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Characterizing the structure and composition of clay minerals on the surface of Mars is important for reconstructing past aqueous processes and environments. Data from the CheMin X-ray diffraction (XRD) instrument on the Mars Science Laboratory Curiosity rover demonstrate a ubiquitous presence of collapsed smectite (basal spacing of 10 Å) in ~3.6-billion-year-old lacustrine mudstone in Gale crater, except for expanded smectite (basal spacing of 13.5 Å) at the base of the stratigraphic section in a location called Yellowknife Bay. Hypotheses to explain expanded smectite include partial chloritization by Mg(OH)2 or solvation-shell H2O molecules associated with interlayer Mg2+. The objective of this work is to test these hypotheses by measuring partially chloritized and Mg-saturated smectite using laboratory instruments that are analogous to those on Mars rovers and orbiters. This work presents Mars-analog XRD, evolved gas analysis (EGA), and visible/shortwave-infrared (VSWIR) data from three smectite standards that were Mg-saturated and partially and fully chloritized with Mg(OH)2. Laboratory data are compared with XRD and EGA data collected from Yellowknife Bay by the Curiosity rover to examine whether the expanded smectite can be explained by partial chloritization and what this implies about the diagenetic history of Gale crater. Spectral signatures of partial chloritization by hydroxy-Mg are investigated that may allow the identification of partially chloritized smectite in Martian VSWIR reflectance spectra collected from orbit or in situ by the SuperCam instrument suite on the Mars 2020 Perseverance rover. Laboratory XRD and EGA data of partially chloritized saponite are consistent with data collected from Curiosity. The presence of partially chloritized (with Mg(OH)2) saponite in Gale crater suggests brief interactions between diagenetic alkaline Mg2+-bearing fluids and some of the mudstone exposed at Yellowknife Bay, but not in other parts of the stratigraphic section. The location of Yellowknife Bay at the base of the stratigraphic section may explain the presence of alkaline Mg2+-bearing fluids here but not in other areas of Gale crater investigated by Curiosity. Early diagenetic fluids may have had a sufficiently long residence time in a closed system to equilibrate with basaltic minerals, creating an elevated pH, whereas diagenetic environments higher in the section may have been in an open system, therefore preventing fluid pH from becoming alkaline.
Developing integrated mental health services focused on the needs of children and young people is a key policy goal in England. The THRIVE Framework and its implementation programme, i-THRIVE, are widely used in England. This study examines experiences of staff using i-THRIVE, estimates its effectiveness, and assesses how local system working relationships influence programme success.
Methods
This evaluation uses a quasi-experimental design (10 implementation and 10 comparison sites.) Measurements included staff surveys and assessment of ‘THRIVE-like’ features of each site. Additional site-level characteristics were collected from health system reports. The effect of i-THRIVE was evaluated using a four-group propensity-score-weighted difference-in-differences model; the moderating effect of system working relationships was evaluated with a difference-in-difference-in-differences model.
Results
Implementation site staff were more likely to report using THRIVE and more knowledgeable of THRIVE principles than comparison site staff. The mean improvement of fidelity scores among i-THRIVE sites was 16.7, and 8.8 among comparison sites; the weighted model did not find a statistically significant difference. However, results show that strong working relationships in the local system significantly enhance the effectiveness of i-THRIVE. Sites with highly effective working relationships showed a notable improvement in ‘THRIVE-like’ features, with an average increase of 16.41 points (95% confidence interval: 1.69–31.13, P-value: 0.031) over comparison sites. Sites with ineffective working relationships did not benefit from i-THRIVE (−2.76, 95% confidence interval: − 18.25–12.73, P-value: 0.708).
Conclusions
The findings underscore the importance of working relationship effectiveness in the successful adoption and implementation of multi-agency health policies like i-THRIVE.
