Dual harm: Violent behaviour to others and self-harm behaviour in adults compulsorily admitted to a Dutch psychiatric hospital.

BACKGROUND: Verbal and physical violence in psychiatric hospitals can have harmful consequences for staff members, such as physical injury, traumatisation, and sick leave, and they often accompany involuntary admission. Harm to others may co-occur with self-harm, i.e., dual harm. However, little is known about the association between dual-harm and violent behaviour towards staff members and its clinical outcomes, such as seclusion and rapid tranquilisation after involuntary admission to a psychiatric inpatient unit. METHOD: A convenience sample of patients admitted involuntarily (N = 384; mean age = 48.03, SD = 19.92) between January 2016 and December 2019 in Western Brabant, the Netherlands, was used to design a retrospective file audit. Distinct harm groups, marked by the presence/absence of self- and/or other-harm, were investigated using multivariate linear regression modelling on the seriousness of violent acts and the total length of admission. Logistic regression analyses were used to study the association between harm groups and the administration of rapid tranquilisation, seclusion, and extended involuntary admissions. RESULTS: Several harm groups were identified, including self-harm only, other-harm only, and dual-harm groups. Psychiatric patients admitted to the hospital because of (the risk of) violence towards others had a higher risk of violent incidents during admission and some restrictive measures. In a subgroup of patients with psychotic disorders, patients with dual harm committed the most serious violent incidents compared to those in the other harm groups. CONCLUSION: Distinct harm groups were identified in a sample of involuntarily admitted patients. In a general adult psychiatric setting, patients at risk for violent behaviour, especially dual-harm patients, should be identified and monitored as part of the risk assessment. Future research is needed to explore more clinical correlates in the proposed distinction between harmful groups and to assess long-term prognosis.

Influence of 3d Transition Metal Doping on Lithium Stabilized Na-ß″-Alumina Solid Electrolytes.

Na-ß″-alumina is the commercially most successful solid electrolyte due to its application in ZEBRA and NAS® batteries. In this work, Li-stabilized Na-ß″-alumina electrolytes were doped with 3d transition metal oxides, namely TiO2, Mn3O4, and NiO, in order to improve their ionic conductivity and fracture strength. Due to XRD and EDX measurements, it was concluded that Mn- and Ni-ions are incorporated into the crystal lattice of Na-ß″-alumina. In contrast, TiO2 doping results in the formation of secondary phases that enable liquid-assisted sintering at temperatures as low as 1500 °C. All dopants increased the characteristic fracture strength of the electrolytes; 1.5 wt% of NiO doping proved to be most efficient and led to a maximal characteristic fracture strength of 296 MPa. Regarding the ionic conductivity, TiO2 doping showed the uppermost value of up to 0.30 S cm-1 at 300 °C. In contrast to the other dopants, TiO2 doping lowered the sintering temperature needed to obtain a dense, stable, and highly conductive Na-ß″-alumina electrolyte suitable for applications in Na based batteries.

The effect of tree shade on ambient conditions and heat stress indicator traits of new-born South African Mutton Merino and Dormer lambs: Preliminary results.

This preliminary study investigated the provision of shade on heat stress indicators of South African Mutton Merino (SAMM) and Dormer lambs shortly after birth, during the autumn 2017 and 2018 lambing seasons. Newborn lambs were assessed to determine whether welfare, as assessed by respiratory response and rectal temperature as heat stress indicators, survival and early growth benefitted from the provision of shade. Groups consisting of 4-17 pregnant SAMM and Dormer ewes were randomly allocated to 5-10 paddocks with natural shade from trees and 5-9 paddocks that were directly in the sun with no shade available. The lambs were recorded within 24 h of birth at noon. Climate data were obtained from a nearby weather station. The lambs were also weighed at 12 (SD = 2) days of age at tail-docking. Tree shade had a moderating effect on temperature, resulting in lower maximum daytime and higher minimum night-time temperatures. There was an interaction between a temperature-humidity index (THI) and the treatments (access to shade or no access to shade) for respiration and rectal temperature (P < 0.01). Both traits were relatively unaffected by the THI at values below 77. Unshaded lambs exhibited a pronounced upwards trend following a THI-threshold of 77-78. Tailing weight tended to be higher while lamb survival of live-born lambs to tail-docking was lower in lambs born in shaded paddocks but these trends did not persist to weaning. Shade is needed to enhance animal welfare by alleviating the effect of high THI-values on hot days in an autumn lambing season.

