We describe the publicly available data from the Global OZone Chemistry And Related trace gas Data records for the Stratosphere (GOZCARDS) project and provide some results, with a focus on hydrogen ...chloride (HCl), water vapor (H2O), and ozone (O3). This data set is a global long-term stratospheric Earth system data record, consisting of monthly zonal mean time series starting as early as 1979. The data records are based on high-quality measurements from several NASA satellite instruments and the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) on SCISAT. We examine consistency aspects between the various data sets. To merge ozone records, the time series are debiased relative to SAGE II (Stratospheric Aerosol and Gas Experiments) values by calculating average offsets versus SAGE II during measurement overlap periods, whereas for other species the merging derives from an averaging procedure during overlap periods. The GOZCARDS files contain mixing ratios on a common pressure-latitude grid, as well as standard errors and other diagnostics; we also present estimates of systematic uncertainties in the merged products. Monthly mean temperatures for GOZCARDS were also produced, based directly on data from the Modern-Era Retrospective analysis for Research and Applications. The GOZCARDS HCl merged product comes from the Halogen Occultation Experiment (HALOE), ACE-FTS and lower-stratospheric Aura Microwave Limb Sounder (MLS) data. After a rapid rise in upper-stratospheric HCl in the early 1990s, the rate of decrease in this region for 1997-2010 was between 0.4 and 0.7 % yr-1. On 6-8-year timescales, the rate of decrease peaked in 2004-2005 at about 1 % yr-1, and it has since levelled off, at ~ 0.5 % yr-1. With a delay of 6-7 years, these changes roughly follow total surface chlorine, whose behavior versus time arises from inhomogeneous changes in the source gases. Since the late 1990s, HCl decreases in the lower stratosphere have occurred with pronounced latitudinal variability at rates sometimes exceeding 1-2 % yr-1. Recent short-term tendencies of lower-stratospheric and column HCl vary substantially, with increases from 2005 to 2010 for northern midlatitudes and deep tropics, but decreases (increases) after 2011 at northern (southern) midlatitudes. For H2O, the GOZCARDS product covers both stratosphere and mesosphere, and the same instruments as for HCl are used, along with Upper Atmosphere Research Satellite (UARS) MLS stratospheric H2O data (1991-1993). We display seasonal to decadal-type variability in H2O from 22 years of data. In the upper mesosphere, the anticorrelation between H2O and solar flux is now clearly visible over two full solar cycles. Lower-stratospheric tropical H2O has exhibited two periods of increasing values, followed by fairly sharp drops (the well-documented 2000-2001 decrease and a recent drop in 2011-2013). Tropical decadal variability peaks just above the tropopause. Between 1991 and 2013, both in the tropics and on a near-global basis, H2O has decreased by ~ 5-10 % in the lower stratosphere, but about a 10 % increase is observed in the upper stratosphere and lower mesosphere. However, such tendencies may not represent longer-term trends. For ozone, we used SAGE I, SAGE II, HALOE, UARS and Aura MLS, and ACE-FTS data to produce a merged record from late 1979 onward, using SAGE II as the primary reference. Unlike the 2 to 3 % increase in near-global column ozone after the late 1990s reported by some, GOZCARDS stratospheric column O3 values do not show a recent upturn of more than 0.5 to 1 %; long-term interannual column ozone variations from GOZCARDS are generally in very good agreement with interannual changes in merged total column ozone (Version 8.6) data from SBUV instruments. A brief mention is also made of other currently available, commonly formatted GOZCARDS satellite data records for stratospheric composition, namely those for N2O and HNO3.
Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and ...there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.
Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.
This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.
Vascular risk factors and diabetic neuropathy Tesfaye, Solomon; Chaturvedi, Nish; Eaton, Simon E M ...
New England journal of medicine/The New England journal of medicine,
01/2005, Letnik:
352, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the ...development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study.
Neuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999), with a mean (+/-SD) follow-up of 7.3+/-0.6 years. A standardized protocol included clinical evaluation, quantitative sensory testing, and autonomic-function tests. Serum lipids and lipoproteins, glycosylated hemoglobin, and the urinary albumin excretion rate were measured in a central laboratory.
At follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors, we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides, a higher body-mass index, higher von Willebrand factor levels and urinary albumin excretion rate, hypertension, and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications, we found that duration of diabetes, current glycosylated hemoglobin value, change in glycosylated hemoglobin value during the follow-up period, body-mass index, and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy, independent of cardiovascular risk factors.
This prospective study indicates that, apart from glycemic control, the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors, including a raised triglyceride level, body-mass index, smoking, and hypertension.
Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches. GSC interactions with their niche influence ...self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the integrin αvβ8 and its latent transforming growth factor β1 (TGFβ1) protein ligand have central roles in promoting niche co-option and GBM initiation. αvβ8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of β8
cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that αvβ8 integrin regulates tumor development, in part, by driving TGFβ1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the αvβ8 integrin-TGFβ1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM.
We aimed to examine the mortality rates, excess mortality and causes of death in diabetic patients from ten centres throughout the world.
A mortality follow-up of 4713 WHO Multinational Study of ...Vascular Disease in Diabetes (WHO MSVDD) participants from ten centres was carried out, causes of death were ascertained and age-adjusted mortality rates were calculated by centre, sex and type of diabetes. Excess mortality, compared with the background population, was assessed in terms of standardised mortality ratios (SMRs) for each of the 10 cohorts.
Cardiovascular disease was the most common underlying cause of death, accounting for 44 % of deaths in Type I (insulin-dependent) diabetes mellitus and 52 % of deaths in Type II (non-insulin-dependent) diabetes mellitus. Renal disease accounted for 21% of deaths in Type I diabetes and 11% in Type II diabetes. For Type I diabetes, all-cause mortality rates were highest in Berlin men and Warsaw women, and lowest in London men and Zagreb women. For Type II diabetes, rates were highest in Warsaw men and Oklahoma women and lowest in Tokyo men and women. Age adjusted mortality rates and SMRs were generally higher in patients with Type I diabetes compared with those with Type II diabetes. Men and women in the Tokyo cohort had a very low excess mortality when compared with the background population.
This study confirms the importance of cardiovascular disease as the major cause of death in people with both types of diabetes. The low excess mortality in the Japanese cohort could have implications for the possible reduction of the burden of mortality associated with diabetes in other parts of the world.
Global satellite observations of temperature and geopotential height (GPH) from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed. The precision, resolution, and accuracy of ...the data produced by the MLS version 2.2 processing algorithms are quantified, and recommendations for data screening are made. Temperature precision is 1 K or better from 316 hPa to 3.16 hPa, degrading to ∼3 K at 0.001 hPa. The vertical resolution is 3 km at 31.6 hPa, degrading to 6 km at 316 hPa and to ∼13 km at 0.001 hPa. Comparisons with analyses (Goddard Earth Observing System version 5.0.1 (GEOS‐5), European Centre for Medium‐range Weather Forecasts (ECMWF), Met Office (MetO)) and other observations (CHAllenging Minisatellite Payload (CHAMP), Atmospheric Infrared Sounder/Advanced Microwave Sounder Unit (AIRS/AMSU), Sounding of the Atmosphere using Broadband Radiometry (SABER), Halogen Occultation Experiment (HALOE), Atmospheric Chemistry Experiment (ACE), radiosondes) indicate that MLS temperature has persistent, pressure‐dependent biases which are between −2.5 K and +1 K between 316 hPa and 10 hPa. The 100‐hPa MLS v2.2 GPH surface has a bias of ∼150 m relative to the GEOS‐5 values. These biases are compared to modeled systematic uncertainties. GPH biases relative to correlative measurements generally increase with height owing to an overall cold bias in MLS temperature relative to correlative temperature measurements in the upper stratosphere and mesosphere.
Aims/hypothesis
The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. ...However, the consequences of exposure during the first trimester are unclear, especially in diabetes. We report the experience from DIRECT (DIabetic REtinopathy and Candesartan Trials), three placebo-controlled studies designed to examine the effects of an ARB, candesartan, on diabetic retinopathy.
Methods
Over 4 years or longer, 178 normotensive women with type 1 diabetes (86 randomised to candesartan, 32 mg once daily, and 92 assigned to placebo) became pregnant (total of 208 pregnancies).
Results
More than half of patients were exposed to candesartan or placebo prior to or in early pregnancy, but all discontinued it at an estimated 8 weeks from the last menstrual period. Full-term pregnancies (51 vs 50), premature deliveries (21 vs 27), spontaneous miscarriages (12 vs 15), elective terminations (15 vs 14) and other outcomes (1 vs 2) were similar in the candesartan and placebo groups. There were two stillbirths and two ‘sick babies’ in the candesartan group, and one stillbirth, eight ‘sick babies’ and one cardiac malformation in the placebo group.
Conclusions/interpretation
The risk for fetal consequences of ARBs in type 1 diabetes may not be high if exposure is clearly limited to the first trimester. Long-term studies in fertile women can be conducted with ARBs during pregnancy, provided investigators diligently stop their administration upon planning or detection of pregnancy.
Trial registration
ClinicalTrials.gov DIRECT-Prevent 1 NCT00252733; DIRECT-Protect 1 NCT00252720; DIRECT-Protect 2 NCT00252694.
