X-ray generation by fs-laser processing of biological material.

The use of ultrashort pulse lasers in medical treatments is increasing and is already an essential tool, particularly in the treatment of eyes, bones and skin. One of the main advantages of laser treatment is that it is fast and minimally invasive. Due to the interaction of ultrashort laser pulses with matter, X-rays can be generated during the laser ablation process. This is important not only for the safety of the patient, but also for the practitioner to ensure that the legally permissible dose is not exceeded. Although our results do not raise safety concerns for existing clinical applications, they might impact future developments at higher peak powers. In order to provide guidance to laser users in the medical field, this paper examines the X-ray emission spectra and dose of several biological materials and describes their dependence on the laser pulse energy.

Differentiating multi-MeV, multi-ion spectra with CR-39 solid-state nuclear track detectors.

The development of high intensity petawatt lasers has created new possibilities for ion acceleration and nuclear fusion using solid targets. In such laser-matter interaction, multiple ion species are accelerated with broad spectra up to hundreds of MeV. To measure ion yields and for species identification, CR-39 solid-state nuclear track detectors are frequently used. However, these detectors are limited in their applicability for multi-ion spectra differentiation as standard image recognition algorithms can lead to a misinterpretation of data, there is no unique relation between track diameter and particle energy, and there are overlapping pit diameter relationships for multiple particle species. In this report, we address these issues by first developing an algorithm to overcome user bias during image processing. Second, we use calibration of the detector response for protons, carbon and helium ions (alpha particles) from 0.1 to above 10 MeV and measurements of statistical energy loss fluctuations in a forward-fitting procedure utilizing multiple, differently filtered CR-39, altogether enabling high-sensitivity, multi-species particle spectroscopy. To validate this capability, we show that inferred CR-39 spectra match Thomson parabola ion spectrometer data from the same experiment. Filtered CR-39 spectrometers were used to detect, within a background of ~ 2 × 1011 sr-1 J-1 protons and carbons, (1.3 ± 0.7) × 108 sr-1 J-1 alpha particles from laser-driven proton-boron fusion reactions.

Reports of deaths are an exaggeration: all-cause and NAA-test-conditional mortality in Germany during the SARS-CoV-2 era.

Counts of SARS-CoV-2-related deaths have been key numbers for justifying severe political, social and economical measures imposed by authorities world-wide. A particular focus thereby was the concomitant excess mortality (EM), i.e. fatalities above the expected all-cause mortality (AM). Recent studies, inter alia by the WHO, estimated the SARS-CoV-2-related EM in Germany between 2020 and 2021 as high as 200 000. In this study, we attempt to scrutinize these numbers by putting them into the context of German AM since the year 2000. We propose two straightforward, age-cohort-dependent models to estimate German AM for the 'Corona pandemic' years, as well as the corresponding flu seasons, out of historic data. For Germany, we find overall negative EM of about -18 500 persons for the year 2020, and a minor positive EM of about 7000 for 2021, unveiling that officially reported EM counts are an exaggeration. In 2022, the EM count is about 41 200. Further, based on NAA-test-positive related death counts, we are able to estimate how many Germans have died due to rather than with CoViD-19; an analysis not provided by the appropriate authority, the RKI. Through 2020 and 2021 combined, our due estimate is at no more than 59 500. Varying NAA test strategies heavily obscured SARS-CoV-2-related EM, particularly within the second year of the proclaimed pandemic. We compensated changes in test strategies by assuming that age-cohort-specific NAA-conditional mortality rates during the first pandemic year reflected SARS-CoV-2-characteristic constants.

Serological Hendra Virus Diagnostics Using an Indirect ELISA-Based DIVA Approach with Recombinant Hendra G and N Proteins.

