Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Updated risk models for lung cancer due to radon exposure in the German Wismut cohort of uranium miners, 1946-2018.

UNSCEAR recently recommended that future research on the lung cancer risk at low radon exposures or exposure rates should focus on more contemporary uranium miners. For this purpose, risk models in the German Wismut cohort of uranium miners were updated extending the follow-up period by 5 years to 1946-2018. The full cohort (n = 58,972) and specifically the 1960 + sub-cohort of miners first hired in 1960 or later (n = 26,764) were analyzed. The 1960 + sub-cohort is characterized by low protracted radon exposure of high quality of measurements. Internal Poisson regression was used to estimate the excess relative risk (ERR) for lung cancer per cumulative radon exposure in Working Level Months (WLM). Applying the BEIR VI exposure-age-concentration model, the ERR/100 WLM was 2.50 (95% confidence interval (CI) 0.81; 4.18) and 6.92 (95% CI < 0; 16.59) among miners with attained age < 55 years, time since exposure 5-14 years, and annual exposure rates < 0.5 WL in the full (n = 4329 lung cancer deaths) and in the 1960 + sub-cohort (n = 663 lung cancer deaths), respectively. Both ERR/WLM decreased with older attained ages, increasing time since exposure, and higher exposure rates. Findings of the 1960 + sub-cohort are in line with those from large pooled studies, and ERR/WLM are about two times higher than in the full Wismut cohort. Notably, 20-30 years after closure of the Wismut mines in 1990, the estimated fraction of lung cancer deaths attributable to occupational radon exposure is still 26% in the full Wismut cohort and 19% in the 1960 + sub-cohort, respectively. This demonstrates the need for radiation protection against radon.

Plasmonic-organic hybrid (POH) modulators for OOK and BPSK signaling at 40 Gbit/s.

We report on high-speed plasmonic-organic hybrid Mach-Zehnder modulators comprising ultra-compact phase shifters with lengths as small as 19 µm. Choosing an optimum phase shifter length of 29 µm, we demonstrate 40 Gbit/s on-off keying (OOK) modulation with direct detection and a BER < 6 × 10(-4). Furthermore, we report on a 29 µm long binary-phase shift keying (BPSK) modulator and show that it operates error-free (BER < 1 × 10(-10)) at data rates up to 40 Gbit/s and with an energy consumption of 70 fJ/bit.

Multilocus sequence typing of canine Giardia duodenalis from South Eastern European countries.

Giardia duodenalis is a worldwide occurring protozoan that can infect various mammalian hosts. While living conditions are getting closer between pet animals and owners, there is discussion whether dogs may contribute to the transmission of these pathogens to humans. The present study was conducted in order to identify the Giardia assemblages in dogs from South Eastern Europe. For this purpose, 1645 faecal samples of household and shelter dogs from Albania, Bulgaria, Hungary, Macedonia, Romania and Serbia were tested for Giardia coproantigen by enzyme-linked immunosorbent assay (ELISA). A subset of 107 faecal samples demonstrating Giardia cysts by direct immunofluorescence assay (IFA) or microscopy (15-22 per country) plus 26 IFA-positive canine faecal samples from Croatia were used for DNA extraction and multilocus sequence typing with nested PCRs targeting five different gene loci: SSU rRNA, ITS1-5.8S-ITS2, beta giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi). One third (33.7%) of the samples tested positive for Giardia antigen in the coproantigen ELISA. Shelter dogs were infected more frequently than household dogs (57.2 vs. 29.7%, p < 0.01). Amplification was obtained in 82.0, 12.8, 11.3, 1.5, and 31.6%, of the investigated samples at the SSU rRNA, bg, gdh and tpi loci and the ITS1-5.8S-ITS2 region, respectively. The dog-specific assemblages C and D were identified in 50 and 68 samples, respectively. The results demonstrate that G. duodenalis should be considered as a common parasite in dogs from South Eastern Europe. However, there was no evidence for zoonotic Giardia assemblages in the investigated canine subpopulation.

Unravelling the conformations of di-(perylene bisimide acrylate) by combining time-resolved fluorescence-anisotropy experiments and molecular modelling.

We compare the results from time-resolved fluorescence anisotropy experiments and molecular modelling on perylene bisimide acrylate dimers which allows us to connect the observed spectral signatures unambiguously with the non-stacked and two (parallel and anti-parallel) stacked conformations. For the parallel stacked conformation the experimental data can be reproduced quantitatively using a model that assumes structural relaxation in the electronically excited state of the stacked aggregate. For the non-stacked conformation we find quantitative agreement between experiment and modelling only if a fast hopping of the electronic excitation between the perylene bisimide subunits is taken into account.

