Background. The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this ...association. Methods. Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time. Results. There were 305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278 seconds. Compared with women with sleep efficiency ≥70%, those with <70% had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio MOR = 1.61; 95% confidence interval CI, 1.20–2.16; Trails B > 278 MOR = 1.96; 95% CI, 1.43–2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13–1.33; Trails B > 278 MOR = 1.13; 95% CI, 1.04–1.24), as was higher WASO (per half hour: MMSE < 26 MOR = 1.15; 95% CI, 1.06–1.23; Trails B > 278 MOR = 1.24; 95% CI, 1.15–1.34). Women who napped ≥2 hours per day had a higher risk (MMSE < 26 MOR = 1.42; 95% CI, 1.05–1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26–2.40). There was no significant relationship for total sleep time. Conclusion. Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.
Context.
Following a multi-year minimum of solar activity, a solar energetic particle event on 2020 Nov. 29 was observed by multiple spacecraft covering a wide range of solar longitudes including ...ACE, the Solar Terrestrial Relations Observatory-A, and the recently launched Parker Solar Probe and Solar Orbiter.
Aims.
Multi-point observations of a solar particle event, combined with remote-sensing imaging of flaring, shocks, and coronal mass ejections allows for a global picture of the event to be synthesized, and made available to the modeling community to test, constrain, and refine models of particle acceleration and transport according to such parameters as shock geometries and particle mass-to-charge ratios.
Methods.
Detailed measurements of heavy ion intensities, time dependence, fluences, and spectral slopes provided the required test data for this study.
Results.
The heavy ion abundances, timing, and spectral forms for this event fall well within the range found in prior surveys at 1 au. The spectra were well fitted by broken power law shapes; the Fe/O ratio was somewhat lower than the average of other events. In addition,
3
He/
4
He was very low, with only the upper limits established here.
Radioactivity induced by cosmic muon spallation is a dominant source of backgrounds for O ( 10 MeV ) neutrino interactions in water Cherenkov detectors. In particular, it is crucial to reduce ...backgrounds to measure the solar neutrino spectrum and find neutrino interactions from distant supernovae. In this paper we introduce new techniques to locate muon-induced hadronic showers and efficiently reject spallation backgrounds. Applying these techniques to the solar neutrino analysis with an exposure of 2790 × 22.5 kton · day increases the signal efficiency by 12.6%, approximately corresponding to an additional year of detector running. Furthermore, we present the first spallation simulation at Super-Kamiokande, where we model hadronic interactions using . The agreement between the isotope yields and shower pattern in this simulation and in the data gives confidence in the accuracy of this simulation, and thus opens the door to use it to optimize muon spallation removal in new data with gadolinium-enhanced neutron capture detection. Published by the American Physical Society 2024
Inflammatory cytokines such as tumor necrosis factor (TNF) have been implicated in the pathogenesis of psoriasis. We evaluated the safety and efficacy of etanercept, a TNF antagonist, for the ...treatment of plaque psoriasis.
In this 24-week, double-blind study, 672 patients underwent randomization and 652 either received placebo or received etanercept subcutaneously at a low dose (25 mg once weekly), a medium dose (25 mg twice weekly), or a high dose (50 mg twice weekly). After 12 weeks, patients in the placebo group began twice-weekly treatment with 25 mg of etanercept. The primary measure of clinical response was the psoriasis area-and-severity index.
At week 12, there was an improvement from base line of 75 percent or more in the psoriasis area-and-severity index in 4 percent of the patients in the placebo group, as compared with 14 percent of those in the low-dose--etanercept group, 34 percent in the medium-dose--etanercept group, and 49 percent in the high-dose-etanercept group (P<0.001 for all three comparisons with the placebo group). The clinical responses continued to improve with longer treatment. At week 24, there was at least a 75 percent improvement in the psoriasis area-and-severity index in 25 percent of the patients in the low-dose group, 44 percent of those in the medium-dose group, and 59 percent in the high-dose group. The responses as measured by improvements in the psoriasis area-and-severity index were paralleled by improvements in global assessments by physicians and the patients and in quality-of-life measures. Etanercept was generally well tolerated.
The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks.
Background. Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the ...era of highly active antiretroviral therapy. Methods. Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates. Results. Among the 635 patients, total annual expenditures for patients with CD4+ cell counts <50 cells/µL ($36,533 per patient) were 2.6-times greater than total annual expenditures for patients with CD4+ cell counts ⩾350 cells/µL ($13,885 per patient), primarily because of increased expenditures for nonantiretroviral medication and hospitalization. Expenditures for highly active antiretroviral therapy were relatively constant at ∼$10,500 per patient per year across CD4+ cell count strata. Outpatient expenditures were $1558 per patient per year; however, the clinic and physician component of these expenditures represented only $359 per patient per year, or 2% of annual expenses. Health care expenditures for patients with HIV infection increased substantially for those with more-advanced disease and were driven predominantly by medication costs (which accounted for 71%–84% of annual expenses). Conclusions. Physician reimbursements, even with 100% billing and collections, are inadequate to support the activities of most clinics providing HIV care. These findings have important implications for the continued support of HIV treatment programs in the United States.