Using two counter-propagating ultra-intense laser interactions with a solid target, we conducted a study on the generation of electron-positron pairs via the multi-photon Breit–Wheeler (BW) process and trident process. These processes were simulated using the particle-in-cell (PIC) code EPOCH. Our proposed scheme involves irradiating two targets with two counter-propagating lasers. High-energy photons are produced when hot electrons collide with the reflected laser pulse at the target's front, leading to electron and positron pair production. In the single-target scenario, electron bunches are extracted from the target by the p-polarized laser electromagnetic field and accelerated by the laser ponderomotive force before colliding with the counter-propagating laser. However, using two targets enhances pair creation compared with the single-target set-up. We observed that in two-target configurations, the increased number of high-energy gamma-rays contributes to higher-energy electron–positron generation. Additionally, the generation of hot electrons is also more pronounced in this scheme. Consequently, the laser demonstrates higher efficiency in generating gamma photons and positrons in the dual-target set-up, which is beneficial for investigating high-energy pair production and gamma-ray emission. The generated positrons exhibit a density of the order of $10^{27}\,\text {m}^{-3}$ and can be accelerated to energies of 1.5 GeV. The involvement of hot electrons in the target is crucial for generating high-energy photons and positrons. The maximum pair yield reaches $8 \times 10^9$ for the BW process and $10^8$ for the trident process. Notably, the total laser energy conversion efficiencies to electrons, $\gamma$-rays and positrons show improvement in the dual-target configuration. Specifically, the laser energy absorbed by positrons increases from 11.62 % in Case A to 13.12 % in Case B. These enhancements in conversion efficiency and electron/positron density have significant practical implications in experimental set-ups. In both the BW and trident processes, the two-target set-up dominates, highlighting its effectiveness. We also compared the strengths of both approaches, suggesting that these simple models of implementing two targets can be used in experiments as well.
Objectives: Loneliness is a modifiable risk factor for depression and dementia in older age. Validated interventions are needed to mitigate the impact of loneliness in older adults. Some evidence suggests that mindfulness meditation may reduce stress, improve mood and cognitive function, and may also impact loneliness per se. Many meditation apps offer an accessible way to meditate at home. However, robust research is needed to assess the benefits of meditation using this technology for older adults. Muse is a meditation app that analyzes brain signals during meditation and provides users with real-time neurofeedback on their level offocus.
Methods: We conducted a pilot, randomized controlled trial to establish the acceptability and feasibility of a remote, mindfulness intervention using Muse in older adults, and to obtain preliminary data on its impact on mood and cognition. Twenty-six adults reporting feeling lonely were enrolled and randomized to an 8-week Muse- based meditation (MM) or a brain- training active control (BT) program. The MM group completed meditation sessions with real- time neurofeedback and guided meditation sessions using Muse. The BT group completed cognitively challenging games on the commercially available Peak app and listened to podcasts. The groups were matched on the amount of interactions with study staff and total program duration. Outcome measures included standardized self-report scales of loneliness, stress, depression, well-being, quality of life, sleep disturbance, resilience, and mindfulness. Staff blinded to program assignment administered cognitive tasks of episodic memory, working memory, and sustained attention, as well as a breath counting task. Assessments were taken at Pre, Mid, and Post intervention, and after a 2-month and 4-month (4M) follow-upperiod.
Results: Participants found both programs engaging and the remote assessments were feasible. The MM group showed a greater improvement in depressive symptoms, and psychological andphysical QOL, compared to the BT group, at Post and at 4M.
Conclusions: A Muse-based mindfulness program is an acceptable and accessible intervention for older adults. A large-scale randomized trial is warranted to evaluate the efficacy of this intervention in this group.
Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one’s living arrangement is linked to BH and CR among unmarried adults.
Method:
Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.
Results:
Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.
Conclusions:
Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.
Edited by
Laurie J. Mckenzie, University of Texas MD Anderson Cancer Center, Houston,Denise R. Nebgen, University of Texas MD Anderson Cancer Center, Houston
Improvements in multimodality treatment of anal and colorectal cancer has led to increased numbers of women survivors who experience gynecologic problems in long-term survivorship. The etiology of gynecologic problems after anal and colorectal cancer treatment is complex and multifactorial. Pelvic radiation, surgery and chemotherapy can all cause anatomic, hormonal and psychological changes. Consideration of preventative measures can ideally reduce the risk of vaginal stenosis, dyspareunia, sexual dysfunction, infertility, premature menopause and pelvic pain after therapy. Proactive screening and appropriate treatment of cancer therapy late effects can improve patients’ quality of life during survivorship.
A set of 68 simple sequence repeat (SSR) markers were selected from existing databases (including Medicago, soybean, cowpea and peanut) for the purpose of exploiting the transferability of SSRs across species and/or genera within the legume family. Primers were tested for cross-species and cross-genus fragment amplification with an array of 24 different legume accessions. Nearly one-third (30.78%) of the SSR primers screened generated reproducible and cross-genus amplicons. One hundred and seventeen cross-species polymorphic amplicons were identified and could be used as DNA markers. These polymorphic markers are now being used for characterization and evaluation of our collected and donated legume germ- plasm. The transferability of SSRs, mis-/multiple-primings, homologous/heterologous amplifications, single/multiple-amplicons and application of these amplicons as DNA markers are discussed. The transfer of SSR markers across species or across genera can be a very efficient approach for DNA marker development, especially for minor crops.
