Six month durability of targeted cognitive training supplemented with social cognition exercises in schizophrenia.

Background:Deficits in cognition, social cognition, and motivation are significant predictors of poor functional outcomes in schizophrenia. Evidence of durable benefit following social cognitive training is limited. We previously reported the effects of 70 h of targeted cognitive training supplemented with social cognitive exercises (TCT + SCT) verses targeted cognitive training alone (TCT). Here, we report the effects six months after training. Methods:111 participants with schizophrenia spectrum disorders were randomly assigned to TCT + SCT or TCT-only. Six months after training, thirty-four subjects (18 TCT + SCT, 16 TCT-only) were assessed on cognition, social cognition, reward processing, symptoms, and functioning. Intent to treat analyses was used to test the durability of gains, and the association of gains with improvements in functioning and reward processing were tested. Results:Both groups showed durable improvements in multiple cognitive domains, symptoms, and functional capacity. Gains in global cognition were significantly associated with gains in functional capacity. In the TCT + SCT group, participants showed durable improvements in prosody identification and reward processing, relative to the TCT-only group. Gains in reward processing in the TCT + SCT group were significantly associated with improvements in social functioning. Conclusions:Both TCT + SCT and TCT-only result in durable improvements in cognition, symptoms, and functional capacity six months post-intervention. Supplementing TCT with social cognitive training offers greater and enduring benefits in prosody identification and reward processing. These results suggest that novel cognitive training approaches that integrate social cognitive exercises may lead to greater improvements in reward processing and functioning in individuals with schizophrenia

On the Modulation Equations and Stability of Periodic GKdV Waves via Bloch Decompositions

In this paper, we complement recent results of Bronski and Johnson and of Johnson and Zumbrun concerning the modulational stability of spatially periodic traveling wave solutions of the generalized Korteweg-de Vries equation. In this previous work it was shown by rigorous Evans function calculations that the formal slow modulation approximation resulting in the Whitham system accurately describes the spectral stability to long wavelength perturbations. Here, we reproduce this result without reference to the Evans function by using direct Bloch-expansion methods and spectral perturbation analysis. This approach has the advantage of applying also in the more general multi-periodic setting where no conveniently computable Evans function is yet devised. In particular, we complement the picture of modulational stability described by Bronski and Johnson by analyzing the projectors onto the total eigenspace bifurcating from the origin in a neighborhood of the origin and zero Floquet parameter. We show the resulting linear system is equivalent, to leading order and up to conjugation, to the Whitham system and that, consequently, the characteristic polynomial of this system agrees (to leading order) with the linearized dispersion relation derived through Evans function calculation.Comment: 19 pages

Orbital stability of periodic waves for the nonlinear Schroedinger equation

The nonlinear Schroedinger equation has several families of quasi-periodic travelling waves, each of which can be parametrized up to symmetries by two real numbers: the period of the modulus of the wave profile, and the variation of its phase over a period (Floquet exponent). In the defocusing case, we show that these travelling waves are orbitally stable within the class of solutions having the same period and the same Floquet exponent. This generalizes a previous work where only small amplitude solutions were considered. A similar result is obtained in the focusing case, under a non-degeneracy condition which can be checked numerically. The proof relies on the general approach to orbital stability as developed by Grillakis, Shatah, and Strauss, and requires a detailed analysis of the Hamiltonian system satisfied by the wave profile.Comment: 34 pages, 7 figure

