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A novel generation of potent gamma-secretase modulators: Combat Alzheimer’s disease and Down syndrome–associated Alzheimer’s disease
Full text linkReal-World Performance of Heat Recovery Chillers with Exhaust Air Coils in an All-Electric Medical Building
Full text linkHeat recovery chillers (HRCs) are systems that utilize waste heat from the condenser side for heating purposes. As an electrification strategy, they offer the potential to reduce operational carbon emissions associated with heating, while providing higher coefficient of performance (COP) than air-to-water heat pumps and a much smaller equipment footprint. However, limited research has been published on the real-world performance of HRCs in this configuration. This study investigates the performance of HRCs in a newly constructed all-electric building located in ASHRAE climate zone 3C. The building is a five-story, 182,800 ft2 (17,000 m2) outpatient surgery and medical office facility. In this facility, HRCs serve as the primary plant equipment to meet the building’s heating and cooling loads, with exhaust air coils functioning as either a heat sink or source to balance loads on the HRCs. The building entirely relies on the HRCs and exhaust air coils for all cooling capacity and has no storage (aside from buffer tanks). We analyze high-resolution measured data from the building’s central plant, including water-side loads and electrical power, across multiple seasons, focusing on how plant performance varies with outdoor air temperature, building heating and cooling load profiles, and the balance between heating and cooling loads. When thermal storage is limited, the balance between heating and cooling load becomes a more critical factor in determining system performance. When there is a mismatch between the two loads, the system either rejects or sources heat to or from the exhaust air to balance the loads on the HRCs. This balance is driven by both outdoor air conditions and building loads. Unlike true simultaneous heating and cooling loads, the exhaust air loads are not used for a purpose within the building and effectively reduce overall system efficiency. This study captures the complexity and variability of actual system performance and proposes a new metric for assessing performance in these systems. The building demonstrates the technical feasibility and high performance of using HRCs with exhaust air coils in all-electric medical buildings
Pubertal timing and tempo and anxiety symptoms, disorders and treatments in Danish adolescents: A population-based follow-up study
No full textOBJECTIVE: Earlier pubertal timing has been associated with anxiety disorders in girls. Research in boys, and for pubertal tempo in both sexes, are sparse. We aimed to investigate associations between pubertal timing, tempo and anxiety outcomes in 13,208 adolescents from the Danish National Birth Cohort (DNBC).
METHODS: Information on self-reported Tanner stages, age at menarche, first ejaculation, and voice break was collected half-yearly throughout puberty. Timing and tempo were modeled continuously and categorically (earlier/faster, average, later/slower). We investigated any anxiety disorder diagnosis from the Danish National Patient Register and self-reported social anxiety disorder (SAD) symptoms from the 18-year DNBC follow-up. Adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated using logistic regression.
RESULTS: In girls, earlier timing and faster tempo tended to be associated with a higher risk of any anxiety disorder diagnosis and self-reported SAD symptoms, whereas later timing and slower tempo appeared to be associated with a lower risk of self-reported SAD symptoms compared to average. Earlier timing of pubic hair development was associated with an OR of 1.49 (95 % CI: 1.05;2.11) for self-reported SAD symptoms, whereas later timing of breast development was associated with an OR of 0.69 (95 % CI: 0.38;1.23) for any anxiety disorder diagnosis compared to average. In boys, findings were inconsistent, with wide CIs crossing the null.
CONCLUSIONS: If earlier and faster puberty increases the risks of an anxiety disorder diagnosis and SAD symptoms, targeted interventions are warranted for girls with early/fast puberty and sub-clinical anxiety. Findings for boys need further exploration
Three dimensional stationary solutions of the Electron MHD equations
Full text linkThe goal of this paper is to construct non-trivial steady-state weak solutions of the three dimensional Electron Magnetohydrodynamics equations in the class of H s ( T 3 ) for some small s > 0 . By exploiting the formulation of the stationary EMHD equations one can treat them as generalized Navier–Stokes equations with half Laplacian. Therefore with convex integration scheme we obtained such stationary weak solutions, which is not yet realizable in the case of classical 3D Navier–Stokes equations
Safely Debriefing Unexpected Simulation Death: How We Did It
Full text linkPURPOSE: Medical students feel inadequately prepared to cope with patient death. Simulation training may provide learners with the opportunity to experience death in a safe environment with a structured debriefing.
