Citalopram and sertraline exposure compromises embryonic bone development

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.Molecular Psychiatry advance online publication, 8 September 2015; doi:10.1038/mp.2015.135.

Risk factors for violence in psychosis: systematic review and meta-regression analysis of 110 studies

Background

Previous reviews on risk and protective factors for violence in psychosis have produced contrasting findings. There is therefore a need to clarify the direction and strength of association of risk and protective factors for violent outcomes in individuals with psychosis.

Method

We conducted a systematic review and meta-analysis using 6 electronic databases (CINAHL, EBSCO, EMBASE, Global Health, PsycINFO, PUBMED) and Google Scholar. Studies were identified that reported factors associated with violence in adults diagnosed, using DSM or ICD criteria, with schizophrenia and other psychoses. We considered non-English language studies and dissertations. Risk and protective factors were meta-analysed if reported in three or more primary studies. Meta-regression examined sources of heterogeneity. A novel meta-epidemiological approach was used to group similar risk factors into one of 10 domains. Sub-group analyses were then used to investigate whether risk domains differed for studies reporting severe violence (rather than aggression or hostility) and studies based in inpatient (rather than outpatient) settings.

Findings

There were 110 eligible studies reporting on 45,533 individuals, 8,439 (18.5%) of whom were violent. A total of 39,995 (87.8%) were diagnosed with schizophrenia, 209 (0.4%) were diagnosed with bipolar disorder, and 5,329 (11.8%) were diagnosed with other psychoses. Dynamic (or modifiable) risk factors included hostile behaviour, recent drug misuse, non-adherence with psychological therapies (p values<0.001), higher poor impulse control scores, recent substance misuse, recent alcohol misuse (p values<0.01), and non-adherence with medication (p value <0.05). We also examined a number of static factors, the strongest of which were criminal history factors. When restricting outcomes to severe violence, these associations did not change materially. In studies investigating inpatient violence, associations differed in strength but not direction.

Conclusion

Certain dynamic risk factors are strongly associated with increased violence risk in individuals with psychosis and their role in risk assessment and management warrants further examination.

Investigating the effects of personality traits on pair programming in a higher education setting through a family of experiments

Evidence from our systematic literature review revealed numerous inconsistencies in findings from the Pair Programming (PP) literature regarding the effects of personality on PP's effectiveness as a pedagogical tool. In particular: i) the effect of differing personality traits of pairs on the successful implementation of pair-programming (PP) within a higher education setting is still unclear, and ii) the personality instrument most often used had been Myers-Briggs Type Indicator (MBTI), despite being an indicator criticized by personality psychologists as unreliable in measuring an individual's personality traits. These issues motivated the research described in this paper. We conducted a series of five formal experiments (one of which was a replicated experiment), between 2009 and 2010, at the University of Auckland, to investigate the effects of personality composition on PP's effectiveness. Each experiment looked at a particular personality trait of the Five-Factor personality framework. This framework comprises five broad traits (Openness to experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism), and our experiments focused on three of these - Conscientiousness, Neuroticism, and Openness. A total of 594 undergraduate students participated as subjects. Overall, our findings for all five experiments, including the replication, showed that Conscientiousness and Neuroticism did not present a statistically significant effect upon paired students' academic performance. However, Openness played a significant role in differentiating paired students' academic performance. Participants' survey results also indicated that PP not only caused an increase in satisfaction and confidence levels but also brought enjoyment to the tutorial classes and enhanced students' motivation.

A preliminary study on machinability of super austenitic stainless steel

Stainless steel is the most widely used alloys of steel. The reputed variety of stainless steel having customised material properties as per the design requirements is Duplex Stainless Steel and Austenitic Stainless Steel. The Austenite Stainless Steel alloy has been developed further to be Super Austenitic Stainless Steel (SASS) by increasing the percentage of the alloying elements to form the half or more than the half of the material composition. SASS (Grade-AL-6XN) is an alloy steel containing high percentages of nickel (24%), molybdenum (6%) and chromium (21%). The chemical elements offer high degrees of corrosion resistance, toughness and stability in a large range of hostile environments like petroleum, marine and food processing industries. SASS is often used as a commercially viable substitute to high cost non-ferrous or non-metallic metals. The ability to machine steel effectively and efficiently is of utmost importance in the current competitive market. This paper is an attempt to evaluate the machinability of SASS which has been a classified material so far with very limited research conducted on it. Understanding the machinability of this alloy would assist in the effective forming of this material by metal cutting. The novelty of research associated with this is paper is reasonable taking into consideration the unknowns involved in machining SASS. The experimental design consists of conducting eight milling trials at combination of two different feed rates, 0.1 and 0.15 mm/tooth; cutting speeds, 100 and 150 m/min; Depth of Cut (DoC), 2 and 3 mm and coolant on for all the trials. The cutting tool has two inserts and therefore has two cutting edges. The trial sample is mounted on a dynamometer (type 9257B) to measure the cutting forces during the trials. The cutting force data obtained is later analyzed using DynaWare supplied by Kistler. The machined sample is subjected to surface roughness (Ra) measurement using a 3D optical surface profilometer (Alicona Infinite Focus). A comprehensive metallography process consisting of mounting, polishing and etching was conducted on a before and after machined sample in order to make a comparative analysis of the microstructural changes due to machining. The microstructural images were capture using a digital microscope. The microhardness test were conducted on a Vickers scale (Hv) using a Vickers microhardness tester. Initial bulk hardness testing conducted on the material show that the alloy is having a hardness of 83.4 HRb. This study expects an increase in hardness mostly due to work hardening may be due to phase transformation. The results obtained from the cutting trials are analyzed in order to judge the machinability of the material. Some of the criteria used for machinability evaluation are cutting force analysis, surface texture analysis, metallographic analysis and microhardness analysis. The methodology followed in each aspect of the investigation is similar to and inspired by similar research conducted on other materials. However, the novelty of this research is the investigation of various aspects of machinability and drawing comparisons between each other while attempting to justify each result obtained to the microstructural changes observed which influence the behaviour of the alloy. Due to the limited scope of the paper, machinability criteria such as chip morphology, Metal Removal Rate (MRR) and tool wear are not included in this paper. All aspects are then compared and the optimum machining parameters are justified with a scope for future investigations