Torn between living or dying—analyses of influencing factors on suicide ambivalence and its longitudinally impact on suicidal ideation and behavior in a high-risk sample

IntroductionFindings on the role of suicide ambivalence, an individual's wish to live (WL), and wish to die (WD) in the development of suicidality have been heterogenous. The main goal of this study was to examine associations of these constructs within the past week with sociodemographic factors and to longitudinally investigate their predictive power for suicidal ideation (SI) and suicide attempts (SA).MethodsN = 308 patients (54% female; M = 36.92 years, SD = 14.30), admitted to a psychiatric ward due to suicidality, were assessed for all constructs after admission, after six, nine, and 12 months. Data were analyzed with univariate fixed-effect models and lagged mixed-effect regression models.ResultsDecreased, WL increased post-baseline. Gender showed no significant link to ambivalence, WD, and WL. Ambivalence and WD correlated negatively with age and positively with depressiveness. More participants in a relationship showed a WL compared with single/divorced/widowed participants. More single participants or those in a relationship showed ambivalence than divorced/widowed participants. More single participants showed a WD than participants in a relationship/divorced/widowed. Longitudinally, ambivalence and WD predicted SI and SA.ConclusionThe findings underscore the importance of taking suicide ambivalence and WD into account in risk assessment and treatment

Suicidal behaviour in the social environment: Does exposure moderate the relationship between an individual's own suicidal ideation and behaviour?

Introduction: Suicidal behaviour still cannot be sufficiently predicted. Exposure to suicidal behaviour in the personal social environment is assumed to moderate the individual's transition from suicidal ideation to suicidal behaviour within the integrated motivational-volitional model of suicidal behaviour (IMV model). This study aimed to investigate this moderating effect in a German high-risk sample. Methods: We interviewed 308 psychiatric inpatients (53% female) aged 18 to 81 years (M = 36.9, SD = 14.30) admitted after attempted suicide (53%) or due to an acute suicidal crisis (47%) regarding exposure events in their social environment. Four types of exposure events were analysed using moderation analyses: familial suicides/suicide attempts and non-familial suicides/suicide attempts. Additionally, the numbers of reported exposure events were compared between patients with and without a recent suicide attempt as well as between patients with lifetime suicide attempts and lifetime suicidal ideation. Results: Neither moderating effects of exposure events on the relationship between lifetime suicidal ideation and recent suicidal behaviour nor group differences between suicidal ideators and suicide attempters regarding the exposure events were found. Conclusions: Exposure events might have differential and possibly protective effects on suicidal behaviour-depending on type and quality (intensity, personal relevance and recency) of event-and on the outcome (suicide vs. suicide attempt)

A Gene for Universal Congenital Alopecia Maps to Chromosome 8p21-22

SummaryComplete or partial congenital absence of hair (congenital alopecia) may occur either in isolation or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal-recessive mode of inheritance (MIM 203655). As yet, no gene has been linked to isolated congenital alopecia, nor has linkage been established to a specific region of the genome. In an attempt to map the gene for the autosomal recessive form of the disorder, we have performed genetic linkage analysis on a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia). We have analyzed individuals of this family, using >175 microsatellite polymorphic markers of the human genome. A maximum LOD score of 7.90 at a recombination fraction of 0 has been obtained with locus D8S258. Haplotype analysis of recombination events localized the disease to a 15-cM region between marker loci D8S261 and D8S1771. We have thus mapped the gene for this hereditary form of isolated congenital alopecia to a locus on chromosome 8p21-22 (ALUNC [alopecia universalis congenitalis]). This will aid future identification of the responsible gene, which will be extremely useful for the understanding of the biochemistry of hair development

The Iceberg Phenomenon: As Soon as One Technological Problem in NOTES Is Solved, the Next One Appears!

Purpose. Though already proclaimed about 7 years ago, natural orifice transluminal endoscopic surgery (NOTES) is still in its early stages. A multidisciplinary working team tried to analyze the technical obstacles and identify potential solutions. Methods. After a comprehensive review of the literature, a group of 3 surgeons, 1 gastroenterologist, 10 engineers, and 1 representative of biomedical industry defined the most important deficiencies within the system and then compiled as well as evaluated innovative technologies that could be used to help overcome these problems. These technologies were classified with regard to the time needed for their implementation and associated hindrances, where priority is based on the level of impact and significance that it would make. Results. Both visualization and actuation require significant improvement. Advanced illumination, mist elimination, image stabilization, view extension, 3-dimensional stereoscopy, and augmented reality are feasible options and could optimize visual information. Advanced mechatronic platforms with miniaturized, powerful actuators, and intuitive human–machine interfaces could optimize dexterity, as long as enabling technologies are used. The latter include depth maps in real time, precise navigation, fast pattern recognition, partial autonomy, and cognition systems. Conclusion. The majority of functional deficiencies that still exist in NOTES platforms could be overcome by a broad range of already existing or emerging enabling technologies. To combine them in an optimal manner, a permanent dialogue between researchers and clinicians is mandatory

GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.</p

Towards a Generic Modeling Language for Contract-Based Design

Abstract-Component-based and model-driven engineering are key paradigms for handling the ever-increasing complexity of technical systems. Surprisingly few component models consider extra-functional properties as first class entities. Contract-based design is a promising paradigm, which has the potential to fill this shortage of methods for dealing with extra-functional properties. By defining the concept of using assumptions in order to determine the environment, and by using the concept of guarantees to state what a component provides to the environment, it enables the analyzability of components and compositions in advance and during system execution. With this work, we aim to create the base for a pragmatic model-driven method that provides reusable modeling concepts for contracts targeting arbitrary extra-functional properties. Furthermore, we expand the current state-of-the-art of contractbased design by introducing the concept of a finite state machine, where single states consist of several valid contracts. It is also assumed that these modeling language features will ease the use of contract-based design. Additionally, we demonstrate the applicability of the presented modeling concepts on an exemplary use case from the automotive domain

H3K4 dimethylation in hepatocellular carcinoma is rare compared with other hepatobiliary and gastrointestinal carcinomas and correlates with expression of the methylase Ash2 and the demethylase LSD1

Methylation of core histones regulates chromatin structure and gene expression. Recent studies have demonstrated that these methylation patterns have prognostic value for some tumors. Therefore, we investigated dimethylation of histone H3 at lysine 4 (H3K4diMe) and H3K4 methylating (Ash2 complex) and demethylating enzymes (LSD1) in carcinomas of the hepatic and gastrointestinal tract. High levels of H3K4diMe were rarely observed in 15.7% of hepatocellular carcinoma (8/51) unlike other carcinomas including, in ascending order, cholangiocellular carcinoma/adenocarcinoma of the extrahepatic biliary tract, gastric carcinoma, pancreatic ductal adenocarcinoma, and neuroendocrine carcinoma (P &lt; .001). Ash2 was expressed in 84.4% of hepatocellular carcinomas (38/45) and correlated directly with H3K4diMe modification (correlation coefficient r = 0.53) and LSD1 expression (r = 0.35). In contrast to other carcinomas, 65.9% (29/44) of hepatocellular carcinomas analyzed showed no LSD1 expression (P &lt; .001). Interestingly, hepatocellular carcinomas without LSD1 expression appeared to be frequently Ash2 and H3K4diMe weak or negative (P = .004). In summary, high H3K4diMe expression is rare in hepatocellular carcinoma compared with other carcinomas (negative predictive value 92.3%), which may aid in the differential diagnosis. Lack of H3K4diMe is possibly due to complex epigenetic regulation involving Ash2 and LSD1

In vivo intratumor angiogenic treatment effects during taxane-based neoadjuvant chemotherapy of ovarian cancer

Abstract Background The aim of our study was to analyze the effect of taxane-based chemotherapy on tumor angiogenesis in patients with advanced epithelial ovarian cancer. Methods Within a prospective phase II trial, 32 patients with stage IIIC and IV ovarian cancer were treated with either two or three cycles of neoadjuvant chemotherapy prior to cytoreductive surgery. Carboplatin (AUC5) and docetaxel (75 mg/m2) were administered intravenously in a 3-weekly schedule. Changes in intratumor microvessel density (MVD) were assessed with immunohistochemistry by staining pre- and posttreatment surgical tumor specimens with panendothelial, neovascular and lymphatic vessel markers. Results Mean values of MVD defined by CD31, CD34, CD105 and D2-40 antibodies showed 12.3, 21.0, 2.7 and 3.1 vessels per high power field (HPF) before chemotherapy and increased after treatment to 15.3, 21.8, 4.8 and 3.6 per HPF, respectively. These changes were significant for CD31 (p = 0.04) and for CD105 (p = 0.02). Conclusion Taxane-based chemotherapy appears to promote tumor vascularization when administered every 3 weeks. A possible explanation is the secondary recovery of MVD in response to immediate cytotoxic and antiangiogenic effects of the chemotherapy. If confirmed prospectively, these findings favor shorter treatment intervals of taxane-based chemotherapy to counteract proangiogenic recovery.</p