Passive oxygenation with non-rebreather face mask (NRFM) has been used during cardiac arrest as an alternative to positive pressure ventilation (PPV) with bag-valve-mask (BVM) to minimize chest compression disruptions. A dual-channel pharyngeal oxygen delivery device (PODD) was created to open obstructed upper airways and provide oxygen at the glottic opening. It was hypothesized for this study that the PODD can deliver oxygen as efficiently as BVM or NRFM and oropharyngeal airway (OPA) in a cardiopulmonary resuscitation (CPR) manikin model.
Methods:
Oxygen concentration was measured in test lungs within a resuscitation manikin. These lungs were modified to mimic physiologic volumes, expansion, collapse, and recoil. Automated compressions were administered. Five trials were performed for each of five arms: (1) CPR with 30:2 compression-to-ventilation ratio using BVM with 15 liters per minute (LPM) oxygen; continuous compressions with passive oxygenation using (2) NRFM and OPA with 15 LPM oxygen, (3) PODD with 10 LPM oxygen, (4) PODD with 15 LPM oxygen; and (5) control arm with compressions only.
Results:
Mean peak oxygen concentrations were: (1) 30:2 CPR with BVM 49.3% (SD = 2.6%); (2) NRFM 47.7% (SD = 0.2%); (3) PODD with 10 LPM oxygen 52.3% (SD = 0.4%); (4) PODD with 15 LPM oxygen 62.7% (SD = 0.3%); and (5) control 21% (SD = 0%). Oxygen concentrations rose rapidly and remained steady with passive oxygenation, unlike 30:2 CPR with BVM, which rose after each ventilation and decreased until the next ventilation cycle (sawtooth pattern, mean concentration 40% [SD = 3%]).
Conclusions:
Continuous compressions and passive oxygenation with the PODD resulted in higher lung oxygen concentrations than NRFM and BVM while minimizing CPR interruptions in a manikin model.
Despite advances in incorporating diversity and structural competency into medical education curriculum, there is limited curriculum for public health research professionals. We developed and implemented a four-part diversity, equity, and inclusion (DEI) training series tailored for academic health research professionals to increase foundational knowledge of core diversity concepts and improve skills.
Methods:
We analyzed close- and open-ended attendee survey data to evaluate within- and between-session changes in DEI knowledge and perceived skills.
Results:
Over the four sessions, workshop attendance ranged from 45 to 82 attendees from our 250-person academic department and represented a mix of staff (64%), faculty (25%), and trainees (11%). Most identified as female (74%), 28% as a member of an underrepresented racial and ethnic minority (URM) group, and 17% as LGBTQI. During all four sessions, attendees increased their level of DEI knowledge, and within sessions two through four, attendees’ perception of DEI skills increased. We observed increased situational DEI awareness as higher proportions of attendees noted disparities in mentoring and opportunities for advancement/promotion. An increase in a perceived lack of DEI in the workplace as a problem was observed; but only statistically significant among URM attendees.
Discussion:
Developing applied curricula yielded measurable improvements in knowledge and skills for a diverse health research department of faculty, staff, and students. Nesting this training within a more extensive program of departmental activities to improve climate and address systematic exclusion likely contributed to the series’ success. Additional research is underway to understand the series’ longer-term impact on applying skills for behavior change.
We investigate the production of intense ү-rays following the interaction of ultraintense laser pulse with a hybrid combination of under-dense plasma associated with a thin foil of fully ionized Al or Cu or Au at the rear side. Relativistic electrons are accelerated following the interaction of high intensity laser pulses with an under-dense plasma. These electrons are then stopped by the thin foils attached to the rear side of the under-dense plasma. This results in the production of intense-ray bursts. So, the enhancement of photon generation is due to the under-dense plasma electrons interacting with different over-dense plasma. Using open-source PIC code EPOCH, we study the effect of different electron densities in the under-plasma on photon emission. Photon emission enhancement is observed by increasing the target Z in the hybrid structure. Hybrid structure can enhance photon emission; it can increase the photon energy and yield and improve photon beam divergence. Simulations were also performed to find the optimal under-dense plasma density for ү-ray production.
