Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE).

Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then 1H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P < 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

High-resolution air-clad imaging fibers.

We present a coherent fiber bundle comprising over 11,000 doped silica cores separated by an air-filled cladding. The fiber is characterized, and its imaging quality is shown to be a substantial improvement over the commercial state of the art, with comparable resolution over an unparalleled spectral range.

Low index contrast imaging fibers.

We present high-resolution imaging fibers made from low-cost commercially available fiber preforms manufactured for the telecommunications industry. Our fabrication method involves multi-stacking arrays of different sized cores in order to suppress core-to-core crosstalk whilst building up a large array of cores. One of the fibers, based on a square array of cores, has comparable imaging performance to commercial imaging fibers but without the need for exceptionally high refractive index contrasts, and will enable the development of economically viable single-use disposable imaging fibers.

The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia. METHOD: This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18-60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 µg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later. RESULTS: SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo. CONCLUSIONS: Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.

Highly birefringent 98-core fiber.

We report on the fabrication and characterization of a polarization-maintaining multicore fiber. The fiber has 98 aligned cores, each with a birefringence of ≈2.3×10-4. The beat length, polarization extinction ratio, and polarization orientation are characterized.

Tobacco smoking in schizophrenia: investigating the role of incentive salience.

BACKGROUND: Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations. METHOD: Twenty-two smokers diagnosed with schizophrenia and 23 control smokers were assessed for smoking-related attentional bias using a modified Stroop task. Craving, nicotine dependence, smoking behaviour and positive and negative symptoms of schizophrenia were also recorded. RESULTS: Both groups showed similar craving scores and smoking behaviour according to self-report and expired carbon monoxide (CO), although the patient group had higher nicotine dependence scores. Attentional bias, as evidenced by significant interference from smoking-related words on the modified Stroop task, was similar in both groups and correlated with CO levels. Attentional bias was positively related to severity of delusions but not hallucinations or other symptoms in the schizophrenia group. CONCLUSIONS: This study supports the hypothesis that the development of delusions and the incentive motivational aspects of smoking may share a common biological substrate. These findings may offer some explanation for the elevated rates of smoking and other drug use in people with psychotic illness.

Cannabis use and first-episode psychosis: relationship with manic and psychotic symptoms, and with age at presentation.

BACKGROUND: Cannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms. METHOD: Clinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points--at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded. RESULTS: Level of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up. CONCLUSIONS: Effective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.

Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk.

BACKGROUND: The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown. METHOD: We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses. RESULTS: The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive-compulsive disorder symptoms. CONCLUSIONS: Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.

Femtosecond pulses at 20 GHz repetition rate through spectral masking of a phase modulated signal and nonlinear pulse compression.

We present a laser system capable of producing 190 femtosecond pulses at a repetition rate of 20 GHz. The spectral masking of a phase modulated diode laser is used to produce a train of picosecond pulses which are compressed using a fibre-grating compressor followed by subsequent adiabatic soliton compression to the femtosecond regime using a tapered photonic crystal fiber.

1064 nm laser-induced defects in pure SiO2 fibers.

We investigate evidence of the formation of nonbridging oxygen hole centers in pure silica photonic crystal fibers from 5 ps 1064 nm pulses. The formation of the defects is attributed to the breaking of stressed silicon-oxygen bonds in the glass matrix through a many-photon process. We compare the photodarkening induced by the 1064 nm pump with photodarkening induced by short wavelength light in a 1064 nm pumped supercontinuum extending to 400 nm. It is shown that the higher peak power at the pump wavelength makes it a more significant cause of photodarkening when compared to the shorter wavelength light generated in the fiber.

Lymphoma studies by the Australasian Leukaemia and Lymphoma Group.

The Australasian Leukaemia and Lymphoma Group (ALLG) can trace its origins to 1973. It now encompasses virtually all the major hospitals in Australia and New Zealand that treat leukaemias and lymphomas. Over the years the Group as a whole, and members individually, have participated in many clinical treatment trials for aggressive lymphomas. Initially trials were conceived and carried out locally, but in recent years, in addition to continuing its own studies, the Group has been a major contributor to international trials including two that have been particularly influential, known as MInT and CORAL. The MInT study confirmed the value of adding rituximab to standard chemotherapy for aggressive lymphomas; CORAL helped define optimum methods of autografting for relapse. The ALLG has contributed and continues to contribute to the improving outcome for patients with aggressive lymphomas.

Early Prophylactic Gastrectomy for the Management of Gastric Adenomatous Proximal Polyposis Syndrome (GAPPS).

Background: Gastric adenomatous proximal polyposis syndrome (GAPPS) is a recently described, rare, autosomal dominant condition characterized by the extensive involvement of the proximal stomach with hundreds of heterogeneous fundic gland polyps with antral and duodenal sparing. GAPPS is caused by a point mutation of the APC gene promoter 1B and is associated with a risk of malignant transformation, distant metastasis, and death. There are no surveillance, screening, or treatment guidelines for managing GAPPS. The few reported cases have been variably managed with endoscopic surveillance or prophylactic gastrectomy. However, there is no consensus on the optimal management approach. Summary: In this case series, we review the relevant literature on GAPPS and present two siblings who underwent early prophylactic total gastrectomies with good outcomes. Conclusion: Due to the poor correlation between the endoscopic findings on sampled polyps and the risk of harboring invasive gastric cancer, patients with GAPPS should be strongly considered for early prophylactic total gastrectomies in the absence of prohibitive comorbidities.

Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation.

OBJECTIVE: It is unknown if cannabis recreates the negative symptoms of schizophrenia. METHODS: Healthy male volunteers (n = 22) completed two experimental sessions in which they received intravenous (IV) delta-9-tetrahydrocannabinol (THC) 2.5 mg or placebo in a randomised counterbalanced order. Negative symptoms were rated using the self-reported community assessment of psychic experiences scale (CAPE). Sedation was rated using the mood-adjective check-list (UMACL). Plasma concentrations of THC were measured over the course of the study. Data were analysed by non-parametric tests. RESULTS: Participants reported an increase in negative symptoms from baseline under THC but not placebo conditions (p < 0.001). Negative symptoms showed no relationship with self-rated sedation or plasma concentrations of THC. CONCLUSIONS: At plasma concentrations resembling recreational use, THC elicited schizophrenia-like negative symptoms which were not merely attributable to sedation. In the community, negative symptoms may be an adverse effect of cannabis use.

Ketamine-induced disruption of verbal self-monitoring linked to superior temporal activation.

INTRODUCTION: Misattribution of distorted self-generated speech in patients with schizophrenia has been associated with increased lateral temporal activation. As a pharmacological model of schizophrenia, we tested whether ketamine would induce the same effects in healthy individuals. METHODS: Participants were 8 healthy male volunteers who were naïve to ketamine (mean age: 28 years). Ketamine (0.23 mg/kg bolus followed by 0.64 mg/kg/h) and placebo infusions were administered in a double-blind, randomised order, during 2 functional magnetic resonance imaging (fMRI) sessions. Each fMRI session consisted of a verbal self-monitoring task in which auditory feedback was experimentally modified. RESULTS: Ketamine was associated with psychotic and dissociative symptoms. Participants made more misattributions of distorted self-generated speech (P < 0.02) during the ketamine infusion. Ketamine led to reduced activation in the left superior temporal cortex during self-distorted speech, regardless of whether the speech was identified correctly or not, as compared to the placebo infusion. Misidentification of speech that had been distorted was not associated with any increase in brain activation in during the placebo infusion, however ketamine-induced misattributions were associated with a relative increase in left superior temporal cortex activation. DISCUSSION: These data are consistent with the notion that self-monitoring impairments underlie psychotic symptoms and suggest that N-methyl-D-aspartate (NMDA) receptor dysfunction may mediate self-monitoring deficits and psychotic phenomena in schizophrenia.

Interaction of a protein phosphatase with an Arabidopsis serine-threonine receptor kinase.

A protein phosphatase was cloned that interacts with a serine-threonine receptor-like kinase, RLK5, from Arabidopsis thaliana. The phosphatase, designated KAPP (kinase-associated protein phosphatase), is composed of three domains: an amino-terminal signal anchor, a kinase interaction (KI) domain, and a type 2C protein phosphatase catalytic region. Association of RLK5 with the KI domain is dependent on phosphorylation of RLK5 and can be abolished by dephosphorylation. KAPP may function as a signaling component in a pathway involving RLK5.

Visibly "white" light generation in uniform photonic crystal fiber using a microchip laser.

We report on visibly white supercontinuum generation in photonic crystal fibers using a sub ns pump source at 1064 nm. The spectra extend from below 400 nm to 2450 nm, some 50 nm further into the blue than previously reported spectra. The extra bandwidth which is achieved by a simple modification to the fiber structure gives a higher apparent color temperature and a truly "white" visual appearance. The mechanism for the generation of the deeper blue to ultraviolet frequencies is outlined and our modified fiber is compared with fibers which have been conventionally used for supercontinuum generation.

Mid-infrared methane detection in a photonic bandgap fiber using a broadband optical parametric oscillator.

We demonstrate methane sensing using a photonic bandgap fiber-based gas cell and broadband idler pulses from a periodically-poled lithium niobate femtosecond optical parametric oscillator. The hollow core of the fiber was filled with a methane:nitrogen mixture, and Fourier transform spectroscopy was used to measure transmission spectra in the 3.15-3.35 mum methane absorption region. The method has applications in gas sensing for remote or hazardous environments and potentially at very low concentrations.

Optical pulse compression in dispersion decreasing photonic crystal fiber.

Improvements to tapered photonic crystal fiber (PCF) fabrication have allowed us to make up to 50 m long PCF tapers with loss as low as 30 dB/km. We discuss the design constraints for tapered PCFs used for adiabatic soliton compression and demonstrate over 15 times compression of pulses from over 830 fs to 55 fs duration at a wavelength of 1.06 lm, an order of magnitude improvement over previous results.