Design of composite asymmetric cellular beams and beams with large web openings

The design of composite asymmetric cellular beams is not fully covered by existing guidance but is an area of important practical application. Asymmetry in the shape of the cross-section of cellular beams causes development of additional bending moments in the web-posts between closely placed openings. Furthermore, the development of local composite action influences the distribution of forces in the web-flange Tees. The design method presented in this paper takes account of high degrees of asymmetry in the cross-section and also the influence of elongated or rectangular openings.

Multicentre randomised control trial comparing real time teledermatology with conventional outpatient dermatological care:societal cost-benefit analysis

Comparison of real time teledermatology with outpatient dermatology in terms of clinical outcomes, cost-benefits, and patient reattendance.

A comparison of real-time and store-and-forward teledermatology:a cost-benefit study

Increasing use of teledermatology should be based on demonstration of favourable accuracy and cost-benefit analysis for the different methods of use of this technique. Objectives To evaluate the clinical efficacy and cost-effectiveness of real-time and store-and-forward teledermatology.

Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

Adjustment in children with intractable epilepsy:importance of seizure duration and family factors

Seventy-five families of children with intractable epilepsy but without a severe learning disability (mean age 7 years 1 month, SD 2 years 6 months; range 2 to 12 years) who attended a regional paediatric neurology service, were surveyed. A postal questionnaire was used which included standardized measures of child and family adjustment; forty-eight families responded (64%; 31 males, 17 females). There was no significant difference between responders and non-responders in terms of age, sex, number of other chronic illnesses and disabilities, age at epilepsy diagnosis, seizure type, nor number of antiepileptic drugs currently prescribed (p > 0.05). The importance of including multidimensional measures of outcome was highlighted by the finding that epilepsy, pharmacological, and psychosocial factors were differentially associated with specific adjustment difficulties. Two factors appeared to be most pervasively implicated across a range of adjustment problems: frequency of rectal diazepam administration and family patterns of relating to each other (p <0.05). It appeared that duration of seizures (as indicated by frequency of rectal diazepam administration), rather than the frequency of seizures per se, was more pernicious in terms of poor adjustment. Intrafamilial relations (degree of conflict/cohesion and soon) were not only associated with adjustment difficulties in the child, but also with the frequency of seizures themselves. Implications for psychological interventions in intractable epilepsy in childhood are highlighted.

Psychological management of intractable seizures in an adolescent with a learning disability

Psychological interventions aimed at seizure management are described with a 14-year-old buy with a learning disability and intractable epilepsy. Baseline records suggested that a majority of tonic seizures and 'drop attacks' were associated with going off to sleep and by environmental 'startles'. Psychological formulation implicated sudden changes in arousal levels as an underlying mechanism of action. Cognitive-behavioural countermeasures were employed to alter arousal levels and processes in different ways in different 'at-risk' situations. A multiple baseline design was used to control for non-specific effects of interventions on non-targeted seizures. Results suggested significant declines in the number of sleep onset and startle-response seizures were attained by these methods. Gains were maintained at 2-month follow-up. (C) 1999 BEA Trading Ltd.

Dietary fiber and the risk of precancerous lesions and cancer of the esophagus:a systematic review and meta-analysis

Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.

Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality.

Methods: Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case–control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users.

Results: The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92).

Conclusions: Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.

Keywords: Colorectal cancer; Breast cancer; Prostate cancer; Mortality; Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study

Objective: Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases.

Design: A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed.

Results: There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect.

Conclusions: The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.

The internal structure of asteroid (25143) Itokawa as revealed by detection of YORP spin-up *’**