Greater maternal depressive symptoms are consistently associated with higher levels of behavioral difficulties in children, emerging in early childhood and with long-lasting consequences for children’s development. Interventions promoting early relational health have been shown to have benefits for children’s behavior; however, these impacts are not always realized in the context of maternal depression. This study examined whether tiered programs could address this limitation by focusing on both parenting, through universal primary prevention, and psychosocial stressors and parent mental health, through tailored secondary prevention. Analysis of a randomized controlled trial (RCT) of the Smart Beginnings (SB) intervention was conducted to determine whether SB attenuated the association between maternal depression and early childhood internalizing and externalizing behaviors. Maternal depression significantly predicted both internalizing and externalizing behaviors in linear regression models. Further, there was a significant interaction between maternal depression and treatment group, such that among mothers with higher depressive symptoms, the SB treatment attenuated the magnitude of the association between depression and child behavior. Findings suggest that while parenting support is important for all families, it may be particularly critical for those with higher levels of depression and underscores the need to consider multidimensional family processes in both research and clinical practice.
Adverse childhood experiences (ACEs) may be a risk factor for later-life cognitive disorders such as dementia; however, few studies have investigated underlying mechanisms, such as cardiovascular health and depressive symptoms, in a health disparities framework.
Method:
418 community-dwelling adults (50% nonHispanic Black, 50% nonHispanic White) aged 55+ from the Michigan Cognitive Aging Project retrospectively reported on nine ACEs. Baseline global cognition was a z-score composite of five factor scores from a comprehensive neuropsychological battery. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Cardiovascular health was operationalized through systolic blood pressure. A mediation model controlling for sociodemographics, childhood health, and childhood socioeconomic status estimated indirect effects of ACEs on global cognition via depressive symptoms and blood pressure. Racial differences were probed via t-tests and stratified models.
Results:
A negative indirect effect of ACEs on cognition was observed through depressive symptoms [β = −.040, 95% CI (−.067, −.017)], but not blood pressure, for the whole sample. Black participants reported more ACEs (Cohen’s d = .21), reported more depressive symptoms (Cohen’s d = .35), higher blood pressure (Cohen’s d = .41), and lower cognitive scores (Cohen’s d = 1.35) compared to White participants. In stratified models, there was a negative indirect effect through depressive symptoms for Black participants [β = −.074, 95% CI (−.128, −.029)] but not for White participants.
Conclusions:
These results highlight the need to consider racially patterned contextual factors across the life course. Such factors could exacerbate the negative impact of ACEs and related mental health consequences and contribute to racial disparities in cognitive aging.
Laboratory primates are often housed in same-sex pairs to avoid single-housing and when breeding is to be prevented. However, pair formation is not without risks, as fights and injuries may occur. No data are available on pair formation in female common marmosets (Callithrix jacchus), a species used extensively in laboratories. Therefore, this study focuses on the pairing of unfamiliar common marmoset females, aiming to assess its success rate and whether age can predict the result. Data on the study animals and success of the pairings were extracted from laboratory back-records: a total of 28 pairings was obtained. In addition, behavioural data were collected on six of the 28 pairs. Almost 80% of pairs were compatible beyond one week, and most of the fights occurred well within the first week after pair formation. Pairs in which one of the females was sexually immature (ie < 15 months) were significantly more compatible than pairs in which both females were post-pubertal. First encounters were characterised by sniffing of the unfamiliar monkey. Aggressive behaviours occurred frequently following pair formation but they were unidirectional, and in only two pairs was veterinary treatment required. This study shows that pairing of unfamiliar common marmoset females is a safe practice if one monkey is sexually immature, a result that supports observations of both group and pair formation in other primate species. However, given the potentially detrimental effects of removing young females from their natal groups, we argue that it is preferable to remove two sisters from their natal group when female pairs are required. However, when a single sexually mature female requires a pair mate so as to avoid single-housing and no mature sibling is available, an older, but still sexually immature, unfamiliar female that has had a normal development within the family should be considered as a pair mate.
Educational attainment is a well-documented predictor of later-life cognition, but less is known about upstream contextual factors. This study aimed to identify which early-life contextual factors uniquely predict later-life global cognition and whether educational attainment mediates these relationships.
