The effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study.

BACKGROUND Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channelling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient years). In a conventional Cox model, recent - but not cumulative - exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past four years increased the risk of a CVD event (hazard ratio 2.06, 95% confidence interval 1.43-2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6 to 36 months caused the greatest increase in risk. CONCLUSIONS Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

Characterization of thin film PV modules under standard test conditions: Results of indoor and outdoor measurements and the effects of sunlight exposure

Photovoltaic modules based on thin film technology are gaining importance in the photovoltaic market, and module installers and plant owners have increasingly begun to request methods of performing module quality control. These modules pose additional problems for measuring power under standard test conditions (STC), beyond problems caused by the temperature of the module and the ambient variables. The main difficulty is that the modules’ power rates may vary depending both on the amount of time they have been exposed to the sun during recent hours and on their history of sunlight exposure. In order to assess the current state of the module, it is necessary to know its sunlight exposure history. Thus, an easily accomplishable testing method that ensures the repeatability of the measurements of the power generated is needed. This paper examines different tests performed on commercial thin film PV modules of CIS, a-Si and CdTe technologies in order to find the best way to obtain measurements. A method for obtaining indoor measurements of these technologies that takes into account periods of sunlight exposure is proposed. Special attention is paid to CdTe as a fast growing technology in the market.

Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin

The presence of endotoxin from Gram-negative bacteria signals the innate immune system to up-regulate bacterial clearance and/or killing mechanisms. Paradoxically, such responses also contribute to septic shock, a clinical problem occurring with high frequency in Gram-negative septicemia. CD14 is a receptor for endotoxin (lipopolysaccharide, LPS) and is thought to have an essential role in innate immune responses to infection and thereby in the development of septic shock. Using a novel rabbit model of endotoxic shock produced by multiple exposures to endotoxin, we show that anti-rabbit CD14 mAb, which blocks LPS-CD14 binding, protects against organ injury and death even when the antibody is administered after initial exposures to LPS. In contrast, anti-rabbit tumor necrosis factor mAb treatment fails to protect when administered after LPS injections. These results support the concept that anti-CD14 treatment provides a new therapeutic window for the prevention of pathophysiologic changes that result from cumulative exposures to LPS during septic shock in man.

Association between in-utero exposure to diesel exhaust and N-acetyl-cysteine supplementation in hyperlipidemic pregnant mice and development of atherosclerosis at multiple vascular sites in the offspring

Thesis (Master's)--University of Washington, 2016-06

Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstuffs and Cigarette Smoke

Cadmium is a cumulative nephrotoxicant that is absorbed into the body from dietary sources and cigarette smoking. The levels of Cd in organs such as liver and kidney cortex increase with age because of the lack of an active biochemical process for its elimination coupled with renal reabsorption. Recent research has provided evidence linking Cd-related kidney dysfunction and decreases in bone mineral density in nonoccupationally exposed populations who showed no signs of nutritional deficiency. This challenges the previous view that the concurrent kidney and bone damage seen in Japanese itai-itai disease patients was the result of Cd toxicity in combination with nutritional deficiencies, notably, of zinc and calcium. Further, such Cd-linked bone and kidney toxicities were observed in people whose dietary Cd intakes were well within the provisional tolerable weekly intake (PTWI) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives of 1 mug/kg body weight/day or 70 mug/day. This evidence points to the much-needed revision of the current PTWI for Cd. Also, evidence for the carcinogenic risk of chronic Cd exposure is accumulating and Cd effects on reproductive outcomes have begun to emerge.

Primary prevention of skin cancer: A review of sun protection in Australia and internationally

