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The Expanded Program for Immunization Consortium – Human Immunology Project Consortium study aims to employ systems biology to identify and characterize vaccine-induced biomarkers that predict immunogenicity in newborns. Key to this effort is the establishment of the Data Management Core (DMC) to provide reliable data and bioinformatic infrastructure for centralized curation, storage, and analysis of multiple de-identified “omic” datasets. The DMC established a cloud-based architecture using Amazon Web Services to track, store, and share data according to National Institutes of Health standards. The DMC tracks biological samples during collection, shipping, and processing while capturing sample metadata and associated clinical data. Multi-omic datasets are stored in access-controlled Amazon Simple Storage Service (S3) for data security and file version control. All data undergo quality control processes at the generating site followed by DMC validation for quality assurance. The DMC maintains a controlled computing environment for data analysis and integration. Upon publication, the DMC deposits finalized datasets to public repositories. The DMC architecture provides resources and scientific expertise to accelerate translational discovery. Robust operations allow rapid sharing of results across the project team. Maintenance of data quality standards and public data deposition will further benefit the scientific community.
OBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 months from the MM Research Clinic at the Abramson Cancer Institute. Sox2 T cell reactivity will be assessed by IFN-γ ELISPOT assays. Rested PBMC will be pulsed with candidate Sox2-derived peptides predicted to display high affinity to HLA class I alleles and known to be processed and presented as determined by “targeted MS/MS” (mass spectrometry). The presence of anti-Sox2-specific CD8+ T cells will be confirmed in peptide/HLA multimer assays using flow cytometry. Anti-Sox2-specific CD8+ T cells will be characterized for HLA restriction and TCR αβ composition. RESULTS/ANTICIPATED RESULTS: Our work is still in progress. From Aug to Dec 2019, 22 MGUS subjects have been analyzed, 11 of which were found to have the HLA of interest. Positive Sox-2 reactivity by ELISpot was found in 3 subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-Sox2 immune responses may maintain MGUS in a clinical indolent state by eliminating Sox2-expressing clonogenic MM cells. A detailed characterization of anti-Sox2 T cells followed by in-vivo assessment of their anti-myeloma activity could provide the foundation for a Sox2 based immunotherapy approach in MM.
The European Commission is an increasingly important source of funding for international research projects and is due to announce its Framework 5 program early in 1999. The Outcomes of Depression International Network (ODIN), funded from the current EC Biomed 2 program, is a case study in European academic co-operation. Its organization has three key elements. First, engaging the principal investigators: this has involved identifying potential partners, ensuring reciprocity of interests, effective co-ordination, `dividing the spoils' in advance, and setting up good personal and electronic communication systems. Second, an esprit de corps has been created amongst the researchers, maintaining contact and consistency, and promoting higher degrees. Third, ongoing problems including difficulties in negotiations with the EC, divergence of detailed study methods, and isolation and demoralization amongst researchers, have been addressed. ODIN may provide a useful model for researchers wishing to set up international collaborative groups.
In 2004, there were 11,092 presentations to Irish hospitals with deliberate self-harm, including 7,933 cases of drug overdose, of which 31% involved paracetamol. Limiting the availability of paracetamol reduces morbidity and mortality associated with paracetamol overdose. The present study aimed to determine the level of compliance with statutory regulations governing the sale of paracetamol in Ireland.
Researchers visited pharmacy and non-pharmacy outlets (newsagents, mini-markets and supermarkets) in Dublin city and attempted to purchase amounts of paracetamol that exceeded the statutory limits for a single transaction. All paracetamol tablets purchased in non-pharmacy outlets were in blister-packs and all non-pharmacy outlets sold packs with 12 tablets or fewer per pack.
Amounts of paracetamol in excess of statutory limits for a single transaction were purchased in
50.0% of pharmacies
81.8% of newsagents/mini-markets
20.0% of supermarkets.
We recommend that
(a) the sale of paracetamol in newsagents/mini-markets should be discontinued
(b) the sale of paracetamol in supermarkets should continue, but automated check-out tills should be programmed to prevent the sales that exceed statutory limits
(c) there should be greater efforts to ensure compliance with statutory regulations in pharmacies.
This study investigated the attitudes of medical students towards psychiatry, both as a subject on the medical curriculum and as a career choice. Three separate questionnaires previously validated on medical student populations were administered prior to and immediately following an 8-week clinical training programme. The results indicate that the perception of psychiatry was positive prior to clerkship and became even more so on completion of training. On completion of the clerkship, there was a rise in the proportion of students who indicated that they might choose a career in psychiatry. Attitudes toward psychiatry correlated positively with the psychiatry examination results. Those that intended to specialise in psychiatry achieved significantly higher examination scores in the psychiatry examination.
