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Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Several aspects of early language skills, including parent-report measures of vocabulary, phoneme discrimination, speech segmentation, and speed of lexical access predict later childhood language outcomes. To date, no studies have examined the long-term predictive validity of novel word learning. We examined whether individual differences in novel word learning at 21 months predict later childhood receptive vocabulary outcomes rather than generalized cognitive abilities. Twenty-eight 21-month-olds were taught novel words using a modified version of the Intermodal Preferential Looking Paradigm. Seventeen children (range 7–10 years) returned to participate in a longitudinal follow-up. Novel word learning in infancy uniquely accounted for 22% of the variance in childhood receptive vocabulary but did not predict later childhood visuospatial ability or non-verbal IQ. These results suggest that the ability to associate novel sound patterns to novel objects, an index of the process of word learning, may be especially important for long-term language mastery.
Roll-to-roll slot-die coating with a meniscus guide is used to deposit several layers in a P-I-N perovskite solar cell stack, including the perovskite layer. The use of various length meniscus guides as part of the slot-die head allows controlled coating of these layers at a common coating speed. The length of meniscus guide used is optimised and related to the rheology of the coated ink and appropriate choice of meniscus guide length provides a way to avoid flooding of the coated area and improve coating definition. Initial coating trial results suggest the low-flow limit of slot-die coating is still applicable when using a meniscus guide, which is an important and previously unreported observation, application of this theory to meniscus guide coating provides a useful tool for rapidly determining the appropriate coating conditions that can be used as part of a manufacturing process. This is further explored through the deposition of perovskite solar cells by roll-to-roll slot-die coating. The perovskite layer is deposited using a sequential slot-die deposition process using a low toxicity dimethyl sulfoxide ink for the lead iodide layer, it is found that increasing the drying oven temperature and air flow rate can be used to improve the uniformity of the layer but this can also result in deformation of the plastic substrate. Functioning perovskite solar cells are demonstrated using this technique, but a large variation is found between device performances which is attributed to the poor uniformity of the perovskite layer and damage caused to the substrate by excessive heating.
Why have accounts of botched executions not played a larger role in the struggle to end capital punishment in the United States? In the twentieth century, when methods of execution became increasingly controlled and sterilized, botched executions would seem to have had real abolitionist potential. This article examines newspaper coverage of botched executions to determine and describe the way they were presented to the public and why they have contributed little to the abolitionist cause. Although botched executions reveal pain, violence, and inhumanity associated with state killing, newspaper coverage of these events neutralizes the impact of that revelation. Throughout the last century, newspapers presented botched executions as misfortunes rather than injustices. We identify three distinct modes by which newspaper coverage neutralized the impact of botched executions and presented them as misfortunes rather than as systemic injustices: (1) the dual narratives of sensationalism and recuperation in the early years of the twentieth century, (2) the decline of sensationalism and the rise of “professionalism” in the middle of the century, and (3) the emphasis on “balanced” reporting toward the end of the century.
Common mental health problems affect a quarter of the population. Online cognitive–behavioural therapy (CBT) is increasingly used, but the factors modulating response to this treatment modality remain unclear.
This study aims to explore the demographic and clinical predictors of response to one-to-one CBT delivered via the internet.
Real-world clinical outcomes data were collected from 2211 NHS England patients completing a course of CBT delivered by a trained clinician via the internet. Logistic regression analyses were performed using patient and service variables to identify significant predictors of response to treatment.
Multiple patient variables were significantly associated with positive response to treatment including older age, absence of long-term physical comorbidities and lower symptom severity at start of treatment. Service variables associated with positive response to treatment included shorter waiting times for initial assessment and longer treatment durations in terms of the number of sessions.
Knowledge of which patient and service variables are associated with good clinical outcomes can be used to develop personalised treatment programmes, as part of a quality improvement cycle aiming to drive up standards in mental healthcare. This study exemplifies translational research put into practice and deployed at scale in the National Health Service, demonstrating the value of technology-enabled treatment delivery not only in facilitating access to care, but in enabling accelerated data capture for clinical research purposes.
