Flow in an experimental micro–magma chamber

The chemical evolution and eruptive behavior of magmas may be controlled largely by convective processes within magma chambers. According to a recent National Research Council Report [Committee on Physics and Chemistry of Earth Materials, 1987], “the style of convection itself, whether it is turbulent, laminar, large-scale, of multiple scales, tiered, or localized and intermittent, is very much at question.” In the U.S. National Report to the International Union of Geodesy and Geophysics, Marsh [1987] reviewed recent theoretical and experimental developments related to the style of convection in magma chambers, noting both significant quantitative advances and also the many remaining uncertainties. With regard to double-diffusive convection, he stated “as ever, the critical question concerns whether or not actual magma chambers convect in this style.” Similarly, Spera et al. [1986] , in discussion of double-diffusive convection, cautioned against “applying results from saltwater tanks to magma chambers.

Predictive value of serial measurements of quality of life on all-cause mortality in prostate cancer patients: data from CaPSURE™ (cancer of the prostate strategic urologic research endeavor) database

Health-related quality of life (HRQOL) is a legitimate construct for evaluating treatment and its side effects. Recently, predictive value of HRQOL on survival also has been of interest. In light of the longer survival in patients with prostate cancer and importance of quality of life, we seek to evaluate the association between HRQOL and survival using traditional and novel techniques. Patients from CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) who were treated within 6 months of diagnosis and had pre-treatment and sufficient post-treatment follow-up information constituted the study population. A sample consisting of 2,899 patients met the study criteria. SF-36 domains were used to measure HRQOL outcomes. Categorical variables were created for HRQOL based on the baseline distribution of the lower 10th percentile and the remainder of the patients. Association between HRQOL and survival (defined by all-cause mortality) in patients with prostate cancer was evaluated using Cox proportional hazards models controlling for age at diagnosis, type of treatment received, clinical risk classification, and number of comorbidities. Sequential bootstrap resampling was implemented to evaluate stability of the model. Univariate and multivariate Cox proportional hazards models were fit using various time points over the course of follow-up. In the analysis looking at association of HRQOL baseline measurements, higher levels of physical function and general health were significantly associated with better survival (HR 0.49 95% CI 0.32–0.78 and HR 0.51 95% CI 0.35–0.75, respectively). Post-treatment analysis demonstrated similar results. In time-dependent analysis, higher levels of physical function, role physical, and general health were significantly associated with better survival (HR ranged from 0.57 to 0.65). In addition, analysis looking at change in HRQOL scores demonstrated an association between higher scores on physical function, role physical, vitality, social function, and general health and longer survival (HR ranged from 0.56 to 0.63). This study demonstrated that several domains of HRQOL were significantly associated with survival in a large group of patients with localized prostate cancer. This association was maintained over the course of disease regardless of the time of the assessment. Results from our study have both research and clinical relevance. They could provide information that enable us to not only improve communication with patients and families, but also to develop interventions and treatments best suited for the patient

Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.

BackgroundPET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared.ResultsPSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition.ConclusionPSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes

Prediction and prevention of the next pandemic zoonosis.

Most pandemics--eg, HIV/AIDS, severe acute respiratory syndrome, pandemic influenza--originate in animals, are caused by viruses, and are driven to emerge by ecological, behavioural, or socioeconomic changes. Despite their substantial effects on global public health and growing understanding of the process by which they emerge, no pandemic has been predicted before infecting human beings. We review what is known about the pathogens that emerge, the hosts that they originate in, and the factors that drive their emergence. We discuss challenges to their control and new efforts to predict pandemics, target surveillance to the most crucial interfaces, and identify prevention strategies. New mathematical modelling, diagnostic, communications, and informatics technologies can identify and report hitherto unknown microbes in other species, and thus new risk assessment approaches are needed to identify microbes most likely to cause human disease. We lay out a series of research and surveillance opportunities and goals that could help to overcome these challenges and move the global pandemic strategy from response to pre-emption

Constitutive expression of Yes-associated protein (Yap) in adult skeletal muscle fibres induces muscle atrophy and myopathy