The incidence of skin cancer is increasing worldwide. Protecting the skin from the sun by wearing protective clothing, using a sunscreen with appropriate sun protection factor, wearing a hat, and avoiding the sun are recommended as primary preventive activities by cancer agencies. In this paper the recent data relating to skin cancer primary preventive behaviour in Australia and other countries is reviewed. Comparison of the studies in a table format summarizing the methods, objectives, participants, findings and implications may be obtained from the corresponding author. The sun protection knowledge, attitudes and behaviour patterns observed in Australia are similar in other countries, although Australian studies generally, report higher knowledge levels about skin cancer and higher levels of sun protection. The findings suggest that sunscreen is the most frequent method of sun protection used across all age groups, despite recommendations that it should be at? adjunct to other forms of protection. While young children's sun protective behaviour is largely influenced by their parents' behaviours, they are still tinder protected, and sun protective measures such as seeking shade, avoiding the sun and protective clothing need to be emphasized. Adolescents have the lowest skin protection rates of all age groups. Within the adult age range, women and people with sensitive skin were most likely to be using skin protection. However, women were also more likely than men to sunbath deliberately and to use sun-tanning booths. The relationship between skin protection knowledge and attitudes, attitudes towards tanning and skin protection behaviour needs further investigation. Further studies need to include detailed assessments of sunscreen use and application patterns, and future health promotion activities need to focus on sun protection by wearing clothing and seeking shade to avoid increases in the sunburn rates observed to date.

Expression of p53 tumor suppressor protein in sun-exposed skin and associations with sunscreen use and time spent outdoors: A community-based study

The p53 gene is a tumor suppressor gene that is commonly mutated in skin cancer and sun-exposed skin, and this can be detected through immunohistochemical expression of the p53 protein. The authors hypothesized that time spent outdoors is associated with p53 protein expression in human skin and that sunscreen use counteracts the association. In 1996, they investigated this in a community-based cross-sectional study in Australia. Detailed information about skin type, time spent outdoors, and sunscreen use was collected from 139 residents of a subtropical township who also provided a skin biopsy from the back of the hand for measurement of p53 expression. Increasing time spent outdoors was positively associated with immuno reactivity in the whole epidermis and in the basal layer of the epidermis. After adjustment for confounders, p53 immunoreactivity was twice as high for people who used sunscreen 1 or 2 days per week as for those who used sunscreen daily (whole epidermis: ratio estimate = 2.0, 95% confidence interval: 1.1, 3.6; basal layer: ratio estimate = 1.7, 95% confidence interval: 0.9, 3.1). The authors conclude that p53 immunoreactivity in the skin is a marker of exposure to ultraviolet light in the past 6 months, but this may be mitigated by regular application of sunscreen.

Ultraviolet damage to the eye revisited:eye-sun protection factor (E-SPF®), a new ultraviolet protection label for eyewear

Ultraviolet (UV) radiation potentially damages the skin, the immune system, and structures of the eye. A useful UV sun protection for the skin has been established. Since a remarkable body of evidence shows an association between UV radiation and damage to structures of the eye, eye protection is important, but a reliable and practical tool to assess and compare the UV-protective properties of lenses has been lacking. Among the general lay public, misconceptions on eye-sun protection have been identified. For example, sun protection is mainly ascribed to sunglasses, but less so to clear lenses. Skin malignancies in the periorbital region are frequent, but usual topical skin protection does not include the lids. Recent research utilized exact dosimetry and demonstrated relevant differences in UV burden to the eye and skin at a given ambient irradiation. Chronic UV effects on the cornea and lens are cumulative, so effective UV protection of the eyes is important for all age groups and should be used systematically. Protection of children's eyes is especially important, because UV transmittance is higher at a very young age, allowing higher levels of UV radiation to reach the crystalline lens and even the retina. Sunglasses as well as clear lenses (plano and prescription) effectively reduce transmittance of UV radiation. However, an important share of the UV burden to the eye is explained by back reflection of radiation from lenses to the eye. UV radiation incident from an angle of 135°-150° behind a lens wearer is reflected from the back side of lenses. The usual antireflective coatings considerably increase reflection of UV radiation. To provide reliable labeling of the protective potential of lenses, an eye-sun protection factor (E-SPF®) has been developed. It integrates UV transmission as well as UV reflectance of lenses. The E-SPF® compares well with established skin-sun protection factors and provides clear messages to eye health care providers and to lay consumers. © 2014 Behar-Cohen et al, This work is published by Dove Medical Press Ltd.

Hough Transform Approach to Identification of Flare Stars in Multi-exposure Plate Images

ACM Computing Classification System (1998): I.2.8 , I.2.10, I.5.1, J.2.