[Inpatient pain consultation service at a university hospital: a retrospective analysis of patient characteristics and the rate of the implementation of recommendations]. / Stationäre Schmerzkonsile einer universitären Schmerzambulanz : Eine retrospektive Analyse der Patientencharakteristika und der Umsetzungsrate der Empfehlungen.

BACKGROUND: The aim of this study was to conduct an audit of a university inpatient pain consultation service and to examine the quality and the implementation of the recommended therapeutic measures. Factors that influenced the implementation should be identified. PATIENTS AND METHODS: All inpatients treated by the consultation service in the years 2009 and 2010 were analyzed retrospectively. Demographic patient characteristics as well as quality parameters of the consultation service and pharmacological and non-pharmacological recommendations and their implementation were analyzed. RESULTS: In total 1,048 requests for the consultation service were processed of which 39.7% of the requests were for patients with acute pain, 33.8% with chronic and 19.9% with tumor-associated pain. Measures recommended most were medication, physiotherapy and psychological treatment. Recommended medications were actually prescribed in more than 80%, physiotherapy recommended in about 75% and psychological treatment recommended in 47% of the cases. Only a few influencing factors for the implementation of the recommended measures could be identified. CONCLUSION: Many different pain states are seen in an inpatient pain consultation service. The recommendations given are implemented in most cases especially concerning the medication.

Non-inversion conservation tillage as an underestimated driver of tillage erosion.

Tillage erosion is a widely underestimated process initiating soil degradation especially in case of large agricultural fields located in rolling topography. It is often assumed that, conservation, non-inversion tillage causes less tillage erosion than conventional inversion tillage. In this study, tillage erosion was determined on three paired plots comparing non-inversion chisel versus inversion mouldboard tillage. The experiments were performed at three sites in Northeast Germany with gentle, moderate, and steep slope, while tillage depth (0.25 m) and speed (≈ 6 km h-1) were kept constant during all experiments. The results indicate that non-inversion tillage produces significantly more soil movement compared to inversion tillage. The soil translocation distance was by a factor of 1.3-2.1 larger in case of chisel tillage. The largest difference in translocation distance and tillage transport coefficient (ktil) was found on the gentle slope exhibiting the lowest soil cohesion. Our results together with an evaluation of ktil values derived from literature and standardised for 0.25 m tillage depth contradict the general assumption that non-inversion tillage reduces tillage erosion. In tillage erosion dominated areas, non-inversion tillage applied with high tillage speed and depth potentially increases tillage erosion and fails its purpose to serve as soil conservation measure.

Psychological and neuroendocrine responses to social stress and to the administration of the alpha-2-receptor antagonist, yohimbine, in highly trained endurance athletes in comparison to untrained healthy controls.

INTRODUCTION: Several clinical studies suggest antidepressive and anxiolytic effects of regular endurance training. The mechanisms by which exercise exerts these effects are still unclear. It was hypothesized that athletes might show a diminished reaction to psychosocial stress and noradrenergic stimulation. METHODS: 12 male athletes and 12 healthy untrained male controls underwent a challenge paradigm on 3 separate days: the alpha-2-receptor antagonist yohimbine (0.4 mg/kg), placebo or a psychosocial stress test (SST) were administered. Responses were measured by psychometric scales, plasma cortisol, blood pressure and heart rate. RESULTS: Before testing, psychometric variables and cortisol levels were not different between the 2 groups. In comparison to placebo conditions, both the social stress test and the administration of yohimbine were followed by significant increases of anxiety symptoms, plasma cortisol, heart rate and blood pressure in both groups. However, these responses were not significantly different between the group of athletes and the control group. DISCUSSION: These results do not support the hypotheses that high aerobic fitness is associated with attenuated psychological and neuroendocrine responses to yohimbine or to psychosocial stress.

Algebraic construction of a Nambu bracket for the two-dimensional vorticity equation.

So far fluid mechanical Nambu brackets have mainly been given on an intuitive basis. Alternatively an algorithmic construction of such a bracket for the two-dimensional vorticity equation is presented here. Starting from the Lie-Poisson form and its algebraic properties it is shown how the Nambu representation can be explicitly constructed as the continuum limit from the structure preserving Zeitlin discretization.

Using simulation mannequins and actors in training for external post-mortem examinations -experiences from use in medical students and police officers.