Microalgae are commonly used in ecotoxicity testing due to their ease of culturing and rapid cell division rates. These tests generally utilise a single species of algae; however, microalgae occur in ...the environment as complex communities of multiple species. To date, routine multispecies toxicity tests using tropical microalgae have not been available. This study investigated four tropical freshwater microalgal species for use in a chronic multispecies toxicity test based on the population growth (cell division) rate: Pediastrum duplex, Monoraphidium arcuatum, Nannochloropsis-like sp. and Chlorella sp. 12. Flow cytometric analysis identified the different fluorescence and light scattering properties of each algal species and quantified each species within multispecies mixtures. Following optimisation of test media nutrients and pH, a toxicity testing protocol was developed with P. duplex, M. arcuatum and Nannochloropsis-like sp. There were no significant differences in growth rates of each alga when tested over 72 h as single species or in multispecies mixtures. Atrazine and imazapic, two herbicides with different modes of action, were used to assess the sensitivity of the multispecies toxicity test. Atrazine was toxic to all species with 72-h IC10 values of 7.2, 63 and 280 μg/L for P. duplex, M. arcuatum and Nannochloropsis-like sp. respectively, while imazapic was not toxic to any species at concentrations up to 1100 μg/L. The toxicity of atrazine and imazapic to each microalgal species in the multispecies toxicity test was the same as that determined from single-species toxicity tests indicating that the presence of these microalgae in a mixture did not affect the toxicity of these two herbicides. This study is the first to develop a multispecies tropical microalgal toxicity test for application in freshwaters. This time- and cost-effective tool can be utilised to generate data to assist environmental decision making and to undertake risk assessments of contaminants in tropical freshwater environments.
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•Multispecies toxicity test developed using three tropical freshwater microalgae.•No differences in growth rate for each species in single or multispecies tests.•Flow cytometric analysis used to identify and quantify individual species.•Toxicity of atrazine and imazapic were assessed for each species simultaneously.•Time and cost effective tool for assessing risk of contaminants in freshwater.
This study developed a novel multispecies microalgal toxicity test for application in assessing environmental risk of contaminants in tropical freshwater systems.
Nanoparticle-drug conjugates enhance drug delivery to tumors. Gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. CRLX101 is a novel nanoparticle–drug ...conjugate containing camptothecin, a potent inhibitor of topoisomerase I and the hypoxia-inducible factors 1α and 2α. In a phase Ib/2 trial, CRLX101+bevacizumab was well tolerated with encouraging activity in metastatic renal cell carcinoma (mRCC). We conducted a randomized phase II trial comparing CRLX101+bevacizumab versus standard of care (SOC) in refractory mRCC.
Patients with mRCC and 2–3 prior lines of therapy were randomized 1:1 to CRLX101+bevacizumab versus SOC, defined as investigator’s choice of any approved regimen not previously received. The primary end point was progression-free survival (PFS) by blinded independent radiological review in patients with clear cell mRCC. Secondary end points included overall survival, objective response rate and safety.
In total, 111 patients were randomized and received≥1 dose of drug (CRLX101+bevacizumab, 55; SOC, 56). Within the SOC arm, patients received single-agent bevacizumab (19), axitinib (18), everolimus (7), pazopanib (4), sorafenib (4), sunitinib (2), or temsirolimus (2). In the clear cell population, the median PFS on the CRLX101+bevacizumab and SOC arms was 3.7months (95% confidence interval, 2.0–4.3) and 3.9months (95% confidence interval 2.2–5.4), respectively (stratified log-rank P=0.831). The objective response rate by IRR was 5% with CRLX101+bevacizumab versus 14% with SOC (Mantel–Haenszel test, P=0.836). Consistent with previous studies, the CRLX101+bevacizumab combination was generally well tolerated, and no new safety signal was identified.
Despite promising efficacy data on the earlier phase Ib/2 trial of mRCC, this randomized trial did not demonstrate improvement in PFS for the CRLX101+bevacizumab combination when compared with approved agents in patients with heavily pretreated clear cell mRCC. Further development in this disease is not planned.
NCT02187302 (NIH).
Welding fumes were reclassified as a Group 1 carcinogen by the International Agency for Research on Cancer in 2017. Gas metal arc welding (GMAW) is a process widely used in industry. Fume generated ...from GMAW-mild steel (MS) is abundant in iron with some manganese, while GMAW-stainless steel (SS) fume also contains significant amounts of chromium and nickel, known carcinogenic metals. It has been shown that exposure to GMAW-SS fume in A/J mice promotes lung tumors. The objective was to determine if GMAW-MS fume, which lacks known carcinogenic metals, also promotes lung tumors in mice. Male A/J mice received a single intraperitoneal injection of corn oil or the initiator 3-methylcholanthrene (MCA; 10 μg/g) and, one week later, were exposed by whole-body inhalation to GMAW-MS aerosols for 4 hours/day x 4 days/week x 8 weeks at a mean concentration of 34.5 mg/m3. Lung nodules were enumerated by gross examination at 30 weeks post-initiation. GMAW-MS fume significantly increased lung tumor multiplicity in mice initiated with MCA (21.86 ± 1.50) compared to MCA/air-exposed mice (8.34 ± 0.59). Histopathological analysis confirmed these findings and also revealed an absence of inflammation. Bronchoalveolar lavage analysis also indicated a lack of lung inflammation and toxicity after short-term inhalation exposure to GMAW-MS fume. In conclusion, this study demonstrates that inhalation of GMAW-MS fume promotes lung tumors in vivo and aligns with epidemiologic evidence that shows MS welders, despite less exposure to carcinogenic metals, are at an increased risk for lung cancer.
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