Polar stratospheric cloud observations by MIPAS on ENVISAT: Detection method, validation and analysis of the northern hemisphere winter 2002/2003

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on ENVISAT has made extensive measurements of polar stratospheric clouds (PSCs) in the northern hemisphere winter 2002/2003. A PSC detection method based on a ratio of radiances (the cloud index) has been implemented for MIPAS and is validated in this study with respect to ground-based lidar and space borne occultation measurements. A very good correspondence in PSC sighting and cloud altitude between MIPAS detections and those of other instruments is found for cloud index values of less than four. Comparisons with data from the Stratospheric Aerosol and Gas Experiment (SAGE) III are used to further show that the sensitivity of the MIPAS detection method for this threshold value of cloud index is approximately equivalent to an extinction limit of 10-3km-1 at 1022nm, a wavelength used by solar occultation experiments. The MIPAS cloud index data are subsequently used to examine, for the first time with any technique, the evolution of PSCs throughout the Arctic polar vortex up to a latitude close to 90° north on a near-daily basis. We find that the winter of 2002/2003 is characterised by three phases of very different PSC activity. First, an unusual, extremely cold phase in the first three weeks of December resulted in high PSC occurrence rates. This was followed by a second phase of only moderate PSC activity from 5-13 January, separated from the first phase by a minor warming event. Finally there was a third phase from February to the end of March where only sporadic and mostly weak PSC events took place. The composition of PSCs during the winter period has also been examined, exploiting in particular an infra-red spectral signature which is probably characteristic of NAT. The MIPAS observations show the presence of these particles on a number of occasions in December but very rarely in January. The PSC type differentiation from MIPAS indicates that future comparisons of PSC observations with microphysical and denitrification models might be revealing about aspects of solid particle existence and location

Public health critical race praxis at the intersection of traffic stops and injury epidemiology

Background: Law enforcement traffic stops are one of the most common entryways to the US justice system. Conventional frameworks suggest traffic stops promote public safety by reducing dangerous driving practices and non-vehicular crime with little to no collateral damage to individuals and communities. Critical frameworks interrogate these assumptions, identifying significant individual and community harms that disparately impact Black, Indigenous, and People of Color (BIPOC) and low-income communities. Methods: The Public Health Critical Race Praxis (PHCRP) and multi-level frameworks from community anti-racist training were combined into a structured diagram to guide intervention and research teams in contrasting conventional and critical perspectives on traffic stops. The diagram divides law enforcement and drivers/residents as two separate agent types that interact during traffic stops. These two agent types have different conventional and critical histories, priorities, and perspectives at multiple levels, including individual, interpersonal, institutional, and cultural levels. Conventional solutions (identifying explicitly racist officers, “meet-a-cop” programs, police interaction training for drivers) are born from conventional frameworks (rewarding crime prevention regardless of cost, the war on drugs saves lives, driver behavior perfectionism). While conventional perspectives focus on individual and interpersonal levels, critical perspectives more deeply acknowledge dynamics at institutional and cultural levels. Critical solutions may be hard to discover without critical frameworks, including that law enforcement creates measurable collateral damage and disparate social control effects; neighborhood patrol priorities can be set without community self-determination or accountability and may trump individual and interpersonal dynamics; and the war on drugs is highly racialized and disproportionally enforced through traffic stop programs. Conclusions: Traffic stop enforcement and crash prevention programs that do not deeply and critically consider these dynamics at multiple levels, not just law enforcement-driver interactions at the individual and interpersonal levels, may be at increased risk of propagating histories of BIPOC discrimination. In contrast, public health and transportation researchers and practitioners engaged in crash and injury prevention strategies that employ law enforcement should critically consider disparate history and impacts of law enforcement in BIPOC communities. PHCRP, anti-racism frameworks, and the included diagram may assist them in organizing critical thinking about research studies, interventions, and impacts

Re-prioritizing traffic stops to reduce motor vehicle crash outcomes and racial disparities

Background: Law enforcement traffic stops are one of the most common entryways to the US justice system. Conventional frameworks suggest traffic stops promote public safety by reducing dangerous driving practices and non-vehicular crime. Law enforcement agencies have wide latitude in enforcement, including prioritization of stop types: (1) safety (e.g. moving violation) stops, (2) investigatory stops, or (3) economic (regulatory and equipment) stops. In order to prevent traffic crash fatalities and reduce racial disparities, the police department of Fayetteville, North Carolina significantly re-prioritized safety stops. Methods: Annual traffic stop, motor vehicle crash, and crime data from 2002 to 2016 were combined to examine intervention (2013-2016) effects. Fayetteville was compared against synthetic control agencies built from 8 similar North Carolina agencies by weighted matching on pre-intervention period trends and comparison against post-intervention trends. Results: On average over the intervention period as compared to synthetic controls, Fayetteville increased both the number of safety stops + 121% (95% confidence interval + 17%, + 318%) and the relative proportion of safety stops (+ 47%). Traffic crash and injury outcomes were reduced, including traffic fatalities - 28% (- 64%, + 43%), injurious crashes - 23% (- 49%, + 16%), and total crashes - 13% (- 48%, + 21%). Disparity measures were reduced, including Black percent of traffic stops - 7% (- 9%, - 5%) and Black vs. White traffic stop rate ratio - 21% (- 29%, - 13%). In contrast to the Ferguson Effect hypothesis, the relative de-prioritization of investigatory stops was not associated with an increase in non-traffic crime outcomes, which were reduced or unchanged, including index crimes - 10% (- 25%, + 8%) and violent crimes - 2% (- 33%, + 43%). Confidence intervals were estimated using a different technique and, given small samples, may be asymmetrical. Conclusions: The re-prioritization of traffic stop types by law enforcement agencies may have positive public health consequences both for motor vehicle injury and racial disparity outcomes while having little impact on non-traffic crime

