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Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia.
National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later.
Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83–0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77–0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83–1.00).
Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research.
OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.
To assess the training and the future workforce needs of paediatric cardiac critical care faculty.
REDCap surveys were sent May−August 2019 to medical directors and faculty at the 120 US centres participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Faculty and directors were asked about personal training pathway and planned employment changes. Directors were additionally asked for current faculty numbers, expected job openings, presence of training programmes, and numbers of trainees. Predictive modelling of the workforce was performed using respondents’ data. Patient volume was projected from US Census data and compared to projected provider availability.
Measurements and main results:
Sixty-six per cent (79/120) of directors and 62% (294/477) of contacted faculty responded. Most respondents had training that incorporated critical care medicine with the majority completing training beyond categorical fellowship. Younger respondents and those in dedicated cardiac ICUs were more significantly likely to have advanced training or dual fellowships in cardiology and critical care medicine. An estimated 49–63 faculty enter the workforce annually from various training pathways. Based on modelling, these faculty will likely fill current and projected open positions over the next 5 years.
Paediatric cardiac critical care training has evolved, such that the majority of faculty now have dual fellowship or advanced training. The projected number of incoming faculty will likely fill open positions within the next 5 years. Institutions with existing or anticipated training programmes should be cognisant of these data and prepare graduates for an increasingly competitive market.
To assess current demographics and duties of physicians as well as the structure of paediatric cardiac critical care in the United States.
REDCap surveys were sent by email from May till August 2019 to medical directors (“directors”) of critical care units at the 120 United States centres submitting data to the Society of Thoracic Surgeons Congenital Heart Surgery Database and to associated faculty from centres that provided email lists. Faculty and directors were asked about personal attributes and clinical duties. Directors were additionally asked about unit structure.
Measurements and main results:
Responses were received from 66% (79/120) of directors and 62% (294/477) of contacted faculty. Seventy-six percent of directors and 54% of faculty were male, however, faculty <40 years old were predominantly women. The majority of both groups were white. Median bed count (n = 20) was similar in ICUs and multi-disciplinary paediatric ICUs. The median service expectation for one clinical full-time equivalent was 14 weeks of clinical service (interquartile range 12, 16), with the majority of programmes (86%) providing in-house attending night coverage. Work hours were high during service and non-service weeks with both directors (37%) and faculty (45%).
Racial and ethnic diversity is markedly deficient in the paediatric cardiac critical care workforce. Although the majority of faculty are male, females make up the majority of the workforce younger than 40 years old. Work hours across all age groups and unit types are high both on- and off-service, with most units providing attending in-house night coverage.
Oxyurid nematodes (Syphacia spp.) from bank (Myodes glareolus) and field/common (Microtus spp.) voles, from disparate geographical sites in the British Isles, were examined morphologically and genetically. The genetic signatures of 118 new isolates are provided, based primarily on the rDNA internal transcribed spacers (ITS1-5.8S-ITS2) region and for representative isolates also on the small subunit 18S rDNA region and cytochrome c oxidase subunit 1 (cox-1) gene locus. Genetic data on worms recovered from Microtus spp. from the European mainland and from other rodent genera from the Palaearctic, North America and West Africa are also included. We test historical hypotheses indicating that S. nigeriana is a generalist species, infecting a range of different rodent genera. Our results establish that S. nigeriana is a parasite of both bank and field voles in the British Isles. An identical genotype was also recorded from Hubert's multimammate mouse (Mastomys huberti) from Senegal, but Mastomys spp. from West Africa were additionally parasitized by a related, although genetically distinct Syphacia species. We found no evidence for S. petrusewiczi in voles from the British Isles but isolates from Russia and North America were genetically distinct and formed their own separate deep branch in maximum likelihood molecular phylogenetic trees.
A decorated copper-alloy key handle was recovered during excavation of a town house in Roman Leicester (Ratae Corieltavorum). The decoration comprises two groups of figures modelled in high relief: a bearded, unarmed man fighting with a lion, arranged above four naked male youths embracing one another in a protective manner. This decoration cannot be paralleled among other similarly elaborate Roman key handles and is best interpreted as a scene of damnatio ad bestias, although it does not directly replicate other known scenes of this punishment and spectacle. Other readings of the image are possible, depending on the context and perspective of the viewer as they handled the object.
