The toxicological pharmacoepidemiology of suicide : population-based studies on psychotropic-medication use in Sweden

The act of completed suicide is a complex phenomenon associated with numerous identified individual and combined risk factors. Mental illness and related disorders confer among the highest risks of completed suicide and have consequently been targeted through pharmacological interventions. However, psychotropic medications and their possible effects on completed suicide have proved notoriously difficult to study. Nonetheless, it is of great importance to further investigate these classes of medications and their role in the suicidal process. The thesis focuses on toxicological verification of psychotropic medication among individuals who have committed suicide or died of other causes in Sweden. We have investigated the potential role of selective serotonin re-uptake inhibitors in the choice of suicide method and demonstrated the level of adherence to and recreational use of the most commonly prescribed non-addictive psychotropic medications in the Swedish population. In yet-to-be-published Study III, we have examined purchasing patterns for psychotropic medications during the year prior to death, as well as the impact of the level of medication adherence upon the risk of completed suicide. All studies are based on Swedish national registry data from a period of nearly ten years (2005-2014). Full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death and diagnoses from inpatient care have been used to operationalize investigated exposures and outcomes and facilitate adjustments for confounders in two case-control studies and one methodological study. By the use of the prescription-based algorithm PRE2DUP, purchases of psychotropic medications and calculated lengths of use were compared with forensic-toxicological findings as a measure of adherence. Logistic regression and Cohen’s kappa have been the principal statistical methods used. A new measure of continued need of treatment – the dispensation ratio (the ratio of initiated and discontinued prescriptions) – was also developed. Two of the main findings are that selective serotonin re-uptake inhibitors are associated with violent completed suicide during early treatment among elderly subjects and that presence of other substances (including other medications and illegal drugs) is an important confounder of associations between treatment with selective serotonin re-uptake inhibitors and choice of suicide method. Overall, rates of adherence in the Swedish general population to psychotropic medication, as reflected by therapeutic blood concentrations at forensic autopsy, are good. Biochemically verified incomplete adherence to antipsychotics, as shown in Study III, is associated with a markedly increased risk of completed suicide. The corresponding effect size for antidepressants was shown to be smaller and no longer statistically significant after adjustments for the dispensation ratio. Forensic-toxicological data are largely conservative biochemically verified measures of the possible impact of psychotropic medication upon the risk of death. By combining such data with national registry data, we have revealed findings of great importance to further suicide prevention and, at the same time, demonstrated a public-health-oriented application of results from medico-legal autopsies, beyond their immediate use in forensic investigations

Computationally Efficient Approach for Preheating of Battery Electric Vehicles before Fast Charging in Cold Climates

This paper investigates battery preheating before fast charging, for a battery electric vehicle (BEV) driving in a cold climate. To prevent the battery from performance degradation at low temperatures, a thermal management (TM) system has been considered, including a high-voltage coolant heater (HVCH) for the battery and cabin compartment heating. Accordingly, an optimal control problem (OCP) has been formulated in the form of a nonlinear program (NLP), aiming at minimising the total energy consumption of the battery. The main focus here is to develop a computationally efficient approach, mimicking the optimal preheating behavior without a noticeable increase in the total energy consumption. The proposed algorithm is simple enough to be implemented in a low-level electronic control unit of the vehicle, by eliminating the need for solving the full NLP in the cost of only 1Wh increase in the total energy consumption

Optimal Thermal Management and Charging of Battery Electric Vehicles over Long Trips

This paper studies optimal thermal management and charging of a battery electric vehicle driving over long distance trips. The focus is on the potential benefits of including a heat pump in the thermal management system for waste heat recovery, and charging point planning, in a way to achieve optimality in time, energy, or their trade-off. An optimal control problem is formulated, in which the objective function includes the energy delivered by the charger(s), and the total charging time including the actual charging time and the detour time to and from the charging stop. To reduce the computational complexity, the formulated problem is then transformed into a hybrid dynamical system, where charging dynamics are modelled in the domain of normalized charging time. Driving dynamics can be modelled in either of the trip time or travel distance domains, as the vehicle speed is assumed to be known a priori, and the vehicle is only stopping at charging locations. Within the hybrid dynamical system, a binary variable is introduced for each charging location, in order to decide to use or skip a charger. This problem is solved numerically, and simulations are performed to evaluate the performance in terms of energy efficiency and time. The simulation results indicate that the time required for charging and total energy consumption are reduced up to 30.6% and 19.4%, respectively, by applying the proposed algorithm

Glucose metabolism in completed suicide: a forensic-pathological pilot study

Aim To determine whether antemortem blood levels of glycated hemoglobin (HbA1c) and glucose predict completed suicide and, by extension, whether markers of glucose metabolism might be associated with a prosuicidal trait or state. Method From consecutively performed autopsies, samples of blood and vitreous humor from 17 suicide victims and 27 non-suicide controls were compared with regard to levels of glucose, lactate, and HbA1c. Results Mean HbA1c was higher, and mean estimated blood glucose lower, among suicide victims, although tests revealed no significant differences (P = 0.171 and P = 0.395, respectively). HbA1c levels exceeding 48.0 mmol/mol, which were indicative of persistent hyperglycemia, were twice as common in suicide victims (59% vs 30%; P = 0.068). Conclusion The finding of this pilot study suggest that deranged glucose metabolism may reflect biological events antecedent to, or concomitant with, completed suicide, with the following clinical implications: recurring hyperglycemia due to defective glucose transport, which may give rise to depression and suicidal ideation, and elevated HbA1c levels, which may represent an assayable correlate to neurobiological conditions predisposing to suicide

