How taphonomic alteration affects the detection and imaging of striations in stab wounds

Stabbing with a kitchen knife is a common methodof homicide in Europe. Serrated knives may leave tool mark-ings (striations) in tissues. Documentation of striations is nec-essary for their use as forensic evidence. Traditional methods(physical casting and photography) have significant limita-tions, and micro-computed tomography (micro-CT) has beentrialled in cartilage toBvirtually cast^wounds. Previous re-search has shown the proportion of striations in cartilage fallsfollowing decomposition. This project has investigated theeffects of taphonomic alteration and documentation methodsof striations in porcine skin. Fresh, decomposed, mummified,burnt and waterlogged stab wounds in a porcine analoguewere excised and imaged using photography, stereo-opticalmicroscopy and micro-CT. The proportion of striations ineach taphonomic group was determined from the images byindependent analysts. Striations were observed more frequent-ly in serrated blade wounds, although they were also identifiedin non-serrated blade wounds. The proportion of woundsshowing striations declined following decomposition. An in-versely proportional linear correlation between advancing de-composition and proportion of striations existed. Dehydration(mummification and burning) rendered serrated and non-serrated blade wounds indistinguishable. Water compositionaffected the preservation of striations. Identification ofstriations gradually declined after decomposition in tap water,but persisted to a point when left in brackish water. All threetechniques imaged striations; however, the optimum tech-nique was stereo-optical microscopy due to practical advan-tages and specific limitations affecting photography and mi-cro-CT. This study demonstrates the effects of taphonomicalteration on striations and suggests stereo-optical microscopyis the optimum method for their documentation

Room temperature plasmon laser by total internal reflection

Plasmon lasers create and sustain intense and coherent optical fields below light's diffraction limit with the unique ability to drastically enhance light-matter interactions bringing fundamentally new capabilities to bio-sensing, data storage, photolithography and optical communications. However, these important applications require room temperature operation, which remains a major hurdle. Here, we report a room temperature semiconductor plasmon laser with both strong cavity feedback and optical confinement to 1/20th of the wavelength. The strong feedback arises from total internal reflection of surface plasmons, while the confinement enhances the spontaneous emission rate by up to 20 times.Comment: 8 Page, 2 Figure

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

<p>Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.</p> <p>Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.</p> <p>Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.</p> <p>Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.</p&gt

Exposure and impact of a mass media campaign targeting sexual health amongst Scottish men who have sex with men: an outcome evaluation

Background: This paper explores the exposure and impact of a Scottish mass media campaign: Make Your Position Clear. It ran from October 2009 to July 2010, targeted gay men and other men who have sex with men (MSM), and had two key aims: to promote regular sexual health and HIV testing every 6 months, and to promote the use of appropriate condoms and water-based lubricant with each episode of anal intercourse. Methods: A cross-sectional survey (anonymous and self-report) was conducted 10 months after the campaign was launched (July 2010). Men were recruited from commercial venues. Outcome measures included use of lubricant, testing for sexually transmitted infections and HIV, and intentions to seek HIV testing within the following six months. Linear-by-linear chi-square analysis and binary logistic regressions were conducted to explore the associations between the outcome measures and campaign exposure. Results: The total sample was 822 men (62.6% response rate). Men self-identifying as HIV positive were excluded from the analysis (n = 38). Binary logistic analysis indicated that those with mid or high campaign exposure were more likely to have been tested for HIV in the previous six months when adjusted for age, area of residence and use of the “gay scene” (AOR = 1.96, 95% CI = 1.26 to 3.06, p = .003), but were not more likely to be tested for STIs (AOR = 1.37, 95% CI = 0.88 to 2.16, p = .167). When adjusted for previous HIV testing, those with mid or high campaign exposure were not more likely to indicate intention to be tested for HIV in the following six months (AOR = 1.30, 95% CI = 0.73 to 2.32, p = .367). Those with no campaign exposure were less likely than those with low exposure to have used appropriate lubricant with anal sex partners in the previous year (AOR = 0.42, 95% CI = 0.23 to 0.77, p = .005). Conclusions: The campaign had demonstrable reach. The analysis showed partial support for the role of mass media campaigns in improving sexual health outcomes. This suggests that a role for mass media campaigns remains within combination HIV prevention

Nonlinear optics: Nonlinear virtues of multimode fibre

Supercontinuum generation — the extreme spectral broadening of laser light (a span from the ultraviolet to the mid-infrared is possible) — is a fascinating process that takes place in a dispersive and strongly nonlinear optical medium

Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.