Ionization and Photofragmentation of Isolated Metalloporphyrin Cations Investigated by VUV Action Spectroscopy*.

We investigated the photoionization and fragmentation of isolated metal protoporphyrin IX cations (MPPIX+ with M=Fe, Co, Zn) by means of vacuum-ultraviolet (VUV) action spectroscopy in the energy range of 8.5-35 eV. Experiments were carried out in the gas phase by interfacing an electrospray ionization tandem mass spectrometer with a synchrotron beamline. The mass spectra and partial ion yields show that photoexcitation of the precursor ions predominantly leads to . CH2 COOH radical side-chain losses of the macrocycle with additional methyl radical (. CH3 ) side-chain losses. Ionization, in contrast, leads to the formation of the intact ionized precursor and various doubly charged fragments which are mostly due to side-chain cleavages. Although statistical fragmentation dominates, we found evidence for non-statistical processes such as new fragments involving for example single and double H2 O losses, indicating that different relaxation mechanisms are at play upon photoionization compared to photoexcitation. The measured ionization energies were 9.6±0.2 eV, 9.4±0.2 eV and 9.6±0.2 eV for FePPIX+ , CoPPIX+ and ZnPPIX+ , respectively.

Long term genetic selection for reproductive success affects neonatal lamb vitality across cold stress conditions.

Adverse weather conditions are important contributors to mortality in new-born lambs. Previous studies have shown variation between lambs in their ability to cope with circumstances of cold stress, and genetic selection could be a viable option for improving animal robustness. The Elsenburg Merino flock was divergently selected on number of lambs weaned (NLW). This resulted in divergent responses in reproduction and lamb survival. This study evaluated lamb vitality and mortality of positively selected H-Line relative to the negatively selected L-Line in response to cold stress. Traits included lamb rectal temperature (RT), surface temperature (ST), shiver score (SS), lamb vigor score (LVS), breaths per minute (BPM), mortality to three days of age (M3) and to weaning (TM). Cold stress was described by a chill index derived from daily rainfall, wind speed and ambient temperature, and represented as the mean of the one (CI), two (CI-2) or three (CI-3) days since parturition. Overall, H-Line lambs had a higher neonatal RT and were less likely to succumb than L-Line contemporaries. In a significant (P < 0.05) interaction, the predicted RT of L-Line showed a non-linear decline with increased levels of CI-2, while H-Line lambs better maintained their core temperature. M3 was also affected by a significant interaction between CI-3 and selection line, further suggesting that observed lower mortality rates in the H-Line depends on H-Line lambs' improved ability to cope with stressful environments. Long term selection for NLW in the H-Line led to improvements in both adaptations associated with lower lamb losses. The continued recording of viability traits to produce larger datasets amenable to genetic analysis is recommended, specifically for rectal temperature.

An Experimental and Theoretical Study of Laser Postionization of Femtosecond-Laser-Desorbed Drug Molecules.

Femtosecond laser desorption postionization mass spectrometry using 7.9 eV single-photon ionization (7.9 eV fs-LDPI-MS) detected three of four drug compounds previously found to have very low ionization efficiencies by secondary ion mass spectrometry. Electronic structure calculations of the ionization energies and other properties of these four drug compounds predicted that all display ionization energies below the 7.9 eV photon energy, as required for single-photon ionization. The 7.9 eV fs-LDPI-MS of carbamazepine, imipramine, and verapamil all showed significant precursor (M+) ion signal, but no representative signal was observed for ciprofloxacin. Furthermore, 7.9 eV fs-LDPI-MS displayed higher M+ signals and mostly similar fragment ions compared with 70 eV electron impact mass spectrometry. Ionization and fragmentation patterns are discussed in terms of calculated wave functions for the highest occupied molecular orbitals. The implications for improving lateral resolution and sensitivity of MS imaging of drug compounds are also considered.

Metabolic Imaging at the Single-Cell Scale: Recent Advances in Mass Spectrometry Imaging.