Correlates of leaf optical properties in tropical forest sun and extreme-shade plants

Thirteens hade-adaptedr ain forest species were comparedw ith twelve sun-adaptedt ropical forest species for correlates to leaf optical properties (described previously in Amer. J. Bot. 73: 1100-1108). The two samples were similar in absorptance of quanta for photosynthesis, but the shade-adaptedt axa: 1) had significantlyl ower specificl eaf weights,i ndicatinga more metabolically efficient production of surface for quantum capture; 2) synthesized less chlorophyll per unit area; and 3) used less chlorophyll for capturing the same quanta for photosynthesis. The anatomical features that best correlate with this increased efficiency are palisade cell shape and chloroplast distribution. Palisade cells with more equal dimensions have more chloroplasts on their abaxial surfaces. This dense layer of chloroplasts maximizes the light capture efficiency limited by sieve effects. The more columnar palisade cells of sun-adapted taxa allow light to pass through the central vacuoles and spaces between cells, making chloroplasts less efficient in energy capture, but allowing light to reach chloroplasts in the spongy mesophyll. Pioneer species may be an exception to these two groups of species. Three pioneer taxa included in this study have columnar palisade cells that are extremely narrow and packed closely together. This layer allows little penetration of light, but exposure of the leaf undersurface may provide illumination of spongy mesophyll chloroplasts in these plants.

Minimization of radiation exposure due to computed tomography in inflammatory bowel disease

Patient awareness and concern regarding the potential health risks from ionizing radiation have peaked recently (Coakley et al., 2011) following widespread press and media coverage of the projected cancer risks from the increasing use of computed tomography (CT) (Berrington et al., 2007). The typical young and educated patient with inflammatory bowel disease (IBD) may in particular be conscious of his/her exposure to ionising radiation as a result of diagnostic imaging. Cumulative effective doses (CEDs) in patients with IBD have been reported as being high and are rising, primarily due to the more widespread and repeated use of CT (Desmond et al., 2008). Radiologists, technologists, and referring physicians have a responsibility to firstly counsel their patients accurately regarding the actual risks of ionizing radiation exposure; secondly to limit the use of those imaging modalities which involve ionising radiation to clinical situations where they are likely to change management; thirdly to ensure that a diagnostic quality imaging examination is acquired with lowest possible radiation exposure. In this paper, we synopsize available evidence related to radiation exposure and risk and we report advances in low-dose CT technology and examine the role for alternative imaging modalities such as ultrasonography or magnetic resonance imaging which avoid radiation exposure.

REIT Capital Structure Choices: Preparation Matters

Sun, Titman, and Twite (2015) find that capital structure risks, namely high leverage and a high share of short-term debt, reduced the cumulative total return of US REITs in the 2007-2009 financial crisis. We find that mitigating capital structure risks ahead of the crisis by reducing leverage and extending debt maturity in 2006, was associated with a significantly higher cumulative total return 2007-2009, after controlling for the levels of those variables at the start of the financial crisis. We further identify two systematic cross-sectional differences between those REITs that reduced capital structure risks prior to the financial crisis and those that did not: the exposure to capital structure risks and the strength of corporate governance. On balance, our findings are consistent with the interpretation of risk-reducing adjustments to capital structure ahead of the crisis as a component of managerial skill and discipline with significant implications for firm value during the crisis.

Is there a health risk concerning the children´s consumption of cereal-based products? A cumulative mycotoxin risk assessment approach

Historically, the health risk of mycotoxins had been evaluated on the basis of single-chemical and single-exposure pathway scenarios. However, the co-contamination of foodstuffs with these compounds is being reported at an increasing rate and a multiple-exposure scenario for humans and vulnerable population groups as children is urgently needed. Cereals are among the first solid foods eaten by child and thus constitute an important food group of their diet. Few data are available relatively to early stages child´s exposure to mycotoxins through consumption of cereal-based foods. The present study aims to perform the cumulative risk assessment of mycotoxins present in a set of cereal-based foods including breakfast cereals (BC), processed cereal-based foods (PCBF) and biscuits (BT), consumed by children (1 to 3 years old, n=75) from Lisbon region, Portugal. Children food consumption and occurrence of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) in cereal-based foods were combined to estimate the mycotoxin daily intake, using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) and aflatoxin daily exposure. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (HQ, ratio between exposure and a reference dose). The concentration addition (CA) concept was used for the cumulative risk assessment of multiple mycotoxins. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. Main results revealed a significant health concern related to aflatoxins and especially aflatoxin M1 exposure according to the MoET and MoE values (below 10000), respectively. HQ and HI values for the remaining mycotoxins were below 1, revealing a low concern from a public health point of view. These are the first results on cumulative risk assessment of multiple mycotoxins present in cereal-based foods consumed by children. Considering the present results, more research studies are needed to provide the governmental regulatory bodies with data to develop an approach that contemplate the human exposure and, particularly, children, to multiple mycotoxins in food. The last issue is particularly important considering the potential synergistic effects that could occur between mycotoxins and its potential impact on human and, mainly, children health.

