Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD

Background: Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age. Methods: All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis. Results: Young susceptible individuals showed significantly higher increases in the expression of Fc gamma RII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients. Conclusions: We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD

Risk of high blood pressure in salt workers working near salt milling plants: A cross-sectional and interventional study

BACKGROUND: Workers working close to salt milling plants may inhale salt particles floating in the air, leading to a rise in plasma sodium, which, in turn, may increase the blood pressure and the risk of hypertension. METHODS: To test the above hypothesis, occupational health check-up camps were organized near salt manufacturing units and all workers were invited for a free health examination. The workers who worked with dry salt in the vicinity of salt milling plants were defined as "non-brine workers," while those working in brine pans located far away from milling plants were defined as "brine workers." Blood pressure (BP) was measured during each clinical examination. In all, 474 non-brine workers and 284 brine workers were studied. RESULTS: Mean systolic blood pressure of non-brine workers (122.1 ± 13.3 mm Hg) was significantly higher than that of brine workers (118.8 ± 12.8 mm Hg, p < 0.01). Mean diastolic blood pressure of non-brine workers (71.5 ± 10.4 mm Hg) was significantly higher than that of brine workers (69.7 ± 9.4 mm Hg, p = 0.02). The prevalence of hypertension was significantly higher in non-brine workers (12.2%) than in brine workers (7.0%, p = 0.02). Nineteen salt workers were monitored while they used face masks and spectacles, for six days. Systolic, as well as diastolic, blood pressure of these workers began declining on the third day and continued to decline on the fourth day, but remained stationary up to the sixth day. The concentration of salt particles in the breathing zone of these workers was 376 mg/m(3 )air. CONCLUSION: Inhalation of salt particles in non-brine workers may be an occupational cause of increased blood pressure

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes. Funding Cancer Research UK, Medical Research Council

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Controls on explosive-effusive volcanic eruption styles

One of the biggest challenges in volcanic hazard assessment is to understand how and why eruptive style changes within the same eruptive period or even from one eruption to the next at a given volcano. This review evaluates the competing processes that lead to explosive and effusive eruptions of silicic magmas. Eruptive style depends on a set of feedbacks involving interrelated magmatic properties and processes. Foremost of these are magma viscosity, gas loss, and external properties such as conduit geometry. Ultimately, these parameters control the speed at which magmas ascend, decompress and outgas en route to the surface, and thus determine eruptive style and evolution

Metal-silicate partitioning and the incompatibility of S and Si during core formation

We have determined the partitioning of a number of siderophile and lithophile elements between liquid metal and liquid silicate phases under the high temperature, low pressure conditions at which core segregation is considered to have originated [2]. Oxygen fugacity was varied from 2 to 6 log units below the iron-wüstite (IW) buffer by increasing the Si content of the metallic phase from 100 ppm up to the 8% proposed by Allègre et al. [8] as being cosmochemically required in the earth's core. We find that Si and S, two of the principal candidates for the light element in the core are mutually exclusive in the metal phase. As oxygen fugacity is reduced, Si becomes increasingly siderophile and S increasingly lithophile. At 8% Si in the metal, all S, up to at least 1%, enters the coexisting ultramafic liquid. Thus, Si and S are incompatible during a single-stage low pressure core formation event. Mn and Cr, which are lithophile under oxidising conditions, become slightly siderophile if there is 8% Si in the metal, corresponding to an oxygen fugacity of about 6 log units below the iron-wüstite (IW) buffer. Ti remains lithophile even under these conditions, only becoming siderophile at about 7 log units below IW. These results demonstrate that the Mn and Cr contents of the core proposed in [8], coupled with lithophile behaviour of Ti, are consistent with core segregation under strongly reducing conditions. Such conditions could not generate a core containing 2% S, however, and the problem of the high contents of oxidised Fe, Ni, Co and other siderophile elements in the mantle would remain. The only plausible way of introducing S into the core is to add it as part of a late-stage accretion of oxidised material to the earth. A second, minor phase of core segregation under oxidising conditions would supply S, but no additional Si, to the core. © 1997 Elsevier Science B.V

Earliest microbially mediated pyrite oxidation in ~3.4 billion-year-old sediments

Pyrite (FeS2) oxidation in modern sedimentary environments is neither a purely chemical nor purely microbial process, but it is significantly enhanced by the activity of microorganisms that use reduced forms of iron and sulphur in their metabolisms. On the early Earth, where oxygen levels were thought to be &lt;10-5 of the present atmospheric level and chemical oxidants scarce, such biological mediation may have been critical in the redox cycles of iron and sulphur. Here, we show that detrital sedimentary pyrite grains in a ~3.4 billion-year-old sandstone were colonised by microbial communities. The detrital pyrite comes from the basal quartz arenite member of the 3.43-3.35Ga Strelley Pool Formation (SPF) in the East Strelley greenstone belt of the Pilbara Craton, Western Australia. Rock chips and petrographic thin sections of black sandstones occurring on two ridges close to the SPF type locality of Strelley Pool were investigated using optical microscopy, SEM, TEM, laser Raman and NanoSIMS. The detrital pyrite grains exhibit laminated carbonaceous coatings of early Archean age, with localised enrichments of nitrogen that are interpreted as the in situ remains of biofilms growing on these nutrient-rich minerals. Pyrite surfaces contain spherical pits, chains of pits and channels that are morphologically distinct from abiotic alteration features. The pits and channels are widespread, have a clustered distribution typical of microbial colonisation, and are closely comparable to biologically mediated microstructures in the younger rock record and those created by extant Fe- and S-oxidising microbes in the laboratory. They are thus interpreted as trace fossils formed by the attachment of bacteria to the pyrite surfaces. A nano-layer and discreet nano-grains of secondary mineral precipitates, namely Fe-oxides belonging to the magnetite-maghaemite group, attest to pyrite oxidation. These are intimately associated with the biofilms and trace fossils, and are interpreted to represent the fossilised mineral products of biologically mediated pyrite oxidation. These data extend the geological range of microbes capable of metabolising reduced Fe and/or S compounds back to the early Archean and indicate that pyrite-rich sedimentary rocks provide promising targets in the search for extraterrestrial life. © 2010 Elsevier B.V