The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

The ventro-medial prefrontal cortex: a major link between the autonomic nervous system, regulation of emotion, and stress reactivity?

Recent progress in neuroscience revealed diverse regions of the CNS which moderate autonomic and affective responses. The ventro-medial prefrontal cortex (vmPFC) plays a key role in these regulations. There is evidence that vmPFC activity is associated with cardiovascular changes during a motor task that are mediated by parasympathetic activity. Moreover, vmPFC activity makes important contributions to regulations of affective and stressful situations

Summary of strong-field QED Workshop

24 pages, 9 figures. Summary by session convenors of workshop on "Probing strong-field QED in electron-photon interactions" in DESY, Hamburg, August 2018A workshop, "Probing strong-field QED in electron--photon interactions", was held in DESY, Hamburg in August 2018, gathering together experts from around the world in this area of physics as well as the accelerator, laser and detector technology that underpins any planned experiment. The aim of the workshop was to bring together experts and those interested in measuring QED in the presence of strong fields at and above the Schwinger critical field. The pioneering experiment, E144 at SLAC, measured multi-photon absorption in Compton scattering and $e^+e^-$ pair production in electron--photon interactions but never reached the Schwinger critical field value. With the advances in laser technology, in particular, new experiments are being considered which should be able to measure non-perturbative QED and its transition from the perturbative regime. This workshop reviewed the physics case and current theoretical predictions for QED and even effects beyond the Standard Model in the interaction of a high-intensity electron bunch with the strong field of the photons from a high-intensity laser bunch. The world's various electron beam facilities were reviewed, along with the challenges of producing and delivering laser beams to the interaction region. Possible facilities and sites that could host such experiments were presented, with a view to experimentally realising the Schwinger critical field in the lab during the 2020s

Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

A quantum-mechanical (QM) method rooted on density functional theory (DFT) linked to the Stochastic Liouville equation (SLE) in the Fokker Planck (FP) form has been employed for the first time to sample the methane-thiosulfonate spin label (MTSL) conformational space attached to the Aurora-A kinase activation loop and to calculate the EPR spectrum. The features of the calculated energy surface allowed us to describe the system in a limited number of rotamers stabilized by interactions of the MTSL side chain and neighbouring residues. The relevant magnetic parameters and the electron paramagnetic resonance (EPR) spectrum were subsequently calculated from the trajectories of the spin probe in the protein environment. The comparison between theoretical and experimental continuous wave (CW) EPR spectra revealed some small differences in the EPR line shape which arises from the combinations of g- and A-values obtained from the conformations selected. The theoretical approach adopted in this work can be used to recognise the contribution of MTSL rotamers to the EPR spectrum in order to help extract structural/dynamics properties of protein from the experimental data

Methamphetamine induces Shati/Nat8L expression in the mouse nucleus accumbens via CREB- and dopamine D1 receptor-dependent mechanism

Shati/Nat8L significantly increased in the nucleus accumbens (NAc) of mice after repeated methamphetamine (METH) treatment. We reported that Shati/Nat8L overexpression in mouse NAc attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference. We recently found that Shati/Nat8L overexpression in NAc regulates the dopaminergic neuronal system via the activation of group II mGluRs by elevated Nacetylaspartylglutamate following N-acetylaspartate increase due to the overexpression. These findings suggest that Shati/Nat8L suppresses METH-induced responses. However, the mechanism by which METH increases the Shati/Nat8L mRNA expression in NAc is unclear. To investigate the regulatory mechanism of Shati/Nat8L mRNA expression, we performed a mouse Shati/Nat8L luciferase assay using PC12 cells. Next, we investigated the response of METH to Shati/Nat8L expression and CREB activity using mouse brain slices of NAc, METH administration to mice, and western blotting for CREB activity of specific dopamine receptor signals in vivo and ex vivo. We found that METH activates CREB binding to the Shati/Nat8L promoter to induce the Shati/Nat8L mRNA expression. Furthermore, the dopamine D1 receptor antagonist SCH23390, but not the dopamine D2 receptor antagonist sulpiride, inhibited the upregulation of Shati/Nat8L and CREB activities in the mouse NAc slices. Thus, the administration of the dopamine D1 receptor agonist SKF38393 increased the Shati/Nat8L mRNA expression in mouse NAc. These results showed that the Shati/ Nat8L mRNA was increased by METH-induced CREB pathway via dopamine D1 receptor signaling in mouse NAc. These findings may contribute to development of a clinical tool for METH addiction

