MT-Toolbox: improved amplicon sequencing using molecule tags

Abstract Background Short oligonucleotides can be used as markers to tag and track DNA sequences. For example, barcoding techniques (i.e. Multiplex Identifiers or Indexing) use short oligonucleotides to distinguish between reads from different DNA samples pooled for high-throughput sequencing. A similar technique called molecule tagging uses the same principles but is applied to individual DNA template molecules. Each template molecule is tagged with a unique oligonucleotide prior to polymerase chain reaction. The resulting amplicon sequences can be traced back to their original templates by their oligonucleotide tag. Consensus building from sequences sharing the same tag enables inference of original template molecules thereby reducing effects of sequencing error and polymerase chain reaction bias. Several independent groups have developed similar protocols for molecule tagging; however, user-friendly software for build consensus sequences from molecule tagged reads is not readily available or is highly specific for a particular protocol. Results MT-Toolbox recognizes oligonucleotide tags in amplicons and infers the correct template sequence. On a set of molecule tagged test reads, MT-Toolbox generates sequences having on average 0.00047 errors per base. MT-Toolbox includes a graphical user interface, command line interface, and options for speed and accuracy maximization. It can be run in serial on a standard personal computer or in parallel on a Load Sharing Facility based cluster system. An optional plugin provides features for common 16S metagenome profiling analysis such as chimera filtering, building operational taxonomic units, contaminant removal, and taxonomy assignments. Conclusions MT-Toolbox provides an accessible, user-friendly environment for analysis of molecule tagged reads thereby reducing technical errors and polymerase chain reaction bias. These improvements reduce noise and allow for greater precision in single amplicon sequencing experiments

Filicide in Austria and Finland - A register-based study on all filicide cases in Austria and Finland 1995-2005

<p>Abstract</p> <p>Background</p> <p>Filicide is the tragic crime of murdering one's own child. Previous research has found that the offending parents are commonly depressed and that suicide is often associated as an actual act or an intention. Yet, filicide is an underreported crime and previous studies have been strained with methodological problems. No comprehensive international studies on filicide have been presented in the literature until now.</p> <p>Methods</p> <p>This was a descriptive, comprehensive, register-based study of all filicides in Austria and Finland during 1995-2005. Filicide-suicide cases were also included.</p> <p>Results</p> <p>Most of the perpetrators were the biological mothers; in Austria 72%, in Finland 52%. Suicide followed filicide either as an attempt or a fulfilled act in 32% and 54% of the cases in Austria and Finland, respectively. Psychotic mood disorders were diagnosed for 10% of the living perpetrators in Austria, and 12% in Finland. Non-psychotic depression was diagnosed in 9% of surviving perpetrators in Austria, 35% in Finland.</p> <p>Conclusion</p> <p>The data from the two countries demonstrated that filicide is such a multifaceted and rare phenomenon that national data from individual countries seldom offer sufficient scope for its thorough study. Further analyses are needed to produce a complete picture of filicide.</p

Women convicted for violent offenses: Adverse childhood experiences, low level of education and poor mental health

<p>Abstract</p> <p>Background</p> <p>In past years, the female offender population has grown, leading to an increased interest in the characteristics of female offenders. The aim of this study was to assess the prevalence of female violent offending in a Swiss offender population and to compare possible socio-demographic and offense-related gender differences.</p> <p>Methods</p> <p>Descriptive and bivariate logistic regression analyses were performed for a representative sample of N = 203 violent offenders convicted in Zurich, Switzerland.</p> <p>Results</p> <p>7.9% (N = 16) of the sample were female. Significant gender differences were found: Female offenders were more likely to be married, less educated, to have suffered from adverse childhood experiences and to be in poor mental health. Female violent offending was less heterogeneous than male violent offending, in fact there were only three types of violent offenses females were convicted for in our sample: One third were convicted of murder, one third for arson and only one woman was convicted of a sex offense.</p> <p>Conclusions</p> <p>The results of our study point toward a gender-specific theory of female offending, as well as toward the importance of developing models for explaining female criminal behavior, which need to be implemented in treatment plans and intervention strategies regarding female offenders.</p

Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas

Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas, and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine (5hmC) and higher 5-methylcytosine (5mC) levels, as well as increased dimethylation of histone H3K79. Mutations in IDH1 or IDH2 were associated with longer overall survival (p = 0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (p = 0.021). IDH1 and IDH2 mutations are significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2,309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors

The role of conversation in health care interventions: enabling sensemaking and learning

<p>Abstract</p> <p>Background</p> <p>Those attempting to implement changes in health care settings often find that intervention efforts do not progress as expected. Unexpected outcomes are often attributed to variation and/or error in implementation processes. We argue that some unanticipated variation in intervention outcomes arises because unexpected conversations emerge during intervention attempts. The purpose of this paper is to discuss the role of conversation in shaping interventions and to explain why conversation is important in intervention efforts in health care organizations. We draw on literature from sociolinguistics and complex adaptive systems theory to create an interpretive framework and develop our theory. We use insights from a fourteen-year program of research, including both descriptive and intervention studies undertaken to understand and assist primary care practices in making sustainable changes. We enfold these literatures and these insights to articulate a common failure of overlooking the role of conversation in intervention success, and to develop a theoretical argument for the importance of paying attention to the role of conversation in health care interventions.</p> <p>Discussion</p> <p>Conversation between organizational members plays an important role in the success of interventions aimed at improving health care delivery. Conversation can facilitate intervention success because interventions often rely on new sensemaking and learning, and these are accomplished through conversation. Conversely, conversation can block the success of an intervention by inhibiting sensemaking and learning. Furthermore, the existing relationship contexts of an organization can influence these conversational possibilities. We argue that the likelihood of intervention success will increase if the role of conversation is considered in the intervention process.</p> <p>Summary</p> <p>The generation of productive conversation should be considered as one of the foundations of intervention efforts. We suggest that intervention facilitators consider the following actions as strategies for reducing the barriers that conversation can present and for using conversation to leverage improvement change: evaluate existing conversation and relationship systems, look for and leverage unexpected conversation, create time and space where conversation can unfold, use conversation to help people manage uncertainty, use conversation to help reorganize relationships, and build social interaction competence.</p

Gender differentials in the presentation of symptoms, assessment, diagnosis and treatment of mentally ill prisoners

Critical criminologists have written extensively about the gendered nature of the criminal justice system and of its deleterious consequences. This chapter will continue in that same tradition and examine the extent to which gender plays a key role in the presentation of symptoms, assessment, diagnosis and treatment of mentally ill prisoners. The importance of such an exercise is clear. The 'Standard Minimum Rules for the Treatment of Prisoners' that was adopted by the First United Nations Congress on the Prevention of Crime and the Treatment of Offenders in 1955 made it very clear via Rule 62 that [t]he medical services of the institution shall seek to detect and shall treat any… mental illnesses or defects which may hamper a prisoner's rehabilitation'. Thus, the ensuing analysis here will explore how the gender of a prisoner influences the way in which a mentally ill inmate presents their symptoms (and seeks medical assistance); as well as, how they are thereafter assessed, diagnosed and treated by prison health services. By doing so, it is hoped that penal administrators and correctional health professionals in India will be made more aware of, or sensitive to, these variances, and that the subsequent assessment, diagnosis and treatment of such prisoners will be more gender-responsive so as to maximize the prospect of successful rehabilitation