Since the identification of Hendra virus (HeV) infections in horses in Australia in 1994, more than 80 outbreaks in horses have been reported, and four out of seven spillover infections in humans had a fatal outcome. With the availability of a subunit vaccine based on the HeV-Glycoprotein (HeV-G), there is a need to serologically Differentiate the Infected from the Vaccinated Animals (DIVA). We developed an indirect ELISA using HeV-G expressed in Leishmania tarentolae and HeV-Nucleoprotein (HeV-N) expressed in recombinant baculovirus-infected insect cells as antigens. During evaluation, we tested panels of sera from naïve, vaccinated and infected horses that either originated from a Hendra-virus free region, or had been pre-tested in validated diagnostic tests. Our data confirm the reliability of this approach, as HeV-N-specific antibodies were only detected in sera from infected horses, while HeV-G-specific antibodies were detected in infected and vaccinated horses with a high level of specificity and sensitivity. Given the excellent correlation of data obtained for German and Australian HeV-negative horses, we assume that this test can be applied for the testing of horse serum samples from a variety of geographical regions.

[Management of critically ill nontrauma patients in a nonuniversity emergency department]. / Nichttraumatologisches Schockraummanagement in einer nichtuniversitären Notaufnahme.

Purpose: Today there exists only limited knowledge regarding the care of critically ill nontrauma (CINT) patients in the resuscitation room (RR) in Germany. The goal of this observational study was to describe the management of CINT patients in the RR of a nonuniversity emergency department. Methods: Data of adult nontrauma patients in the RR were prospectively collected in this study from 26 January 2019 to 18 May 2021 using the OBSERvE­2 evaluation protocol. Results: In all, 213 patients were included in the study (age: 70 ± 15 years, 55% male; admission to the RR by emergency medical service 93%). 28% were brought in after out-of-hospital cardiac arrest. Leading admission causes were C (47%) and B problems (39%). Diagnoses at the end of RR treatment were 30% pulmonary and 26% cardiovascular diseases without myocardial infarction as well as pulmonary embolism (8% and 5%, respectively). Measures performed were airway protection (20%), invasive (46%) and noninvasive ventilation (25%), cardiopulmonary resuscitation (13%), catecholamine therapy (34%), emergency ultrasound (62%). The initial treatment lasted for 41 ± 22 min. Computed tomography was subsequently performed in 51%. On average 4-5 persons were involved in the treatment during the RR period. In total, 9% of the patients died during RR treatment and 40% in the hospital. Conclusion: Patients in a nonuniversity nontrauma RR are resource-intensive and have a high in-hospital lethality. RR care can be completed within 60 min. In order to achieve better comparability between patient populations of different locations, it is necessary to uniformly define admission criteria for the nontrauma resuscitation room.

Measurement of Compton Scattering at MAMI for the Extraction of the Electric and Magnetic Polarizabilities of the Proton.

A precise measurement of the differential cross sections dσ/dΩ and the linearly polarized photon beam asymmetry Σ_{3} for Compton scattering on the proton below pion threshold has been performed with a tagged photon beam and almost 4π detector at the Mainz Microtron. The incident photons were produced by the recently upgraded Glasgow-Mainz photon tagging facility and impinged on a cryogenic liquid hydrogen target, with the scattered photons detected in the Crystal Ball/TAPS setup. Using the highest statistics Compton scattering data ever measured on the proton along with two effective field theories (both covariant baryon and heavy-baryon) and one fixed-t dispersion relation model, constraining the fits with the Baldin sum rule, we have obtained the proton electric and magnetic polarizabilities with unprecedented precision: α_{E1}=10.99±0.16±0.47±0.17±0.34, ß_{M1}=3.14±0.21±0.24±0.20±0.35; in units of 10^{-4} fm^{3} where the errors are statistical, systematic, spin polarizability dependent, and model dependent.

Forward-looking insights in laser-generated ultra-intense γ-ray and neutron sources for nuclear application and science.

Ultra-intense MeV photon and neutron beams are indispensable tools in many research fields such as nuclear, atomic and material science as well as in medical and biophysical applications. For applications in laboratory nuclear astrophysics, neutron fluxes in excess of 1021 n/(cm2 s) are required. Such ultra-high fluxes are unattainable with existing conventional reactor- and accelerator-based facilities. Currently discussed concepts for generating high-flux neutron beams are based on ultra-high power multi-petawatt lasers operating around 1023 W/cm2 intensities. Here, we present an efficient concept for generating γ and neutron beams based on enhanced production of direct laser-accelerated electrons in relativistic laser interactions with a long-scale near critical density plasma at 1019 W/cm2 intensity. Experimental insights in the laser-driven generation of ultra-intense, well-directed multi-MeV beams of photons more than 1012 ph/sr and an ultra-high intense neutron source with greater than 6 × 1010 neutrons per shot are presented. More than 1.4% laser-to-gamma conversion efficiency above 10 MeV and 0.05% laser-to-neutron conversion efficiency were recorded, already at moderate relativistic laser intensities and ps pulse duration. This approach promises a strong boost of the diagnostic potential of existing kJ PW laser systems used for Inertial Confinement Fusion (ICF) research.

