Validation of the 'polymorphic light eruption severity index'.
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Adult↗
Biomedical subjects
A R Young
Publications and source records attributed to A R Young.
Estimating population served by sewage treatment works from readily available GIS data.
Environmental risk assessment of household chemicals at the catchment scale requires an estimate of the load at individual Sewage Treatment Works (STWs). This can be achieved based upon population served and market consumption data. Although the population served is difficult to obtain, this paper shows that reasonable estimates can be made using readily available spatially referenced data. A new method is developed using STW data from the Exe and the Aire and Calder catchments and validated using 193 STWs within the Environment Agency's Anglian region. The estimated populations served were compared with available estimates of Population Equivalents (PEs). The population estimates were broadly similar to PEs for small works but agreement was lower for larger plants. The discrepancy for larger works is consistent with trade influent inclusion in the PE. The method is suitable for application to both rural areas and large urbanised areas, although the interpretation of corroborating data becomes increasingly difficult in very large urban areas serving more than one STW.
Geographic Information Systems↗
Measurement of neutrino oscillation with KamLAND: evidence of spectral distortion.
We present results of a study of neutrino oscillation based on a 766 ton/year exposure of KamLAND to reactor antineutrinos. We observe 258 nu (e) candidate events with energies above 3.4 MeV compared to 365.2+/-23.7 events expected in the absence of neutrino oscillation. Accounting for 17.8+/-7.3 expected background events, the statistical significance for reactor nu (e) disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from nu (e) oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2). A global analysis of data from KamLAND and solar-neutrino experiments yields Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2) and tan((2)theta=0.40(+0.10)(-0.07), the most precise determination to date.
Journal Article↗
Dispersion of helically corrugated waveguides: analytical, numerical, and experimental study.
Helically corrugated waveguides have recently been studied for use in various applications such as interaction regions in gyrotron traveling-wave tubes and gyrotron backward-wave oscillators and as a dispersive medium for passive microwave pulse compression. The paper presents a summary of various methods that can be used for analysis of the wave dispersion of such waveguides. The results obtained from an analytical approach, simulations with the three-dimensional numerical code MAGIC, and cold microwave measurements are analyzed and compared.
Journal Article↗
Promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK tumour suppressor genes in granulosa cell tumours (GCTs) of ovarian origin.
Ovarian carcinoma (OC) is a leading cause of death among women throughout the world. A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during tumorigenesis. We tested the hypothesis that methylation status of MGMT, CDH1, RAR-beta and SYK could be important in the ovarian tumorigenic process and can lead to the gene(s) inactivation. Therefore, we assessed the promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK in 43 ovarian granulosa cell tumours (GCTs) (adult type) using methylation-specific PCR. These tumours are relatively rare, accounting for approximately 3% of all ovarian cancers. Hypermethylation of MGMT (in 14 tumours), CDH1 (in nine tumours), RAR-beta (in eight tumours) and SYK (in seven tumours) have been found. Selective loss of RAR-beta and RAR-beta2 mRNA has been found in seven patients, while that of MGMT and SYK in three patients who also show aberrant methylation in promoter region of RAR-beta in addition to MGMT, SYK and CDH1 genes. Promoter CpG hypermethylation may be an alternative to mutation(s) to inactivate tumour suppressor genes such as MGMT, CDH1, RAR-beta and SYK, and this can also be an early event in the pathogenesis of OCs. Moreover, hypermethylation of the MGMT and CDH1, MGMT and RAR-beta and CDH1 and RAR-beta promoters occurred concordantly (P< 0.001, 0.0421 and 0.0005 respectively; Fischer's exact test). In addition to this, monosomy 22 and trisomy 14 have also been found in 10 tumours. It is clear from the results that hypermethylation of the promoter region of these tumour suppressor genes, monosomy 22 and trisomy 14, may be critical steps in the tumorigenesis, which consequently play a permissive role for tumour aggressiveness. All these events might play an important role in the early clinical diagnosis of the disease. Our results, therefore, suggest a potential role for epigenetic modification of these critical tumour suppressor genes in pathways relevant to the transformation and differentiation of rare type of ovarian cancer (GCTs).
Adult↗
High sensitivity search for nu;e's from the sun and other sources at KamLAND.
Data corresponding to a KamLAND detector exposure of 0.28 kton yr has been used to search for nu;(e)'s in the energy range 8.3<E(nu;(e))<14.8 MeV. No candidates were found for an expected background of 1.1+/-0.4 events. This result can be used to obtain a limit on nu;(e) fluxes of any origin. Assuming that all nu;(e) flux has its origin in the Sun and has the characteristic 8B solar nu(e) energy spectrum, we obtain an upper limit of 3.7 x 10(2) cm(-2) s(-1) (90% C.L.) on the nu;(e) flux. We interpret this limit, corresponding to 2.8 x 10(-4) of the standard solar model 8B nu(e) flux, in the framework of spin-flavor precession and neutrino decay models.
