ACUTE ASEPTIC MENINGITIS IN CHILDREN

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Molecular astronomy of cool stars and sub-stellar objects

The optical and infrared spectra of a wide variety of `cool' astronomical objects including the Sun, sunspots, K-, M- and S-type stars, carbon stars, brown dwarfs and extrasolar planets are reviewed. The review provides the necessary astronomical background for chemical physicists to understand and appreciate the unique molecular environments found in astronomy. The calculation of molecular opacities needed to simulate the observed spectral energy distributions is discussed

Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits

Background Height and other anthropometric measures are consistently found to associate with differential cancer risk. However, both genetic and mechanistic insights into these epidemiological associations are notably lacking. Conversely, inherited genetic variants in tumour suppressors and oncogenes increase cancer risk, but little is known about their influence on anthropometric traits. Methods By integrating inherited and somatic cancer genetic data from the Genome-Wide Association Study Catalog, expression Quantitative Trait Loci databases and the Cancer Gene Census, we identify SNPs that associate with different cancer types and differential gene expression in at least one tissue type, and explore the potential pleiotropic associations of these SNPs with anthropometric traits through SNP-wise association in a cohort of 500,000 individuals. Results We identify three regulatory SNPs for three important cancer genes, FANCA, MAP3K1 and TP53 that associate with both anthropometric traits and cancer risk. Of particular interest, we identify a previously unrecognised strong association between the rs78378222[C] SNP in the 3' untranslated region (3'-UTR) of TP53 and both increased risk for developing non-melanomatous skin cancer (OR=1.36 (95% 1.31 to 1.41), adjusted p=7.62E−63), brain malignancy (OR=3.12 (2.22 to 4.37), adjusted p=1.43E−12) and increased standing height (adjusted p=2.18E−24, beta=0.073±0.007), lean body mass (adjusted p=8.34E−37, beta=0.073±0.005) and basal metabolic rate (adjusted p=1.13E−31, beta=0.076±0.006), thus offering a novel genetic link between these anthropometric traits and cancer risk. Conclusion Our results clearly demonstrate that heritable variants in key cancer genes can associate with both differential cancer risk and anthropometric traits in the general population, thereby lending support for a genetic basis for linking these human phenotypes

Value of EUS in Determining Curative Resectability in Reference to CT and FDG-PET: The Optimal Sequence in Preoperative Staging of Esophageal Cancer?

Background: The separate value of endoscopic ultrasonography (EUS), multidetector computed tomography (CT), and18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the optimal sequence in staging esophageal cancer has not been investigated adequately. Methods: The staging records of 216 consecutive operable patients with esophageal cancer were reviewed blindly. Different staging strategies were analyzed, and the likelihood ratio (LR) of each module was calculated conditionally on individual patient characteristics. A logistic regression approach was used to determine the most favorable staging strategy. Results: Initial EUS results were not significantly related to the LRs of initial CT and FDG-PET results. The positive LR (LR+) of EUS-fine-needle aspiration (FNA) was 4, irrespective of CT and FDG-PET outcomes. The LR+ of FDG-PET varied from 13 (negative CT) to 6 (positive CT). The LR+ of CT ranged from 3-4 (negative FDG-PET) to 2-3 (positive FDG-PET). Age, histology, and tumor length had no significant impact on the LRs of the three diagnostic tests. Conclusions: This study argues in favor of PET/CT rather than EUS as a predictor of curative resectability in esophageal cancer. EUS does not correspond with either CT or FDG-PET. LRs of FDG-PET were substantially different between subgroups of negative and positive CT results and vice versa

Perinatal mental ill health - the experiences of women from ethnic minority groups

This study aimed to investigate ethnic minority women’s experiences and opinions of perinatal mental health problems and the provision of perinatal mental health support services. An exploratory survey was undertaken using a questionnaire. Quantitative data were analysed using descriptive statistics and a simple thematic analysis was used for the qualitative data. A total of 51 responses from women of 14 different ethnic minority backgrounds were analysed. Women from minority ethnic groups face barriers to seeking help for perinatal mental ill health as a result of ongoing stigma and the poor attitudes and behaviours of health professionals and inappropriately designed services. Future interventions should focus on providing adequate cultural competency for health care professionals and ensure that all women are able to access culturally appropriate spaces to talk and be listened to within community settings and wider services

