Sensitivity to environmental irritants and quality of life in COPD

It is a common clinical experience that patients with chronic obstructive pulmonary disease (COPD) complain of airway symptoms provoked by environmental irritants like chemicals and scents, although few studies can confirm such connections. The aim was to study the prevalence of airway symptoms induced by chemicals and scents in a group of patients with newly diagnosed CPOD and to analyze any relation to illness severity and quality of life. Eighty-one patients with COPD were recruited to the study. By mail they were asked to answer three questionnaires regarding symptoms, quality of life, and social and emotional influence of airway symptoms induced by environmental irritants. A majority (62%) of the COPD patients claimed to be hyperreactive to chemicals and scents. As a group they scored higher on a questionnaire measuring social and emotional influences of such environmental irritants compared to healthy control subjects. Further, high scores were more common among patients with a very severe form of COPD and among patients with regular use of β2-stimulants. High scores were also associated with significantly more airway symptoms and, in some aspects, with impaired quality of life. In conclusion, the results of this study show that airway symptoms induced by environmental irritants are common in patients with COPD and that this increased airway sensitivity follows the impairment of lung capacity. The mechanisms behind this remain unclear

Identification of bacterial and fungal components in tobacco and tobacco smoke

The microbiological composition of tobacco products was studied using culture and chemical analysis (of tobacco leaves) or chemical analysis only (tobacco and tobacco smoke). The chemical analyses utilized gas chromatography-tandem mass spectrometry for determining 3-hydroxy fatty acids, muramic acid, and ergosterol as markers of respectively lipopolysaccharide (LPS), peptidoglycan, and fungal biomass. Mesophilic bacteria dominated in both fresh and cured tobacco leaves; a range of additional bacteria and fungi were also found albeit in minor amounts. The peptidoglycan and LPS concentrations were approximately the same in tobacco leaves as in cigarette tobacco. The concentrations of the measured microbial components were much lower in some cigarettes locally produced in China, Korea, and Vietnam than in cigarettes of international brands purchased in the same countries, and the concentrations in the smoke were in general agreement with the concentrations in cigarette tobacco. No differences in microbial load in tobacco of "light" and "full flavor" cigarettes were seen. Storing cigarettes at high humidity resulted in elevated levels of fungi in the cigarette tobacco leading to increased ergosterol concentrations in the smoke. The fact that tobacco smoke is a bioaerosol may help to explain the high prevalence of respiratory disorders among smokers and non-smokers exposed to second hand smoke since the same symptoms are also commonly associated with exposure to bioaerosols

1060 nm Single-Mode VCSEL and Single-Mode Fiber Links for Long-Reach Optical Interconnects

We investigate the use of a 1060 nm single-mode vertical-cavity surface-emitting laser (VCSEL) and a 1060 nm single-mode fiber as a competitive single-mode technology for cost-and power-efficient long-reach optical interconnects. Error-free transmission (bit error rate < 10-12) over 2 km is demonstrated at bitrates up to 40 Gb/s under on-off keying non-return-to-zero (OOK-NRZ) modulation, without equalization, forward-error correction, or other forms of digital signal processing. The VCSEL is extensively characterized with respect to its static and dynamic performances, including the power-voltage-current characteristics, spectral characteristics, beam divergence, modulation response, relative intensity noise, and frequency chirp. The measured dependence of power penalty on fiber length is consistent with an analysis of chirp-induced pulse compression and broadening along the negative chromatic dispersion fiber

Two-level system with noise: Blue's function approach

By using the random matrix approach and generalized Blue's function representation we solve analytically the model of an effective two-level system coupled to a noise reservoir. We show that calculated spectral properties of the system are in agreement with the numerically simulated results. We outline possible applications of the model in the field of condensed phase reactions.Comment: 17 pages LaTeX, 5 EPS figures include

Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

<p>Abstract</p> <p>Background</p> <p>The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP.</p> <p>Methods</p> <p>Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-γ 200 U/ml and/or tumor necrosis factor (TNF)-α, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC.</p> <p>Results</p> <p>At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-γ and TNF-α treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN-γ, but not TNF-α, treatments.</p> <p>Conclusions</p> <p>All of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation.</p

Impacts of direct payments – lessons for CAP post-2020 from a quantitative analysis