Journal Article↗
A simple method to assess severity of polymorphic light eruption.
BACKGROUND: The severity of polymorphic light eruption (PLE) is highly variable. The results of studies of the prevalence, pathogenesis, provocation and treatment of PLE may be highly dependent on the severity of disease in the patients studied. OBJECTIVES: To produce a simple, valid and reproducible method to assess the severity of PLE. PATIENTS AND METHODS: Eighty patients were asked about the PLE they had experienced during the preceding 12 months, using a standardized interview comprising 16 questions. The answer to each question received a score. A PLE Severity Index (PLESI) was formulated, consisting of 10 questions, with a possible total score of 2-100. The internal consistency of the PLESI (the extent to which the responses to different questions correlated with each other) was assessed by reliability analysis, using Cronbach's method. Twenty patients were re-interviewed 7-27 days later to assess the repeatability of the PLESI. The ease of provocation of PLE by exposure at 24-h intervals to solar-simulated radiation was assessed on a five-point scale in nine of the 80 subjects (the EOPSSR score). RESULTS: The value of Cronbach's alpha for the PLESI was 0.77. The distribution of the PLESI was consistent with a normal distribution, with a mean value of 52.7 and standard deviation of 19.4. It had a coefficient of repeatability of 20.1. The PLESI was positively correlated with EOPSSR (rs =0.69, P = 0.039) and the number of years since onset of PLE (rs = 0.25, P = 0.03). There was no association between the PLESI and the duration of persistence of the eruption after ceasing sun exposure (rs = 0.12, P = 0.30), the development of tolerance as summer progressed (rs = -0.14, P = 0.39), gender (P = 0.50) or skin type (P = 0.87). CONCLUSIONS: This study has (i) validated the concept that a single score can reflect disease severity in PLE by showing that the principal characteristics of the condition, including, for example, the extent of anatomical distribution and the ease of provocation of the eruption, correlate with each other; (ii) formulated the PLESI, which is a simple, valid and reproducible way of assessing disease severity; we suggest it could be used worldwide to determine the severity of PLE among patients enrolled in future PLE research; (iii) shown that the ease with which the eruption is provoked by solar-simulated radiation correlates with the severity of the condition; and (iv) shown that the duration of persistence of the eruption after sun exposure does not correlate with the severity of the condition.
Adolescent↗
First results from KamLAND: evidence for reactor antineutrino disappearance.
KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.
Journal Article↗
Low Flows 2000: a national water resources assessment and decision support tool.
Information on the magnitude and variability of flow regimes at the river reach scale is a central component of most aspects of water resource and water quality management. However, many decisions are made within catchments for which there are no measured flow data. To meet this challenge, a suite of modelling techniques to assist in the estimation of natural and artificially influenced river-flows at ungauged sites has been developed. This paper summarises these models and how they are incorporated within the GIS framework of the Low Flows 2000 software package. The paper will also describe the implementation of Low Flows 2000 within England and Wales by the Environment Agency, and the use of the system in supporting the implementation of the Environment Agency's Catchment Abstraction Management Strategy. This strategy is focused on the delivery of sustainable abstraction licensing and will contribute to the implementation of the Water Framework Directive within England and Wales.
Decision Support Techniques↗
Measurements of ultracold-neutron lifetimes in solid deuterium.
We present the first measurements of the survival time of ultracold neutrons (UCNs) in solid deuterium (SD2). This critical parameter provides a fundamental limitation to the effectiveness of superthermal UCN sources that utilize solid ortho-deuterium as the source material. These measurements are performed utilizing a SD2 source coupled to a spallation source of neutrons, providing a demonstration of UCN production in this geometry and permitting systematic studies of the influence of thermal up-scatter and contamination with para-deuterium on the UCN survival time.
Journal Article↗
Relationship between 2,4-dinitrochlorobenzene elicitation responses and individual irritant threshold.
Contact dermatitis shows significant interindividual variation. We studied the relationship between an individual's irritant threshold and the elicitation of experimentally induced allergic sensitization. The results suggest that there is an association between reactivity to an irritant and the likelihood of positive elicitation reactions to lower hapten concentrations. This novel finding would be compatible with the proposal that contact allergy is best explained using a danger model with cutaneous irritancy determining sensitization. However, the enhanced allergic reactivity of individuals with a lower irritant threshold was not apparent on visual inspection, suggesting that the determinants of skin reactivity to haptens are multifactorial.
