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Abstract Background High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level.

Since 1998, driving under the influence of drugs such as amphetamine, MDMA, MDE, cannabis, cocaine, heroine and morphine is sanctioned due to Section 24a of the Road Traffic Regulations of Germany. Therefore, from December 2000 to June 2002 altogether 751 roadside tests with the immunochemical test device Toxiquick® were conducted on 302 drivers (273 male and 29 female) on oral fluid samples obtained during control actions in Franconia. The results of the tests are compared to the results obtained through quantification of corresponding blood samples by GC/MS. In general, in 75% the roadside test produced correct results and therefore gave helpful assistance to the police officers into the right direction regarding drug abuse. Except for cannabinoids, the number of false negative results was relatively small, whereas false positive results ranged between 32.2% for opiates and 10.7% for benzoylecgonine. [Copyright &y& Elsevier]

Purpose: The potential of dual energy computed tomography (DECT) for the analysis of gallstone compounds was investigated. The main goal was to find parameters, that can reliably define high percentage (>70%) cholesterol stones without calcium components. Materials and Methods: 35 gallstones were analyzed with DECT using a phantom model. Stone samples were put into specimen containers filled with formalin. Containers were put into a water-filled cylindrical acrylic glass phantom. DECT scans were performed using a tube voltage/current of 140 kV/83 mAs (tube A) and 80 kV/340 mAs (tube B). ROI-measurements to determine CT attenuation of each sector of the stones that had different appearance on the CT images were performed. Finally, semi-quantitative infrared spectroscopy (FTIR) of these sectors was performed for chemical analysis. Results: ROI-measurements were performed in 45 different sectors in 35 gallstones. Sectors containing >70% of cholesterol and no calcium component (n=20) on FTIR could be identified with 95% sensitivity and 100% specificity on DECT. These sectors showed typical attenuation of -8+/-4 HU at 80 kV and +22+/-3 HU at 140 kV. Even the presence of a small calcium component (<10%) hindered the reliable identification of cholesterol components as such. Conclusion: Dual energy CT allows for reliable identification of gallstones containing a high percentage of cholesterol and no calcium component in this pre-clinical phantom model. Results from in vivo or anthropomorphic phantom trials will have to confirm these results. This may enable the identification of patients eligible for non-surgical treatment options in the future. [ABSTRACT FROM AUTHOR]

Introduction: Non-natural deaths associated with sexual activity may occur either with or without the involvement of other persons., Aim: The present study provides an overview of cases of non-natural death related to sexual activities as well as recommendations of how to handle these cases and to identify potentially dangerous pleasure-enhancing techniques., Methods: This medicolegal, postmortem, retrospective, and prospective study is based on data of autopsies performed at the Institute of Legal Medicine at University Hospital, Goethe University, Frankfurt, Germany., Main Outcome Measure: Identification of circumstances, sexual practices, and gender distribution of cases of non-natural death in this context., Results: Between 1993 and 2017 (25 years), 16,437 medicolegal autopsies were performed, of which 74 cases (43 males, 31 females) of non-natural death were found to relate to sexual activities (0.45%). One female and 21 males had died in the course of autoerotic practices (group I, n = 22). Nine males and 14 females had performed sexual practices with mutual consent (group II, n = 23), and 13 males and 16 females without mutual consent (group III, n = 29). The average age in group I was 45.4 years; in group II, 40.6 years; and in group III, 39.2 years. Most of the deceased were found in their own apartments. Forms of stimulation included vaginal, anal, and oral intercourse; insertion of foreign bodies; use of chemical substances; and tools for respiratory depression/hypoxia. Three cases of death occurred during sexual activities involving bondage and discipline, sadism, and masochism (BDSM). Death due to strangulation was the main cause in group I, whereas intoxications were predominant in group II. Sharp force (eg, knife) was mainly responsible for death in group III. Anogenital injuries were documented in all groups in approximately equal percentages., Clinical Implications: The cases presented show a high variety of circumstances in which non-natural death connected to sexual activity may occur., Strengths & Limitations: This study presents a large postmortem collection of non-natural death cases with associated sexual activity. As the main limiting factor, it must be stated that mutual consent for a sexual practice or consumption of substances was presumed based on the information provided and a lack of evidence against this assumption., Conclusion: In cases of death associated with sexual activity, medical staff should perform thorough unbiased examinations and documentations. Strangulation and the consumption of stimulants should be classified as life-threatening, pleasure-enhancing techniques. Patients and young people should be informed about these risks. Bunzel L, Koelzer SC, Zedler B, et al. Non-Natural Death Associated with Sexual Activity: Results of a 25-Year Medicolegal Postmortem Study. J Sex Med 2019;16:1547-1556., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Pregnancy-associated deaths are extremely rare in Germany. Most deaths are from natural causes, and a range of causes are possible., Method: The deaths of 22 women who died of pregnancy-associated causes and who were autopsied in the Institute of Forensic Medicine of Justus-Liebig University Gießen between 1992 and 2016 were analyzed., Results: The autopsy results and histological examinations for the majority of women who died of pregnancy-associated causes between 1992 and 2016 showed that they had died of natural causes, although complications of pregnancy were a leading cause of death., Conclusion: The death of a pregnant woman should not automatically raise the suspicion of malpractice, although the question does arise in cases of bleeding complications only detected at very late stages. Experts must prove that a real mistake was made during treatment and provide evidence of the causality between malpractice and patient death. Particularly when well-known complications of pregnancy were present, this is only the case if poor monitoring resulted in the complication being detected too late or if treatment was not in accordance with accepted standards of care. The majority of pregnancy-associated deaths are from natural causes and the death of a pregnant woman does not mean that medical malpractice was involved, although this accusation is often levelled in cases where rupture was not immediately diagnosed or in cases of fatal postpartum hemorrhage.