The Influence of Sirtuins on Brain Metabolism

Sirtuins (SIRTs) comprise a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, capable of affecting health-span and DNA expression. In cell-culture and peripheral-tissue models, researchers have identified that SIRT1 and SIRT2 are also capable of changing enzymatic activity in glycolysis and Krebs cycle. In brain, the impact of SIRT1 and SIRT2 deacetylase activity on metabolism is poorly understood. The aim of this project was to determine if metabolic pathways in brain could be regulated by SIRT1 and SIRT2-mediated deacetylation in mammalian systems. An established ex vivo reductionist model of brain metabolism was used to test the hypothesis that direct inhibition, activation or ablation of SIRT1 or SIRT2 deacetylase activity would result in significant changes in brain metabolism. Alterations in brain metabolism were assessed by examining changes in 13C-enriched substrates, and metabolite pools with 13C and 1H nuclear magnetic resonance spectroscopy. Chapter three provides evidence that approximately 30% of the GABA synthesized from [1,2-13C]acetate was made directly in neurons. Activation of neuronal specific SIRT1 caused an increase in the incorporation of [1,2-13C]acetate into brain, while activation of astrocytes with potassium depolarization caused a decrease in [1,2-13C]acetate incorporation. These results indicate that acetate is not a reliable marker, nor exclusively metabolised in astrocytes. Further, brain metabolism of acetate is modulated through enzyme acetylation regulated by SIRT1 deacetylase activity. Results in chapter four posit that activation of SIRT1 with SRT 1720 directly stimulated incorporation of 13C into Krebs cycle intermediates and reduced incorporation into lactate. Several off-target effects were observed for SIRT1 activator resveratrol and SIRT1 inhibitory EX-527 that questions their suitability for study of SIRT1 activity. Chapter five concludes that inhibition of SIRT deacetylase activity by AGK2 produced an effect consistent with glutamatergic AMPA receptor activation, in keeping with known SIRT2 targets. Potent SIRT2 inhibitor C64 increased 13C label incorporation into GABA from [1-13C]D-glucose in guinea pigs, and glutamine from [1,2-13C]acetate in WT mice, an effect that was also observed in SIRT2 KO mice. These results indicate that SIRT2 deacetylase activity may impact neurotransmitter systems. This thesis supports the theory that SIRT1 and SIRT2 deacetylase activity can influence brain metabolism in mammalian systems

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative

Serendipitous Geodesy from Bennu's Short-Lived Moonlets

The Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx; or OREx) spacecraft arrived at its target, near-Earth asteroid (101955) Bennu, on December 3, 2018. The OSIRIS-REx spacecraft has since collected a wealth of scientific information in order to select a suitable site for sampling. Shortly after insertion into orbit on December 31, 2018, particles were identified in starfield images taken by the navigation camera (NavCam 1). Several groups within the OSlRlS-REx team analyzed the particle data in an effort to better understand this newfound activity of Bennu and to investigate the potential sensitivity of the particles to Bennu's geophysical parameters. A number of particles were identified through automatic and manual methods in multiple images, which could be turned into short sequences of optical tracking observations. Here, we discuss the precision orbit determination (OD) effort focused on these particles at NASA GSFC, which involved members of the Independent Navigation Team (INT) in particular. The particle data are combined with other OSIRIS-REx tracking data (radiometric from OSN and optical landmark data) using the NASA GSFC GEODYN orbit determination and geodetic parameter estimation software. We present the results of our study, particularly those pertaining to the gravity field of Bennu. We describe the force modeling improvements made to GEODYN specifically for this work, e.g., with a raytracing-based modeling of solar radiation pressure. The short-lived, low-flying moonlets enable us to determine a gravity field model up to a relatively high degree and order: at least degree 6 without constraints, and up to degree 10 when applying Kaula-like regularization. We can backward- and forward-integrate the trajectory of these particles to the ejection and landing sites on Bennu. We assess the recovered field by its impact on the OSIRIS-REx trajectory reconstruction and prediction quality in the various mission phases (e.g., Orbital A, Detailed Survey, and Orbital B)

THE EFFECT OF HOUSEHOLD CHARACTERISTICS ON TOTAL AND PEAK ELECTRICITY USE IN SUMMER

We analyzed hourly electricity use data from households in southern Ontario, Canada (N=284) for which we also had survey data on some household characteristics. Dependent variables were total annual electricity use, summer use, summer use during on-peak hours defined by the local time-of-use tariff, use during the 1% of highest systemwide demand hours in summer, and the correlation between household demand and systemwide demand during summer on-peak hours. Results show, as expected, that larger houses with more occupants tend to use more electricity during all periods. However, in the very highest demand periods in the summer, ownership of a central air conditioner is the most important predictor of energy use. This suggests that utilities wishing to reduce systemwide peak usage should focus their summer demand reduction programs on houses with central air conditioners. The impending roll-out of advanced metering infrastructure in North America will facilitate this kind of analysis in many other jurisdictions in the future

Psychosocial aspects of the lived experience of long-COVID: a systematic review and thematic synthesis of qualitative studies

