Sagittarius II, Draco II and Laevens 3: Three New Milky Way Satellites Discovered in the Pan-STARRS 1 3 Survey

We present the discovery of three new Milky Way satellites from our search for compact stellar overdensities in the photometric catalog of the Panoramic Survey Telescope and Rapid Response System 1 (Pan-STARRS 1, or PS1) 3π survey. The first satellite, Laevens 3, is located at a heliocentric distance of d = 67 ± 3 kpc. With a total magnitude of MV = −4.4 ± 0.3 and a half-light radius of rh = 7 ± 2 pc, its properties resemble those of outer halo globular clusters. The second system, Draco II/Laevens 4, is a closer and fainter satellite (d ~ 20 kpc, MV = −2.9 ± 0.8), whose uncertain size (${r}_{h}={19}_{-6}^{+8}\;\mathrm{pc}$) renders its classification difficult without kinematic information; it could either be a faint and extended globular cluster or a faint and compact dwarf galaxy. The third satellite, Sagittarius II/Laevens 5 (Sgr II), has an ambiguous nature, as it is either the most compact dwarf galaxy or the most extended globular cluster in its luminosity range (${r}_{h}={37}_{-8}^{+9}\;\mathrm{pc}$ and MV = −5.2 ± 0.4). At a heliocentric distance of 67 ± 5 kpc, this satellite lies intriguingly close to the expected location of the trailing arm of the Sagittarius stellar stream behind the Sagittarius dwarf spheroidal galaxy (Sgr dSph). If confirmed through spectroscopic follow up, this connection would locate this part of the trailing arm of the Sagittarius stellar stream that has so far gone undetected. It would further suggest that Sgr II was brought into the Milky Way halo as a satellite of the Sgr dSph

Strategies to design clinical studies to identify predictive biomarkers in cancer research

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework—the DESIGN guidelines—to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field

Diagnostic value of exome and whole genome sequencing in craniosynostosis

Background Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ~1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. Methods We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative. Results We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (two families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). Conclusions This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The Heat Transfer and Pressure Drop Behavior of a Zeotropic Refrigerant Mixture in a Microfinned Tube

Air Conditioning and Refrigeration Center Project 3

The Behavior of a Near-Azeotropic Refrigerant Mixture of R-321R-125 in an Enhanced Tube

Condensation of a near-azeotropic mixture of 45% R-32 and 55% R-125 has been studied in a microfinned tube. The local behavior of heat transfer coefficient and the pressure drop was found to be a function of both quality and mass flux. The overall enhancement for a microfinned tube was determined to be a result of increased heat transfer combined with an increase in surface area due to the addition of the fins. Another important t result of this study was that the flow regime was found to be an important factor in characterizing the enhancement of the microfinned tube. The effect of the fins on the pressure drop was not readily apparent, but needs further testing in order to be determined.Air Conditioning and Refrigeration Center Project 3

Effect of Oil on Condensation in a Microfinned Tube

The effects of an ester oil, in concentrations up to 5% by mass, on the behavior of R -134a condensing in a microfinned tube with an 18?? helix angle were studied experimentally. The flow patterns were only minimally affected with some indication that a shift from wavy towards annular flow may be caused by the oil at the low mass fluxes. The heat transfer followed similar trends due to the presence of oil in a microfinned tube as those that occurred in a smooth tube. At low qualities there was no significant effect but, as quality increased, the heat transfer in the oil carrying refrigerant began to be depressed compared to the pure refrigerant. At some high quality the heat transfer reached a peak value. Beyond this quality the heat transfer decreased rather rapidly. The oil did not seem to have a large effect on the pressure drop in the test section. Only at the highest qualities were slight increases. measured at increased oil concentrations.Air Conditioning and Refrigeration Center Project 3