Background: Although sexual activity can cause moderate stress, it can cause natural death in individuals with pre-existing illness. The aim of this study was to identify additional pre-existing health problems, sexual practices, and potential circumstances that may trigger fatal events., Methods: This medicolegal postmortem, retrospective, and prospective study is based on data of autopsies performed at the Institute of Legal Medicine of the University hospital, Goethe-University, Frankfurt/Main, Germany., Outcomes: Identification of pre-existing health problems, sexual practices, and potential circumstances than could trigger fatal events., Results: From 1972 to 2016 (45 years) approximately 38,000 medicolegal autopsies were performed, of which 99 cases of natural death were connected to sexual activities (0.26%). Except for eight women, men represented most cases. The women's mean age was 45 years (median = 45) and the men's mean age was 57.2 years (median = 57). Causes of death were coronary heart disease (n = 28), myocardial infarction (n = 21) and reinfarction (n = 17), cerebral hemorrhage (n = 12), rupture of aortic aneurysms (n = 8), cardiomyopathy (n = 8), acute heart failure (n = 2), sudden cardiac arrest (n = 1), myocarditis (n = 1), and a combination of post myocardial infarction and cocaine intoxication (n = 1). Most cases showed increased heart weights and body mass indices. Death occurred mainly during the summer and spring and in the home of the deceased. If sexual partners were identified, 34 men died during or after sexual contact with a female prostitute, two cases at least two female prostitutes. Nine men died during or after sexual intercourse with their wife, in seven cases the sexual partner was a mistress, and in four cases the life partner. Five men died during homosexual contacts. Based on the situation 30 men were found in, death occurred during masturbation. Of the women, five died during intercourse with the life partner, two died during intercourse with a lover or friend, and in one case no information was provided., Clinical Translation: Natural deaths connected with sexual activity appear to be associated with male sex and pre-existing cardiovascular disorders. Most cases recorded occurred with mistresses, prostitutes, or during masturbation. If death occurs, the spouse or life partner might need psychological support., Strength and Limitations: To our knowledge, the present study contains the largest collection of postmortem data on natural deaths connected with sexual activities. However, the cases presented were of forensic interest; a larger number of undetected cases especially in the marital or stable relationship sector must be assumed., Conclusion: Patients should be informed about the circumstances that could trigger the "love death." Lange L, Zedler B, Verhoff MA, Parzeller M. Love Death-A Retrospective and Prospective Follow-Up Mortality Study Over 45 Years. J Sex Med 2017;14:1226-1231., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The Total Exposure Study was a stratified, multi-center, cross-sectional study designed to estimate levels of biomarkers of tobacco-specific and non-specific exposure and of potential harm in U.S. adult current cigarette smokers (≥one manufactured cigarette per day over the last year) and tobacco product non-users (no smoking or use of any nicotine containing products over the last 5 years). The study was designed and sponsored by a tobacco company and implemented by contract research organizations in 2002-2003. Multiple analyses of smoking behavior, demographics, and biomarkers were performed. Study data and banked biospecimens were transferred from the sponsor to the Virginia Tobacco and Health Research Repository in 2010, and then to SRI International in 2012, for independent analysis and dissemination., Methods: We analyzed biomarker distributions overall, and by biospecimen availability, for comparison with existing studies, and to evaluate generalizability to the entire sample. We calculated genome-wide statistical power for a priori hypotheses. We performed clinical chemistries, nucleic acid extractions and genotyping, and report correlation and quality control metrics., Results: Vital signs, clinical chemistries, and laboratory measures of tobacco specific and non-specific toxicants are available from 3585 current cigarette smokers, and 1077 non-users. Peripheral blood mononuclear cells, red blood cells, plasma and 24-h urine biospecimens are available from 3073 participants (2355 smokers and 719 non-users). In multivariate analysis, participants with banked biospecimens were significantly more likely to self-identify as White, to be older, to have increased total nicotine equivalents per cigarette, decreased serum cotinine, and increased forced vital capacity, compared to participants without. Effect sizes were small (Cohen's d-values ≤ 0.11). Power for a priori hypotheses was 57 % in non-Hispanic Black (N = 340), and 96 % in non-Hispanic White (N = 1840), smokers. All DNA samples had genotype completion rates ≥97.5 %; 68 % of RNA samples yielded RIN scores ≥6.0., Conclusions: Total Exposure Study clinical and laboratory assessments and biospecimens comprise a unique resource for cigarette smoke health effects research. The Total Exposure Study Analysis Consortium seeks to perform molecular studies in multiple domains and will share data and analytic results in public repositories and the peer-reviewed literature. Data and banked biospecimens are available for independent or collaborative research.