Declaration of interest
A.C., S.B., V.T., K.I., S.F., A.R., A.H. and A.D.B. are employees or board members of the sponsor. S.R.C. consults for Cambridge Cognition and Shire. Keywords: Anxiety disorders; cognitive behavioural therapies; depressive disorders; individual psychotherapy
Infection with STEC O157 is relatively rare but has potentially serious sequelae, particularly for children. Large outbreaks have prompted considerable efforts designed to reduce transmission primarily from food and direct animal contact. Despite these interventions, numbers of infections have remained constant for many years and the mechanisms leading to many sporadic infections remain unclear.
Here, we show that two-thirds of all cases reported in England between 2009 and 2015 were sporadic. Crude rates of infection differed geographically and were highest in rural areas during the summer months. Living in rural areas with high densities of cattle, sheep or pigs and those served by private water supplies were associated with increased risk. Living in an area of lower deprivation contributed to increased risk but this appeared to be associated with reported travel abroad. Fresh water coverage and residential proximity to the coast were not risk factors.
To reduce the overall burden of infection in England, interventions designed to reduce the number of sporadic infections with STEC should focus on the residents of rural areas with high densities of livestock and the effective management of non-municipal water supplies. The role of sheep as a reservoir and potential source of infection in humans should not be overlooked.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Background: Guilt is commonly associated with distress and psychopathology. However, there is a lack of validated measures that assess how people cope with this aversive emotional and cognitive experience. Aims: We therefore developed and validated a self-report measure that assesses how people manage their guilt: the Guilt Management Scale (GMS). Method: The GMS was administered to a non-clinical (n = 339) and clinical (n = 67) sample, alongside other validated measures of guilt severity, coping, thought control and psychological distress. Results from a principal component analysis (PCA) and assessments of test–retest reliability and internal consistency are presented. Results: The PCA yielded a six subscale solution (Self-Punishment, Reparation, People-Focused, Spirituality, Avoidance and Metacognition), accounting for 56.14% of variance. Test–retest reliability and internal consistency was found to be good–excellent for the majority of subscales. Across samples, Self-Punishment was related to higher levels of guilt and distress whilst Metacognition and Reparation were related to less guilt and distress in the non-clinical sample only. Conclusions: This paper provides preliminary evidence for the psychometric properties of the GMS in a non-clinical sample. With development and validation in clinical samples, the GMS could be used to inform psychological formulations of guilt and assess therapy outcomes.
OBJECTIVES/SPECIFIC AIMS: The aim of this study was to assess the ultra-dose Na18F dPET protocol feasibility for skeleton imaging in a canine model with reduced radiation dose and preserved quantitative characteristics. We hypothesized that administering an ultra-low Na18F dose would provide suitable image quality while reducing subject’s exposure to radiation. METHODS/STUDY POPULATION: In total, 13 adult male beagles [weight (kg) mean±SD; 14.3±2.2] were scanned. The dogs were administered 3 different Na18F doses: 3 (standard dose/SD), 1 (low dose/LD), and 0.05 (ultra-low dose/ULD) mCi. Imaging started ≃45 minutes post injection for ≃ 33 minute total acquisition time. Covering the whole body, 11 bed positions, acquiring 120 (3 mCi) and 180 (1, 0.05 mCi) seconds per bed position. All imaging was performed on a digital photon counting system (Philips Vereos, pre-commercial release). PET list mode data were reconstructed using Time-of-flight with 4, 2, and 1 mm3 voxel volumes. Point spread function, and Gaussian filtering were applied. Two experienced blinded readers evaluated image sets overall quality, tissue characterization, and quality of background in the whole body skeleton. Three-dimensional (3D) regions of interest (ROI) were traced over the distal femur, first lumbar vertebra, and a portion of the liver, recording standard uptake values (SUVmax and SUVmean). RESULTS/ANTICIPATED RESULTS: All the scans and reconstructions were successfully completed in all subjects. Decreasing Na18F dose from the standard dose (3 mCi) to the ultra-low dose/ULDO (0.05 mCi), demonstrated acceptable image quality and quantification. Ultra-low dose Na18F SUVmean values for the 3D ROIs reported (mean±SD) 2.6±0.7, 2.5±1.1, 9±1.6, and 0.6±0.3 from the right and left distal femur, first lumbar vertebra, and a portion of the liver, respectively. When compared the SD with the LD and ULD, dPET demonstrated acceptable image quality and definition for qualitative overall assessment. This was also found for the overall quantitative ROI assessment of the healthy canine skeletons. DISCUSSION/SIGNIFICANCE OF IMPACT: Ultra-low dose Na18F at a level of 50 μCi for a 14 kg canine appears to be diagnostically feasible and a robust option to reduce (60-fold) radiotracer doses in a translational animal model using