Method:
Participants were drawn from the Michigan Cognitive Aging Project (N = 485; Mage = 63.51; SDage = 3.13; 50% non-Hispanic Black). Early-life exposures included U.S. region of elementary school (Midwest, South, Northeast), average parental education, household composition (number of adults (1, 2, 3+), number of children), school racial demographics (predominantly White, predominantly Black, diverse), self-reported educational quality, and school type (public/private). Later-life global cognition was operationalized with a factor score derived from a comprehensive neuropsychological battery. Sequential mediation models controlling for sociodemographics estimated total, direct, and indirect effects of early-life contextual factors on cognition through educational attainment (years).
Results:
Higher educational quality, higher parental education, and attending a private school were each associated with better cognition; attending a predominantly Black or diverse school and reporting three or more adults in the household were associated with lower cognition. After accounting for educational attainment, associations remained for educational quality, school type, and reporting three or more adults in the household. Indirect effects through educational attainment were observed for school region, educational quality, school racial demographics, and parental education.
Conclusions:
School factors appear to consistently predict later-life cognition more than household factors, highlighting the potential long-term benefits of school-level interventions for cognitive aging. Future research should consider additional mediators beyond educational attainment such as neighborhood resources and childhood adversity.
There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS.
Objectives
This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS.
Methods
Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.
Results
We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS.
Conclusions
Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance.
Disclosure
DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp
Motivational processes underlie behaviors that enrich the human experience, and impairments in motivation are commonly observed in psychiatric illness. While motivated behavior is often examined with respect to extrinsic reinforcers, not all actions are driven by reactions to external stimuli; some are driven by ‘intrinsic’ motivation. Intrinsically motivated behaviors are computationally similar to extrinsically motivated behaviors, in that they strive to maximize reward value and minimize punishment. However, our understanding of the neurocognitive mechanisms that underlie intrinsically motivated behavior remains limited. Dysfunction in intrinsic motivation represents an important trans-diagnostic facet of psychiatric symptomology, but due to a lack of clear consensus, the contribution of intrinsic motivation to psychopathology remains poorly understood. This review aims to provide an overview of the conceptualization, measurement, and neurobiology of intrinsic motivation, providing a framework for understanding its potential contributions to psychopathology and its treatment. Distinctions between intrinsic and extrinsic motivation are discussed, including divergence in the types of associated rewards or outcomes that drive behavioral action and choice. A useful framework for understanding intrinsic motivation, and thus separating it from extrinsic motivation, is developed and suggestions for optimization of paradigms to measure intrinsic motivation are proposed.
OBJECTIVES/GOALS: Whole-genome viral sequencing is vital to inform public health and study evolution. Arboviruses evolve in vectors, reservoir hosts, and humans, and require surveillance at all points. We developed a new rigorous method of sequencing that captures whole viral genomes in field-collected and clinical samples. METHODS/STUDY POPULATION: ClickSeq is a novel method of Next Generation Sequencing (NGS) library synthesis using azido-nucleotides to terminate reverse transcription. The cDNA generated can be ligated to sequencing and indexing primers at room temperature using copper (Cu I) and vitamin C. With this approach, we designed primers located ~250 bp apart along the genomes of the arboviruses Chikungunya 37797, Zika Dakar, Yellow Fever Asibi, Dengue serotype 2, West Nile 385-99, and St. Louis Encephalitis Virus (SLEV) clade II. We tested this method with varying viral titers: lab-infected mosquito pools, field-collected mosquito pools from a Texas West Nile and SLEV outbreak, and patient isolates from a Pakistani CHIKV outbreak. The cDNA was sequenced in the UTMB NGS Core and aligned using bowtie. RESULTS/ANTICIPATED RESULTS: The use of a single protocol to capture whole viral genomes including UTRs for multiple viruses from different sample collection styles is ideal for arboviruses. Primers for multiple viruses were pooled and used to sequence mosquito pools. The Tiled ClickSeq method captured whole viral genomes without the need for host depletion. UTRs were captured even when the viral strain used for primer design differed from the resulting strain. Discreet variants were captured in both the hypervariable nsP3 region and the UTR in the patient isolates from the CHIKV outbreak compared to the 2017 outbreak. Texas WNV and SLEV outbreaks are now defined from the 2020 outbreak and can be further tracked to update public health measures and understand viral evolution. DISCUSSION/SIGNIFICANCE: UTRs impact both human and mosquito fitness, leading to further outbreaks. Tiled ClickSeq aims to capture whole viral genomes with a method and cost that can be implemented by public health researchers to understand disease evolution as it happens to update both public health and basic virology to the effects of evolution on arboviruses.