Tropical tropospheric responses to a sudden stratospheric warming (SSW) event that occurred over Antarctica in September 2019 have been investigated by conducting a series of ensemble forecast ...experiments. Comparative examinations between the normal forecast and the partially nudged forecast, whose stratospheric circulation is constrained to a reanalysis, reveal a significant enhancement/suppression in the convective activity (upwelling/downwelling) over the northern/southern part of the tropics. Such an acceleration of the Hadley circulation is set up by thermal structural changes in the upper troposphere and lower stratosphere. The tropical cooling caused by the enhanced Brewer‐Dobson circulation destabilizes the environment there and stimulates deep cumulus convections. In this case, the southern area of the Asian monsoon region is particularly sensitive. Although details of the triggered response depend on the adopted cumulus parameterization scheme, a boosting tendency of the convective upwelling via the SSW is robust.
Plain Language Summary
A rare Antarctic sudden stratospheric warming (SSW) event that occurred in September 2019 provides an opportunity to investigate its impact on convective activity in the tropics. By comparing the normal forecast and a “perfect stratosphere” forecast, this study confirmed the robust influence of the SSW on the cumulus convection over the Northern Hemisphere tropics. In other words, the Antarctic SSW could enhance the probability of extreme weather in boreal summer to early autumn, including the genesis and development of tropical cyclones. Therefore, this process of the teleconnection between the Antarctic stratosphere and the tropical troposphere has the potential to be a valuable source of extended‐range predictability in practical seasonal forecasts.
Key Points
Enhancement in the tropical convective activity during the 2019 Antarctic sudden warming is confirmed by ensemble nudging integrations
Enhanced Brewer‐Dobson circulation is linked to Hadley cells via thermal structure changes in the upper troposphere and lower stratosphere
For certain parameterizations, the large stratospheric effect is observed in cumulus convections at the south of the Asian monsoon zone
The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with ...hormone-receptor-positive (HR+), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.
BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR+ advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.
At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months 95% confidence interval (CI) 28.0–34.6 months compared with 26.6 months (95% CI 22.6–33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73–1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.
In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P < 0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.
NCT00863655.
Stroke impacts nearly 14 million people annually. Muscle strength and physical function are often affected by stroke and important determinants of stroke recovery. Resistance exercise training (RT) ...has been shown to improve muscle strength, but RT prescriptions may be suboptimal for other aspects of stroke recovery. Parameters such as frequency, intensity, type, and duration may influence the effectiveness of RT interventions but have not been systematically evaluated.
1) To determine the effects of RT on stroke recovery, and 2) to examine the influence of RT parameters on intervention effects.
Randomized controlled trials examining the effects of RT will be eligible for this systematic review if they: 1) included only adults with stroke or transient ischemic attack, 2) compared RT to no exercise or usual care, and 3) did not apply a co-intervention.
Eight databases (MEDLINE, EMBASE, EMCARE, AMED, PsychINFO, CINAHL, SPORTDiscus, and Web of Science) and 2 clinical trials registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) will be searched from inception. Two independent pairs of authors will compare titles, abstracts, and full-text reports against the eligibility criteria. Conflicts will be resolved by consensus or third author.
The construct of interest is stroke recovery. An advisory group of clinicians, researchers, and partners with lived experience of stroke will be consulted to determine specific outcome measures of interest, and to rank their relative importance. We expect to include measures of physical function, strength, cognition, and quality of life. Random-effects meta-analyses will be used to pool results for each outcome across studies, and RT parameters (frequency, intensity, type, and duration) will be used as covariates in meta-regression analyses.
The results of this review will inform the optimal RT prescription parameters for promoting stroke recovery.
Individuals with type 1 diabetes (T1D) experience a complex set of alterations to skeletal muscle metabolic, neuromuscular, and vascular health; collectively referred to as diabetic myopathy. While ...the full scope of diabetic myopathy is still being elucidated, evidence suggests that even when individuals with T1D are physically active, indices of myopathy still exist. As such, there is a question if adherence to current physical activity guidelines elicits improvements in skeletal muscle health indices similarly between individuals with and without T1D. The objectives of this trial are to: 1) compare baseline differences in skeletal muscle health between adults with and without T1D, 2) examine the association between participation in a home-based exercise program, detraining, and retraining, with changes in skeletal muscle health, and 3) examine the roles of age and sex on these associations.