a dPET system. Furthermore, it allows us to move preclinical nuclear medicine imaging forward with substantial reduced exposure levels while preserving image quality. Both visual and quantitative results indicate that the standard-dose bone Na18F dPET can be decreased with a satisfactory diagnostic image quality. Ultra-low Na18F dose is indeed important for younger populations, control patients, and nononcological diseases/conditions. Favorable pharmacokinetics of Na18F (such as high bone uptake, minimal binding to serum proteins, rapid single-pass extraction, and fast clearance from the soft tissues) in addition to the technological capabilities of dPET/CT demonstrated feasibility enabling dose reduction strategies. Ultra-low dose has diagnostic reproducibility and lower radiation burden compared with higher fixed dose techniques in current available guidelines [Society of Nuclear Medicine and Molecular Imaging; SNMMI (5–10 mCi)]. Na18F dPET/CT provides higher sensitivity and diagnostic accuracy, which enables high-quality images with lower tracer activity in this translational animal model. Future research will apply the same methodology to other anatomical targets as well as to the use of different tracers. Preclinical nuclear medicine imaging using ultra-low tracer doses, demonstrated the potential to obtain reasonable quality images and diminishing radiation surveillance in accordance with as low as reasonably achievable tracer levels.
Post-harvest drying prolongs seed survival in air-dry storage; previous research has shown a benefit of drying moist rice seeds at temperatures greater than recommended for genebanks (5–20°C). The aim of this study was to determine whether there is a temperature limit for safely drying rice seeds, and to explore whether the benefit to longevity is caused by high-temperature stress or continued seed development. Seeds of two rice varieties were harvested at different stages of development and dried initially either over silica gel, or intermittently (8 h day–1) or continuously (24 h day–1) over MgCl2 at temperatures between 15 and 60°C for up to 3 days. Seeds dried more rapidly the warmer the temperature. Subsequent seed longevity in hermetic storage (45°C and 10.9% moisture content) was substantially improved by increase in drying temperature up to 45°C in both cultivars, and also with further increase from 45 to 60°C in cv. ‘Macassane’. The benefit of high-temperature drying to subsequent longevity tended to diminish the later the stage of development at seed harvest. Intermittent or continuous drying at high temperatures provided broadly similar improvements to longevity, but with the greatest improvements detected in a few treatment combinations with continuous drying. Heated-air drying of rice seeds harvested before maturity improved their subsequent storage longevity by more than that which occurred during subsequent development in planta, which may have resulted from the triggering of protection mechanisms in response to high-temperature stress.
Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators.
Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps.
Forty-eight competency statements in 8 domains were developed.
Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.
The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel.
In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized.
This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP.
We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.
Objectives: Kids in Control OF Food (KICk-OFF) is a 5-day structured education program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are using multiple daily insulin injections. This study evaluates the cost-effectiveness of the KICk-OFF education program compared with the usual care using data from the KICk-OFF trial.
Methods: The short-term within-trial analysis covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c), severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year follow-up period. Sub-group analyses have been defined on the basis of baseline HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high group). The long-term cost-effectiveness evaluation has been conducted by using The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization, and angina) diabetes-related complications and acute adverse events (severe hypoglycemia and DKA).
Results: The most favorable within-trial scenario for the KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of £23,688 (base year 2009) with a cost-effectiveness probability of 41.3 percent. Simulating the long-term complications using the full cohort data, the mean ICER for the base case was £28,813 (base year 2011) and the probability of the KICk-OFF intervention being cost-effective at £20,000/QALY threshold was 42.6 percent, with considerable variation due to treatment effect duration. For the high HbA1c sub-group, the KICk-OFF arm was “dominant” (meaning it provided better health gains at lower costs than usual care) over the usual care arm in each scenario considered.
Conclusions: For the whole study population, the cost-effectiveness of KICk-OFF depends on the assumption for treatment effect duration. For the high baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the usual care arm regardless of the assumption on the treatment effect duration.
Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders'.
