We report on a non-interferometric technique enabling dark-field imaging by using incoherent illumination and two achromatic optical elements. The simultaneous retrieval of absorption and differential phase images in the hard X-ray regime is also provided. We show that three projection images are sufficient to separate three signals: absorption, differential phase, and scattering. The method is highly efficient, also in terms of the dose delivered to the sample, flexible, robust against environmental vibrations, and scalable. It can be easily implemented in laboratories and translated into commercial systems, lending itself to a wide range of applications. V

Upregulation of p53 protein induces either growth arrest or apoptosis in response to cellular injury This is signaled from a highly conserved p53 domain between codons 64 and 92, where a functional polymorphism results in either a proline (p53-72P) or an arginine (p53-72R) at codon 72. Preliminary studies suggest that p53-72R may be a risk factor for cervical cancer and, consistent with this, preferential mutation and retention of the p53-72R allele has also been demonstrated in other cancers of squamous cell origin. Here we examine the relationship between allelic forms of p53 and nonmelanoma skin cancer, by determining the correlation with susceptibility to sunburn, which is a known risk factor, and then by p53 sequence analysis of a large series of tumors. We found a significant positive association between p53-72R and susceptibility to sunburn, as assessed by skin phototype and minimal erythemal dose following solar-simulated radiation (p = 0.0001 for trend). We also found a significant association between p53-72R homozygosity and nonmelanoma skin cancer in renal transplant recipients (basal cell carcinoma, p < 0.01; squamous cell carcinoma, p < 0.05) but not in immunocompetent patients compared with skin type matched controls. p53 sequence data revealed mutations in 30 of 70 (42.9%) nonmelanoma skin cancers, 28 (93%) of which were in the p53-72R allele. Loss of heterozygosity occurred more frequently in p53-72RP than in p53-72RR tumors (p = 0.0001) with preferential loss of p53-72P in heterozygotes (p = 0.016), irrespective of the mutant status of the concomitant allele. Together these data infer functional differences between polymorphic forms of p53 that are likely to be relevant to skin carcinogenesis.

No abstract

Polymorphic light eruption is classified as an acquired idiopathic photodermatosis, yet it appears to cluster in families, suggesting a possible genetic component. In this study, we assess the heritability of polymorphic light eruption using the classical twin model. Polymorphic light eruption was investigated by a nurse-administered questionnaire in a sample of 420 pairs of adult female twins from St Thomas' Hospital UK Adult Twin Registry, including 119 monozygotic and 301 dizygotic pairs. Probandwise concordance for the presence and absence of disease was calculated and the heritability of polymorphic light eruption assessed by a quantitative genetic model fitting approach using Mx software. The prevalence of polymorphic light eruption was 21% and 18% in monozygotic and dizygotic twins, respectively. A family history of polymorphic light eruption in first-degree relatives (not including the cotwin) was present in 12% of affected twin pairs (where at least one twin had polymorphic light eruption) compared with 4% of unaffected twin pairs, providing evidence of familial clustering (p < 0.0001). The probandwise concordance for polymorphic light eruption was higher in monozygotic (0.72) than in dizygotic twin pairs (0.30), indicating a strong genetic effect. Quantitative genetic modeling found that a model comprising additive genetic (A) and unique environmental (E) factors provided the most parsimonious fit, although a dominant gene effect could also explain our data. In the AE model, 84% (95% confidence interval 65-94%) of the variance in susceptibility to polymorphic light eruption is attributed to additive genetic factors with the remaining 16% (95% confidence interval 6-35%) to unique environmental effects. These data establish a clear genetic influence in the expression of polymorphic light eruption and provide a basis for examining candidate genes that may be pathogenic in this common condition.

Reduced bone mineral density (BMD), the major risk factor for osteoporotic fracture, has been linked to palmoplantar pustular psoriasis, but no significant studies have examined BMD in chronic plaque psoriasis (CPP). In this study, in-patients with severe CPP had their BMD measured at the nondominant hip and lumbar spine using dual energy X-ray absorbtiometry. Ten male and 10 female Caucasian patients were recruited, with a mean age of 47 years (range 20--71 years). There were no significant differences in BMD between patients and controls. However, patients with psoriatic arthropathy in addition to CPP had a significantly lower mean lumbar spine Z-score (- 1.16) than those without arthropathy (+1.38, P = 0.015). Neither previous nor current treatment with systemic steroids, retinoids or methotrexate significantly affected BMD. We found no evidence that patients with CPP, despite risk factors, have a significantly low BMD, although the subgroup with joint involvement appear be at significantly higher risk of osteoporosis and may therefore require preventative treatment.

The high prevalence of PLE in LE patients, together with clustering of PLE among first-degree relatives of SCLE and DLE probands, suggests that there may be a shared pathogenetic basis for PLE and cutaneous LE. We propose that predisposition to PLE may contribute to the LE phenotype in otherwise susceptible individuals.

A wide variety of skin conditions may present in patients with lupus erythematosus (LE). These can be broadly divided into three main groups: cutaneous forms of LE ('LE-specific skin disease'), non-specific cutaneous manifestations of SLE ('LE non-specific skin disease') and cutaneous complications of drug treatments for LE. This review examines clinical photosensitivity in LE, a trait most commonly associated with cutaneous forms of LE but which may also manifest in SLE. All humans are photosensitive, developing reddening of the skin if exposed to sufficient ultraviolet radiation (UVR). Therefore we define photosensitivity in clinical practice as an abnormal cutaneous response to UVR. Abnormal photosensitivity in LE may manifest in a number of different forms. The lesions of LE-specific skin disease may be induced or exacerbated by UVR. Patients with LE who are prescribed photosensitizing medications such as thiazide diuretics, neuroleptics and tetracyclines may also develop phototoxic reactions which usually present as easy sunburn. Photosensitivity may also, rarely, manifest as fragile skin and blistering in patients with both LE and porphyria cutanea tarda. Several other photosensitive disorders have been reported in association with LE, including solar urticaria and erythropoetic protoporphyria (EPP), but these appear to be chance associations. Assessment of patients with LE and photosensitivity requires a careful history and examination. Phototesting and photoprovocation tests may be used to demonstrate photosensitivity in some cases, but these are rarely required for diagnosis. Photosensitive patients should be advised about sun avoidance, photoprotection and sunscreen use as a first line treatment.

Here we present a general alignment algorithm for an edge illumination x-ray phase contrast imaging system, which is used with the laboratory systems developed at UCL. It has the flexibility to be used with all current mask designs, and could also be applied to future synchrotron based systems. The algorithm has proved to be robust experimentally, and can be used for the automatization of future commercial systems through automatic alignment and alignment correction.