In the daily practice of external post-mortem examinations and dealing with surviving dependents, striking failures can be observed regularly, pointing to an increased demand for training of the various professional groups involved. In this study, the experience gained from using simulation mannequins and actors for post-mortem examination training in medical students and police officers are presented. Since 2017, a training station has been offered at the Medical Faculty of the Technical University of Dresden (Germany) for practicing examinations in death scene and establishing communication with grieving relatives. It is conducted in small groups of up to 5 people, both for medical students and for police officers and police recruits. These courses are evaluated by means of questionnaires including 3 and 11 items respectively for the different groups. The questionnaires have been completed by 679 medical students and 67 police participants. Both groups of participants evaluated their previous experience as average. They assessed the course as having a high degree of practical and professional relevance. The didactic transfer of the teaching contents and its competent support were rated remarkably positive by the participants. Additionally, the police group reported high rates of approval for the use of feedback, the learning effect, and the appropriateness of the group size. The establishment and continuation of the simulation-based external post-mortem examination in the form of small-group teaching is associated with a considerable expenditure of equipment, material and personnel. In addition, its implementation requires sound cooperation structures. On the other hand, introduction and continuation of these types of additional teaching and learning methods, with a large practical component, can increase confidence in daily practice, and thus improve the quality of external post-mortem examination. Ultimately, this can also improve the cooperation between forensic medicine and the investigating authorities.

Predictors of physical and emotional recovery 6 and 12 months after surgery.

BACKGROUND: A proportion of patients do not recover fully from surgery or they develop chronic postsurgical pain. The aim of this study was to examine the incidence and predictors of unfavourable long-term outcome after surgery using a prospective cohort design. METHODS: Some 401 patients undergoing various elective surgical procedures filled in the RAND 36-item Health Survey 1.0 health-related quality-of-life questionnaire before operation and at 6 and 12 months of follow-up to assess changes in pain, physical functioning, mental health and vitality. Preoperative psychological assessment was obtained. RESULTS: Most patients showed improvement in the various aspects of health-related quality of life after surgery, but a considerable proportion (14-24 per cent) still showed deterioration at 6 and 12 months. Multivariable linear regression analysis identified acute postoperative pain, duration of the operation and preoperative physical condition as the most important predictors of long-term pain and physical functioning. Preoperative surgical fear also had a small but significant contribution. The main predictors of mental health and vitality were physical condition before surgery, surgical fear and optimism. CONCLUSION: Up to a quarter of patients experienced suboptimal recovery after surgery. Both somatic and psychological factors were associated with the long-term outcome. Optimal recovery could be promoted by effective interventions on malleable factors.

Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy.

This patient presented on the first day of life with pronounced lactic acidosis with an elevated lactate/pyruvate ratio. Urine organic acids showed Krebs cycle metabolites and mildly elevated methylmalonate and methylcitrate. The acylcarnitine profile showed elevated propionylcarnitine and succinylcarnitine. Amino acids showed elevated glutamic acid, glutamine, proline, and alanine. From the age 2 of mo on, she had elevated transaminases and intermittent episodes of liver failure. Liver biopsy showed steatosis and a decrease of mitochondrial DNA to 50% of control. She had bilateral sensorineural hearing loss. Over the course of the first 2 y of life, she developed a progressively severe myopathy with pronounced muscle weakness eventually leading to respiratory failure, Leigh disease, and recurrent hepatic failure. The hepatic symptoms and the metabolic parameters temporarily improved on treatment with aspartate, but neither muscle symptoms nor brain lesions improved. Laboratory testing revealed a deficiency of succinyl-CoA ligase enzyme activity and protein in fibroblasts because of a novel homozygous mutation in the SUCLG1 gene: c.40A>T (p.M14L). Functional analysis suggests that this methionine is more likely to function as the translation initiator methionine, explaining the pathogenic nature of the mutation. Succinyl-CoA ligase deficiency due to an SUCLG1 mutation is a new cause for mitochondrial hepatoencephalomyopathy.

Marginal bone loss one year after implantation: a systematic review of different loading protocols.