Bacterial composition in Swedish raw drinking water reveals three major interacting ubiquitous metacommunities

Background Surface raw water used as a source for drinking water production is a critical resource, sensitive to contamination. We conducted a study on Swedish raw water sources, aiming to identify mutually co-occurring metacommunities of bacteria, and environmental factors driving such patterns. Methods The water sources were different regarding nutrient composition, water quality, and climate characteristics, and displayed various degrees of anthropogenic impact. Water inlet samples were collected at six drinking water treatment plants over 3 years, totaling 230 samples. The bacterial communities of DNA sequenced samples (n = 175), obtained by 16S metabarcoding, were analyzed using a joint model for taxa abundance. Results Two major groups of well-defined metacommunities of microorganisms were identified, in addition to a third, less distinct, and taxonomically more diverse group. These three metacommunities showed various associations to the measured environmental data. Predictions for the well-defined metacommunities revealed differing sets of favored metabolic pathways and life strategies. In one community, taxa with methanogenic metabolism were common, while a second community was dominated by taxa with carbohydrate and lipid-focused metabolism. Conclusion The identification of ubiquitous persistent co-occurring bacterial metacommunities in freshwater habitats could potentially facilitate microbial source tracking analysis of contamination issues in freshwater sources

Development of single-tube nested real-time PCR assays with long internally quenched probes for detection of norovirus genogroup II

Publisher Copyright: © 2016, Eaton Publishing Company. All rights reserved.The high sequence variation of RNA viruses necessitates use of degenerate primers and probes or multiple primers and probes in molecular diagnostic assays. We showed previously that PCR amplification in two rounds, first with long target-specific primers and then with short generic primers, followed by detection using long probes, can tolerate sequence variation. Here we demonstrate that long primers and probes of up to 56 nucleotides can also be applied in real-time PCR for the detection of norovirus genogroup II with improved sensitivity. Probe design (method of incorporating quenchers, use of Zen internal quencher or traditional quenchers) greatly affects the sensitivity of the real-time PCR assays.Peer reviewe

Sandbox university: Estimating influence of institutional action

The approach presented in this article represents a generalizable and adaptable methodology for identifying complex interactions in educational systems and for investigating how manipulation of these systems may affect educational outcomes of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A virtual Sandbox University is created in order to facilitate effective identification of successful and stable initiatives within higher education, which can affect students' credits and student retention - something that has been lacking up until now. The results highlight the importance of teacher feedback and teacher-student rapport, which is congruent with current educational findings, illustrating the methodology's potential to provide a new basis for further empirical studies of issues in higher education from a complex systems perspective

Using a disciplinary discourse lens to explore how representations afford meaning making in a typical wave physics course

We carried out a case study in a wave physics course at a Swedish university in order to investigate the relations between the representations used in the lessons and the experience of meaning making in interview–discussions. The grounding of these interview–discussions also included obtaining a rich description of the lesson environment in terms of the communicative approaches used and the students’ preferences for modes of representations that best enable meaning making. The background for this grounding was the first two lessons of a 5-week course on wave physics (70 students). The data collection for both the grounding and the principal research questions consisted of video recordings from the first two lessons: a student questionnaire of student preferences for representations (given before and after the course) and video-recorded interview–discussions with students (seven pairs and one on their own). The results characterize the use of communicative approaches, what modes of representation were used in the lectures, and the trend in what representations students’ preferred for meaning making, all in order to illustrate how students engage with these representations with respect to their experienced meaning making. Interesting aspects that emerged from the study are discussed in terms of how representations do not, in themselves, necessarily enable a range of meaning making; that meaning making from representations is critically related to how the representations get situated in the learning environment; and how constellations of modes of disciplinary discourse may be necessary but not always sufficient. Finally, pedagogical comments and further research possibilities are presented.Web of Scienc

Phenol-Soluble Modulin α Peptide Toxins from Aggressive Staphylococcus aureus Induce Rapid Formation of Neutrophil Extracellular Traps through a Reactive Oxygen Species-Independent Pathway

Neutrophils have the ability to capture and kill microbes extracellularly through the formation of neutrophil extracellular traps (NETs). These are DNA and protein structures that neutrophils release extracellularly and are believed to function as a defense mechanism against microbes. The classic NET formation process, triggered by, e.g., bacteria, fungi, or by direct stimulation of protein kinase C through phorbol myristate acetate, is an active process that takes several hours and relies on the production of reactive oxygen species (ROS) that are further modified by myeloperoxidase (MPO). We show here that NET-like structures can also be formed by neutrophils after interaction with phenol-soluble modulin α (PSMα) that are cytotoxic membrane-disturbing peptides, secreted from community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). The PSMα-induced NETs contained the typical protein markers and were able to capture microbes. The PSMα-induced NET structures were disintegrated upon prolonged exposure to DNase-positive S. aureus but not on exposure to DNase-negative Candida albicans. Opposed to classic NETosis, PSMα-triggered NET formation occurred very rapidly, independently of ROS or MPO, and was also manifest at 4°C. These data indicate that rapid NETs release may result from cytotoxic membrane disturbance by PSMα peptides, a process that may be of importance for CA-MRSA virulence