Genetic variation in cell cycle regulatory gene AURKA and association with intrinsic breast cancer subtype

AURKA is a putative low-penetrance tumor susceptibility gene due to its prominent role in cell cycle regulation and centrosomal function. Germline variation in AURKA was evaluated for association with breast cancer and intrinsic breast cancer subtypes in the Carolina Breast Cancer Study (CBCS), a population-based case-control study of African Americans (AA) and Caucasians (Cau). Tag and candidate single nucleotide polymorphisms (SNPs) on AURKA were genotyped in 1946 cases and 1747 controls. In race-stratified analyses adjusted for age and African ancestry, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate SNP associations with breast cancer. In a race-combined analysis with similar adjustment, these associations were also examined by intrinsic breast cancer subtype. Using dominant models, most AURKA SNPs demonstrated no association with breast cancer in the race-stratified analyses. Among AA, rs6092309 showed an inverse association with breast cancer (OR=0.69, 95% CI=0.53-0.90). In the race-combined analyses, rs6099128 had reduced ORs for luminal A (OR=0.76, 95% CI=0.60-0.95) and basal-like breast cancer (OR=0.54, 95% CI=0.37-0.80). Rs6092309 showed a similar pattern of association with each subtype. Three SNPs (rs6014711, rs911162, rs1047972) had positive associations with basal-like breast cancer, and ORs reduced or close to 1.00 for other subtypes. Our results suggest inverse associations between some AURKA SNPs and overall breast cancer in AA. We found differential associations by specific subtypes and by race. Replication of these findings in larger AA populations would allow more powerful race-stratified subtype analyses

Aging dynamics of heterogeneous spin models

We investigate numerically the dynamics of three different spin models in the aging regime. Each of these models is meant to be representative of a distinct class of aging behavior: coarsening systems, discontinuous spin glasses, and continuous spin glasses. In order to study dynamic heterogeneities induced by quenched disorder, we consider single-spin observables for a given disorder realization. In some simple cases we are able to provide analytical predictions for single-spin response and correlation functions. The results strongly depend upon the model considered. It turns out that, by comparing the slow evolution of a few different degrees of freedom, one can distinguish between different dynamic classes. As a conclusion we present the general properties which can be induced from our results, and discuss their relation with thermometric arguments.Comment: 39 pages, 36 figure

Spatially heterogeneous ages in glassy dynamics

We construct a framework for the study of fluctuations in the nonequilibrium relaxation of glassy systems with and without quenched disorder. We study two types of two-time local correlators with the aim of characterizing the heterogeneous evolution: in one case we average the local correlators over histories of the thermal noise, in the other case we simply coarse-grain the local correlators. We explain why the former describe the fingerprint of quenched disorder when it exists, while the latter are linked to noise-induced mesoscopic fluctuations. We predict constraints on the pdfs of the fluctuations of the coarse-grained quantities. We show that locally defined correlations and responses are connected by a generalized local out-of-equilibrium fluctuation-dissipation relation. We argue that large-size heterogeneities in the age of the system survive in the long-time limit. The invariance of the theory under reparametrizations of time underlies these results. We relate the pdfs of local coarse-grained quantities and the theory of dynamic random manifolds. We define a two-time dependent correlation length from the spatial decay of the fluctuations in the two-time local functions. We present numerical tests performed on disordered spin models in finite and infinite dimensions. Finally, we explain how these ideas can be applied to the analysis of the dynamics of other glassy systems that can be either spin models without disorder or atomic and molecular glassy systems.Comment: 47 pages, 60 Fig

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

NikA binds heme: a new role for an Escherichia coli periplasmic nickel-binding protein.

NikA is a periplasmic binding protein involved in nickel uptake in Escherichia coli. NikA was identified as a heme-binding protein in the periplasm of anaerobically grown cells overexpressing CydDC, an ABC transporter that exports reductant to the periplasm. CydDC-overexpressing cells accumulate a heme biosynthesis-derived pigment, P-574. For further biochemical and spectroscopic analysis, unliganded NikA was overexpressed and purified. NikA was found to comigrate with both hemin and protoporphyrin IX during gel filtration. Furthermore, tryptophan fluorescence quenching titrations demonstrated that both hemin and protoporphyrin IX bind to NikA with similar affinity. The binding affinity of NikA for these pigments (Kd approximately 0.5 microM) was unaltered in the presence and absence of saturating concentrations of nickel, suggesting that these tetrapyrroles bind to NikA in a manner independent of nickel. To test the hypothesis that NikA is required for periplasmic heme protein assembly, the effects of a nikA mutation (nikA::Tn5, Km(R) insertion) on accumulation of P-574 by CydDC-overexpressing cells was assessed. This mutation significantly lowered P-574 levels, implying that NikA may be involved in P-574 production. Thus, in the reducing environment of the periplasm, NikA may serve as a heme chaperone as well as a periplasmic nickel-binding protein. The docking of heme onto NikA was modeled using the published crystal structure; many of the predicted complexes exhibit a heme-binding cleft remote from the nickel-binding site, which is consistent with the independent binding of nickel and heme. This work has implications for the incorporation of heme into b- and c-type cytochromes