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Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training.

We report the first direct turbulence observations in the Samoan Passage (SP), a 40 km wide notch in the South Pacific bathymetry through which flows most of the water supplying the North Pacific abyssal circulation. The observed turbulence is 1000 to 10,000 times typical abyssal levels —strong enough to completely mix away the densest water entering the passage—confirming inferences from previous coarser temperature and salinity sections. Accompanying towed measurements of velocity and temperature with horizontal resolution of about 250 m indicate the dominant processes responsible for the turbulence. Specifically, the flow accelerates substantially at the primary sill within the passage, reaching speeds as great as 0.55 m s−1. A strong hydraulic response is seen, with layers first rising to clear the sill and then plunging hundreds of meters downward. Turbulence results from high shear at the interface above the densest fluid as it descends and from hydraulic jumps that form downstream of the sill. In addition to the primary sill, other locations along the multiple interconnected channels through the Samoan Passage also have an effect on the mixing of the dense water. In fact, quite different hydraulic responses and turbulence levels are observed at seafloor features separated laterally by a few kilometers, suggesting that abyssal mixing depends sensitively on bathymetric details on small scales.

We have derived values of the Ultraviolet Index (UVI) at solar noon using the Tropospheric Ultraviolet Model (TUV) driven by ozone, temperature and aerosol fields from climate simulations of the first phase of the Chemistry-Climate Model Initiative (CCMI-1). Since clouds remain one of the largest uncertainties in climate projections, we simulated only the clear-sky UVI. We compared the modelled UVI climatologies against present-day climatological values of UVI derived from both satellite data (the OMI-Aura OMUVBd product) and ground-based measurements (from the NDACC network). Depending on the region, relative differences between the UVI obtained from CCMI/TUV calculations and the ground-based measurements ranged between −5.9% and 10.6%. We then calculated the UVI evolution throughout the 21st century for the four Representative Concentration Pathways (RCPs 2.6, 4.5, 6.0 and 8.5). Compared to 1960s values, we found an average increase in the UVI in 2100 (of 2–4%) in the tropical belt (30°N-30°S). For the mid-latitudes, we observed a 1.8 to 3.4 % increase in the Southern Hemisphere for RCP 2.6, 4.5 and 6.0, and found a 2.3% decrease in RCP 8.5. Higher increases in UVI are projected in the Northern Hemisphere except for RCP 8.5. At high latitudes, ozone recovery is well identified and induces a complete return of mean UVI levels to 1960 values for RCP 8.5 in the Southern Hemisphere. In the Northern Hemisphere, UVI levels in 2100 are higher by 0.5 to 5.5% for RCP 2.6, 4.5 and 6.0 and they are lower by 7.9% for RCP 8.5. We analysed the impacts of greenhouse gases (GHGs) and ozone-depleting substances (ODSs) on UVI from 1960 by comparing CCMI sensitivity simulations (1960–2100) with fixed GHGs or ODSs at their respective 1960 levels. As expected with ODS fixed at their 1960 levels, there is no large decrease in ozone levels and consequently no sudden increase in UVI levels. With fixed GHG, we observed a delayed return of ozone to 1960 values, with a corresponding pattern of change observed on UVI, and looking at the UVI difference between 2090s values and 1960s values, we found an 8 % increase in the tropical belt during the summer of each hemisphere. Finally we show that, while in the Southern Hemisphere the UVI is mainly driven by total ozone column, in the Northern Hemisphere both total ozone column and aerosol optical depth drive UVI levels, with aerosol optical depth having twice as much influence on the UVI as total ozone column does.

AbstractTo determine the role of familial factors in head and neck cancer, we analysed data from a hospital‐based case‐control study of squamous cell carcinoma of the head and neck in Brazil. There were 754 cases of squamous cell carcinoma of the head and neck (SCCHN) and 1,507 age‐ and gender‐matched hospital‐based controls with non‐malignant diseases. Subjects provided information on the occurrence of cancer in first‐degree relatives, as well as about other risk factors, including tobacco and alcohol consumption. Relative risks (RRs) were estimated for developing mouth, pharynx and larynx cancer when cancers in relatives were observed. RRs were adjusted for age, sex, city of admission and alcohol and tobacco consumption. The RR for developing SCCHN if a first‐degree relative had cancer at any site was significantly elevated at 1.97. The RR was 3.65 (95% Cl: 1.97–6.76) if the relative had head and neck cancer. Significantly elevated risks for developing head and neck cancer were associated with siblings with head and neck cancer (RR = 8.57) and, to a lesser extent, with fathers with head and neck cancer (RR = 2.49). There was no significantly increased risk associated with mothers with head and neck cancer, but these tumours were rare among mothers. Our data show that familial, possibly genetic, factors are important in the aetiology of head and neck cancer. © 1995 Wiley‐Liss, Inc.

Intracranial cysts are common findings on both computed tomography (CT) and magnetic resonance imaging (MRI) and represent a wide range of diagnoses. A cyst can be defined as a spherical growth with an epithelial lining, forming a cavity that is filled with fluid, cellular products, or debris. Histo

Metastatic breast cancer is a very heterogeneous disease. Recent advances in genomic sequencing have revealed genetic diversity between patients and across distinct subclonal cell populations within the same patient that may evolve across metastatic tumor sites and during treatment. With the increasing availability of commercial and laboratory-developed tests that can detect genomic alterations from patient tumor and blood samples, translating this knowledge into improved clinical care remains a challenge. The goals of this review are to outline the clinical relevance of tumor genomic heterogeneity and clonal evolution, to help clinicians understand how to interpret genomic testing reports, and to provide an overview of recurrent genomic alterations that may be relevant for clinical trials with investigational drug treatments.

We present an analysis of six independent on-sky datasets taken with the Keck-II/NIRC2 instrument. Using the off-axis point spread function (PSF) reconstruction software AIROPA, we extract stellar astrometry, photometry, and other fitting metrics in order to characterize the performance of this package. We test the effectiveness of AIROPA to reconstruct the PSF across the field of view in varying atmospheric conditions, number and location of PSF reference stars, stellar crowding and telescope position angle (PA). We compare the astrometric precision and fitting residuals between a static PSF model and a spatially varying PSF model that incorporates instrumental aberrations and atmospheric turbulence during exposures. Most of the fitting residuals we measure show little to no improvement in the variable-PSF mode over the single-PSF mode. For one of the data sets, we find photometric performance is significantly improved (by ${\sim}10\times$) by measuring the trend seen in photometry as a function of off-axis location. For nearly all other metrics we find comparable astrometric and photometric precision across both PSF modes, with a ${\sim}13$% smaller astrometric uncertainty in variable-PSF mode in the best case. We largely confirm that the spatially variable PSF does not significantly improve the astrometric and other PSF fitting residuals over the static PSF for on-sky observations. We attribute this to unaccounted instrumental aberrations that are not characterized through afternoon adaptive optics (AO) bench calibrations. Comment: 23 pages, 13 figures, submitted to JATIS