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Infection rates associated with epidural indwelling catheters for seven days or longer: systematic review and meta-analysis

BACKGROUND: To determine infection rate with use of epidural catheters in place for seven days or more. METHODS: Systematic review and pooled analysis of observational studies. RESULTS: Twelve studies with 4,628 patients (median 197 patients) provided information, of which nine (4,334 patients) were published after 1990. Eight studies (3,893 patients) were retrospective, and four studies (735 patients) prospective. Electronic searches identified three studies and searching reference lists nine. There were 257 catheter-related infections in total, of which 211 were superficial and 57 deep, giving rates of 6.1%, 4.6% and 1.2% respectively. Ten of the 12 studies had deep infection rates of 2% or less. The incidence of deep infection was 1 per 2391 days of treatment, or 0.4 per 1000 catheter treatment days. In nine studies (1503 patients), predominantly in cancer, and with average catheter duration of 74 days, the deep infection rate was 2.8%. The proportion of patients with infection of any type was higher in cancer patients with longer catheter duration. Limited numbers of events meant that no reliable estimate of the impact of prospective and retrospective design could be made. There appeared to be a relationship between catheter duration and infection rate from this and other recent estimates. Four of 57 (7%) patients with deep infection died. CONCLUSION: The best estimate is that one person in 35 with an epidural catheter in place for 74 days for relief of cancer pain can be expected to have a deep epidural infection, and that about 1 in 500 may die of infection-related causes. This is a most uncertain estimate given the limited nature of the evidence

Challenges in multidisciplinary cancer care among general surgeons in Canada

<p>Abstract</p> <p>Background</p> <p>While many factors can influence the way that cancer care is delivered, including the way that evidence is packaged and disseminated, little research has evaluated how health care professionals who manage cancer patients seek and use this information to identify whether and how this could be supported. Through interviews we identified that general surgeons experience challenges in coordinating care for complex cancer patients whose management is not easily addressed by guidelines, and conducted a population-based survey of general surgeon information needs and information seeking practices to extend these findings.</p> <p>Methods</p> <p>General surgeons with privileges at acute care hospitals in Ontario, Canada were mailed a questionnaire to solicit information needs (task, importance), information seeking (source, frequency of and reasons for use), key challenges and suggested solutions. Non-responders received up to three reminder packages. Significant differences among sub-groups (age, setting) were examined statistically (Kruskal Wallis, Mann Whitney, Chi Square). Standard qualitative methods were used to thematically analyze open-ended responses.</p> <p>Results</p> <p>The response rate was 44.2% (170/385) representing all 14 health regions. System resource constraints (60.4%), comorbidities (56.4%) and physiologic factors (51.8%) were top-ranked issues creating information needs. Local surgical colleagues (84.6%), other local colleagues (82.2%) and the Internet (81.1%) were top-ranked sources of information, primarily due to familiarity and speed of access. No resources were considered to be highly applicable to patient care. Challenges were related to limitations in diagnostics and staging, operative resources, and systems to support multidisciplinary care, together accounting for 76.0% of all reported issues. Findings did not differ significantly by surgeon age or setting of care.</p> <p>Conclusion</p> <p>General surgeons appear to use a wide range of information resources but they may not address the complex needs of many cancer patients. Decision-making is challenged by informational and logistical issues related to the coordination of multidisciplinary care. This suggests that limitations in system capacity may, in part, contribute to variable guideline compliance. Further research is required to evaluate the appropriateness of information seeking, and both concurrent and consecutive mechanisms by which to achieve multidisciplinary care.</p