Background: Despite increasing recognition of long-COVID, the psychosocial impacts of the lived experience on individuals remain under-explored. This systematic review sought to fill this gap by identifying key themes that describe the psychosocial dimensions of long-COVID.Objective: To identify key themes illustrating the psychosocial aspects of individuals’ lived experience of long-COVID.Search Strategy: Searches were conducted in multiple databases and grey literature sources for qualitative studies published between November 2019 and June 2024.Inclusion Criteria: Eligible studies involved adult participants self-reporting long-COVID. The studies needed to provide qualitative data that could be synthesised thematically.Data Extraction and Synthesis: Data extraction and thematic synthesis were conducted by at least two independent reviewers at each stage. Quality appraisal was performed using the Critical Appraisal Skills Programme tool.Results: The review included 34 studies. Thematic synthesis yielded five themes: ‘Debilitation’, ‘Uncertainty’, ‘Sources of Support’, ‘Meaning Making: Adjusting to a New Normal’, and ‘Experiences with Healthcare Services’. Individuals with long-COVID reported experiencing physical, economic, and social challenges. Uncertainty and scepticism from others caused anxiety. Support from healthcare services, friends, and online groups played an important role. Acceptance and gratitude were found to be meaningful in adjusting to the new normal. Experiences with healthcare services varied.Discussion and Conclusions: This review provides valuable insights into the psychosocial impact of long-COVID, highlighting the profound changes and challenges individuals face. Healthcare services should adopt a holistic approach to integrate psychosocial support within their management strategies, to improve overall patient outcomes

Nationwide seagrass mapping using analysis-ready Sentinel-2 and PlanetScope data to support the Nationally Determined Contributions of Seychelles

There is a notable lack of spatially-explicit knowledge on seagrass meadows in many parts of the world, which hinders seagrass research, conservation, and carbon accounting efforts. With the recent introduction of the pan-tropical PlanetScope basemaps onto the Google Earth Engine (GEE) cloud platform through the Planet & Norway’s International Climate and Forests Initiative (NICFI), anyone can now freely access and process the entire pan-tropical archive of the PlanetScope between 2015 and today. In comparison to other public optical satellite archives available within GEE, like the Sentinel-2, Planet’s imagery has a shorter global revisit interval of 30.3 h, a better spatial resolution of 4.77m, but a worse spectral resolution of only the blue, green, red and near infrared bands. Despite the NICFI’s focus on terrestrial forest monitoring in the tropics, a vast pan-tropical area of optically shallow coastal waters is included in the cloud-native public archives. This paves the way for high-resolution seamless pan-tropical seagrass mapping with large time and cost efficiency. Here, we adapt our multitemporal composition approach on GEE, initially developed for Sentinel-2, to the six-year PlanetScope archive, to map the nationwide seagrass meadows in Seychelles. We compare the feasibility and performance of the PlanetScope data to Sentinel-2 in national seagrass mapping, leveraging the synergy of cloud computing, artificial intelligence, and open reference data. The development of this approach could and will provide a comprehensive blueprint seagrass mapping and monitoring system to quantify national seagrass blue carbon stocks for the Nationally Determined Contributions, both within and beyond Seychelles

Quantifying the relative intensity of free-living physical activity: differences across age, association with mortality and clinical interpretation—an observational study

Objectives: To describe age-related differences in the absolute and relative intensity of physical activity (PA) and associations with mortality. Methods: UK Biobank participants with accelerometer-assessed PA (mg) and fitness data (N=11 463; age: 43–76 years) were included. The intensity distribution of PA was expressed in absolute and relative terms. The outcome was mortality. Results: PA volume (average acceleration) and absolute intensity were lower with increasing age (~−0.03 to −0.04 SD of mean value across all ages per year; p<0.001) but differences in relative intensity by age were markedly smaller in women (−0.003 SD; p<0.184) and men (−0.012 SD; p<0.001). Absolute intensity was higher in men, but relative intensity higher in women (p<0.001). Over a median (IQR) follow-up of 8.1 (7.5–8.6) years, 121 (2.4 per 1000-person-years) deaths occurred in women and 203 (5.0 per 1000-person-years) in men. Lower risk of mortality was observed for increasing absolute or relative intensity in women, but for absolute intensity only in men. In men, the lowest risk (HR 0.62, 95% CI 0.43, 0.91) was observed in those with high absolute intensity (80th centile), but low relative intensity (20th centile). Conversely, in women, the lowest risk was associated with high levels (80th centile) of both absolute and relative intensity (HR 0.59, 95% CI 0.41, 0.86). Conclusion: Absolute PA intensity dropped with age, while relative intensity was fairly stable. Associations between PA intensity and mortality suggest that prescribing intensity in absolute terms appears appropriate for men, while either absolute or relative terms may be appropriate for women