Objective: Develop a risk index to estimate the likelihood of life-threatening respiratory depression or overdose among medical users of prescription opioids., Subjects, Design, and Methods: A case-control analysis of administrative health care data from the Veterans' Health Administration identified 1,877,841 patients with a pharmacy record for an opioid prescription between October 1, 2010 and September 30, 2012. Overdose or serious opioid-induced respiratory depression (OSORD) occurred in 817. Ten controls were selected per case (n = 8,170). Items for an OSORD risk index (RIOSORD) were selected through logistic regression modeling, with point values assigned to each predictor. Modeling of risk index scores produced predicted probabilities of OSORD; risk classes were defined by the predicted probability distribution., Results: Fifteen variables most highly associated with OSORD were retained as items, including mental health disorders and pharmacotherapy; impaired drug metabolism or excretion; pulmonary disorders; specific opioid characteristics; and recent hospital visits. The average predicted probability of experiencing OSORD ranged from 3% in the lowest risk decile to 94% in the highest, with excellent agreement between predicted and observed incidence across risk classes. The model's C-statistic was 0.88 and Hosmer-Lemeshow goodness-of-fit statistic 10.8 (P > 0.05)., Conclusion: RIOSORD performed well in identifying medical users of prescription opioids within the Veterans' Health Administration at elevated risk of overdose or life-threatening respiratory depression, those most likely to benefit from preventive interventions. This novel, clinically practical, risk index is intended to provide clinical decision support for safer pain management. It should be assessed, and refined as necessary, in a more generalizable population, and prospectively evaluated., (© 2015 The Authors Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.)

Objective: Prescription opioid use and deaths related to serious toxicity, including overdose, have increased dramatically in the United States since 1999. However, factors associated with serious opioid-related respiratory or central nervous system (CNS) depression or overdose in medical users are not well characterized. The objective of this study was to examine the factors associated with serious toxicity in medical users of prescription opioids., Design: Retrospective, nested, case-control analysis of Veterans Health Administration (VHA) medical, pharmacy, and health care resource utilization administrative data., Subjects: Patients dispensed an opioid by VHA between October 1, 2010 and September 30, 2012 (N=8,987)., Methods: Cases (N=817) experienced life-threatening opioid-related respiratory/CNS depression or overdose. Ten controls were randomly assigned to each case (N=8,170). Logistic regression was used to examine associations with the outcome., Results: The strongest associations were maximum prescribed daily morphine equivalent dose (MED)≥ 100 mg (odds ratio [OR]=4.1, 95% confidence interval [CI], 2.6-6.5), history of opioid dependence (OR=3.9, 95% CI, 2.6-5.8), and hospitalization during the 6 months before the serious toxicity or overdose event (OR=2.9, 95% CI, 2.3-3.6). Liver disease, extended-release or long-acting opioids, and daily MED of 20 mg or more were also significantly associated., Conclusions: Substantial risk for serious opioid-related toxicity and overdose exists at even relatively low maximum prescribed daily MED, especially in patients already vulnerable due to underlying demographic factors, comorbid conditions, and concomitant use of CNS depressant medications or substances. Screening patients for risk, providing education, and coprescribing naloxone for those at elevated risk may be effective at reducing serious opioid-related respiratory/CNS depression and overdose in medical users of prescription opioids., (Wiley Periodicals, Inc.)