To compare white matter integrity in patients with gambling disorder with healthy controls; to explore relationships between white matter integrity and disease severity in gambling disorder.
In total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics.
Gambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity.
Reduced corpus callosum fractional anisotropy is suggestive of disorganised/damaged tracts in patients with gambling disorder, and this may represent a trait/vulnerability marker for the disorder. Future research should explore these measures in a larger sample, ideally incorporating a range of imaging markers (for example functional MRI) and enrolling unaffected first-degree relatives of patients.
The Framework Convention on Tobacco Control (FCTC) set standards for global tobacco control, including the implementation of evidence-based tobacco dependence treatment. However, efforts to implement tobacco treatment programmes globally have been few. In order to expand tobacco treatment expertise and programmes, a new network called Global Bridges (GB) was established. This network provided training in tobacco treatment and opportunities to share best practices on implementation of tobacco dependence treatment and training programmes. In this analysis of the GB network, we found that 75% of the network members attended trainings, 60% disseminated knowledge gained through GB training, and network centralization was high (0.85). These results demonstrate initial success in network implementation, and create a foundation for expanded focus on tobacco treatment globally.
Introduction: Global Bridges, hosted at Mayo Clinic since 2010, is the only international network of healthcare professionals dedicated to tobacco dependence treatment. Globally, fewer resources have been dedicated to treatment than to other evidence-based tobacco control policies. The Global Bridges network seeks to aid in filling this gap in tobacco control.
Aims: This paper identifies ways to advance tobacco dependence treatment, as well as tobacco control, through efficient and effective use of a global health care provider network.
Methods: Observation and critical analysis of lessons learned, project outcomes to date, and network analysis.
Results/Findings: The initiative has built a strong global foundation, with training curricula developed and delivered in a number of countries, including low- and middle-income countries. While basic evaluation of content mastery and learner satisfaction has been conducted, more intensive evaluation and follow-up to confirm public health impact are essential needs. Finally, program analysis and application of management theory can be used in aiding future activities aimed at providing support for health care providers in the delivery of tobacco dependence treatment and in similar global public health endeavors.
Conclusions: The Global Bridges healthcare professional network, now in its sixth year, has developed training curricula and expanded evidence-based tobacco dependence education among healthcare professionals. Global Bridges comprises a unique and important component of the broader tobacco control community, and can play an integral role in furthering global tobacco control progress.
Residual herbicides are routinely recommended to aid in control of glyphosate-resistant (GR) Palmer amaranth in cotton. Acetochlor, a chloroacetamide herbicide, applied PRE, controls Palmer amaranth. A microencapsulated (ME) formulation of acetochlor is now registered for PRE application in cotton. Field research was conducted in North Carolina to evaluate cotton tolerance and Palmer amaranth control by acetochlor ME alone and in various combinations. Treatments, applied PRE, consisted of acetochlor ME, pendimethalin, or no herbicide arranged factorially with diuron, fluometuron, fomesafen, diuron plus fomesafen, and no herbicide. The PRE herbicides were followed by glufosinate applied twice POST and diuron plus MSMA directed at layby. Acetochlor ME was less injurious to cotton than pendimethalin. Acetochlor ME alone or in combination with other herbicides reduced early season cotton growth 5 to 8%, whereas pendimethalin alone or in combinations injured cotton 11 to 13%. Early season injury was transitory, and by 65 to 84 d after PRE treatment, injury was no longer noticeable. Before the first POST application of glufosinate, acetochlor ME and pendimethalin controlled Palmer amaranth 84 and 64%, respectively. Control by acetochlor ME was similar to control by diuron plus fomesafen and greater than control by diuron, fluometuron, or fomesafen alone. Greater than 90% control was obtained with acetochlor ME mixed with diuron or fomesafen. Palmer amaranth control was similar with acetochlor ME plus a full or reduced rate of fomesafen. Acetochlor ME controlled large crabgrass and goosegrass at 91 and 100% compared with control at 83 and 91%, respectively, by pendimethalin. Following glufosinate, applied twice POST, and diuron plus MSMA, at layby, 96 to 99% control was obtained late in the season by all treatments, and no differences among herbicide treatments were noted for cotton yield. This research demonstrated that acetochlor ME can be safely and effectively used in cotton weed management programs.