METHODS: Nineteen fourth-year medical students who matched into surgical specialties participated in a 2-week surgical intern preparatory course. During an individual surgical decision-making simulation, 6 learners experienced unexpected patient death at the hands of a facilitator who deviated from the simulation script. Subjectively, these learners displayed high anxiety before the debriefing. Objectively, their self-reported anxiety after the structured debriefing was similar to the self-reported anxiety of learners who did not experience simulation death.
RESULTS: We formalized a bi-directional debriefing instrument using the Gather Analyze Summarize (GAS) model as a framework. We recognized that learners who experienced simulation death need to debrief on 2 aspects of the simulation: 1) Simulation death and 2) Scientific content.
CONCLUSION: Our unexpected experience with simulation death led to the development of a debriefing tool that can be used by other surgical educators. Learning how to process the ensuing emotional response to patient death in simulation may benefit trainees provided they undergo a structured debriefing
Improving the Integration of Diversity, Equity, Inclusion, and Justice Goals in Total Maximum Daily Load Model Implementation for Water Quality Management
Full text linkWater quality modeling is used globally to assess surface water impairment and manage watershed pollution in formal programs like the United States' (US) total maximum daily load and in less structured initiatives elsewhere. Despite these programs, progress toward realizing equitable water quality benefits to society is stymied through an inability to recognize, plan, and incorporate diversity, equity, inclusion, and justice (DEIJ) principles in the modeling efforts. In this paper, we describe the major barriers and limitations to the inclusion of DEIJ principles in the design and implementation of pollution load reduction programs in the US. We offer a blueprint to embrace participatory modeling approaches to engage more openly, honestly, and fairly with relevant participants (stakeholders) to achieve just and equitable water quality outcomes and upgrade water quality management principles nationwide. We provide case studies where the DEIJ principles have been applied and synthesized, showing how participatory modeling can enhance water quality management in more inclusive ways, providing specific pathways to support such a transformation in diverse communities
Which treatment do you believe you received? A randomised blinding feasibility trial of spinal manual therapy.
Full text linkBACKGROUND: Blinding is essential for mitigating biases in trials of low back pain (LBP). Our main objectives were to assess the feasibility of blinding: (1) participants randomly allocated to active or placebo spinal manual therapy (SMT), and (2) outcome assessors. We also explored blinding by levels of SMT lifetime experience and recent LBP, and factors contributing to beliefs about the assigned intervention. METHODS: A two-parallel-arm, single-centre, placebo-controlled, blinding feasibility trial. Adults were randomised to active SMT (n = 40) or placebo SMT (n = 41). Participants attended two study visits for their assigned intervention, on average seven days apart. The primary outcome was participant blinding (beliefs about assigned intervention) using the Bang blinding index (BI) at two study visits. The Bang BI is arm-specific, chance-corrected, and ranges from - 1 (all incorrect beliefs) to 1 (all correct beliefs), with 0 indicating equal proportions of correct and incorrect beliefs. Secondary outcomes included factors contributing to beliefs about the assigned intervention. RESULTS: Of 85 adults screened, 81 participants were randomised (41 [51%] with SMT lifetime experience; 29 [39%] with recent LBP), and 80 (99%) completed follow-up. At study visit 1, 50% of participants in the active SMT arm (Bang BI: 0.50 [95% confidence interval (CI), 0.26 to 0.74]) and 37% in the placebo SMT arm (0.37 [95% CI, 0.10 to 0.63]) had a correct belief about their assigned intervention, beyond chance. At study visit 2, BIs were 0.36 (0.08 to 0.64) and 0.29 (0.01 to 0.57) for participants in the active and placebo SMT