Isolated coronary anomalies are rare abnormalities that can be divided into benign and malignant forms. Malignant coronary artery abnormalities generally present already during infancy or early childhood by causing symptoms or sudden death. Benign abnormalities often remain asymptomatic because they are hemodynamically irrelevant. Among the 12,985 autopsies performed at the Institute of Legal Medicine at the University of Frankfurt (Germany) between 1995 and 2013, there were eight cases (0.062%) with isolated coronary artery abnormalities. Five of these cases (0.039%) could be included in our retrospective study. These involved one deceased female and four deceased male subjects, aged between 2 and 57 years. In three of these cases (aged 6, 9, and 11 years old), the coronary anomaly was classified as malignant and was recorded as the cause of death. Benign isolated coronary anomalies are often incidental findings during autopsies. However, in one of the cases in our study, coronary sclerosis in precisely the anomalous vessel was found to be the origin of a fatal myocardial infarction. Malignant isolated coronary artery anomalies attain medicolegal significance when they remain undetected despite advanced early detection protocols and cause sudden death in childhood.

This study examines differences in the rates of depression and anxiety symptoms in overweight vs. normal weight women before and after the menopause. In a population sample of 1 416 participants of the KORA-Survey F3 2004-2005 (age 35-74 years), body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) und waist-to-height-ratio (WHtR) were measured via physical examination. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. Compared with normal weight, obesity was associated with depression in premenopausal women. This held for elevated BMI-, WC- and WHtR-scores (OR=3.7, 4.2, and 2.8), underlining the relevance of both general and abdominal obesity. Menopausal status may be a moderator for the association of obesity and depression, which - given the interaction between these 2 risk factors - may be of preventive importance in regard to the development of cardiovascular outcomes such as coronary heart disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

The article deals with the new regulations in the German Civil Code (Bürgerliches Gesetzbuch - BGB), which came into effect in Germany as the Patient Rights Act (PatRG) on the 2/26/2013. In the third part, the burden of proof in liability questions (and 630h BGB) are discussed and critically analysed. In the discussion and a final resume points of criticism of the new law are pointed out.

The article deals with the new regulations in the German Civil Code (BGB) which came into effect in Germany on 26 Feb 2013 as the Patient Rights Act (PatRG). In the second part, the consent of the patient (Section 630d Civil Code), the physician's duties to inform the patient (Section 630e Civil Code), the documentation of treatment (Section 630f Civil Code), and the right of access to the patient file (Section 630g Civil Code) are discussed and critically analysed.

The article deals with the new regulations in the German Civil Code (BGB) which came into effect in Germany on 26 Feb 2013 as the Patient Rights Act (PatRG). In Part I, the legislative procedure, the treatment contract and the contracting parties (Section 630a Civil Code), the applicable regulations (Section 630b Civil Code) and the obligations to cooperate and inform (Section 630c Civil Code) are discussed and critically analysed.

Background: In international epidemiological studies, associations between suicides and body height, or body mass index (BMI) were found. Because of the recently growing number of suicides in Germany, a closer look on different anthropometric measures of suicide victims autopsied at the Institute of Forensic Medicine of the Goethe-University in Frankfurt/Main, Germany, was taken., Method: A retrospective analysis of 1,271 non-natural death cases autopsied between 2006 and 2010 was performed. A total of 566 other than suicide (control group) and 245 suicide cases (study group) with a given body height and weight aged between 18 and 96 years were examined., Results: Body mass indices of the 18-59-year-old male and 60-79-year-old female suicide victims were significantly lower. Old-aged women who committed suicide exhibited beside a significant lower body mass a significantly slender body shape measured as smaller pelvic circumference, waist circumference, and waist-to-tallness ratio. Self-poisoning was by far the leading suicide method in both genders. The victims of the suicide method hanging were the youngest on average, and this method was most common in the male underweight and female lightly normal weight BMI categories, whereas old, overweight, and obese men killed themselves predominantly with firearms., Conclusion: The analysis showed that body measures of suicide cases in comparison to other non-natural death circumstance cases differ. For criminal procedural reasons, all suicide cases should be autopsied. But high autopsy rates are also needed for scientific research and to ensure a high level of patient safety.

