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NeuroStar transcranial magnetic stimulation (TMS) is an effective acute treatment for patients with major depressive disorder (MDD). In order to further understand use of the NeuroStar in a clinical setting, Neuronetics has established a patient treatment and outcomes registry to collect and analyze utilization information on patients receiving treatment with the NeuroStar.
Individual NeuroStar providers are invited to participate in the registry and agree to provide their de-identified patient treatment data. The NeuroStar has an integrated electronic data management system (TrakStar) which allows for the data collection to be automated. The data collected for the registry include Demographic Elements (age, gender), Treatment Parameters, and Clinical Ratings. Clinical assessments are: Clinician Global Impression - Severity of Illness (CGI-S) and thePatient Health Questionnaire 9-item (PHQ-9). De-identified patient data is uploaded to Registry server; an independent statistical service then creates final data reports.
Over 500 patients have entered the NeuroStar Outcomes Registry since Sept 2016. Mean patient age: 48.0 (SD±16.0); 64% Female. Baseline PHQ-9, mean 18.8 (SD±5.0.) Response/Remission Rate, PHQ-9: 61%/33% CGI-S: 78%/59%.
For the initial 500 patients in the Outcomes Registry, approximately 2/3 patients achieve respond and 1/3 patients achieve remission with an acute course of NeuroStar. These treatment outcomes consistent with NeuroStar open-label study data (Carpenter, 2012). The TrakStar data management system makes large scale data collection feasible. The NeuroStarOutcomes Registry is ongoing, and expected to reach 6000 outpatients from more than 47 clinical sites in 36 months.
The Pacific oyster Crassostrea gigas contributes significantly to global aquaculture; however, C. gigas culture has been affected by ostreid herpesvirus-1 (OsHV-1) and variants. The dynamics of how the virus maintains itself at culture sites is unclear and the role of carriers, reservoirs or hosts is unknown. Both wild and cultured mussels Mytilus spp. (Mytilus edulis, Mytilus galloprovincialis and hybrids) are commonly found at C. gigas culture sites. The objective of this study was to investigate if Mytilus spp. can harbour the virus and if viral transmission can occur between mussels and oysters. Mytilus spp. living at oyster trestles, 400–500 m higher up the shore from the trestles and up to 26 km at non-culture sites were screened for OsHV-1 and variants by all the World Organization for Animal Health (OIE) recommended diagnostic methods including polymerase chain reaction (PCR), quantitative PCR (qPCR), histology, in situ hybridization and confirmation using direct sequencing. The particular primers that target OsHV-1 and variants, including OsHV-1 microVar (μVar), were used in the PCR and qPCR. OsHV-1 μVar was detected in wild Mytilus spp. at C. gigas culture sites and more significantly the virus was detected in mussels at non-culture sites. Cohabitation of exposed wild mussels and naïve C. gigas resulted in viral transmission after 14 days, under an elevated temperature regime. These results indicate that mussels can harbour OsHV-1 μVar; however, the impact of OsHV-1 μVar on Mytilus spp. requires further investigation.
The aim of the study was to assess the effect on rectal consistency, of introducing a micro-enema in the preparation of patients receiving radiotherapy treatment of urinary bladder cancer.
Materials and methods
The treatment cone beam computed tomography (CBCT) images from patients receiving radiotherapy for bladder cancer were retrospectively assessed. CBCT datasets from nine patients treated without rectal preparation (97 CBCT), and 13 patients (134 CBCT) treated following micro-enema use before planning and treatment were evaluated. CBCT were compared with the planning computed tomography for rectal status, rectal diameter and presence of gas.
Reproducibility of an empty rectum was achieved in 70% of treatment fractions delivered using an enema protocol compared with 33% of fractions delivered without preparation. In total, 10% of fractions were delivered with the presence of faeces or faeces and gas, compared with 46% of fractions for the non-intervention group. Enemas did not affect the proportion of fractions delivered with gas, however, where gas was present, 65% of CBCT fractions had <5% gas for patients using enemas compared with 32% without.
The use of a micro-enema before planning scan and each fraction was well tolerated and proved effective in managing and reducing inter-fraction variations in rectal volume and contents.
