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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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the articles "Zero is an important number," by L. Smith, "The comparative safety of buprenorphine versus methadone in pregnancy--what about confounding?," by S. Brogly et al. and "Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child," by B.K. Zedler.

Background: Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy., Objective: The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden., Methods: Pregnant women and their corresponding births during 2005-2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population., Results: A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father., Conclusions: An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders.

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.

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.

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.