Single π 0 production off neutrons bound in deuteron with linearly polarized photons.

The quasifree γ → d → π 0 n ( p ) photon beam asymmetry, Σ , has been measured at photon energies, E γ , from 390 to 610 MeV, corresponding to center of mass energy from 1.271 to 1.424 GeV, for the first time. The data were collected in the A2 hall of the MAMI electron beam facility with the Crystal Ball and TAPS calorimeters covering pion center-of-mass angles from 49 ∘ to 148 ∘ . In this kinematic region, polarization observables are sensitive to contributions from the Δ ( 1232 ) and N(1440) resonances. The extracted values of Σ have been compared to predictions based on partial-wave analyses (PWAs) of the existing pion photoproduction database. Our comparison includes the SAID, MAID and Bonn-Gatchina analyses; while a revised SAID fit, including the new Σ measurements, has also been performed. In addition, isospin symmetry is examined as a way to predict π 0 n photoproduction observables, based on fits to published data in the channels π 0 p , π + n and π - p .

Cross motor innervation of the hypoglossal nerve-a pilot study of predictors for successful opening of the soft palate.

PURPOSE: Selective hypoglossal nerve stimulation has proven to be a successful treatment option in patients with obstructive sleep apnea. The aim of this pilot study was to investigate if there is a cross-innervation of the hypoglossal nerve in humans and if patients with this phenotype show a different response to hypoglossal nerve stimulation compared to those with ipsilateral-only innervation METHODS: Nineteen patients who previously received a selective hypoglossal nerve stimulation system (Inspire Medical Systems, Golden Valley, USA) were implanted with a nerve integrity system placing electrodes on both sides of the tongue. Tongue motions were recorded one and two months after surgery from transoral and transnasal views. Polysomnography (PSG) was also performed at two months. Electromyogram (EMG) signals and tongue motions after activation were compared with PSG findings. RESULTS: Cross-innervation showed significant correlation with bilateral tongue movement and bilateral tongue base opening, which were associated with better PSG outcomes. CONCLUSION: Cross motor innervation of the hypoglossal nerve occurs in approximately 50% of humans, which is associated with a positive effect on PSG outcomes. Bilateral stimulation of the hypoglossal nerve may be a solution for non-responding patients with pronounced collapse at the soft palate during drug-induced sleep endoscopy.

Identification of African swine fever virus-like elements in the soft tick genome provides insights into the virus' evolution.

BACKGROUND: African swine fever virus (ASFV) is a most devastating pathogen affecting swine. In 2007, ASFV was introduced into Eastern Europe where it continuously circulates and recently reached Western Europe and Asia, leading to a socio-economic crisis of global proportion. In Africa, where ASFV was first described in 1921, it is transmitted between warthogs and soft ticks of the genus Ornithodoros in a so-called sylvatic cycle. However, analyses into this virus' evolution are aggravated by the absence of any closely related viruses. Even ancient endogenous viral elements, viral sequences integrated into a host's genome many thousand years ago that have proven extremely valuable to analyse virus evolution, remain to be identified. Therefore, the evolution of ASFV, the only known DNA virus transmitted by arthropods, remains a mystery. RESULTS: For the identification of ASFV-like sequences, we sequenced DNA from different recent Ornithodoros tick species, e.g. O. moubata and O. porcinus, O. moubata tick cells and also 100-year-old O. moubata and O. porcinus ticks using high-throughput sequencing. We used BLAST analyses for the identification of ASFV-like sequences and further analysed the data through phylogenetic reconstruction and molecular clock analyses. In addition, we performed tick infection experiments as well as additional small RNA sequencing of O. moubata and O. porcinus soft ticks. CONCLUSION: Here, we show that soft ticks of the Ornithodoros moubata group, the natural arthropod vector of ASFV, harbour African swine fever virus-like integrated (ASFLI) elements corresponding to up to 10% (over 20 kb) of the ASFV genome. Through orthologous dating and molecular clock analyses, we provide data suggesting that integration could have occurred over 1.47 million years ago. Furthermore, we provide data showing ASFLI-element specific siRNA and piRNA in ticks and tick cells allowing for speculations on a possible role of ASFLI-elements in RNA interference-based protection against ASFV in ticks. We suggest that these elements, shaped through many years of co-evolution, could be part of an evolutionary virus-vector 'arms race', a finding that has not only high impact on our understanding of the co-evolution of viruses with their hosts but also provides a glimpse into the evolution of ASFV.