Adult↗
Matrix metalloproteinase-1 and skin ageing in smokers.
Smokers look older than non-smokers of the same age. We have compared the concentrations of mRNA for matrix metalloproteinase 1 (MMP-1) in the buttock skin of smokers and non-smokers with quantitative real-time polymerase chain reactions. MMP-1 degrades collagen, which accounts for at least 70% of the dry weight of dermis. We report significantly more MMP-1 mRNA in the skin of smokers than non-smokers whereas no difference was seen for the tissue inhibitor of metalloproteinases 1 (TIMP-1) or the housekeeping gene GAPDH (glyceraldehyde-3-phosphate dehydrogenase). We suggest that smoking-induced MMP-1 might be important in the skin-ageing effects of tobacco smoking.
Adult↗
The molecular determinants of sunburn cell formation.
Sunburn cell (SBC) formation in the epidermis is a characteristic consequence of ultraviolet radiation (UVR) exposure at doses around or above the minimum erythema dose. SBC have been identified morphologically and biologically as keratinocytes undergoing apoptosis. There is evidence that SBC formation is a protective mechanism to eliminate cells at risk of malignant transformation. The level of DNA photodamage is a major determinant of SBC induction by a process controlled by the tumor suppressor gene p53. However, extra-nuclear events also contribute to SBC formation, such as the activation of death receptors including CD95/Fas. UVR triggers death receptors either by direct activation of these surface molecules or by inducing the release of their ligands such as CD95 ligand or tumor necrosis factor. Oxidative stress also appears to be involved, probably via mitochondrial pathways, resulting in the release of cytochrome C. Pathways which modify SBC formation are now extensively studied given the importance of apoptosis in eliminating irreparably damaged cells. A greater understanding of the mechanisms that induce and prevent UVR-induced apoptosis will contribute to our understanding of mechanisms relevant in genomic integrity.
Animals↗
Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells and CD11b+ macrophages in human skin.
BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.
Adult↗
Starving the brain: structural abnormalities and cognitive impairment in adolescents with anorexia nervosa.
Anorexia nervosa (AN) is one of the most common chronic illnesses afflicting adolescent girls and is associated severe medical complications. The structural abnormalities found in the brain of adolescents with AN are among the earliest and most striking physical consequences. In the past, it had been assumed that the brain abnormalities found in patients with AN reverse with weight-recovery. Recent evidence has shown that not all of these changes are completely reversible with weight recovery. To date, very little is known about the functional significance of these brain abnormalities. Several studies have shown that cognitive dysfunction is also a common feature of AN. Although current evidence suggests that there may be some degree of improvement in cognition with weight-recovery, it is unclear whether cognition recovers fully or equally across all neuropsychological domains. Furthermore, it remains unknown whether the reported functional consequences are associated with these structural brain changes. This article will review the current literature on structural brain abnormalities and cognitive dysfunction in adolescents with AN.
Anorexia Nervosa↗
Induction of mRNA for matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 in human skin in vivo by solar simulated radiation.
Repeated exposure to solar ultraviolet radiation results in premature skin aging due, in part, to the degradation of dermal collagen by fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). We have established TaqMan reverse transcription (RT) polymerase chain reaction (PCR) systems to quantify the messenger RNA (mRNA) expression of MMP-1 and its specific inhibitor TIMP-1 in human buttock skin exposed in vivo to solar simulated radiation (SSR). A time-course study (n = 6) with two minimal erythema doses (MED) of SSR showed maximal induction of MMP-1 and TIMP-1 at 24 h. A dose-response study (n = 6) sampled at 24 h revealed that doses of about 1 MED were necessary to induce expression of MMP-1 mRNA, and our data suggest that the response is saturated at about 2 MED. We also investigated SSR-induced gene expression in the dermis and epidermis separately (n = 5). MMP-1 was present in both tissues, but TIMP-1 was only detected in the dermis. In general, we could only measure MMP-1 mRNA in the nonirradiated control skin of volunteers who were smokers. We hypothesize very large interpersonal variation with MMP-1 induction compared with TIMP-1 which was detected in all the control sites. This suggests a lack of relationship between MMP-1 and TIMP-1 mRNA expression. The large donor variability for MMP-1 in all the studies demonstrates that it is important to analyze gene expression individually.
Adult↗
More about: Sunscreen use and duration of sun exposure: a double-blind, randomized trial.
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Adult↗
Sensitivity to sunburn is associated with susceptibility to ultraviolet radiation-induced suppression of cutaneous cell-mediated immunity.
Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer.
Adult↗