The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells

d=3 Bosonic Vector Models Coupled to Chern-Simons Gauge Theories

We study three dimensional O(N)_k and U(N)_k Chern-Simons theories coupled to a scalar field in the fundamental representation, in the large N limit. For infinite k this is just the singlet sector of the O(N) (U(N)) vector model, which is conjectured to be dual to Vasiliev's higher spin gravity theory on AdS_4. For large k and N we obtain a parity-breaking deformation of this theory, controlled by the 't Hooft coupling lambda = 4 \pi N / k. For infinite N we argue (and show explicitly at two-loop order) that the theories with finite lambda are conformally invariant, and also have an exactly marginal (\phi^2)^3 deformation. For large but finite N and small 't Hooft coupling lambda, we show that there is still a line of fixed points parameterized by the 't Hooft coupling lambda. We show that, at infinite N, the interacting non-parity-invariant theory with finite lambda has the same spectrum of primary operators as the free theory, consisting of an infinite tower of conserved higher-spin currents and a scalar operator with scaling dimension \Delta=1; however, the correlation functions of these operators do depend on lambda. Our results suggest that there should exist a family of higher spin gravity theories, parameterized by lambda, and continuously connected to Vasiliev's theory. For finite N the higher spin currents are not conserved.Comment: 34 pages, 29 figures. v2: added reference

Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

Long term time variability of cosmic rays and possible relevance to the development of life on Earth

An analysis is made of the manner in which the cosmic ray intensity at Earth has varied over its existence and its possible relevance to both the origin and the evolution of life. Much of the analysis relates to the 'high energy' cosmic rays ($E>10^{14}eV;=0.1PeV$) and their variability due to the changing proximity of the solar system to supernova remnants which are generally believed to be responsible for most cosmic rays up to PeV energies. It is pointed out that, on a statistical basis, there will have been considerable variations in the likely 100 My between the Earth's biosphere reaching reasonable stability and the onset of very elementary life. Interestingly, there is the increasingly strong possibility that PeV cosmic rays are responsible for the initiation of terrestrial lightning strokes and the possibility arises of considerable increases in the frequency of lightnings and thereby the formation of some of the complex molecules which are the 'building blocks of life'. Attention is also given to the well known generation of the oxides of nitrogen by lightning strokes which are poisonous to animal life but helpful to plant growth; here, too, the violent swings of cosmic ray intensities may have had relevance to evolutionary changes. A particular variant of the cosmic ray acceleration model, put forward by us, predicts an increase in lightning rate in the past and this has been sought in Korean historical records. Finally, the time dependence of the overall cosmic ray intensity, which manifests itself mainly at sub-10 GeV energies, has been examined. The relevance of cosmic rays to the 'global electrical circuit' points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics

Autophosphorylation is a mechanism of inhibition in twitchin kinase

Titin-like kinases are muscle-specific kinases that regulate mechanical sensing in the sarcomere. Twitchin kinase (TwcK) is the best-characterized member of this family, both structurally and enzymatically. TwcK activity is auto-inhibited by a dual intrasteric mechanism, in which N- and C-terminal tail extensions wrap around the kinase domain, blocking the hinge region, the ATP binding pocket and the peptide substrate binding groove. Physiologically, kinase activation is thought to occur by a stretch-induced displacement of the inhibitory tails from the kinase domain. Here, we now show that TwcK inhibits its catalysis even in the absence of regulatory tails, by undergoing auto-phosphorylation at mechanistically important elements of the kinase fold. Using mass spectrometry, site-directed mutagenesis and catalytic assays on recombinant samples, we identify residues T212, T301, T316 and T401 as primary auto-phosphorylation sites in TwcK in vitro. Taken together, our results suggest that residue T316, located in the peptide substrate binding P + 1 loop, is the dominantly regulatory site in TwcK. Based on these findings, we conclude that TwcK is regulated through a triple-inhibitory mechanism consisting of phosphorylation and intrasteric blockage, which is responsive not only to mechanical cues but also to biochemical modulation. This implies that mechanically stretched conformations of TwcK do not necessarily correspond to catalytically active states, as previously postulated. This further suggests a phosphorylation-dependent desensitization of the TwcK-mediated mechanoresponse of the sarcomere in vivo