Helicity-Dependent Cross Sections for the Photoproduction of π

The double-polarization observable E and helicity-dependent cross sections σ_{1/2}, σ_{3/2} have been measured for the photoproduction of π^{0} pairs off quasifree protons and neutrons at the Mainz MAMI accelerator with the Crystal Ball/TAPS setup. A circularly polarized photon beam was produced by bremsstrahlung from longitudinally polarized electrons and impinged on a longitudinally polarized deuterated butanol target. The reaction products were detected with an almost 4π covering calorimeter. The results reveal for the first time the helicity- and isospin-dependent structure of the γN→Nπ^{0}π^{0} reaction. They are compared to predictions from reaction models in view of nucleon resonance contributions and also to a refit of one model that predicted results for the proton and for the neutron target. The comparison of the prediction and the refit demonstrates the large impact of the new data.

Signatures of the d

We report a measurement of the spin polarization of the recoiling neutron in deuterium photodisintegration, utilizing a new large acceptance polarimeter within the Crystal Ball at MAMI. The measured photon energy range of 300-700 MeV provides the first measurement of recoil neutron polarization at photon energies where the quark substructure of the deuteron plays a role, thereby providing important new constraints on photodisintegration mechanisms. A very high neutron polarization in a narrow structure centered around E_{γ}∼570 MeV is observed, which is inconsistent with current theoretical predictions employing nucleon resonance degrees of freedom. A Legendre polynomial decomposition suggests this behavior could be related to the excitation of the d^{*}(2380) hexaquark.

Antipsychotic Overdosing and Polypharmacy in Schizophrenic Delinquents Explored.

A logistic regression model for 289 cases of schizophrenic offenders in a Swiss forensic hospital between 1995 and 2016 revealed the following factors for above average levels of antipsychotic overdosing and polypharmacy: Odds for overdosing increased in absence of a personality disorder (237%), for each point increase in emotional withdrawal (63.5%) and motor retardation (71.7%), and decreased for poor rapport (42.3%) recorded at admission. Odds for polypharmacy increased with complaints about physicians (157%), for each point increase in IQ (3.6%; range = 65-131, M = 92, SD = 14), reduction of the security level of the ward (36.8%; four levels), and for each point increase in poor attention (27.6%) at admission. It decreased with each previous conviction (10.9%; range = 1-21, M = 3, SD = 2), breaking of rules (46.4%) and the administration of compulsory measures (55.7%) on the ward, a poor legal prognosis (29.4%, four levels), and each point increase in grandiosity (40.3%), passive social withdrawal (42.3%), and depressive symptoms (38.7%) at admission.

Dairy goat producers' understanding, knowledge and attitudes towards biosecurity and Q-fever in Australia.