This chapter explores Aristotle’s criticism of the Platonic idea of a cosmic soul as a first principle of motion, in the theory of animal voluntary motion that he offers in the De Motu Animalium. According to Aristotle, animal self-motion and the movement of the heavens are alike in that they both depend on an unmoved mover. But it is not immediately clear how this comparison works in detail, since for Aristotle the unmoved mover in animal motion is not directly an external object of desire but the animal’s thinking about an object of desire. Hence, there must, for Aristotle, be some parallel thinking involved in the movement of celestial bodies. Such an account, however, is missing from the De Motu Animalium. To find one, we need to consider the metaphysical cosmology set forth in Lambda, chapters 6–10 of Metaphysics, which posits a soul for each of the moved heavenly bodies, a soul which thinks of the sole absolutely unmoved mover of the universe, in desiring it through a form of rational desire. Thus Aristotle departs sharply from both Plato in the Timaeus and the subsequent Platonic, Stoic and Neoplatonic traditions, according to which celestial motion is not be explained by individual souls in each of the moved celestial bodies but by a single soul of the cosmos as a whole , located at the outermost sphere of the cosmos.
The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.
Presenting research conducted by the ‘St Stephen’s Chapel, Westminster’ project at the University of York, this article focuses on the Great Seal devised in 1649 and re-issued in 1651 to enable the Commonwealth to function following the execution of Charles i. As a familiar and ancient image of monarchy, the Great Seal posed an obvious challenge to the authority of the Rump Parliament. A radical new design, authorised by parliamentary committee and executed by engraver Thomas Simon, replaced royal iconography with images of popular sovereignty and nationhood: a map of England and Ireland on the obverse of the Seal, and the interior of the House of Commons chamber (formerly St Stephen’s Chapel) on the reverse. The result was a striking evocation of political authority located in the House of Commons and deriving from the English people. Engravings of the Commons chamber, in circulation since the 1620s, are identified as a probable source for Simon’s work. The Great Seal also re-asserted England’s dominion over Ireland and the waters surrounding the British Isles. Overall, this article argues for continuity as well as alteration in the iconography of the Great Seal of England, at a time of revolutionary political change.
This chapter reviews sociological perspectives on emissions trading programs for greenhouse gases and reflects on how the study of carbon markets can contribute to concepts and theories central to environmental sociology. Since the emergence of the global climate change regime in the 1990s, carbon markets have been a cornerstone of efforts to govern greenhouse gas emissions. The chapter frames its study of sociological research on carbon markets by examining the origins and development of emissions trading programs and debates about their function within capitalist economies, their effectiveness at achieving emissions reductions, and their implications for environmental justice. Research on carbon markets has also contributed to fundamental debates within environmental sociology and strengthened dialogue between environmental sociology and economic sociology, political sociology, and sociology of science. The chapter analyzes these contributions and reflects on the potential for future studies of carbon markets to advance key debates within the discipline, offer critical perspectives on climate change mitigation policy, and yield practical contributions for the future of environmental governance.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Background: Central-line–associated blood stream infections (CLABSIs) are linked with significant morbidity and mortality. A NHSN laboratory-confirmed bloodstream infection (LCBSI) has specific criteria to ascribe an infection to the central line or not. The criteria used to associate the pathogen to another site are restrictive. This objective to better classify CLABSIs using enhanced criteria to gain a comprehensive understanding of the error so that appropriate reduction efforts are utilized. Methods: We conducted a retrospective review of medical records with NHSN-identified CLABSI from July 2017 to December 2018 at 2 geographically proximate hospitals. Trained infectious diseases personnel from tertiary-care academic medical centers, the University of Virginia Health System, a 600-bed medical center in Charlottesville, Virginia, and Virginia Commonwealth University Health System with 865 beds in Richmond, Virginia, reviewed charts. We defined “overcaptured” or O-CLABSI into different categories: O-CLABSI-1 is bacteremia attributable to a primary infectious source; O-CLABSI-2 is bacteremia attributable to neutropenia with gastrointestinal translocation not meeting mucosal barrier injury criteria; O-CLABSI-3 is a positive blood culture attributable to a contaminant; and O-CLABSI-4 is a patient injecting line, though not officially documented. Descriptive analyses were performed using the χ2 and the Fisher exact tests. Results: We found a large number of O-CLABSIs on chart review (79 of 192, 41%). Overall, 56 of 192 (29%) LCBSIs were attributable to a primary infectious source not meeting NHSN definition. O-CLABSI proportions between the 2 hospitals were statistically different; hospital A identified 34 of 59 (58%) of their NHSN-identified CLABSIs as O-CLABSIs, and hospital B identified a 45 of 133 (34%) as O-CLABSIs (P = .0020) (Table 1). When comparing O-CLABSI types, hospital B had a higher percentage of O-CLABSI-1 compared to hospital B: 76% versus 64%. Hospital A had a higher proportion of O-CLABSI-2: 21 versus 7%. Hospitals A and B had similar proportion of O-CLABSI-3: 15% versus 18%. These values were all statistically significant (P < .0001). Discussions: The results of these 2 geographically proximate systems indicate that O-CLABSIs are common. Attribution can vary significantly between institutions, likely depending on differences in incidence of true CLABSI, patient populations, protocols, and protocol compliance. These findings have implications for interfacility comparisons of publicly reported data. Most importantly, erroneous attribution can result in missed opportunity to direct patient safety efforts to the root cause of the bacteremia and could lead to inappropriate treatment.