There is an increasing appreciation that every cell, even of the same type, is different. This complexity, when additionally combined with the variety of different cell types in tissue, is driving the need for spatially resolved omics at the single-cell scale. Rapid advances are being made in genomics and transcriptomics, but progress in metabolomics lags. This is partly because amplification and tagging strategies are not suited to dynamically created metabolite molecules. Mass spectrometry imaging has excellent potential for metabolic imaging. This review summarizes the recent advances in two of these techniques: matrix-assisted laser desorption ionization (MALDI) and secondary ion mass spectrometry (SIMS) and their convergence in subcellular spatial resolution and molecular information. The barriers that have held back progress such as lack of sensitivity and the breakthroughs that have been made including laser-postionization are highlighted as well as the future challenges and opportunities for metabolic imaging at the single-cell scale.

Rapid deconvolution of low-resolution time-of-flight data using Bayesian inference.

The deconvolution of low-resolution time-of-flight data has numerous advantages, including the ability to extract additional information from the experimental data. We augment the well-known Lucy-Richardson deconvolution algorithm using various Bayesian prior distributions and show that a prior of second-differences of the signal outperforms the standard Lucy-Richardson algorithm, accelerating the rate of convergence by more than a factor of four, while preserving the peak amplitude ratios of a similar fraction of the total peaks. A novel stopping criterion and boosting mechanism are implemented to ensure that these methods converge to a similar final entropy and local minima are avoided. Improvement by a factor of two in mass resolution allows more accurate quantification of the spectra. The general method is demonstrated in this paper through the deconvolution of fragmentation peaks of the 2,5-dihydroxybenzoic acid matrix and the benzyltriphenylphosphonium thermometer ion, following femtosecond ultraviolet laser desorption.

Soft Picosecond Infrared Laser Extraction of Highly Charged Proteins and Peptides from Bulk Liquid Water for Mass Spectrometry.

We report the soft laser extraction and production of highly charged peptide and protein ions for mass spectrometry directly from bulk liquid water at atmospheric pressure and room temperature, using picosecond infrared laser ablation. Stable ion signal from singly charged small molecules, as well as highly charged biomolecular ions, from aqueous solutions at low laser pulse fluence (∼0.3 J cm-2) is demonstrated. Sampling via single picosecond laser pulses is shown to extract less than 27 pL of volume from the sample, producing highly charged peptide and protein ions for mass spectrometry detection. The ablation and ion generation is demonstrated to be soft in nature, producing natively folded proteins ions under sample conditions described for native mass spectrometry. The method provides laser-based sampling flexibility, precision and control with highly charged ion production directly from water at low and near neutral pH. This approach does not require an additional ionization device or high voltage applied directly to the sample.

Engineering oxidative stability in human hemoglobin based on the Hb providence (ßK82D) mutation and genetic cross-linking.

Previous work suggested that hemoglobin (Hb) tetramer formation slows autoxidation and hemin loss and that the naturally occurring mutant, Hb Providence (HbProv; ßK82D), is much more resistant to degradation by H2O2 We have examined systematically the effects of genetic cross-linking of Hb tetramers with and without the HbProv mutation on autoxidation, hemin loss, and reactions with H2O2, using native HbA and various wild-type recombinant Hbs as controls. Genetically cross-linked Hb Presbyterian (ßN108K) was also examined as an example of a low oxygen affinity tetramer. Our conclusions are: (a) at low concentrations, all the cross-linked tetramers show smaller rates of autoxidation and hemin loss than HbA, which can dissociate into much less stable dimers and (b) the HbProv ßK82D mutation confers more resistance to degradation by H2O2, by markedly inhibiting oxidation of the ß93 cysteine side chain, particularly in cross-linked tetramers and even in the presence of the destabilizing Hb Presbyterian mutation. These results show that cross-linking and the ßK82D mutation do enhance the resistance of Hb to oxidative degradation, a critical element in the design of a safe and effective oxygen therapeutic.

Extensive tumoral melanosis associated with ipilimumab-treated melanoma.

Tumoral melanosis describes a pigmented lesion clinically similar to melanoma but on histology reveals dense aggregates of melanin-laden, benign macrophages without malignant cells. In the few reported cases so far, tumoral melanosis has arisen in the skin or lymph node of a patient with a regressed melanoma or an epithelioid tumour. As a marker of regressed primary melanoma, its discovery may prompt investigation and surveillance for undiagnosed local or metastatic disease. Here, we present a unique case of extensive tumoral melanosis arising during ipilimumab treatment of in-transit metastases from a previously excised melanoma.