Application of mathematical models to mycotoxins children risk assessment: a case study of Portuguese children exposure to co-occurring mycotoxins in processed cereal-based foods

People, animals and the environment can be exposed to multiple chemicals at once from a variety of sources, but current risk assessment is usually carried out based on one chemical substance at a time. In human health risk assessment, ingestion of food is considered a major route of exposure to many contaminants, namely mycotoxins, a wide group of fungal secondary metabolites that are known to potentially cause toxicity and carcinogenic outcomes. Mycotoxins are commonly found in a variety of foods including those intended for consumption by infants and young children and have been found in processed cereal-based foods available in the Portuguese market. The use of mathematical models, including probabilistic approaches using Monte Carlo simulations, constitutes a prominent issue in human health risk assessment in general and in mycotoxins exposure assessment in particular. The present study aims to characterize, for the first time, the risk associated with the exposure of Portuguese children to single and multiple mycotoxins present in processed cereal-based foods (CBF). Portuguese children (0-3 years old) food consumption data (n=103) were collected using a 3 days food diary. Contamination data concerned the quantification of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) were evaluated in 20 CBF samples marketed in 2014 and 2015 in Lisbon; samples were analyzed by HPLC-FLD, LC-MS/MS and GC-MS. Daily exposure of children to mycotoxins was performed using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) to the aflatoxin exposure. The magnitude of the MoE gives an indication of the risk level. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (ratio between exposure and a reference dose, HQ). For the cumulative risk assessment of multiple mycotoxins, the concentration addition (CA) concept was used. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. 71% of CBF analyzed samples were contaminated with mycotoxins (with values below the legal limits) and approximately 56% of the studied children consumed CBF at least once in these 3 days. Preliminary results showed that children exposure to single mycotoxins present in CBF were below the TDI. Aflatoxins MoE and MoET revealed a reduced potential risk by exposure through consumption of CBF (with values around 10000 or more). HQ and HI values for the remaining mycotoxins were below 1. Children are a particularly vulnerable population group to food contaminants and the present results point out an urgent need to establish legal limits and control strategies regarding the presence of multiple mycotoxins in children foods in order to protect their health. The development of packaging materials with antifungal properties is a possible solution to control the growth of moulds and consequently to reduce mycotoxin production, contributing to guarantee the quality and safety of foods intended for children consumption.

Fish Reproduction Is Disrupted upon Lifelong Exposure to Environmental PAHs Fractions Revealing Different Modes of Action

Polycyclic aromatic hydrocarbons (PAHs) constitute a large family of organic pollutants emitted in the environment as complex mixtures, the compositions of which depend on origin. Among a wide range of physiological defects, PAHs are suspected to be involved in disruption of reproduction. In an aquatic environment, the trophic route is an important source of chronic exposure to PAHs. Here, we performed trophic exposure of zebrafish to three fractions of different origin, one pyrolytic and two petrogenic. Produced diets contained PAHs at environmental concentrations. Reproductive traits were analyzed at individual, tissue and molecular levels. Reproductive success and cumulative eggs number were disrupted after exposure to all three fractions, albeit to various extents depending on the fraction and concentrations. Histological analyses revealed ovary maturation defects after exposure to all three fractions as well as degeneration after exposure to a pyrolytic fraction. In testis, hypoplasia was observed after exposure to petrogenic fractions. Genes expression analysis in gonads has allowed us to establish common pathways such as endocrine disruption or differentiation/maturation defects. Taken altogether, these results indicate that PAHs can indeed disrupt fish reproduction and that different fractions trigger different pathways resulting in different effects.