The Australian dairy goat sector is an emerging animal industry undergoing rapid expansion. Limited information is available within this industry in relation to socio-demographic characteristics and biosecurity implementation. Q-Fever, caused by the bacterium Coxiella burnetii, is a zoonotic disease endemic in Australia, with a range of domestic and wild-animal reservoir species, including goats, with infected pregnant goats posing a significant public health risk. The aim of the current study was to investigate the socio-demographics of Australian dairy goat producers, their biosecurity implementation and levels of understanding, knowledge and attitudes towards Q-Fever. To achieve this aim, a cross-sectional study was conducted, using an online survey and follow-up semi-structured interviews among dairy goat producers. A total of 106 goat producers participated in the online survey (35.3% response rate) and 14 participated in the semi-structured interviews. Findings from this study suggest that most goat producers implement biosecurity practices related to direct animal husbandry, such as separating sick goats (86%), vaccinations (79%) and providing separate kidding space (75%); and, practices minimizing the risk of disease introduction, such as maintaining boundary fences (86%) and isolating incoming animals (67%). However, implementation of other biosecurity practices, such as keeping records of visitors and visitor biosecurity requirements, was inadequate. Furthermore, this study identifies a deficit of knowledge and understanding surrounding Q-Fever in the Australian dairy goat sector, and a disconnect between producers' perception of risk and implementation of known appropriate biosecurity measures. The research has identified that producers rely on 'trusted' community networks to provide advice on biosecurity implementation, due to a perceived absence of industry-specific, reputable information sources. Producers identified those outside of these networks as the 'other'. The creation of this other allows producers to deflect responsibility for individual biosecurity on to the other. A multifaceted approach is necessary to increase knowledge, understanding and perception of risk surrounding Q-fever, and promote positive uptake of biosecurity measures, for improved outcomes for animal and human health.

Latent class analysis identified phenotypes in individuals with schizophrenia spectrum disorder who engage in aggressive behaviour towards others.

Prior research on Hodgins' (2008) typology of offenders with schizophrenia spectrum disorders (SSD) has revealed inconsistencies in the number of subgroups and the operationalization of the concept. This study addressed these inconsistencies by applying latent class analysis (LCA) based on the most frequently explored variables in prior research. This novel case-centred methodology identified similarities and differences between the subjects contained in the sample instead of the variables explored. The LCA was performed on 71 variables taken from data on a previously unstudied sample of 370 case histories of offenders with SSD in a centre for inpatient forensic therapies in Switzerland. Results were compared with Hodgins' theoretically postulated patient typologies and confirm three separate homogeneous classes of schizophrenic delinquents. Previous inconsistencies and differences in operationalizations of the typology of offenders with SDD to be found in the literature are discussed.

Productive replication of peste des petits ruminants virus Nigeria 75/1 vaccine strain in vero cells correlates with inefficiency of maturation of the viral fusion protein.

Peste des petits ruminants virus (PPRV), a member of the genus Morbillivirus, in the family Paramyxoviridae expresses two membrane glycoproteins, the fusion (F) and haemagglutinin (H) glycoproteins which mediate virus-to-cell fusion and cell-to-cell fusion leading to the induction of syncytia in PPRV infected cells. In the context of the characterization of the virulent lineage IV strain PPRV Kurdistan 2011, isolated from wild goats from the Kurdistan region in Iraq, we observed that both PPRV Kurdistan 2011 and the PPRV Nigeria 75/1 vaccine strain led to induction of large syncytia in Vero-dogSLAM cells within 48 h whereas both failed to induce detectable cell-cell fusion events in two Vero cell lines of differing passage histories. We were unable to detect syncytium formation in transiently transfected cells expressing PPRV F or H alone whereas co-expression of F and H induced large syncytia - in Vero-dogSLAM cells only. In VeroMontpellier cells expressing PPRV F and H, fused cells were rarely detectable indicating that PPRV mediated cell fusion activity is impaired in this cell line. Surprisingly, on Vero-dogSLAM cells the vaccine strain grew to titers of 105.25 TCID50/ml, whereas infectious virus yield was about 200-fold higher on VeroMontpellier and Vero-76 cells. In contrast, the virulent Kurdistan 2011 strain grew to a maximum titer of 107.0 TCID50/ml on Vero-dogSLAM cells and only 104.5 TCID50/ml on normal Vero cells. This was as expected since Vero cells lacking the SLAM receptor for PPRV are regarded as not so permissive for infection. To elucidate the divergent productive replication behaviour of PPRV Nigeria 75/1 vaccine strain on Vero vs Vero-dogSLAM cells, we examined whether intracellular transport and/or maturation of the viral envelope glycoproteins F and H might be implicated with this phenomenon. The results indicate that F in contrast to the H glycoprotein matures inefficiently during intracellular transport in VeroMontpellier cells, thus leading to an absence of detectable syncytia formation. However, in the case of the PPRV Nigeria 75/1 vaccine strain this did not impair efficient virus assembly and release.