High prevalence of early onset mental disorders among long-term disability claimants.

PURPOSE: To provide information on prevalence, comorbidity, age-of-onset and severity of mental disorders among persons claiming disability after long-term sickness absence. METHOD: Cross-sectional analysis of a cohort of Dutch disability claimants (n = 346). Composite International Diagnostic Interview (CIDI) 3.0 was used to generate DSM-IV classifications of mental disorder, age-of-onset and severity; registry data were used on demographics and ICD-10 classifications of somatic disorder. RESULTS: The mean age of respondents was 49.8 (range 22-64). The most prevalent broad categories of mental disorders were mood and anxiety disorder with a 12-month prevalence of 28.6% and 32.9%, respectively. Mood and most anxiety disorders had ages of onset in adolescence and early adulthood. The phobias start at school age. Of all respondents, 33.7% had ≥1 12-month mental disorder. Co-occurrence of substance use disorders, phobias and depression/anxiety disorders is frequent. Urogenital and gastrointestinal diseases, and cancer coincide with 12-month mental disorder in 66.7%, 53.9% and 51.7% of cases, respectively. More than two out of three specific mental disorders are serious in terms of disability and days out of working role. CONCLUSIONS: Disability claimants constitute a vulnerable population with a high prevalence of serious mental disorder, substantial comorbidity and ages-of-onset in early working careers. More research is needed to help prevent long-term sickness absence and disability of claimants with mental health problems. IMPLICATIONS FOR REHABILITATION: This study shows common mental disorders, such as mood and anxiety disorders, to be highly prevalent among persons claiming disability benefit after long-term sickness absence, to have early onsets and to often co-occur with somatic disorders. Professionals in primary and occupational health care should assess need for treatment of workers at risk, while at the same time being careful not to medicalize normal life problems. Insurance physicians assessing disability benefit claims should identify factors that caused claimants to call in sick and start interventions to promote return to work.

Gender-specific differences in the development of sarcopenia in the rodent model of the ageing high-fat rat.

BACKGROUND: Sarcopenia is linked to functional impairments, loss of independence, and mortality. In the past few years, obesity has been established as being a risk factor for a decline in muscle mass and function. There are several molecular pathological mechanisms, which have been under discussion that might explain this relationship. However, most studies were conducted using male animals and for a short period of time. METHODS: In this study, the gender-specific effect of long-term, high-fat content feeding in Sprague-Dawley rats was examined. Development of the quadriceps muscle of the animals was monitored in vivo using magnetic resonance. The results of these measurements and of the biochemical analysis of the aged muscle were compared. RESULTS: Surprisingly, only male but not female rats showed a decline in muscle cross-sectional area at 16 months of age as a result of a chronic oversupply of dietary fats. This loss of muscle mass could not be explained by either de-regulation of the anabolic Akt pathway or by up-regulation of the main ubiquitin ligases of muscle, MAFbx and MuRF-1. However, fusion of satellite cells to myotubes was induced by the high-fat diet in male rats, possibly as a result of an increased need for compensatory regeneration processes. Caspase-3-dependent apoptosis induction, irrespective of diet, seems to be the major determinant of muscle decline during ageing in male but not female rats. CONCLUSION: Taken together, activation of the apoptosis-inducing Caspase-3 seems to be the most important trigger for the age-related muscle loss. Male rats were more prone to the decline of muscle during ageing than female animals, which was further enforced by a long-term, high fat diet.

Predictors of functional improvement and future work status after the disability benefit claim: a prospective cohort study.