In this report we aim to analyse the economic and environmental impacts of Pillar I direct payments, and to demonstrate alternative instruments that are better suited to achieve CAP objectives. The instruments—a targeted payment to land at risk of abandonment and a tax on mineral fertilisers—were selected on the basis of the Polluter Pays and Provider Gets Principles. We do this using two state‐of‐the‐art agricultural economic simulation models. The first model, CAPRI, is used to quantify the large‐scale or aggregate impacts for individual countries, the EU and the world. The other model, AgriPoliS, is used to quantify the fine‐scale or farm and field level impacts in a selection of contrasting agricultural regions, to consider the potential influence of the large spatial variability in agricultural and environmental conditions across the EU. The results show that direct payments are keeping more farms in the sector and more land in agricultural use than would otherwise be the case, and thus avoiding land abandonment, principally in marginal regions. Particularly the area of grassland is substantially higher, because it is generally less productive than arable land and hence more dependent on direct payments for keeping it in agricultural use. The magnitudes of the impacts of direct payments on land use therefore vary strongly across regions due to spatial variability in productivity: marginal regions with large areas of less productive land are heavily influenced by direct payments, while regions with large areas of relatively productive land are hardly affected, because this land would be farmed in any case. By keeping more farmers in the sector longer, direct payments are slowing structural change, which can hamper agricultural development. However the potential benefits of faster structural change vary considerably among our study regions. In relatively productive regions direct payments are hindering development, because too many farmers are staying in the sector and preventing the consolidation of land in larger farms, which would improve their competitiveness and increase farm profits. On the contrary, the mass departure of farms that is currently avoided, will not lead to the same general benefits in marginal regions. Instead of freed land being absorbed by remaining farms, large areas of relatively unproductive land are abandoned without payments. This land is unprofitable to maintain in agricultural land use, even if integrated into larger farms, because current market prices are too low to motivate farming it. Consequently direct payments pose a serious goal conflict: the avoidance of land abandonment on the one hand, which can have negative impacts on public goods, and restricting agricultural development on the other hand. Once again this goal conflict is rooted in the spatial variability of agricultural conditions in the EU. Maintaining extensively managed farmland, particularly semi‐natural pastures, is central for conservation of biodiversity and preservation of the cultural landscape. Therefore direct payments are contributing to the provisioning of these public goods, but principally in marginal areas. Further, abandonment of land can reduce its agricultural productivity due to erosion or afforestation. Thus, direct payments are contributing to food security by preserving the productive potential of land for the future, but only marginal land since relatively productive land is farmed in any case. Production of agricultural commodities is affected to a lesser degree by direct payments than land use per se. Nevertheless, food exports from the EU are higher and imports lower as a consequence of direct payments. However, the additional supply generated by direct payments also lowers output prices, which reduces the profitability of commodity production; thereby partially offsetting the additional revenues from direct payments. The higher agricultural output brought about by direct payments causes higher levels of environmentally damaging greenhouse‐gas emissions, nutrient surpluses and pesticide use. The higher greenhouse‐gas emissions for the EU are, to some extent, moderated by lower emissions in the rest of the world. Nevertheless, the net effect of direct payments is higher global emissions of greenhouse gases. The environmental impacts of higher nutrient surpluses and pesticide inputs are less conclusive, since these depend also on spatial factors, i.e., where the emissions occur. Although EU‐scale and regional emissions are higher due to direct payments, agricultural production is less intensive generally, on account of the lower output prices. Analysing the net effects of these two opposing forces requires additional biophysical modelling at relevant spatial scales, such as watersheds or landscapes, which is beyond the scope of this study. Pillar I direct payments generate a significant transfer of income to farmers and land owners who are not necessarily farmers; 40 billion euro annually. Of this transfer a substantial proportion goes to farmers in relatively productive regions and, further, to a minority of farmers that need them least. In relatively productive regions payments are not needed for continued agricultural production and preservation of farmland, but instead rather fuel higher land and rental prices, which hampers structural change. On the contrary, the need for support is greatest in marginal regions, because some form of payment to marginal land is needed to avoid its abandonment and the loss of associated public goods. Finally, the direct payments even come at the cost of lower market returns for farmers due to slower structural change (smaller and less competitive farms) and lower output prices (due to greater EU output). On the other hand the lower output prices lead to somewhat lower food prices, but at the greater cost of financing the direct payments. Our main conclusion is that Pillar I direct payments are generating serious goal conflicts due to spatial variability in conditions across the EU. On the one hand these payments are contributing to the provisioning of public goods by preserving marginal agricultural land. On the other hand they are hampering agricultural development, primarily in relatively productive regions. Payments to relatively productive land that would be farmed any way not only inflate land values (capitalisation) but also slow structural change, which are both likely to hinder agricultural development and hence the competitiveness of the EU on the global market. The direct payments also increase environmental pressure; by subsidising land use generally and the associated production, they are incapable of controlling environmentally damaging emissions, which is also in conflict with broad CAP objectives. The goal conflict arises because direct payments are universal, a payment principal that does not consider spatial variability in the EU and the associated trade‐offs in regard to development and environmental effectiveness. Our analysis considered two alternative policy instruments that have the potential to curb the identified goal conflicts associated with direct payments, by applying the Polluter Pays and Provider (of public goods) Gets Principles at appropriate spatial scales. Replacing direct payments with a payment targeted on marginal land (and associated public goods) prevents land abandonment at a lower cost, by avoiding payments to relatively productive land that is farmed in any case. This also allows surviving farms in regions with relatively productive land to compensate for lost direct payments through expansion and associated scale economies, as well as higher output prices. This instrument therefore finances the provisioning of public goods without adverse effects on development and the efficiency of agricultural production. The EU‐wide tax on mineral fertiliser demonstrates that this instrument has the potential to reduce nutrient surpluses. Since direct payments cause higher levels of polluting emissions, policy instruments targeting emissions at relevant spatial scales are needed to achieve cost‐effective abatement. Overall we find that Pillar I direct payments are not addressing the diversity of challenges facing European agriculture. In fact our quantitative analysis indicates that the potential for the current system to meet these challenges is seriously impaired by goal conflicts and spatial variability across the EU. A better policy requires that instruments are targeted on desired outcomes and designed according to sound principles, specifically the Polluter Pays and Provider Gets Principles. These principles would ensure that farmers are provided with appropriate incentives to i) generate public goods that otherwise would be underprovided; ii) mitigate environmentally damaging emissions at the lowest possible cost to society; and iii) continually strive to improve environmental performance. Such instruments are also fairer and promote a more competitive or viable agricultural sector by not obstructing structural change and hence agricultural development