Despite being commonly used in research and clinical practice, the evidence regarding the factor structure of the Beck Depression Inventory-II (BDI-II) remains equivocal and this has implications on how the scale scores should be aggregated. Researchers continue to debate whether the BDI-II is best viewed as a unidimensional scale, or whether specific subscales have utility. The present study sought to test a comprehensive range of competing factor analytic models of the BDI-II, including traditional non-hierarchical multidimensional models and confirmatory bifactor models.
Participants (n=370) were clinical outpatients diagnosed with either depressive episode or adjustment disorder. Confirmatory factor analysis and confirmatory bifactor modelling were used to test 15 competing models. The unidimensionality of the best fitting model was assessed using three strength indices (explained common variance, percentage of uncontaminated correlations and ω hierarchical).
Overall, bifactor solutions provided superior fit than both unidimensional and non-hierarchical multidimensional models. The best fitting model consisted of a general depression factor and three specific factors: cognitive, somatic and affective. High factor loadings and strength indices for the general depression factor supported the view that the BDI-II measures a single latent construct.
The BDI-II should primarily be viewed as a unidimensional scale, and should be scored as such. Although it is not recommended that scores on individual subscales are used in isolation, they may prove useful in clinical assessment and/or treatment planning if used in conjunction with total scores.
A few studies have examined the association between vitamin D and telomere length, and fewer still have examined the relationship in black or male populations. We investigated the cross-sectional association between the vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) concentration in plasma and relative leucocyte telomere length (LTL) in 1154 US radiologic technologists who were 48–93 years old (373 white females, 278 white males, 338 black females, 165 black males). Plasma 25(OH)D concentration was measured by the chemiluminescence immunoassay, and relative LTL was measured by quantitative PCR. Logistic regression was used to obtain OR and 95 % CI for long v. short (based on median) LTL in relation to continuous 25(OH)D, quartiles of 25(OH)D and 25(OH)D deficiency. We found no significant association between continuous 25(OH)D and long LTL in all participants (Ptrend=0·440), nor in white females (Ptrend=0·845), white males (Ptrend=0·636), black females (Ptrend=0·967) or black males (Ptrend=0·484). Vitamin D deficiency (defined as 25(OH)D<30 nmol/l), however, was significantly associated with short LTL in whites (P=0·024), but not in other groups. In this population, we found little evidence to support associations between 25(OH)D and long LTL over the entire range of 25(OH)D in the overall study population or by sex and race.
The editorial considers how psychiatrists can deal with concerns relating to confidentiality that are prominent in patients and their carers. Confidentiality is paramount but there are situations when it can be breached. Some of these relate to emergency situations, others apply in less compelling circumstances. The ethical principles relating to confidentiality will be discussed. An assessment of capacity is central to the person’s ability to consent/refuse information gathering or disclosure. Even when capacity is present, there are strategies that psychiatrists can use to respect patient autonomy while meeting the needs of carers. The possibility of training in negotiating these should be considered, as should advance directives.
We report the case of a 52-year-old male with pre-motor Huntington’s disease (HD) who has undergone detailed clinical and neuropsychological examination. This patient’s negative symptomatology and behavioural change are having a detrimental impact on his social, occupational and interpersonal life, in the absence of motor symptoms.
The patient has undergone repeat neuropsychological testing (T1 aged 50; T2 aged 52) with particular focus on executive function and social cognition on repeat testing.
This case details a specific manifestation of HD relating to behavioural, psychiatric and social affective deficits.
This case illustrates how social cognitive changes can occur in HD, months and even years prior to the onset of motor features and how such unrecognized deficits can have a deleterious impact on an individual’s functional ability and lifestyle, before the disease is traditionally considered to have become manifest.