The aim of this study was to analyse the influence of different loading protocols on marginal bone loss (MBL). The outcomes of different implant loading protocols were assessed at 1year after implantation, with focus on MBL; protocols included immediate, immediate non-occlusal, early, and conventional loading. The search strategy resulted in 889 studies. Twenty-two of these studies fulfilled the inclusion criteria. Among the included studies, the lowest MBL was for immediately loaded implants (0.05±0.67mm) and the highest for immediate non-occlusally loaded implants (1.37±0.5mm). The results of the meta-analysis showed an estimated mean MBL of 0.457mm (95% confidence interval (CI) 0.133-0.781) for immediate loading, 0.390mm (95% CI 0.240-0.540) for immediate non-occlusal loading, 0.488mm (95% CI 0.289-0.687) for early loading (>2 days to <3 months), and 0.852mm (95% CI 0.429-1.275) for conventional loading (>3 months) implant protocols. The lowest decrease in 1-year implant survival per millimetre increase in MBL was observed for immediate loading and the highest for conventional loading. Conventional loading showed a significantly higher MBL than the other three loading protocols. This systematic review and meta-analysis indicates that the immediate loading protocol is a reasonable alternative to the conventional loading protocol.

ROSAT Observations of X-ray Emissions from Jupiter During the Impact of Comet Shoemaker-Levy 9.

Röntgensatellit (ROSAT) observations made shortly before and during the collision of comet Shoemaker-Levy 9 with Jupiter show enhanced x-ray emissions from the planet's northern high latitudes. These emissions, which occur at System III longitudes where intensity enhancements have previously been observed in Jupiter's ultraviolet aurora, appear to be associated with the comet fragment impacts in Jupiter's southern hemisphere and may represent brightenings of the jovian x-ray aurora caused either by the fragment impacts themselves or by the passage of the fragments and associated dust clouds through Jupiter's inner magnetosphere.

Changes of diversity pattern of proteolytic bacteria over time and space in an agricultural soil.

The genetic heterogeneity of neutral metalloprotease (npr) gene fragments from soil proteolytic bacteria was investigated at a cultivated field site with four different soil types and at three different depths in April, July, and October. Terminal restriction fragment length polymorphism (T-RFLP) analyses of polymerase chain reaction-amplified npr gene fragments were applied to study the dynamic of the npr gene pool with regard to environmental conditions. The aim of this study was to relate differences in npr community structure and richness to the vertical, site, and seasonal variations naturally occurring at the field site under investigation. T-RFLP analysis revealed a noticeable seasonal variability in the community structure of npr-containing bacteria. The data suggest that the composition of the npr proteolytic bacterial population in July differed from those at the other dates. Additionally, the diversity of npr genes decreased with increasing soil depth revealing the highest values in upper layers. The reasons behind the observed patterns in the community structure might be mainly seasonal and vertical variation of the quantity and heterogeneity of available substrates as well as spatial isolation caused by a varying water amount and the connectivity of soil particles among the soil profile. Sequencing and phylogenetical analysis of 120 npr clones from the top soils collected in July revealed that most of the clones exhibit only poor homology to npr genes of isolates previously obtained from various environments, indicating the presence of until now uncharacterized npr coding proteolytic bacteria at the study site.

[Leipzig fast-track protocol for cardio-anesthesia. Effective, safe and economical]. / Leipziger "Fast-track"-Protokoll in der Kardioanästhesie. Effektiv, sicher und ökonomisch sinnvoll.

BACKGROUND: In November 2005 a complex, multimodal anesthesia fast-track protocol (FTP) was introduced for elective cardiac surgery patients in the Cardiac Center of the University of Leipzig which included changing from an opioid regime to remifentanil and postoperative treatment in a special post-anesthesia recovery and care unit. The goal was to speed up recovery times while maintaining safety and improving costs. METHOD: A total of 421 patients who underwent the FTP and were treated in the special recovery room were analyzed retrospectively. These patients were compared with patients who had been treated by a standard protocol (SP) prior to instituting the FTP. Primary outcomes were time to extubation, length of stay in the intensive care unit (ICU) and treatment costs. RESULTS: The times to extubation were significantly shorter in the FTP group with 75 min (range 45-110 min) compared to 900 min (range 600-1140 min) in the SP group. Intensive care unit stay and hospital length of stay were also significantly shorter in the FTP group (p<0.01). The reduction of treatment costs of intensive care for FTP patients was 53.5% corresponding to savings of EUR 738 per patient in the FTP group compared with the SP group. CONCLUSIONS: The Leipzig fast-track protocol for cardio-anesthesia including the central elements of switching opiate therapy to remifentanil and switching patient recovery to a special post-anesthesia recovery and care unit, shortened therapy times, is safe and economically effective.

Neuronal tuning: Selective targeting of neuronal populations via manipulation of pulse width and directionality.