Serum levels of Cartilage Oligomeric Matrix Protein (COMP) increase temporarily after physical exercise in patients with knee osteoarthritis

BACKGROUND: COMP (Cartilage oligomeric matrix protein) is a matrix protein, which is currently studied as a potential serum marker for cartilage processes in osteoarthritis (OA). The influence of physical exercise on serum COMP is not fully elucidated. The objective of the present study was to monitor serum levels of COMP during a randomised controlled trial of physical exercise vs. standardised rest in individuals with symptomatic and radiographic knee OA. METHODS: Blood samples were collected from 58 individuals at predefined time points before and after exercise or rest, one training group and one control group. The physical exercise consisted of a one-hour supervised session twice a week and daily home exercises. In a second supplementary study 7 individuals were subjected to the same exercise program and sampling of blood was performed at fixed intervals before, immediately after, 30 and 60 minutes after the exercise session and then with 60 minutes interval for another five hours after exercise to monitor the short-term changes of serum COMP. COMP was quantified with a sandwich-ELISA (AnaMar Medical, Lund, Sweden). RESULTS: Before exercise or rest no significant differences in COMP levels were seen between the groups. After 60 minutes exercise serum COMP levels increased (p < 0.001). After 60 minutes of rest the serum levels decreased (p = 0.003). Median serum COMP values in samples obtained prior to exercise or rest at baseline and after 24 weeks did not change between start and end of the study. In the second study serum COMP was increased immediately after exercise (p = 0.018) and had decreased to baseline levels after 30 minutes. CONCLUSION: Serum COMP levels increased during exercise in individuals with knee OA, whereas levels decreased during rest. The increased serum COMP levels were normalized 30 minutes after exercise session, therefore we suggest that samples of blood for analysis of serum COMP should be drawn after at least 30 minutes rest in a seated position. No increase was seen after a six-week exercise program indicating that any effect of individualized supervised exercise on cartilage turnover is transient

1060 nm VCSELs for long-reach optical interconnects

Reach extension of high capacity optical interconnects based on vertical-cavity surface-emitting lasers (VCSELs) and multimode fibers (MMFs), as needed for large-scale data centers, would benefit from high-speed GaAs-based VCSELs at 1060 nm. At this wavelength, the chromatic dispersion and attenuation of the optical fiber are much reduced in comparison with 850 nm. We present single and multimode 1060 nm VCSELs based on designs derived partly from our high-speed 850 nm VCSEL designs. The single-mode VCSEL, with a modulation bandwidth exceeding 22 GHz, supports back-to-back data rates up to 50 Gbps at 25 \ub0C and 40 Gbps at 85 \ub0C under binary NRZ (OOK) modulation. Using mode-selective launch, we demonstrate error-free 25 Gbps transmission over 1000 m of 1060 nm optimized MMF. Higher data rates and/or longer distances will be possible with equalization, forward-error-correction, and/or multilevel modulation

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis