation compared to the control treatments. Co-administration of the study drugs had minimal effect on their respective exposure levels, and on levels of total cholesterol and high-density lipoprotein cholesterol. These data support concomitant use of CSL112 with alirocumab and/or atorvastatin with no anticipated negative impact on liver safety and TK.

BACKGROUND: Firearm-related injury is an important and preventable cause of death and disability. We describe the burden, baseline characteristics and regional rates of firearm-related injury and death in Ontario. METHODS: We conducted a population-based cross-sectional study using linked data from health administrative data sets held at ICES. We identified residents of Ontario of all ages who were injured or died as a result of a firearm discharge between Apr. 1, 2002, and Dec. 31, 2016. We included injuries classified as assault, unintentional, self-harm or undetermined intent secondary to handguns, rifles, shotguns and larger firearms. The primary outcome was the incidence of nonfatal and fatal injuries resulting in an emergency department visit, hospital admission or death. We also describe regional and temporal rates. RESULTS: We identified 6483 firearm-related injuries (annualized injury rate 3.54 per 100 000 population), of which 2723 (42.3%) were fatal. Assault accounted for 40.2% (1494/3715) of nonfatal injuries and 25.5% (694/2723) of deaths. Young men, predominantly in urban neighbourhoods, within the lowest income quintile were overrepresented in this group. Injuries secondary to self-harm accounted for 68.0% (1366/2009) of injuries and occurred predominantly in older men living in rural Ontario across all income quintiles. The case fatality rate of injuries secondary to self-harm was 91.7%. Self-harm accounted for 1842 deaths (67.6%). INTERPRETATION: We found that young urban men were most likely to be injured in firearm-related assaults and that more than two-thirds of self-harm-related injuries occurred in older rural-dwelling men, most of whom died from their injuries. This highlights a need for suicide-prevention strategies in rural areas targeted at men aged 45 or older.

The Theory of Planned Behavior (TPB) predicts that a combination of attitudes, perceived norms, and perceived behavioral control predict intentions, and that intentions ultimately predict behavior. Previous studies have found that the TPB can predict students’ engagement in plagiarism. Furthermore, the General Theory of Crime suggests that self-control is particularly important in predicting engagement in unethical behavior such as plagiarism. In Study 1 (N = 229), we incorporated self-control in a TPB model and tested whether norms, attitudes, and self-control predicted intention to plagiarize and plagiarism behavior. The best statistical fit for the path-analytic model was achieved when a direct path from self-control to plagiarism engagement was specified. In Study 2 (N = 320), we added a measure of perceived behavioral control and split the measurement of norms into descriptive (normal behavior) and injunctive (good behavior) components. This study found that both self-control and perceived-behavioral control additively contributed to the prediction of plagiarism and the path-analytic model achieved its best fit when direct paths from perceived norms to plagiarism behavior were specified. These studies suggest that setting strong anti-plagiarism norms, such as by the use of honor codes, and seeking to enhance students’ self-control may reduce engagement in plagiarism.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare, potentially devastating autoimmune disease of the skin. IgG autoantibodies directed against type VII collagen (Col7), the major component of anchoring fibrils, induce skin fragility leading to cutaneous and mucocutaneous blister formation, which is mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays are critical to establish the diagnosis of EBA early to avoid irreversible sequelae. OBJECTIVES: The present international, retrospective multicentre study included a large cohort of patients with EBA and evaluated the diagnostic power of four different diagnostic assays for the detection of anti-Col7 IgG autoantibodies. METHODS: Overall, 95 EBA sera and 200 control sera consisting of 100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy controls were tested for anti-Col7 IgG autoantibodies using indirect immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay (ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients with positive direct immunofluorescence and IgG reactivity in at least one of the immunoserological assays (IIF, ELISA, WB). RESULTS: A Col7-NC1/NC2 ELISA (MBL, Nagoya, Japan) showed the highest sensitivity (97·9%), followed by a Col7-NC1 ELISA (Euroimmun, Lübeck, Germany) (89·5%), WB with Col7-NC1 (85·3%), and IIF on saline-split human skin (74·7%). The specificities of both ELISA systems were comparable (NC1 98·7%, NC1/NC2 99·3%). Furthermore, WB was more sensitive than IIF, which was more specific. CONCLUSIONS: The two commercially available ELISA systems allow for a highly sensitive and specific diagnosis of EBA. The sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the ELISA based on the Col7-NC1 domain only.

Modern cosmology has sharpened questions posed for millennia about the origin of our cosmic habitat. The age-old questions have been transformed into two pressing issues primed for attack in the coming decade: How did the Universe begin? and What physical laws govern the Universe at the highest energies? The clearest window onto these questions is the pattern of polarization in the Cosmic Microwave Background (CMB), which is uniquely sensitive to primordial gravity waves. A detection of the special pattern produced by gravity waves would be not only an unprecedented discovery, but also a direct probe of physics at the earliest observable instants of our Universe. Experiments which map CMB polarization over the coming decade will lead us on our first steps towards answering these age-old questions., Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 212 author available at http://cmbpol.uchicago.edu

We review how initial state effects generically yield an oscillatory component in the primordial power spectrum of inflationary density perturbations. These oscillatory corrections parametrize unknown new physics at a scale $M$ and are potentially observable if the ratio $H_{infl}/M$ is sufficiently large. We clarify to what extent present and future CMB data analysis can distinguish between the different proposals for initial state corrections., Comment: Invited talk by B. Greene at the XXII Texas Symposium on Relativistic Astrophysics, Stanford University, 13-17 December 2004, (TSRA04-0001), 8 pages, LaTeX, some references added, added paragraph at the end of section 2 and an extra note added after the conclusions regarding modifications to the large k power spectra deduced from galaxy surveys

A new type of log-periodic antenna, the wire log-spiral, has been designed and implemented on low temperature grown GaAs substrates. The new antenna is compared to two traditional antenna designs (log-periodic and dipole) for the detection of pulsed THz radiation.

In 1982, the Fort Sill Field Unit of the Army Research Institute (ARI) developed a method for estimating how many launchers a Corps Support Weapon System (CSWS) platoon leader will be able to control. The Director of the CSWS Special Task Force was concerned with the tradeoff between number of launchers controlled and platoon leader workload. Although having each platoon leader control many launchers would conserve resources, it would also increase workload. At some point, the number of launchers would exceed what the platoon leader could adequately control, he would fall behind in completing his tasks, and the performance of the platoon would suffer. The Field Unit developed a computer-based simulation model that can be used to predict the platoon leader's ability to keep up with his work. The simulation model consists of two components. The first component is a task library, the second a computer program that operates upon the data contained in the library. This report describes the development of the simulation model, some findings generated when we ran the model to estimate the span of control for CSWS platoon leaders, and the uses to which the model could be put by system developers.

The report presents the results obtained from seven additional quasi- instantaneous, line-source releases. A finely divided particulate tracer was used in three of these trials, and a vapor tracer was used in the remaining four trials. Tabular summaries of the dosage measurements and graphs of the vertical expansion rates are presented., Supplement to its final rept., Contract DA-42-007-AMC-36(R).

This eighth volume of the ASTRA documentation gives a brief introduction of the ASTRA Computer System. Major design specifications are presented, and the two user-oriented input languages of ASTRA, SAIL and SAUL, are discussed. Brief descriptions of the major computational modules are given and finally, a few engineering applications are presented. (Author)

To evaluate the effect of forging and heat treatment parameters on titanium 6A1-4V alloy (AMS 4928), various microstructures were investigated and compared in a deflection-controlled low cycle fatigue test program. The test specimen was designed to simulate the strain state observed in gas turbine engine components. The results of this study will be used to optimize the design of compressor disks. Parameters investigated include environment, mean strain, and surface condition. The number of cycles to initiate a fatigue crack and the rate of crack propagation were measured to evaluate the microstructures. The number of cycles to crack initiation was correlated with a mechanistic theory based on the static properties of the materials investigated., Presented at Materials Engineering and Exposition and Congress, Detroit, MI, 14-17 Oct 1968.