INTRODUCTION: Motor evoked potentials (MEP) in response to anteroposterior transcranial (AP) magnetic stimulation (TMS) are sensitive to the TMS pulse shape. We are now able to isolate distinct pulse properties, such as pulse width and directionality and evaluate them individually. Different pulse shapes induce different effects, likely by stimulating different populations of neurons. This implies that not all neurons respond in the same manner to stimulation, possibly, because individual segments of neurons differ in their membrane properties. OBJECTIVES: To investigate the effect of different pulse widths and directionalities of TMS on MEP latencies, motor thresholds and plastic aftereffects of rTMS. METHODS: Using a controllable pulse stimulator TMS (cTMS), we stimulated fifteen subjects with quasi-unidirectional TMS pulses of different pulse durations (40 µs, 80 µs and 120 µs) and determined thresholds and MEP AP latencies. We then compared the effects of 80 µs quasi-unidirectional pulses to those of 80 µs pulses with different pulse directionality characteristics (0.6 and 1.0 M ratios). We applied 900 pulses of the selected pulse shapes at 1 Hz. RESULTS: The aftereffects of 1 Hz rTMS depended on pulse shape and duration. 40 and 80 µs wide unidirectional pulses induced inhibition, 120 µs wide pulses caused excitation. Bidirectional pulses induced inhibition during the stimulation but had facilitatory aftereffects. Narrower pulse shapes caused longer latencies and higher resting motor thresholds (RMT) as compared to wider pulse shapes. CONCLUSIONS: We can tune the aftereffects of rTMS by manipulating pulse width and directionality; this may be due to the different membrane properties of the various neuronal segments such as dendrites. SIGNIFICANCE: To date, rTMS frequency has been the main determinant of the plastic aftereffects. However, we showed that pulse width also plays a major role, probably by recruiting novel neuronal targets.

Immune response mediated by Th1 / IL-17 / caspase-9 promotes evolution of periodontal disease.

INTRODUCTION: Periodontitis is characterized by inflammatory mediators beyond T lymphocyte function and phenotype (Th1/Th2/Th17). The clinical diversity in periodontitis makes it difficult to characterize the immune response in patients. This study evaluated the profile of the adaptive immune response in the periodontal disease model. METHODS: 72 rats (Wistar) were divided into a control group (CTL/day 0) and periodontitis (PD15/15 days and PD60/60 days). In the PD15 and PD60 groups, periodontal disease was induced by ligature with a silk thread placed in the cervical region of the upper first molar. After euthanasia, the periodontal tissue was analyzed by flow cytometry (CD4, CD8, CD25, CD44), semi-quantitative RT-PCR (T-bet, GATA-3, RORγt), semi-quantitative RT-PCR and ELISA IFN-γ, TNF-α, IFN-γ, IL-4, IL-6, IL-10, IL-17) and by Western blotting (Caspase-9, PCNA). RESULTS: The number of CD4+CD25+, CD4+CD44+, CD8+CD25+ and CD8+CD44+ cells and expression levels of T-bet and GATA-3 are increased in the PD60 group compared to PD15 and CTL. The RORγ-t gene transcript increased in the PD15 group in relation to PD60 and CTL. The cytokines IFN-γ, TNF-α and IL-17 increased in the PD60 group in relation to PD15. The expression of Caspase-9 was higher in the PD60 group than in PD15. CONCLUSIONS: The results suggest that the evolution of gingivitis to periodontitis is related to the accumulation of activated Th1 cells (IFN-γ and TNF-α) associated with the presence of increased IL-17. Studies with inhibitors of these cytokines in periodontal disease may lead to therapy directed at blocking the inflammatory process in this pathology, interrupting bone loss.

Optimizing BM harvesting from normal adult donors.

The experience at a single institution of BM harvesting (BMH) in general anesthetic for allogeneic transplantation from 49 healthy adult donors since March 2002 is presented in detail, together with an analysis of all the donor complications. In this study, we analyzed the advantages through the change from an aspiration needle with one hole (group A, n=18) to a system with additional five side holes (group B, n=31) in April 2005 for faster aspiration of large volumes of BM. In group B, the operation time was reduced by 50%, which is 12 min to date (1006 ml BM). Furthermore, the collection rate (volume BM/time) was significantly increased, namely to 81.9 ml/min in group B. The yields of total nucleated cells and CD34+ cells are nearly identical and adequate in both systems. The proportion of donors treated as day cases--that is, able to be discharged on the same day as the procedure--was 56% in group A and 81% in group B. There was no significant operative site morbidity. BMH accomplished by trained personal is a safe procedure for healthy adult donors on an outpatient basis as standard in our collection center.