The Wind Imaging Interferometer (WINDII) was launched on the NASA's Upper Atmosphere Research Satellite on 12 September 1991 and operated until 2003. Its role in the mission was to measure vector ...winds in the Earth's atmosphere from 80 to 110 km, but its measurements extended to nearly 300 km. The approach employed was to measure Doppler shifts from a suite of visible region airglow lines emitted over this altitude range. These included atomic oxygen O(1S) and O(1D) lines, as well as lines in the OH Meinel (8,3) and O2 Atmospheric (0,0) bands. The instrument employed was a Doppler Michelson Interferometer that measured the Doppler shift as a phase shift of the cosinusoidal interferogram generated by single airglow lines. An extensive validation program was conducted after launch to confirm the accuracy of the measurements. The dominant wind field, the first one observed by WINDII, was that of the migrating diurnal tide at the equator. The overall most notable WINDII contribution followed from this: determining the influence of dynamics on the transport of atmospheric species. Currently, nonmigrating tides are being studied in the thermosphere at both equatorial and high latitudes. Other aspects investigated included solar and geomagnetic influences, temperatures from atmospheric‐scale heights, nitric oxide concentrations, and the occurrence of polar mesospheric clouds. The results of these observations are reviewed from a perspective of 20 years. A future perspective is then projected, involving more recently developed concepts. It is intended that this description will be helpful for those planning future missions.
Key Points
Doppler Michelson interferometers excel in atmospheric space wind measurements
Upper atmosphere winds dramatically influence atomic oxygen concentrations
The thermosphere has enormous scope for future atmospheric dynamics measurements
1 Human Performance Laboratory,
Ball State University, Muncie, Indiana 47306;
2 Center for Sports Medicine/Noll
Physiological Research Center, Pennsylvania State University,
University Park, ...Pennsylvania 16802;
3 Department of Biology of
Physical Activity, University of Jyväskylä,
Jyväskylä, Finland;
4 School of Exercise Science
and Sport Management, Southern Cross University, Lismore, New South
Wales, Australia; 5 Nutrition,
Metabolism, and Exercise Laboratory, Donald W. Reynolds Department
of Geriatrics, University of Arkansas for Medical Sciences, North
Little Rock, Arkansas 72114-1706; and
6 Department of Sport Science,
Colorado College, Colorado Springs, Colorado 80913
To examine the adaptations of the endocrine system to
heavy-resistance training in younger vs. older men, two groups of men (30 and 62 yr old) participated in a 10-wk periodized strength-power training program. Blood was obtained before, immediately after, and 5, 15, and 30 min after exercise at rest before and after training and at
rest at 3, 0, 6, and 10 wk for analysis of total testosterone,
free testosterone, cortisol, growth hormone, lactate, and ACTH
analysis. Resting values for insulin-like growth factor (IGF)-I and
IGF-binding protein-3 were determined before and after training. A
heavy-resistance exercise test was used to evaluate the
exercise-induced responses (4 sets of 10-repetition maximum squats with
90 s of rest between sets). Squat strength and thigh muscle
cross-sectional area increased for both groups. The younger group
demonstrated higher total and free testosterone and IGF-I than the
older men, training-induced increases in free testosterone at rest and
with exercise, and increases in resting IGF-binding protein-3. With
training the older group demonstrated a significant increase in total
testosterone in response to exercise stress along with significant
decreases in resting cortisol. These data indicate that older men do
respond with an enhanced hormonal profile in the early phase of a
resistance training program, but the response is different from that of
younger men.
endocrine; aging; sarcopenia; strength; muscle; andropause; somatopause; growth factors
Effects of a 10-week progressive strength training program composed of a mixture of exercises for increasing muscle mass, maximal peak force, and explosive strength (rapid force production) were ...examined in 8 young (YM) (29 ± 5 yrs) and 10 old (OM) (61 ± 4 yrs) men. Electromyographic activity, maximal bilateral isometric peak force, and maximal rate of force development (RFD) of the knee extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF), muscle fiber proportion, and fiber areas of types I, IIa, IIb, and IIab of the vastus lateralis were evaluated. Maximal and explosive strength values remained unaltered in both groups during a 3-week control period with no training preceding the strength training. After the 10-week training period, maximal isometric peak force increased from 1311 ± 123 N by 15.6% (p < .05) in YM and from 976 ± 168 N by 16.5% (p < .01) in OM. The pretraining RFD values of 4049 ± 791 N*s−1 in YM and 2526 ± 1197 N*s−1 in OM remained unaltered. Both groups showed significant increases (p < .05) in the averaged maximum IEMGs of the vastus muscles. The CSA of the QF increased from 90.3 ± 7.9 cm2 in YM by 12.2% (p < .05) and from 74.7 ± 7.8 cm2 in OM by 8.5% (p < .001). No changes occurred in the muscle fiber distribution of type I during the training, whereas the proportion of subtype IIab increased from 2% to 6% (p < .05) in YM and that of type IIb decreased in both YM from 25% to 16% (p < .01) and in OM from 15% to 6% (p < .05). The mean fiber area of type I increased after the 10-week training in YM (p < .001) and OM (p < .05) as well as that of type IIa in both YM (p < .01) and OM (p < .01). The individual percentage values for type I fibers were inversely correlated with the individual changes recorded during the training in the muscle CSA of the QF (r = −.56, p < .05). The present results suggest that both neural adaptations and the capacity of the skeletal muscle to undergo training-induced hypertrophy even in older people explain the gains observed in maximal force in older men, while rapid force production capacity recorded during the isometric knee extension action remained unaltered during the present mixed strength training program.