Disclosures: Michelle Doll, Research Grant from Molnlycke Healthcare
Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.
The foetal programming hypothesis posits that optimising early life factors e.g. maternal diets can help avert the burden of adverse childhood outcomes e.g. childhood obesity. To improve applicability to public health messaging, we investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity in a large consortium.
We harmonized and pooled individual participant data from up to 8,769 mother-child pairs in 7 European mother-offspring cohorts. Maternal early-, late-, and whole-pregnancy dietary quality and inflammatory potential were assessed with Dietary Approaches to Stop Hypertension (DASH) and energy-adjusted Dietary Inflammatory Index (E-DII), respectively. Primary outcome was childhood overweight and obesity (OWOB), defined as age- and sex-specific body-mass-index-z score (BMIz) > 85th percentile based on WHO growth standard. Secondary outcomes were sum-of-skinfold-thickness (SST), fat-mass-index (FMI) and fat-free-mass-index (FFMI) in available cohorts. Outcomes were assessed in early- [mean (SD) age: 2.8 (0.3) y], mid- [6.2 (0.6) y], and late-childhood [10.6 (1.2) y]. We used multivariable regression analyses to assess the associations of maternal E-DII and DASH with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Analyses were adjusted for maternal age, pre-pregnancy BMI, parity, lifestyle factors, energy intake, educational attainment, offspring age and sex.
A more pro-inflammatory maternal diet, indicated by higher E-DII, was associated with a higher risk of offspring late-childhood OWOB [pooled-OR (95% CI) comparing highest vs. lowest E-DII quartiles: 1.22 (1.01,1.47) for whole-pregnancy and 1.38 (1.05,1.83) for early-pregnancy; both P < 0.05]. Moreover, higher late-pregnancy E-DII was associated with higher mid-childhood FMI [pooled-β (95% CI): 0.11 (0.003,0.22) kg/m2; P < 0.05]; trending association was observed for whole-pregnancy E-DII [0.12 (-0.01,0.25) kg/m2; P = 0.07]. A higher maternal dietary quality, indicated by higher DASH score, showed a trending inverse association with late-childhood OWOB (pooled-OR (95% CI) comparing highest vs. lowest DASH quartiles: 0.58 (0.32,1.02; P = 0.06). Higher early-pregnancy DASH was associated with lower late-childhood SST [pooled-β (95% CI): -1.9 (-3.6,-0.1) cm; P < 0.05] and tended to be associated with lower late-childhood FMI [-0.34 (-0.71,0.04) kg/m2; P = 0.08]. Higher whole-pregnancy DASH tended to associate with lower early-childhood SST [-0.33 (-0.72,0.06) cm; P = 0.10]. Results were similar when modelling DASH and E-DII continuously.
Analysis of pooled data suggests that pro-inflammatory, low-quality maternal antenatal diets may influence offspring body composition and obesity risk, especially during mid- or late-childhood. Due to variation of data availability at each timepoint, our results should be interpreted with caution. Because most associations were observed at mid-childhood or later, future studies will benefit from a longer follow-up.
Pelagic seabirds often nest on islands that are far from productive foraging areas. The Procellariiformes (petrels, shearwaters and albatrosses) are among the longest-ranging seabirds; they have several adaptations that permit them to efficiently utilize distant foraging areas and fast for long periods during incubation (Phillips & Hamer 1999). Giant petrels (Macronectes spp.) are large surface-nesting procellariiforms. They feed both by direct predation and by scavenging carrion, and they are the largest avian predator-scavengers in the Southern Ocean. Among procellariiform seabirds, one partner forages while their mate remains on the nest to incubate their single egg (Warham 1990). Northern giant petrels (Macronectes halli) have incubation shifts lasting up to 17 days (Cooper et al. 2001). In general, incubating procellariiform seabirds do not feed during their shift (Warham 1990). We report the first case to our knowledge of a procellariiform seabird, a northern giant petrel, actively feeding at its nest whilst incubating.
The conjunction in our title requires some explanation, if not justification, in the context in which this book is published. This book aims to introduce the undergraduate, postgraduate and general reader to a literary and intellectual relationship which is richer in German than in any other European culture. That is the constant and reciprocal relationship in the German-speaking world since the Middle Ages between literary and religious practice and discourse.