Accidents constitute one of the greatest risks to children, yet there are few medical reports that discuss the subject of accidental asphyxia. However, a systematic analysis of all documented cases in Germany over the years 2000-2008 has now been conducted, aiming at identifying patterns of accidental asphyxia, deducing findings, defining avoidance measures and recommending ways of increasing product safety and taking possible precautions. The analysis is based on a detailed retrospective analysis of all 91 relevant autopsy reports from 24 different German forensic institutes. A variety of demographic and morphological data was systematically collected and analysed. In 84 of the 91 cases, the sex of the victim was reported, resulting in a total of 57 boys (68 %) and 27 girls (32 %). The age spread ranged between 1 day and 14 years, with an average of 5.9 years. Most accidents occurred in the first year of life (20 %) or between the ages of 1 and 2 years (13 %). In 46 % of cases, the cause of death was strangulation, with the majority occurring in the home environment. In 31 % of all cases, the cause of death was positional asphyxia, the majority resulting from chest compression. In 23 % of cases, the cause of death was aspiration, mainly of foreign bodies. Today, accidental asphyxiation is a rare cause of death in children in Germany. Nevertheless, the majority of cases could have been avoided. Future incidence can be reduced by implementing two major precautions: increasing product safety and educating parents of potentially fatal risks. Specific recommendations relate to children's beds, toys and food.

In clinical practice diagnoses can be found which are partially based on body measurements. By measuring body height and body weight the patient is categorised, for example by Body-Mass Index (BMI), in different adipose grades. Different diseases are associated with specific biometric parameters. Abdominal adiposity measured by waist circumference correlates with the risk of colon carcinoma and is one diagnostic criteria of the metabolic syndrome. An unhealthy waist-hip ratio (WHR) can cause a higher risk of a cardiovascular disease and dementia. By combining body measurement with cause of death found during the medicolegal autopsy, clinical relevant correlations can be uncovered. Research in medical databases (e.g. PubMed) was carried out to find studies showing possible associations between body measurements, their indices and morbidity or causes of death. This article is a selective survey of these published studies, current guidelines and the German Institute for Standardisation - Norm (DIN-Norm). We give a wide thematic overview and select relevant parameters, which should be taken during medico-legal autopsies in future. The ascertainment of those parameters and their adjustment with the findings of the medico-legal autopsies can be a key to finding predictors of history of disease and relevant morbidity risks in the institutes of forensic medicine. Such findings are very important in the assessment of risk for living patients and necessary preventive actions. Beside the measurement of waist and hip circumference mentioned in specific clinical guidelines in Germany, we suggest, after analysing the parameters, to measure the thickness of the subcutaneous fat on the anterior chest and the thigh circumference as well.

In the last few years, male circumcision has become the subject of controversial discussion. On the one hand, medical and hygienic arguments, ideology, freedom of religion, cultural identity and social adequacy are claimed by those supporting male circumcision. On the other hand, the justification of this practice also has to be critically scrutinized just as the question whether the parents have the right to consent to the operation. Today, opinions range from those who claim that religion and culture alone justify the practice to those who consider circumcision of minors unable to give their consent as bodily injury subject to punishment. In contrast to female genital mutilation, most positions do not postulate that circumcision violates morality. If the person concerned is able to give his consent, freedom of religion may also justify circumcision after weighing its pros and cons as well as its risks and potential side effects.

Female genital mutilation (FGM) is considered to be against the law and against morality not only in Western countries, although a woman of age and able to consent may sometimes think differently. The procedure may have serious physical and emotional consequences for the girl or woman. Nevertheless there are attempts to justify the procedure with medical and hygienic pseudoarguments, ideology, freedom of religion, cultural identity and social adequacy. Outside the Western world, some people claim that religion and culture alone justify the practice. In Germany, parents can lose the right to determine the residence of their daughter, if she is faced with the risk of genital mutilation in order to prevent that the child or girl is taken to her home country. Genital mutilation as a gender-specific threat is recognized as a reason to grant asylum or prevent deportation. Proposals to make genital mutilation a separate punishable offence are presently discussed by the legislator.