OBJECTIVE: In most industrialized countries, disability benefit rates have increased substantially in the past decade. Few beneficiaries return into employment once disability benefit is awarded. The present study aims to investigate which factors predict functional improvement and future work status among persons claiming disability benefit after having been on long-term sickness leave. METHODS: Prospective cohort study with 1 year follow-up among disability claimants (n = 375; response rate: 24.3 %) conducted in the Netherlands (October 2008-April 2011). Logistic regression was used to analyze associations between predictors [demographics; outcomes of the 12-item General Health Questionnaire (GHQ-12); 10-item Kessler Psychological Distress scale; Alcohol Use Disorders Identification Test; Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness; Utrecht Coping List; Social Support Questionnaire for Transactions and Satisfaction; certified International Classification of Diseases 10th edition (ICD-10) diagnosis; loss of earning capacity (LEC)] and outcomes [functional improvement on the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) exceeding the standard error of measurement; work status at follow-up]. RESULTS: Functional improvement on total WHODAS was reported by 84 (31.9 % of 263 claimants included in analysis). Of those not having work at baseline (n = 338), 34 (9.1 %) respondents had paid work 1 year later. Predictors of functional improvement: GHQ-12 sum score >20 [odds ratios (OR) 2.9; 95 % confidence intervals (CI) 1.54-5.34]; of future work status: work status at baseline (OR 16.8; 95 % CI 6.55-43.14), LEC < 80 % (OR 4.6; 95 % CI 1.87-11.42), contact with a medical specialist (OR 0.4; 95 % CI 0.19-0.87). CONCLUSIONS: Only a limited number of factors were found to significantly predict functional improvement and return to paid work after the disability benefit claim, having paid work at baseline being by far the most important factor.

New generation multi-modal antidepressants: focus on vortioxetine for major depressive disorder.

Vortioxetine is a novel antidepressant with effects on multiple 5-HT receptors and on the serotonin transporter. This paper reviews preclinical and clinical evidence regarding its mechanism of action, its tolerability, and its efficacy in treating major depression. Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators. There may be a clinically meaningful advantage in terms of tolerability.

Development and validation of the Diagnostic Interview Adjustment Disorder (DIAD).

Adjustment disorders (ADs) are under-researched due to the absence of a reliable and valid diagnostic tool. This paper describes the development and content/construct validation of a fully structured interview for the diagnosis of AD, the Diagnostic Interview Adjustment Disorder (DIAD). We developed the DIAD by partly adjusting and operationalizing DSM-IV criteria. Eleven experts were consulted on the content of the DIAD. In addition, the DIAD was administered by trained lay interviewers to a representative sample of disability claimants (n = 323). To assess construct validity of the DIAD, we explored the associations between the AD classification by the DIAD and summary scores of the Kessler Psychological Distress 10-item Scale (K10) and the World Health Organization Disability Assessment Schedule (WHODAS) by linear regression. Expert agreement on content of the DIAD was moderate to good. The prevalence of AD using the DIAD with revised criteria for the diagnosis AD was 7.4%. The associations of AD by the DIAD with average sum scores on the K10 and the WHODAS supported construct validity of the DIAD. The results provide a first indication that the DIAD is a valid instrument to diagnose AD. Further studies on reliability and on other aspects of validity are needed.

Predicting improvement of functioning in disability claimants.

PURPOSE: In the Netherlands, disability claimants are assessed after 2 years of sick leave, but their functioning may still improve. An accurate prognosis of functioning is difficult. Self predictions may be more accurate than those of professionals. The aim of this study, is to assess and compare the accuracy of predictions by disability claimants and insurance physicians (IPs) working at the Social Security Institute. It is further studied whether the accuracy differs between subgroups of claimants with mental or somatic health conditions. METHODS: We used data from the prospective cohort study cohort study. Following the assessment of the disability claim (n = 375) and after 1 year follow up (T1, n = 276) data on functioning were obtained from respondents by self-report questionnaire World Health Organization Disability Schedule 2.0. Both claimants and IPs were asked to predict improvement of functioning. Accuracy of their predictions were assessed by sensitivity, specificity, and area under the receiver operating curves (AUC). Mixed logistic regression was conducted to explore differences in accuracy between claimants with mental and somatic conditions. RESULTS: One-third (32 %) of disability claimants improved beyond the standard error of measurement. Disability claimants' and IPs were able to predict this improvement of functioning, but to a limited extent, with an AUC of 0.61 for IPs and 0.62 for disability claimants. We found no statistically significant differences in the accuracy of the predictions in claimants with mental or somatic health conditions. CONCLUSIONS: Improvements of functioning were not uncommon. However, both IPs and disability claimants were unable to predict improvement with high levels of accuracy in both mental and somatic health conditions.