The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational ...modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET–KAc binding has emerged as an attractive therapeutic strategy with a number of small molecule inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochemical, pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technology, with an N-methyl pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose.
The Moderate Resolution Imaging Spectroradiometer (MODIS) will add a significant new capability for investigating the 70% of the Earth's surface that is covered by oceans, in addition to contributing ...to the continuation of a decadal scale time series necessary for climate change assessment in the oceans. Sensor capabilities of particular importance for improving the accuracy of ocean products include high SNR and high stability for narrow or spectral bands, improved onboard radiometric calibration and stability monitoring, and improved science data product algorithms. Spectral bands for resolving solar-stimulated chlorophyll fluorescence and a split window in the 4-/spl mu/m region for SST will result in important new global ocean science products for biology and physics. MODIS will return full global data at 1-km resolution. The complete suite of Levels 2 and 3 ocean products is reviewed, and many areas where MODIS data are expected to make significant, new contributions to the enhanced understanding of the oceans' role in understanding climate change are discussed. In providing a highly complementary and consistent set of observations of terrestrial, atmospheric, and ocean observations, MODIS data will provide important new information on the interactions between Earth's major components.
A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a ...second maintenance course of PARPi was unknown.
Phase II trial with two entry points (EP1, EP2). Patients were recruited prior to rechallenge platinum. Patients with relapsed, gBRCAm-HGSOC were enrolled at EP1 if they were PARPi-naïve. Patients enrolled at EP2 had received their first course of olaparib prior to trial entry. EP1 patients were retreated with olaparib after RECIST complete/partial response (CR/PR) to platinum. EP2 patients were retreated with olaparib ± cediranib after RECIST CR/PR/stable disease to platinum and according to the platinum-free interval. Co-primary outcomes were the proportion of patients who received a second course of olaparib and the proportion who received olaparib retreatment for ≥6 months. Functional homologous recombination deficiency (HRD), somatic copy-number alteration (SCNA), and BRCAm reversions were investigated in tumor and liquid biopsies.
Twenty-seven patients were treated (EP1 = 17, EP2 = 10), and 19 were evaluable. Twelve patients (63%) received a second course of olaparib and 4 received olaparib retreatment for ≥6 months. Common grade ≥2 adverse events during olaparib retreatment were anemia, nausea, and fatigue. No cases of MDS/AML occurred. Mean duration of olaparib treatment and retreatment differed (12.1 months vs. 4.4 months; P < 0.001). Functional HRD and SCNA did not predict PFS. A BRCA2 reversion mutation was detected in a post-olaparib liquid biopsy.
A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious. See related commentary by Gonzalez-Ochoa and Oza, p. 2563.
Background
Asthma is a chronic inflammatory disease of the airways affecting an estimated 334 million people worldwide. During severe exacerbations, patients may need to attend a medical centre or ...hospital emergency department for treatment with systemic corticosteroids, which can be administered intravenously or orally. Some people with asthma are prescribed oral corticosteroids (OCS) for self‐administration (i.e. patient‐initiated) or to administer to their child with asthma (i.e. parent‐initiated), in the event of an exacerbation. This approach to treatment is becoming increasingly common.
Objectives
To evaluate the effectiveness and safety of patient‐ or parent‐initiated oral steroids for adults and children with asthma exacerbations.
Search methods
We identified trials from Cochrane Airways' Specialised Register (CASR) and also conducted a search of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch). We searched CASR from its inception to 18 May 2016 and trial registries from their inception to 24 August 2016; we imposed no restriction on language of publication.
Selection criteria
We looked for randomised controlled trials (RCTs), reported as full‐text, those published as only, and unpublished data; we excluded cross‐over trials.
We looked for studies where adults (aged 18 years or older) or children of school age (aged 5 years or older) with asthma were randomised to receive: (a) any patient‐/parent‐initiated OCS or (b) placebo, normal care, alternative active treatment, or an identical personalised asthma action plan without the patient‐ or parent‐initiated OCS component.
Data collection and analysis
Two review authors independently screened the search results to identify any studies that met the prespecified inclusion criteria.
The prespecified primary outcomes were hospital admissions for asthma, asthma symptoms at follow‐up and serious adverse events.
Main results
Despite comprehensive searches of electronic databases and clinical trial registries, we did not identify any studies meeting the inclusion criteria for this review. Five potentially relevant studies were excluded for two reasons: the intervention did not meet the inclusion criteria for this review (three studies) and studies had a cross‐over design (two studies). Two of the excluded studies asked the relevant clinical question. However, these studies were excluded due to their cross‐over design, as per the protocol. We contacted the authors of the cross‐over trials who were unable to provide data for the first treatment period (i.e. prior to cross‐over).
Authors' conclusions
There is currently no evidence from randomised trials (non‐cross‐over design) to inform the use of patient‐ or parent‐initiated oral corticosteroids in people with asthma.
Background: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone ...pain, their potential combined therapeutic value has not been reported in OSA‐bearing dogs.
Hypothesis: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA‐bearing dogs.
Animals: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline.
Methods: Randomized, prospective, double‐blinded, placebo‐controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N‐telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis.
Results: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate 11/26 and placebo 9/24) of dogs experienced durable analgesia, defined by pain alleviation ≥112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA‐bearing dogs.
Conclusions and Clinical Importance: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment.
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