"Death may come on like a stroke of lightening ...”: Phenomenological and morphological aspects of fatalities caused by manure gas

Due to the decomposition of biological material, hydrogen sulphide (H2S) is produced. In low concentrations, the well-known smell of "rotten eggs” is associated with H2S. In higher concentrations, H2S is an odourless and colourless gas that may cause rapid loss of consciousness, neurological and respiratory depression and imminent death—"... like a stroke of lightening”. Hydrogen sulphide poisoning is an un-common incident that is often associated with colleague fatalities. In this study, 4 fatal accidents with 10 deceased victims are reported and the morphological and phenomenological aspects are presented. In these cases, the morphological findings, namely, discolouration of the livores, pulmonary pathologies and sub-mucosal or sub-serosal congestion bleeding were found in nearly all cases. Also the impending threat for colleagues, first aid helpers and professional rescue teams is demonstrated. The suspicion of a fatal H2S intoxication should be based on a precise scene analysis with respect to the possibility of life-threatening H2S intoxication for the helpers, the typical scent of rotten eggs, which may be noted on the corpses and the abovementioned morphological findings. The diagnosis should be confirmed by a qualitative and, if possible, quantitative analysis of H2

Radiosektion: Computertomographie-assistierte Rekonstruktion eines erweiterten Suizids

Zusammenfassung: Erweiterte Suizide durch Schusswaffen sind häufig durch eine sorgfältige Fundortanalyse zu klären. Im dargestellten Fall wurde eine 38-jährige Frau in Rückenlage auf dem Bett im Schlafzimmer aufgefunden. Im Bereich der linken Brust fand sich eine rundliche Einschusswunde. Neben dem Bett wurde eine Schusswaffe gefunden. Im Wohnzimmer lag ein 40-jähriger Mann in Bauchlage auf der Erde in einer größeren Blutlache. Ein unvollendeter Abschiedsbrief fand sich auf dem Esstisch. Nach der äußeren Leichenschau am Fundort erfolgte eine Röntgenschichtuntersuchung. Hierdurch wurde bei der Frau ein absteigender Schusskanal von der linken Brust durch die Herzspitze dargestellt. Das Projektil konnte im Rippenzwischenraum nahe der Wirbelsäule lokalisiert werden. Bei dem Mann wurden ein Schusskanal durch den harten Gaumen und ein Projektil in der Schädelhöhle festgestellt; dieses lag nicht in einer Linie mit dem Schusskanal, sodass ein "Ringelschuss" diagnostiziert wurde. Die nachfolgende Sektion beider Leichen bestätigte die Befunde. Die bei der Autopsie sichergestellten Projektile konnten durch ballistische Untersuchungen der am Ereignisort sichergestellten Waffe zugeordnet werde

Incidental prostate cancer prevalence at radical cystoprostatectomy—importance of the histopathological work-up

The reported incidental prostate cancer prevalence rates at radical cystoprostatectomy cover a range from 4 to 60%. We investigated the influence of the histopathological work-up on prostate cancer prevalence rates. We identified 114 patients who had undergone cystoprostatectomy for bladder cancer between 2000 and 2012. Complete histopathological assessment was defined as follows: (i) complete embedding of the prostate gland, (ii) sectioning of 15 or more prostate sections, and (iii) processing as whole mount slides. Prostate cancer prevalence rates derived from complete and incomplete histopathological assessments were compared. The overall prostate cancer prevalence rate was 59.6%. A mean of 14.4 macroscopic tissue sections (thickness 3-5mm) were sectioned. Sectioning ≥15 sections resulted in a prostate cancer detection rate of 75%, compared to 42.6% when sectioning <15 sections (p < 0.001). Complete embedding yielded a prostate cancer detection rate of 72.3 and of 23.1% for partly embedded prostates (p < 0.0001). Prostate cancer was detected in 68.8% of the whole mounted samples and in 38.2% of the samples sectioned as standard slides (p < 0.01); according to the criteria described by Epstein and Ohori, 44.1% of the detected prostate cancers were clinically significant. The quality of the histopathological work-up significantly influences prostate cancer detection rates and might at least partially explain the highly variable reported incidental prostate cancer prevalence rates at cystoprostatectomy (CP). The high proportion of significant prostate cancer found in our series calls for a careful surgical approach to the prostate during CP

Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes

Enhanced ion acceleration from transparency-driven foils demonstrated at two ultraintense laser facilities

Laser-driven ion sources are a rapidly developing technology producing high energy, high peak current beams. Their suitability for applications, such as compact medical accelerators, motivates development of robust acceleration schemes using widely available repetitive ultraintense femtosecond lasers. These applications not only require high beam energy, but also place demanding requirements on the source stability and controllability. This can be seriously affected by the laser temporal contrast, precluding the replication of ion acceleration performance on independent laser systems with otherwise similar parameters. Here, we present the experimental generation of >60 MeV protons and >30 MeV u-1 carbon ions from sub-micrometre thickness Formvar foils irradiated with laser intensities >1021 Wcm2. Ions are accelerated by an extreme localised space charge field ≳30 TVm-1, over a million times higher than used in conventional accelerators. The field is formed by a rapid expulsion of electrons from the target bulk due to relativistically induced transparency, in which relativistic corrections to the refractive index enables laser transmission through normally opaque plasma. We replicate the mechanism on two different laser facilities and show that the optimum target thickness decreases with improved laser contrast due to reduced pre-expansion. Our demonstration that energetic ions can be accelerated by this mechanism at different contrast levels relaxes laser requirements and indicates interaction parameters for realising application-specific beam delivery

Multiple Promoters and Alternative Splicing: Hoxa5 Transcriptional Complexity in the Mouse Embryo

The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein

Quantum algorithms for algebraic problems

Quantum computers can execute algorithms that dramatically outperform classical computation. As the best-known example, Shor discovered an efficient quantum algorithm for factoring integers, whereas factoring appears to be difficult for classical computers. Understanding what other computational problems can be solved significantly faster using quantum algorithms is one of the major challenges in the theory of quantum computation, and such algorithms motivate the formidable task of building a large-scale quantum computer. This article reviews the current state of quantum algorithms, focusing on algorithms with superpolynomial speedup over classical computation, and in particular, on problems with an algebraic flavor.Comment: 52 pages, 3 figures, to appear in Reviews of Modern Physic