Drillholes made by naticid and muricid gastropods are frequently used in evolutionary and ecological studies because they provide direct, preservable evidence of predation. The muricid Ecphora is common in many Neogene Atlantic Coastal Plain assemblages in the United States, but is frequently ignored in studies of naticid predation. We used a combination of Pliocene fossil, modern beach, and experimentally derived samples to evaluate the hypothesis that Ecphora was an important source of drillholes in infaunal bivalve prey shared with naticids. We focused on the large, thick-shelled venerid, Mercenaria, which is commonly drilled by naticids today. Laboratory experiments, modern beach samples, and the published literature confirm that naticids preferentially drill near the umbo (significant clumping of holes), show a significant correlation between prey size and predator size (estimated by outer borehole diameter), and prefer Mercenaria <50 mm antero-posterior width when other prey are present. Fossil samples containing Ecphora (with or without other large muricids) show no drillhole site stereotypy (no significant clumping, greater variability in placement), no significant predator: prey size correlation, drilled prey shells larger than the largest modern naticids could produce in an experimental setting, and drillholes larger in diameter than those estimated for the largest Pliocene naticids, thus supporting our hypothesis. Substantial overlap in the placement of holes drilled by naticids and muricids, however, made identifying predators from drillhole position problematic. The lack of overlapping ranges of prey shell thickness between fossil and other samples precluded the use of drillhole morphology to establish predator identity (e.g., ratio of inner borehole diameter to outer borehole diameter, drillhole angle). Whereas the difficulty in determining predator identity from drillholes limits the types of analyses that can be reliably performed in mixed-predator assemblages, recognizing Ecphora as a prominent drilling predator creates the opportunity to investigate previously unrecognized questions.
We present star formation rates and nebular abundances of 59 different star-forming regions in 16 nearby galaxies. The star-forming regions were selected to be bright in Hα and were observed with the SNIFS integral field spectrograph on the UH 2.2m telescope. The spectra span the wavelength range between 3200Å and 1μm. We find that the local star formation rates depend on the local abundances in that low SFRs show a dependence but high SFR appear insensitive to it.
There is evidence for health benefits from ‘Palaeolithic’ diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.
In the 1970s a public controversy erupted over the proposed use of brain operations to curtail violent behavior. Civil libertarians, civil rights and community activists, leaders of the anti-psychiatry movement, and some U.S. Congressmen charged psychosurgeons and the National Institute of Mental Health, with furthering a political project: the suppression of dissent. Several government-sponsored investigations into psychosurgery rebutted this charge and led to an official qualified endorsement of the practice while calling attention to the need for more “scientific” understanding and better ethical safeguards. This paper argues that the psychosurgery debate of the 1970s was more than a power struggle between members of the public and the psychiatric establishment. The debate represented a clash between a postmodern skepticism about science and renewed focus on ultimate ends, on the one hand, and a modern faith in standards and procedures, a preoccupation with means, on the other. These diverging commitments made the dispute ultimately irresolvable.
Carbon dioxide is the major greenhouse gas that is a bi-product of industrial approaches to energy production. Forests and nonagricultural lands act as a natural sink for CO2 removal from the atmosphere; however, the amount of emitted CO2 is significantly larger than the capacity of these natural sinks. This is particularly problematic as two cornerstones of our modern world, electricity generation and transportation, hold the largest share in greenhouse gas (such as CO2) emission. This leads to malignant impacts on the natural environment and human life, such as global warming. The obvious approach to reduce the amount of generated CO2 is to limit the use of fossil fuels. However, coal-fired power plants remain the largest source of electricity generation in 2014 and an equally potent and financially reasonable source is yet to be fully developed. Hence, new systems and strategies are crucial for the remediation of CO2. In this work, we present novel TiO2 nanoparticles, synthesized via a facile solution-phase method, which show a significant visible light absorption. The synthesized nanoparticles can be applied towards photoreduction of CO2 for hydrocarbon solar fuels production. A thorough photoemission spectroscopy analysis outlined the energy structure of the materials which uncovered a sub-bandgap absorption in the visible range due to the presence of intragap states. The origins of intragap states were investigated in greater detail using various characterization techniques. An in-depth chemical composition study of the developed material using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) indicated that the synthesized material is considerably un-doped. Further structural analysis using transmission electron microscopy (TEM) showed that distances between visible lattice fringes are matched with ordered crystalline phases of TiO2. The core emission study using XPS revealed that the oxygen vacancy defects in the structure--i.e. likely due the synthesis--are responsible for intragap states formation. Charge dynamics were investigated using Electron Paramagnetic Resonance (EPR) spectroscopy. EPR spectra were dominated by signals from oxygen-centered surface hole trapping sites with principle g values [2.003, 2.010, 2.023]--i.e. Ti4+ ˗ O2- on anatase. A faint signal was also observed as a function of visible light illumination at 5 K with principle g value of 1.975 that is suggestive of Ti3+ in rutile, a typical product of UV light exposure. In general, this study demonstrates the potential of a relatively inexpensive material for photoreduction of CO2 and generation of solar fuels.