This will be a prospective interventional trial. Younger (18-30 years) and older (45-65 years) males and females with T1D and matched individuals without T1D will engage in a four-phase, 18-week study sequentially consisting of a one-week lead-in period, 12-week exercise training program, one-week detraining period, and four-week retraining period. The exercise program will consist of aerobic and resistance exercise based on current guidelines set by Diabetes Canada. Metabolic, neuromuscular, and vascular outcome measures will be assessed four times: at baseline, post-exercise program, post-detraining, and post-retraining. Differences in baseline metrics between those with and without T1D will be examined with independent sample t-tests, and with two-way analyses of variance for age- and sex-stratified analyses. Changes across the duration of the study will be examined using mixed-model analyses.
Findings from this research will be shared locally and internationally with research participants, clinicians, diabetes educators, and patient advocacy organizations via in-person presentations, social media, and scientific fora.
NCT05740514.
The observational impacts of satellite data assimilation on extended‐range forecasts of sudden stratospheric warmings (SSWs) are investigated by conducting ensemble forecast experiments. We use two ...Japanese novel reanalysis products: the Japanese 55‐year reanalysis (JRA‐55) and its subset that assimilates conventional observations only (JRA‐55C). A comparative examination on the reproducibility for SSWs between the two ensemble forecasts reveals that the impact of satellite observations is significant for forecasts starting 5 days before the SSW onset, with 20% less accuracy in the JRA‐55C forecasts. Moreover, some of forecasts of vortex‐splitting SSWs show a sudden appearance of deep difference, which lasts over a few months in the lower stratosphere and significantly affects the surface climate. These results highlight an important role of mesospheric and upper stratospheric circulations on the onset and development of SSWs.
Plain Language Summary
Satellite observations are valuable for producing initial conditions for numerical weather prediction (NWP) systems, especially over the upper stratosphere that typical upper‐air observations cannot cover. However, many NWP models suffer from biases associated with unresolved processes. This study explores how the NWP system benefited from satellite data in forecasting the breakdown events of stratospheric polar vortexes/sudden stratospheric warmings (SSWs) by making many forecasts from typical initial conditions, both with and without satellite data. Due to unresolved bias over the upper stratosphere, some forecasts from no‐satellite initial conditions miss the onset of SSWs and subsequent anomalous tropospheric conditions. Thus, the deteriorated grasp of the upper atmosphere in the absence of satellite observations degrades the deterministic predictability of extreme stratospheric events and following downward‐propagating signals.
Key Points
Mesospheric and upper stratospheric initial conditions play an important role in forecasting the onset and development of sudden warmings
The 5‐day lead capture rate of the onset of major sudden stratospheric warmings degrades about 20% if satellite data are not assimilated
The absence of satellite observations could also affect the extended‐range forecast skill related to downward‐propagating signals
In the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane ...(EXE) in postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.
Patients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.
The safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).
Most EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.
NCT00863655.
Stroke is a highly disabling condition and is the second leading cause of death globally. Engaging in aerobic exercise is important for the prevention of a recurrent stroke through improving markers ...of cardiovascular health such as blood pressure and arterial stiffness. While higher intensities of aerobic exercise generally elicit greater cardioprotective effects, little is known about the acute cardiovascular effects of a single session of high intensity aerobic exercise in people with stroke. The objective of this study was to model the recovery of arterial stiffness (carotid-femoral pulse wave velocity, cfPWV), heart rate and blood pressure following peak intensity aerobic exercise in individuals with chronic stroke.
Ten participants with chronic stroke (mean ± SD age = 56.9 ± 11.8 years, median IQR years post-stroke = 2.9 1.9) performed a symptom-limited cardiopulmonary exercise test (CPET) on a recumbent stepper. Before the CPET, resting cfPWV, heart rate and blood pressure were measured. Immediately following the CPET, all outcomes were measured again continuously for 20 min to use all available observations (
= 245 observations) and capture any potential non-linear changes. Mixed model analyses were then applied to model post-exercise changes of cfPWV, heart rate and blood pressure.