Context. Near-Earth asteroid (25143) Itokawa was visited by the Hayabusa spacecraft in 2005, resulting in a highly detailed shape and surface topography model. This model has led to several predictions for the expected radiative torques on this asteroid, suggesting that its spin rate should be decelerating. Aims. To detect changes in rotation rate that may be due to YORP-induced radiative torques, which in turn may be used to investigate the interior structure of the asteroid. Methods. Through an observational survey spanning 2001 to 2013 we obtained rotational lightcurve data at various times over the last five close Earth-approaches of the asteroid. We applied a polyhedron-shape-modelling technique to assess the spin-state of the asteroid and its long term evolution. We also applied a detailed thermophysical analysis to the shape model determined from the Hayabusa spacecraft. Results. We have successfully measured an acceleration in Itokawa's spin rate of dω/dt = (3.54 ± 0.38) × 10 rad day, equivalent to a decrease of its rotation period of ~45 ms year. From the thermophysical analysis we find that the centre-of-mass for Itokawa must be shifted by ~21 m along the long-axis of the asteroid to reconcile the observed YORP strength with theory. Conclusions. This can be explained if Itokawa is composed of two separate bodies with very different bulk densities of 1750 ± 110 kg m and 2850 ± 500 kg m, and was formed from the merger of two separate bodies, either in the aftermath of a catastrophic disruption of a larger differentiated body, or from the collapse of a binary system. We therefore demonstrate that an observational measurement of radiative torques, when combined with a detailed shape model, can provide insight into the interior structure of an asteroid. Futhermore, this is the first measurement of density inhomogeneity within an asteroidal body, that reveals significant internal structure variation. A specialised spacecraft is normally required for this.

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration

Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10,337 cases and 11,174 controls (OR=1.10; p-value=3.79×10(-5)). Thus, it appears that rare and common variants in a single gene - FBN2 - can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Direct Detection of YORP Spin-up on Asteroid (25143) Itokawa and Implications for its Internal Structure

Near-Earth asteroid (25143) Itokawa was visited by the Hayabusa spacecraft in 2005, resulting in a highly detailed surface shape and topography model. This model has led to several predictions for the expected radiative torques on this asteroid, suggesting that its spin rate should be decelerating. Through an observational survey spanning 2001 to 2013 we have successfully measured an acceleration in its spin rate of dω/dt = 3.54 (± 0.38) × 10^(-8) rad day^(-2), equivalent to a decrease of its rotation period of ~ 45 ms year^(-1). Using the shape model determined from the Hayabusa spacecraft, we applied a detailed thermophysical analysis, to reconcile the predicted YORP strength with that observed. We find that the center-of-mass for Itokawa must be shifted by ~20 m along the long-axis of the asteroid to reconcile observations with theory. This can be explained if Itokawa is composed of two separate bodies with very different bulk densities of 1740 ± 110 kg m^(-3) and 2730 ± 440 kg m^(-3), and was formed from the merger of two separate bodies, consistent with the collapse of a binary system or the re-accumulation of material from a catastrophic collisional disruption. We demonstrate that an observational measurement of radiative torques, when combined with a detailed shape model, can provide insight into the interior structure of an asteroid.

Shape and Rotation Modeling and Thermophysical Analysis of Near-Earth Asteroid (1917) Cuyo

We are conducting an ESO Large Program that includes optical photometry, thermal-IR observations, and optical-NIR spectroscopy of selected NEAs. Among the principal goals of the program are shape and spin-state modeling, and searching for YORP-induced changes in rotation periods. One of our targets is asteroid (1917) Cuyo, a near-Earth asteroid from the Amor group. We carried out an extensive observing campaign on Cuyo between April 2010 and April 2013, operating primarily at the ESO 3.6m NTT for optical photometry, and the 8.2m VLT at Paranal for thermal-IR imaging. Further optical observations were acquired at the ESO 2.2m telescope, the Palomar 200" Hale telescope (California), JPL’s Table Mountain Observatory (California) and the Faulkes Telescope South (Australia). We obtained optical imaging data for rotational lightcurves throughout this period, as the asteroid passed through a wide range of observational geometries, conducive to producing a good shape model and spin state solution. The preliminary shape and spin state model indicates a nearly spherical shape and a rotation pole at ecliptic longitude λ = 53° ± 20° and latitude β = -37° ± 10° (1-sigma error bars are approximate). The sidereal rotation period was measured to be 2.6899522 ± (3 × 10^-7) hours. Linkage with earlier lightcurve data shows possible evidence of a small change in rotation rate during the period 1989-2013. We applied the NEATM thermal model (Harris A., Icarus 131, 291, 1998) to our VLT thermal-IR measurements (8-19.6 μm), obtained in September and December 2011. The derived effective diameter ranges from 3.4 to 4.2 km, and the geometric albedo is 0.16 (+0.07, -0.04). Using the shape model and thermal fluxes we will perform a detailed thermophysical analysis using the new Advanced Thermophysical Model (Rozitis, B. & Green, S.F., MNRAS 415, 2042, 2011; Rozitis, B. & Green, S.F., MNRAS 423, 367, 2012). This work was performed in part at the Jet Propulsion Laboratory under a contract with NASA.