During the four years the Sample Preparation Laboratory (SPL) at the National Ocean Sciences Accelerator Mass Spectrometer (NOSAMS) Facilty has been in operation we have accumulated much data from which we can assess our progress. We evaluate our procedural blanks here and describe modifications in our procedures that have improved our analyses of older samples. In the SPL, we convert three distinct types of samples—seawater, CaCO3 and organic carbon—to CO2 prior to preparing graphite for the accelerator and have distinct procedural blanks for each procedure. Dissolved inorganic carbon (∑CO2) is extracted from acidified seawater samples by sparging with a nitrogen carrier gas. We routinely analyze “line blanks” by processing CO2 from a 14C-dead source through the entire stripping procedure. Our hydrolysis blank, IAEA C-1, is prepared by acidifying in vacuo with 100% H3PO4 at 60° overnight, identical to our sample preparation. We use a dead graphite, NBS-21, or a commercially available carbon powder for our organic combustion blank; organic samples are combusted at 850° for 5 h using CuO to provide the oxidant. Analysis of our water stripping data suggests that one step in the procedure contributes the major portion of the line blank. At present, the contribution from the line blank has no effect on our seawater analyses (fraction modern (fm) between 0.7 and 1.2). Our hydrolysis blanks can have an fm value as low as 0.0006, but are more routinely between 0.0020 and 0.0025. The fm of our best organic combustion blanks is higher than those routinely achieved in other laboratories and we are currently altering our methods to reduce it.
Commission 15 of the International Astronomical Union (IAU), entitled Physical Study of Comets and Minor Planets, was founded in 1935 and dissolved in 2015, following the reorganization of IAU. In 80 years of Commission 15, tremendous progress has been made on the knowledge of these objets, thanks to the combined efforts of ground- and space-based observations, space mission rendezvous and flybys, laboratory simulation and analyses of returned samples, and theoretical and numerical modeling. Together with dynamical studies of the Solar System, this discipline has provided a much deeper understanding of how the Solar System formed and evolved. We present a legacy report of Commission 15, which highlights key milestones in the exploration and knowledge of the small bodies of the Solar System.
Immediate-release (IR) quetiapine has been used to treat schizophrenia since 1997, although all the principal placebo-controlled trials have >50% missing outcome data. New studies with relatively lower rates of participant withdrawal have since been published.
To assess the efficacy and adverse effects of quetiapine IR for schizophrenia, with consideration of outcome quality and clinical meaningfulness of results, and to examine the potential impact of missing data on the main efficacy findings.
We conducted a systematic review and meta-analysis of randomised controlled trials comparing quetiapine IR and placebo (or subtherapeutic dose in relapse prevention trials) for the treatment of schizophrenia (PROSPERO registration CRD4201100165). Primary outcomes were change in overall symptoms and response rates. We also examined whether high rates of participant withdrawal (⩾50%) attenuated effect sizes, and assessed the impact of making different assumptions about these people's outcomes.
We identified 15 relevant trials (including 2 unpublished), providing the first 12-week data for this drug and the first data on self-reported quality of life. We found quetiapine IR to have a weighted mean difference (WMD) of 6.5 points (95% CI −8.9 to −4) on Positive and Negative Syndrome Scale (PANSS) total scores, which corresponds to a standardised mean difference (SMD) of −0.33 (95% CI −0.46 to −0.21). Longer trials reported larger mean differences favouring quetiapine IR, but the overall estimate was smaller if more conservative assumptions about the outcomes of people who left the trial early were made. Approximately 21 people needed to take quetiapine IR for 1 person to experience at least a 50% improvement in PANSS score. No difference in quality of life was observed (two RCTs), although small to moderate improvements in social functioning were found (three RCTs). Quetiapine IR caused sedation and increased rates of clinically significant weight gain, but no extrapyramidal effects were observed.
Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2–12 weeks, but also leads to weight gain and sedation.
Suicide and self-harm are prevalent in individuals diagnosed with psychotic disorders. However, less is known about the level of self-injurious thinking and behaviour in those individuals deemed to be at ultra-high risk (UHR) of developing psychosis, despite growing clinical interest in this population. This review provides a synthesis of the extant literature concerning the prevalence of self-harm and suicidality in the UHR population, and the predictors and correlates associated with these events.
A search of electronic databases was undertaken by two independent reviewers. A meta-analysis of prevalence was undertaken for self-harm, suicidal ideation and behaviour. A narrative review was also undertaken of analyses examining predictors and correlates of self-harm and suicidality.
Twenty-one eligible studies were identified. The meta-analyses suggested a high prevalence of recent suicidal ideation (66%), lifetime self-harm (49%) and lifetime suicide attempts (18%). Co-morbid psychiatric problems, mood variability and a family history of psychiatric problems were among the factors associated with self-harm and suicide risk.
Results suggest that self-harm and suicidality are highly prevalent in the UHR population, with rates similar to those observed in samples with diagnosed psychotic disorders. Appropriate monitoring and managing of suicide risk will be important for services working with the UHR population. Further research in this area is urgently needed considering the high rates identified.