Carotid-femoral pulse wave velocity was increased from rest following the CPET (9.0 ± 0.53 to 9.9 ± 0.52 m/s,
< 0.001) and remained elevated for 20 min into post-exercise recovery, independent of heart rate (
= 0.001). Heart rate also increased from baseline (71.2 ± 3.2 to 77.4 ± 3.1 bpm,
< 0.001) and remained elevated for 10 min post-exercise (
< 0.001). Finger systolic blood pressure was reduced from rest (117.3 ± 4.7 to 111.8 ± 4.6 mmHg,
< 0.001) and remained reduced for 15 min after exercise (
< 0.001). There were no significant differences in finger diastolic or mean arterial pressures from rest.
This was the first study to capture continuous changes in cfPWV following peak aerobic exercise in any clinical population. The present study revealed that cfPWV is elevated for 20 min after peak aerobic exercise in individuals with stroke, which was independent of heart rate. These findings suggest there may be autonomic imbalances in large arteries following peak intensity aerobic exercise in individuals with stroke.
Atmospheric gravity waves (GWs) during the February 2018 sudden stratospheric warming (SSW) event are simulated using the T639L340 whole neutral atmosphere general circulation model. Their ...characteristic morphology around the drastically evolving polar vortex is revealed by three‐dimensional (3D) visualization and ray‐tracing analyses. The 3D morphology of simulated GWs is described for the three key days that represent the pre‐SSW conditions, the mature stage for the vortex splitting, and the late SSW. The combination of strong winds along the polar vortex edge and underneath the tropospheric winds with similar wind directions consist of the deep waveguide for the upward‐propagating GWs, forming GW hot spots in the middle atmosphere. The GW hot spots associated with the development of the SSW are limited to North America and Greenland, and they include the typical upward‐propagating orographic GWs with relatively long vertical wavelengths. Different types of characteristic GW signatures are also recognized around the Canadian sub‐vortex (CV). GWs having short vertical wavelengths form near the surface and obliquely propagate over long distances along the CV winds. The non‐orographic GWs with short vertical wavelengths form in the middle stratosphere through the spontaneous adjustment of flow imbalance around the CV. Those GWs cyclonically ascend into the mesosphere along CV winds.
Plain Language Summary
Atmospheric gravity waves (GWs) have three‐dimensional (3D) phase structures and propagate three‐dimensionally from their sources. Examples include flow over mountains, convection, fronts, and dynamically imbalanced flow systems. For the first time, we simulated and visualized their 3D global morphology from the surface to an altitude of ∼100 km by focusing on the February 2018 sudden stratospheric warming event, when the stratospheric polar vortex split into two sub‐vortices. The most interesting findings in the 3D and ray‐tracing analyses are the formation of narrow GW hotspots along the south to east rim of the Canadian sub‐vortex (CV) and the cyclonical ascent of GWs around the edge of the CV.
Key Points
Gravity waves during the 2018 sudden stratospheric warming were simulated using a whole neutral atmosphere general circulation model
Three‐dimensional visualization analyses revealed their characteristic morphology around the dramatically evolving polar vortex
Paths of gravity waves near the Canadian sub‐vortex were estimated by ray tracing, highlighting long‐distance gravity wave propagation
The aim of this study was to construct a novel prediction model for the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) using immune-related gene expression data.
DNA ...microarray data were used to perform a gene expression analysis of tumor samples obtained before NAC from 117 primary breast cancer patients. The samples were randomly divided into the training (n = 58) and the internal validation (n = 59) sets that were used to construct the prediction model for pCR. The model was further validated using an external validation set consisting of 901 patients treated with NAC from six public datasets.
The training set was used to construct an immune-related 23-gene signature for NAC (IRSN-23) that is capable of classifying the patients as either genomically predicted responders (Gp-R) or non-responders (Gp-NR). IRSN-23 was first validated using an internal validation set, and the results showed that the pCR rate for Gp-R was significantly higher than that obtained for Gp-NR (38 versus 0%, P = 1.04E-04). The model was then tested using an external validation set, and this analysis showed that the pCR rate for Gp-R was also significantly higher (40 versus 11%, P = 4.98E-23). IRSN-23 predicted pCR regardless of the intrinsic subtypes (PAM50) and chemotherapeutic regimens, and a multivariate analysis showed that IRSN-23 was the most important predictor of pCR (odds ratio = 4.6; 95% confidence interval = 2.7–7.7; P = 8.25E-09).
The novel prediction model (IRSN-23) constructed with immune-related genes can predict pCR independently of the intrinsic subtypes and chemotherapeutic regimens.
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