Beta-HPV E6 Contributes To Skin Cancer by Hindering DNA Repair

<div><p>Recent work has explored a putative role for the E6 protein from some β-human papillomavirus genus (β-HPVs) in the development of non-melanoma skin cancers, specifically β-HPV 5 and 8 E6. Because these viruses are not required for tumor maintenance, they are hypothesized to act as co-factors that enhance the mutagenic capacity of UV-exposure by disrupting the repair of the resulting DNA damage. Supporting this proposal, we have previously demonstrated that UV damage signaling is hindered by β-HPV 5 and 8 E6 resulting in an increase in both thymine dimers and UV-induced double strand breaks (DSBs). Here we show that β-HPV 5 and 8 E6 further disrupt the repair of these DSBs and provide a mechanism for this attenuation. By binding and destabilizing a histone acetyltransferase, p300, β-HPV 5 and 8 E6 reduce the enrichment of the transcription factor at the promoter of two genes critical to the homology dependent repair of DSBs (BRCA1 and BRCA2). The resulting diminished BRCA1/2 transcription not only leads to lower protein levels but also curtails the ability of these proteins to form repair foci at DSBs. Using a GFP-based reporter, we confirm that this reduced foci formation leads to significantly diminished homology dependent repair of DSBs. By deleting the p300 binding domain of β-HPV 8 E6, we demonstrate that the loss of robust repair is dependent on viral-mediated degradation of p300 and confirm this observation using a combination of p300 mutants that are β-HPV 8 E6 destabilization resistant and p300 knock-out cells. In conclusion, this work establishes an expanded ability of β-HPV 5 and 8 E6 to attenuate UV damage repair, thus adding further support to the hypothesis that β-HPV infections play a role in skin cancer development by increasing the oncogenic potential of UV exposure.</p></div

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Mycobacterium tuberculosis monoarthritis in a child

A child with isolated Mycobacterium tuberculosis monoarthritis, with features initially suggesting oligoarthritis subtype of juvenile idiopathic arthritis, is presented. This patient illustrates the need to consider the possibility of tuberculosis as the cause of oligoarthritis in high-risk pediatric populations even in the absence of a tuberculosis contact history and without evidence of overt pulmonary disease

Ranked Adjusted Rand: integrating distance and partition information in a measure of clustering agreement

BACKGROUND: Biological information is commonly used to cluster or classify entities of interest such as genes, conditions, species or samples. However, different sources of data can be used to classify the same set of entities and methods allowing the comparison of the performance of two data sources or the determination of how well a given classification agrees with another are frequently needed, especially in the absence of a universally accepted "gold standard" classification. RESULTS: Here, we describe a novel measure – the Ranked Adjusted Rand (RAR) index. RAR differs from existing methods by evaluating the extent of agreement between any two groupings, taking into account the intercluster distances. This characteristic is relevant to evaluate cases of pairs of entities grouped in the same cluster by one method and separated by another. The latter method may assign them to close neighbour clusters or, on the contrary, to clusters that are far apart from each other. RAR is applicable even when intercluster distance information is absent for both or one of the groupings. In the first case, RAR is equal to its predecessor, Adjusted Rand (HA) index. Artificially designed clusterings were used to demonstrate situations in which only RAR was able to detect differences in the grouping patterns. A study with larger simulated clusterings ensured that in realistic conditions, RAR is effectively integrating distance and partition information. The new method was applied to biological examples to compare 1) two microbial typing methods, 2) two gene regulatory network distances and 3) microarray gene expression data with pathway information. In the first application, one of the methods does not provide intercluster distances while the other originated a hierarchical clustering. RAR proved to be more sensitive than HA in the choice of a threshold for defining clusters in the hierarchical method that maximizes agreement between the results of both methods. CONCLUSION: RAR has its major advantage in combining cluster distance and partition information, while the previously available methods used only the latter. RAR should be used in the research problems were HA was previously used, because in the absence of inter cluster distance effects it is an equally effective measure, and in the presence of distance effects it is a more complete one