Funding
The study was funded jointly by AstraZeneca and Takeda.
Aims/hypothesis We compiled up to date estimates of the absolute and relative risk of all-cause mortality in patients with type 1 diabetes in the UK. Materials and methods We selected patients with ...type 1 diabetes (n=7,713), and for each of these diabetic subjects five age- and sex-matched control subjects without diabetes (n=38,518) from the General Practice Research Database (GPRD). Baseline was 1 January 1992; subjects were followed until 1999. The GPRD is a large primary-care database containing morbidity and mortality data of a large sample representative of the UK population. Deaths occurring in the follow-up period were identified. Results The study comprised 208,178 person-years of follow-up. The prevalence of type 1 diabetes was 2.15/1,000 subjects in 1992 (mean age 33 years, SD 15). Annual mortality rates were 8.0 per 1,000 person-years (95% CI 7.2-8.9) in type 1 diabetic subjects compared with 2.4 per 1,000 person-years (95% CI 2.2-2.6) in those without diabetes (hazard ratio HR=3.7, 95% CI 3.2-4.3). The increased mortality rates in patients with type 1 diabetes were apparent across all age-bands. The HR was higher in women (HR=4.5, 95% CI 3.5-5.6 compared with non-diabetic women) than men (HR=3.3, 95% CI 2.7-4.0), such that the sex difference (p<0.0001) in mortality in the non-diabetic population was abolished (p=0.3) in the type 1 diabetic patients. The predominant cause of death in patients with type 1 diabetes was cardiovascular disease. Conclusions/interpretation Despite advances in care, UK mortality rates in the past decade continue to be much greater in patients with type 1 diabetes than in those without diabetes.
Objectives: To undertake a detailed, large scale epidemiological study of match injuries sustained by professional rugby union players in order to define their incidence, nature, severity, and ...causes. Methods: A two season prospective design was used to study match injuries associated with 546 rugby union players at 12 English Premiership clubs. Team clinicians reported all match injuries on a weekly basis and provided details of the location, diagnosis, severity, and mechanism of each injury. Match exposures for individual players were recorded on a weekly basis. Loss of time from training and match play was used as the definition of an injury. Results: The overall incidence of injury was 91 injuries/1000 player-hours, and each injury resulted on average in 18 days lost time. Recurrences, which accounted for 18% of injuries, were significantly more severe (27 days) than new injuries (16 days). Thigh haematomas were the most common injury for forwards and backs, but anterior cruciate ligament injuries for forwards and hamstring injuries for backs caused the greatest number of days absence. Contact mechanisms accounted for 72% of injuries, but foul play was only implicated in 6% of injuries. The ruck and maul elements of the game caused most injuries to forwards, and being tackled caused most injuries to backs. The hooker and outside centre were the playing positions at greatest risk of injury. Conclusions: On average, a club will have 18% of their players unavailable for selection as a consequence of match injuries.
A comprehensive quality assessment of the ozone products from 18 limb‐viewing satellite instruments is provided by means of a detailed intercomparison. The ozone climatologies in form of monthly ...zonal mean time series covering the upper troposphere to lower mesosphere are obtained from LIMS, SAGE I/II/III, UARS‐MLS, HALOE, POAM II/III, SMR, OSIRIS, MIPAS, GOMOS, SCIAMACHY, ACE‐FTS, ACE‐MAESTRO, Aura‐MLS, HIRDLS, and SMILES within 1978–2010. The intercomparisons focus on mean biases of annual zonal mean fields, interannual variability, and seasonal cycles. Additionally, the physical consistency of the data is tested through diagnostics of the quasi‐biennial oscillation and Antarctic ozone hole. The comprehensive evaluations reveal that the uncertainty in our knowledge of the atmospheric ozone mean state is smallest in the tropical and midlatitude middle stratosphere with a 1σ multi‐instrument spread of less than ±5%. While the overall agreement among the climatological data sets is very good for large parts of the stratosphere, individual discrepancies have been identified, including unrealistic month‐to‐month fluctuations, large biases in particular atmospheric regions, or inconsistencies in the seasonal cycle. Notable differences between the data sets exist in the tropical lower stratosphere (with a spread of ±30%) and at high latitudes (±15%). In particular, large relative differences are identified in the Antarctic during the time of the ozone hole, with a spread between the monthly zonal mean fields of ±50%. The evaluations provide guidance on what data sets are the most reliable for applications such as studies of ozone variability, model‐measurement comparisons, detection of long‐term trends, and data‐merging activities.
Key Points
Quality assessment of ozone products from 18 limb‐viewing satellite instruments
Detailed intercomparison of monthly zonal mean ozone climatologies
Derived uncertainty in our knowledge of the atmospheric ozone mean state
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