Peer reviewedPublisher PD

Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing

Aprataxin (APTX) deficiency causes progressive cerebellar degeneration, ataxia and oculomotor apraxia in man. Cell free assays and crystal structure studies demonstrate a role for APTX in resolving 5'-adenylated nucleic acid breaks, however, APTX function in vertebrates remains unclear due to the lack of an appropriate model system. Here, we generated a murine model in which a pathogenic mutant of superoxide dismutase 1 (SOD1(G93A)) is expressed in an Aptx-/- mouse strain. We report a delayed population doubling and accelerated senescence in Aptx-/- primary mouse fibroblasts, which is not due to detectable telomere instability or cell cycle deregulation but is associated with a reduction in transcription recovery following oxidative stress. Expression of SOD1(G93A) uncovers a survival defect ex vivo in cultured cells and in vivo in tissues lacking Aptx. The surviving neurons feature numerous and deep nuclear envelope invaginations, a hallmark of cellular stress. Furthermore, they possess an elevated number of high-density nuclear regions and a concomitant increase in histone H3 K9 trimethylation, hallmarks of silenced chromatin. Finally, the accelerated cellular senescence was also observed at the organismal level as shown by down-regulation of insulin-like growth factor 1 (IGF-1), a hallmark of premature ageing. Together, this study demonstrates a protective role of Aptx in vivo and suggests that its loss results in progressive accumulation of DNA breaks in the nervous system, triggering hallmarks of premature ageing, systemically

Improving the LSST dithering pattern and cadence for dark energy studies

The Large Synoptic Survey Telescope (LSST) will explore the entire southern sky over 10 years starting in 2022 with unprecedented depth and time sampling in six filters, $ugrizy$. Artificial power on the scale of the 3.5 deg LSST field-of-view will contaminate measurements of baryonic acoustic oscillations (BAO), which fall at the same angular scale at redshift $z \sim 1$. Using the HEALPix framework, we demonstrate the impact of an "un-dithered" survey, in which $17\%$ of each LSST field-of-view is overlapped by neighboring observations, generating a honeycomb pattern of strongly varying survey depth and significant artificial power on BAO angular scales. We find that adopting large dithers (i.e., telescope pointing offsets) of amplitude close to the LSST field-of-view radius reduces artificial structure in the galaxy distribution by a factor of $\sim$10. We propose an observing strategy utilizing large dithers within the main survey and minimal dithers for the LSST Deep Drilling Fields. We show that applying various magnitude cutoffs can further increase survey uniformity. We find that a magnitude cut of $r < 27.3$ removes significant spurious power from the angular power spectrum with a minimal reduction in the total number of observed galaxies over the ten-year LSST run. We also determine the effectiveness of the observing strategy for Type Ia SNe and predict that the main survey will contribute $\sim$100,000 Type Ia SNe. We propose a concentrated survey where LSST observes one-third of its main survey area each year, increasing the number of main survey Type Ia SNe by a factor of $\sim$1.5, while still enabling the successful pursuit of other science drivers.Comment: 9 pages, 6 figures, published in SPIE proceedings; corrected typo in equation

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies

Abnormalities at chromosome region 3p12–14 characterize clear cell renal carcinoma

In an effort to determine whether or not any characteristic chromosomal abnormalities exist in renal cancer, cytogenetic findings were correlated with tumor histology in nine cases of renal adenocarcinoma. Metaphase preparations adequate for analysis were obtained from cultures harvested between day 3 and day 21. Model chromosome number was diploid in three cases, hypodiploid in three, and hyperdiploid in the remaining three. One clear cell adenocarcinoma failed to reveal any chromosomal abnormality. Two tumors, a tubular/papillary carcinoma and an acinar/papillary carcinima, showed the clonal abnormalities del(1)(p21),+2,+7,+8,+12,+13,+16,+17,-21 and t(2;lO)(q14-21;q26),+7q,+11q,-18, respectively. Interestingly, five of six clear cell tumors studied had clonal abnormalities affecting the short arm of chromosome #3 in the 3p12-21 region, and in the remaining case, of 15 karyotyped metaphases suitable for interpretation, one showed a deletion in 3p. These data indicate that clear cell carcinoma of the kidney may be associated with a nonrandom chromosomal abnormality involving the 3p12-14 region