The point is sometimes made that in primitive trade psychological satisfaction is obtained rather by the exchange of gifts and enhancement of prestige than by any economic advantage to the traders. It is possible, I think, to lay too much stress on this aspect of primitive trade at the expense of the more prosaic motive of material economic gain, though I do not, of course, wish to belittle the non-economic factors involved and indeed propose to draw attention to some of them. Naturally I shall take instances from my own experience, and these are mostly in areas with regular land contacts where the non-economic aspects of trade are likely to be less prominent than they are in self-contained and self-sufficient island communities. At the same time the first case I wish to examine is one of the inter-island trade in the Nicobar Islands.
Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.
We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.
At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.
These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
Clinical equipoise regarding preventative treatments for psychosis has encouraged the development and evaluation of psychosocial treatments, such as cognitive behavioural therapy (CBT).
A systematic review and meta-analysis was conducted, examining the evidence for the effectiveness of CBT-informed treatment for preventing psychosis in people who are not taking antipsychotic medication, when compared to usual or non-specific control treatment. Included studies had to meet basic quality criteria, such as concealed and random allocation to treatment groups.
Our search produced 1940 titles, out of which we found seven completed trials (six published). The relative risk (RR) of developing psychosis was reduced by more than 50% for those receiving CBT at every time point [RR at 6 months 0.47, 95% confidence interval (CI) 0.27–0.82, p = 0.008 (fixed-effects only: six randomized controlled trials (RCTs), n = 800); RR at 12 months 0.45, 95% CI 0.28–0.73, p = 0.001 (six RCTs, n = 800); RR at 18–24 months 0.41, 95% CI 0.23–0.72, p = 0.002 (four RCTs, n = 452)]. Heterogeneity was low in every analysis and the results were largely robust to the risk of an unpublished 12-month study having unfavourable results. CBT was also associated with reduced subthreshold symptoms at 12 months, but not at 6 or 18–24 months. No effects on functioning, symptom-related distress or quality of life were observed. CBT was not associated with increased rates of clinical depression or social anxiety (two studies).
CBT-informed treatment is associated with a reduced risk of transition to psychosis at 6, 12 and 18–24 months, and reduced symptoms at 12 months. Methodological limitations and recommendations for trial reporting are discussed.
Improving health through better nutrition of the population may contribute to enhanced efficiency and sustainability of healthcare systems. A recent expert meeting investigated in detail a number of methodological aspects related to the discipline of nutrition economics. The role of nutrition in health maintenance and in the prevention of non-communicable diseases is now generally recognised. However, the main scope of those seeking to contain healthcare expenditures tends to focus on the management of existing chronic diseases. Identifying additional relevant dimensions to measure and the context of use will become increasingly important in selecting and developing outcome measurements for nutrition interventions. The translation of nutrition-related research data into public health guidance raises the challenging issue of carrying out more pragmatic trials in many areas where these would generate the most useful evidence for health policy decision-making. Nutrition exemplifies all the types of interventions and policy which need evaluating across the health field. There is a need to start actively engaging key stakeholders in order to collect data and to widen health technology assessment approaches for achieving a policy shift from evidence-based medicine to evidence-based decision-making in the field of nutrition.
Early Proterozoic rapakivi intrusions in S Greenland occur as thick sheets which have ramp–flat geometry and were intruded along the median planes of active ductile extensional shear zones. These shear zones and their intrusions were linked via transfer zones in a major three-dimensional framework. At high structural levels (c. 6 km) the rapakivi intrusions developed thermal aureoles which overprint the regional assemblages, whereas at deeper levels in the regional structure they are contemporaneous with regional metamorphism. Thermobarometry on the regional and contact assemblages indicates low pressure granulite facies conditions (200–400 MPa, 650°-800°C) suggesting very high thermal gradients. The rapakivi suite and associated norites have low initial 87Sr/86Sr together with positive εNd values, indicating the involvement of predominantly young crust and/or mantle component in the generation of the igneous suite. It is considered that the voluminous norites are closely related to the mafic melts which underplated the juvenile crust to trigger the generation of the monzonitic rapakivi suite. Taken together, the data are consistent with a model of Proterozoic lithospheric extension, thinning of relatively juvenile continental crust and compression of mantle isotherms, resulting in high crustal heat flow, mafic underplating, and crustal melting with emplacement of magmas along a linked network of extensional shear zones.
Although antipsychotic medication is the first line of treatment for schizophrenia, many service users choose to refuse or discontinue their pharmacological treatment. Cognitive therapy (CT) has been shown to be effective when delivered in combination with antipsychotic medication, but has yet to be formally evaluated in its absence. This study evaluates CT for people with psychotic disorders who have not been taking antipsychotic medication for at least 6 months.