arms, respectively. BIs among outcome assessors suggested adequate blinding at both study visits (active SMT: 0.08 [- 0.05 to 0.20] and 0.03 [- 0.11 to 0.16]; placebo SMT: - 0.12 [- 0.24 to 0.00] and - 0.07 [- 0.21 to 0.07]). BIs varied by participant levels of SMT lifetime experience and recent LBP. Participants and outcome assessors described different factors contributing to their beliefs. CONCLUSIONS: Adequate blinding of participants assigned to active SMT may not be feasible with the intervention protocol studied, whereas blinding of participants in the placebo SMT arm may be feasible. Blinding of outcome assessors seemed adequate. Further methodological work on blinding of SMT is needed. TRIAL REGISTRATION NUMBER: NCT05778396
Racial/ethnic differences in the associations between social support and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA)
Full text linkBackgroundDespite the established link between social support and cardiovascular disease (CVD) outcomes, few studies have examined racial/ethnic variation in these associations. This study utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA) to investigate racial/ethnic differences in perceived social support and in the link between support and incident hard CVD events and mortality.MethodParticipants (N = 6,814) were 45–84 years of age who identified as White, Black, Hispanic/Latino, or Chinese without known clinical CVD at baseline (2000–2002). Racial/ethnic differences in perceived support (overall, emotional, informational, and instrumental) were tested using multiple regression with adjustments for demographic, socioeconomic, lifestyle/psychosocial, and clinical risk factors, and immigration history. Racial/ethnic differences in the association between perceived support and incident CVD events or mortality were tested using Cox proportional hazards models with progressive adjustments for the same covariates.ResultsAt baseline, the mean age was 62.15 years (SD = 10.23); 38.5% identified as White, 27.8% as Black, 22.0% as Hispanic/Latino, and 11.8% as Chinese. Black and Hispanic/Latino participants reported higher levels of overall support, emotional support, and informational support than White participants (p’s < 0.05). Chinese participants reported less informational support (p = .010) than White participants. Higher informational support was associated with decreased risk for hard CVD events. This association did not differ by race/ethnic group.ConclusionDespite racial/ethnic differences in perceptions of support, perceived informational support was protective against CVD for participants of all racial/ethnic backgrounds
Improving the solubility of pseudo-hydrophobic chemicals through co-crystal formulation.
Full text linkNatural products are ligands and in vitro inhibitors of Alzheimers disease (AD) tau. Dihydromyricetin (DHM) bears chemical similarity to known natural product tau inhibitors. Despite having signature polyphenolic character, DHM is ostensibly hydrophobic owing to intermolecular hydrogen bonds that shield hydrophilic phenols. Our research shows DHM becomes ionized at near-neutral pH, allowing the formulation of salts with transformed solubility. The MicroED co-crystal structure with trolamine reveals DHM salts as metastable co-crystalline solids with unlocked hydrogen bonding and a thermodynamic bent to solubilize in water. All co-crystal formulations show better inhibitory activity against AD tau than the nonsalt form, with efficacies correlating to enhanced solubilities. In vitro and in vivo pharmacokinetic measures demonstrate that DHM co-crystals display enhanced absorption and distribution with altered rates of elimination, suggesting that co-crystal formulations could be strategically used to fine-tune delivery properties. These results underscore the role of structural chemistry in guiding the selection of solubilizing agents for chemical formulation. We propose DHM co-crystals are appropriate formulations for research as dietary supplements to promote healthy aging by combating protein misfolding, although central nervous system (CNS) delivery remains a major limitation. DHM may be a suitable backbone for medicinal chemistry and possible development of pharmaceuticals with enhanced CNS exposure