229 research outputs found
Formation of Subtropical Mode Water in a high-resolution ocean simulation of the Kuroshio Extension region
Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Ocean Modelling 17 (2007): 338-356, doi:10.1016/j.ocemod.2007.03.002.A high-resolution numerical model is used to examine the formation and variability of the North Pacific Subtropical
ModeWater (STMW) over a 3-year period. The STMW distribution is found to be highly variable in both
space and time, a characteristic often unexplored because of sparse observations or the use of coarse resolution
simulations. Its distribution is highly dependent on eddies, and where it was renewed during the previous winter.
Although the potential vorticity fluxes associated with down-front winds can be of the same order of magnitude
or even greater than the diabatic ones due to air-sea temperature differences, the latter dominate the potential
vorticity budget on regional and larger scales. Air-sea fluxes, however, are dominated by a few strong wind events,
emphasizing the importance of short time scales in the formation of mode waters. In the Kuroshio Extension
region, both advection and mixing play important roles to remove the STMW from the formation region.This work was sponsored by the National Science Foundation OCE-0220161 (S.J.) and OCE-0221781/0549225 (J.M.), the Office of Naval Research (J.M., M.M.), Department of Energy/CCPP (M.M.), and the Office of Science (BER), US Department of Energy, Grant No. DE-FG02-05ER64119 (J.M.)
A whole genome screen for association with multiple sclerosis in portuguese patients
Multiple sclerosis (MS) is common in Europe affecting up to 1:500 people. In an effort to identify genes influencing susceptibility
to the disease, we have performed a population-based whole genome screen for association. In this study, 6000 microsatellite markers
were typed in separately pooled DNA samples from MS patients (n = 188) and matched controls (n = 188). Interpretable data was
obtained from 4661 of these markers. Refining analysis of the most promising markers identified 10 showing potential evidence for
association.SERONO (Portugal).Fundação para a CiĂȘncia e a Tecnologia (FCT) - grant FRH/BD/9111/2002.British Council/ICCTI.Wellcome Trust, Multiple Sclerosis Societies of the United States and Great Britain, Multiple Sclerosis International Federation - GAMES project - grant 057097
Energy dependence of Cronin momentum in saturation model for and collisions
We calculate dependence of Cronin momentum for and
collisions in saturation model. We show that this dependence is consistent with
expectation from formula which was obtained using simple dimentional
consideration. This can be used to test validity of saturation model (and
distinguish among its variants) and measure dependence of saturation
momentum from experimental data.Comment: LaTeX2e, 12 pages, 8 figure
The energy spectrum of cosmic rays beyond the turn-down around 10^17 eV as measured with the surface detector of the Pierre Auger Observatory
We present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays
The Physics of Star Cluster Formation and Evolution
© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe
Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women
Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. Results: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. Conclusions: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure
Clinical standards for the diagnosis and management of asthma in low- and middle-income countries
BACKGROUND : The aim of these clinical standards is
to aid the diagnosis and management of asthma in lowresource
settings in low- and middle-income countries
(LMICs).
METHODS : A panel of 52 experts in the field of asthma
in LMICs participated in a two-stage Delphi process to
establish and reach a consensus on the clinical standards.
RESULTS : Eighteen clinical standards were defined: Standard
1, Every individual with symptoms and signs compatible
with asthma should undergo a clinical assessment;
Standard 2, In individuals (>6 years) with a clinical assessment
supportive of a diagnosis of asthma, a hand-held spirometry
measurement should be used to confirm variable
expiratory airflow limitation by demonstrating an acute
response to a bronchodilator; Standard 3, Pre- and postbronchodilator
spirometry should be performed in individuals
(>6 years) to support diagnosis before treatment is
commenced if there is diagnostic uncertainty; Standard 4,
Individuals with an acute exacerbation of asthma and clinical
signs of hypoxaemia or increased work of breathing
should be given supplementary oxygen to maintain saturation
at 94â98%; Standard 5, Inhaled short-acting beta-2
agonists (SABAs) should be used as an emergency reliever
in individuals with asthma via an appropriate spacer
device for metered-dose inhalers; Standard 6, Short-course
oral corticosteroids should be administered in appropriate
doses to individuals having moderate to severe acute
asthma exacerbations (minimum 3â5 days); Standard 7,
Individuals having a severe asthma exacerbation should
receive emergency care, including oxygen therapy, systemic
corticosteroids, inhaled bronchodilators (e.g., salbutamol
with or without ipratropium bromide) and a single
dose of intravenous magnesium sulphate should be considered;
Standard 8, All individuals with asthma should
receive education about asthma and a personalised action
plan; Standard 9, Inhaled medications (excluding drypowder
devices) should be administered via an appropriate
spacer device in both adults and children. Children
aged 0â3 years will require the spacer to be coupled to a
face mask; Standard 10, Children aged <5 years with
asthma should receive a SABA as-needed at step 1 and an
inhaled corticosteroid (ICS) to cover periods of wheezing
due to respiratory viral infections, and SABA as-needed
and daily ICS from step 2 upwards; Standard 11, Children
aged 6â11 years with asthma should receive an ICS
taken whenever an inhaled SABA is used; Standard 12,
All adolescents aged 12â18 years and adults with asthma
should receive a combination inhaler (ICS and rapid
onset of action long-acting beta-agonist [LABA] such as
budesonide-formoterol), where available, to be used either
as-needed (for mild asthma) or as both maintenance and
reliever therapy, for moderate to severe asthma; Standard
13, Inhaled SABA alone for the management of patients
aged >12 years is not recommended as it is associated
with increased risk of morbidity and mortality. It should
only be used where there is no access to ICS.
The following standards (14â18) are for settings where
there is no access to inhaled medicines. Standard 14,
Patients without access to corticosteroids should be provided
with a single short course of emergency oral prednisolone;
Standard 15, Oral SABA for symptomatic relief
should be used only if no inhaled SABA is available.
Adjust to the individualâs lowest beneficial dose to minimise
adverse effects; Standard 16, Oral leukotriene receptor
antagonists (LTRA) can be used as a preventive
medication and is preferable to the use of long-term oral
systemic corticosteroids; Standard 17, In exceptional circumstances,
when there is a high risk of mortality from
exacerbations, low-dose oral prednisolone daily or on
alternate days may be considered on a case-by-case basis;
Standard 18. Oral theophylline should be restricted for
use in situations where it is the only bronchodilator treatment
option available.
CONCLUS ION : These first consensus-based clinical standards
for asthma management in LMICs are intended to
help clinicians provide the most effective care for people in
resource-limited settings.The Oskar-Helene-Heim Foundation (OHH; Berlin, Germany) and the Gunther Labes Foundation (Berlin, Germany).https://theunion.org/our-work/journals/ijtldam2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein
Comparative effectiveness of autologous hematopoietic stem cell transplant vs fingolimod, natalizumab, and ocrelizumab in highly active relapsing-remitting multiple sclerosis
Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).
Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.
Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.
Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab.
Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.
Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09â[0.30] vs 0.20â[0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10â[0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).
Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time
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