Twenty participants with schizophrenia spectrum disorders received CT in an open trial. Our primary outcome was psychiatric symptoms measured using the Positive and Negative Syndromes Scale (PANSS), which was administered at baseline, 9 months (end of treatment) and 15 months (follow-up). Secondary outcomes were dimensions of hallucinations and delusions, self-rated recovery and social functioning.
T tests and Wilcoxon's signed ranks tests revealed significant beneficial effects on all primary and secondary outcomes at end of treatment and follow-up, with the exception of self-rated recovery at end of treatment. Cohen's d effect sizes were moderate to large [for PANSS total, d=0.85, 95% confidence interval (CI) 0.32–1.35 at end of treatment; d=1.26, 95% CI 0.66–1.84 at follow-up]. A response rate analysis found that 35% and 50% of participants achieved at least a 50% reduction in PANSS total scores by end of therapy and follow-up respectively. No patients deteriorated significantly.
This study provides preliminary evidence that CT is an acceptable and effective treatment for people with psychosis who choose not to take antipsychotic medication. An adequately powered randomized controlled trial is warranted.
Genetic resistance to gastrointestinal worms is a complex trait of great importance in both livestock and humans. In order to gain insights into the genetic architecture of this trait, a mixed breed population of sheep was artificially infected with Trichostrongylus colubriformis (n=3326) and then Haemonchus contortus (n=2669) to measure faecal worm egg count (WEC). The population was genotyped with the Illumina OvineSNP50 BeadChip and 48 640 single nucleotide polymorphism (SNP) markers passed the quality controls. An independent population of 316 sires of mixed breeds with accurate estimated breeding values for WEC were genotyped for the same SNP to assess the results obtained from the first population. We used principal components from the genomic relationship matrix among genotyped individuals to account for population stratification, and a novel approach to directly account for the sampling error associated with each SNP marker regression. The largest marker effects were estimated to explain an average of 0·48% (T. colubriformis) or 0·08% (H. contortus) of the phenotypic variance in WEC. These effects are small but consistent with results from other complex traits. We also demonstrated that methods which use all markers simultaneously can successfully predict genetic merit for resistance to worms, despite the small effects of individual markers. Correlations of genomic predictions with breeding values of the industry sires reached a maximum of 0·32. We estimate that effective across-breed predictions of genetic merit with multi-breed populations will require an average marker spacing of approximately 10 kbp.
There is a new merging of health economics and nutrition disciplines to assess the impact of diet on health and disease prevention and to characterise the health and economic aspects of specific changes in nutritional behaviour and nutrition recommendations. A rationale exists for developing the field of nutrition economics which could offer a better understanding of both nutrition, in the context of having a significant influence on health outcomes, and economics, in order to estimate the absolute and relative monetary impact of health measures. For this purpose, an expert meeting assessed questions aimed at clarifying the scope and identifying the key issues that should be taken into consideration in developing nutrition economics as a discipline that could potentially address important questions. We propose a first multidisciplinary outline for understanding the principles and particular characteristics of this emerging field. We summarise here the concepts and the observations of workshop participants and propose a basic setting for nutrition economics and health outcomes research as a novel discipline to support nutrition, health economics and health policy development in an evidence and health-benefit-based manner.
Cornwall (UK) has suffered extensive arsenic contamination due to the historic mining and processing of mineral ores. Standard procedures for contaminated land risk assessment (DEFRA and Environment Agency, 2002a) are probably unworkable in Cornwall, with a very large number of sites classified as contaminated by arsenic. Methods of measuring the speciation and mobility of arsenic are essential for effective and rapid risk assessments of arsenic contamination.
Three clusters of lysimeters were installed in three different areas of an arsenic-contaminated Cornish site. A novel phosphoric acid microwave extraction technique was applied to the soils removed from the lysimeter holes; HPLC-HG-AFS analysis showed the majority of solid-phase arsenic to be arsenate (AsV). Pore waters obtained from the lysimeters showed variable, relatively low levels of arsenite (AsIII) and arsenate (AsV) to be present (<1–129 μg l–1). Less toxic arsenate predominated in most pore waters, with the presence of minor amounts of arsenite suggesting heterogeneous redox conditions. Pore-water arsenic concentrations were strongly positively related to solid-phase arsenate concentrations.
The use of techniques that assess the speciation of arsenic both in the solid and aqueous phases of a soil provides important information about the mobility of arsenic. The methodology presented in this paper may offer a novel basis for risk assessments of other contaminated sites.