Tailoring anatomical muscle paths: a sheath-like solution for muscle routing in musculoskeletal computer models.

Muscle wrapping geometry has a major impact on the muscle force as well as the torque onto the joint exerted by this muscle since these torques highly depend on the muscle's line of action or, in other words, the muscle moment arm. Most common redirection methods focus on two-dimensional motions and optimise path geometry for only one isolated movement, either flexion, abduction or rotation, instead of covering all degrees of freedom (DOFs). Others can only imitate anatomical paths in a small working range or for single joint movements. For biomechanical simulations of sweeping movements like running or throwing, however, a correct representation of muscle paths for a large range of joint configurations is mandatory. We introduce a new computational algorithm for modelling the muscle path in three-dimensional biomechanical simulations, based on a model description of muscles as massless, visco-elastic strands and the assumption that the muscle acts along a continuous path consisting of piecewise straight lines. In the presented approach, anatomical constraints including bones, tendon sheaths and other surrounding tissue are represented by areas the muscle has to pass. We model these redirection constraints as ellipses, allowing the muscle path to move within these areas and along their frictionless, inner edges. We show that - by only adjusting ellipse parameters - we are able to achieve reasonable moment arms for all (DOFs) and for a large range of joint configurations of uniarticular muscles as well as muscles spanning more than one joint - even for complex geometries.

The intracellular proteome of African swine fever virus.

African swine fever (ASF) is a viral disease that affects members of the Suidae family such as African bush pigs, warthogs, but also domestic pigs, and wild boar. It is transmitted by direct contact of naïve with infected animals, by soft ticks of the Ornithodoros genus, or indirectly by movement of infected animals, improper disposal of contaminated animal products or other sources related to human activity. The recent spread of ASF into Eastern and Central European countries is currently threatening the European pig industry. The situation is aggravated as to-date no efficient vaccine is available. African swine fever virus (ASFV) is a large enveloped ds DNA-virus encoding at least 150 open reading frames. Many of the deduced gene products have not been described, less functionally characterized. We have analysed ASFV protein expression in three susceptible mammalian cell lines representing a susceptible host (wild boar) and two non-susceptible species (human and green monkey) by mass spectrometry and provide first evidence for the expression of 23 so far uncharacterized ASFV ORFs. Expression levels of several newly identified ASFV proteins were remarkably high indicating importance in the viral replication cycle. Moreover, expression profiles of ASFV proteins in the three cell lines differed markedly.

Efficient transgene insertion in a pseudorabies virus vector by CRISPR/Cas9 and marker rescue-enforced recombination.

For development of vectored vaccines against porcine pathogens the genome of the pseudorabies virus vaccine strain Bartha (PrV-Ba) was previously cloned as an infectious bacterial artificial chromosome (BAC), containing the bacterial replicon and a reporter gene cassette encoding enhanced green fluorescent protein (EGFP) at the nonessential glycoprotein G locus. To facilitate substitution of this insertion, this BAC was now modified by deletion of the adjacent promoter and initiation codon of the essential glycoprotein D (gD) gene of PrV-Ba. Furthermore, rabbit kidney (RK13) cells stably expressing Cas9 nuclease and an EGFP gene-specific guide RNA were prepared to induce site specific cleavage of the BAC DNA. After co-transfection of these cells with the modified BAC and recombination plasmids containing expression cassettes for new transgenes flanked by PrV DNA sequences including the intact 5'-end of the gD gene, >95% of the recombinants exhibited the desired gene substitutions, while no EGFP-expressing progeny virus was detectable. This approach was used for insertion and expression of the open reading frames E199L, CP204L (p30) and KP177R (p22) of African swine fever virus. The studies revealed that codon adaptation significantly enhanced expression of E199L, and that the chimeric CAG promoter increased transgene expression compared to cytomegalovirus immediate-early promoters.