Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion

An equilibrium model for RFP plasmas in the presence of resonant tearing modes

The equilibrium of a finite-beta RFP plasma in the presence of saturated-amplitude tearing modes is investigated. The singularities of the MHD force balance equation JXB=grad(p) at the modes rational surfaces are resolved through a proper regularization of the zeroth-order (equilibrium) profiles, by setting to zero there the gradient of the pressure and parallel current density. An equilibrium model, which satisfies the regularization rule at the various rational surfaces, is developed. The comparison with the experimental data from the Reversed Field eXperiment (RFX) gives encouraging results. The model provides an easy tool for magnetic analysis: many aspects of the perturbations can be analyzed and reconstructed.Comment: Final accepted version. 36 page

Incidence and risk factors for placenta accreta/increta/percreta in the UK: a national case-control study.

Placenta accreta/increta/percreta is associated with major pregnancy complications and is thought to be becoming more common. The aims of this study were to estimate the incidence of placenta accreta/increta/percreta in the UK and to investigate and quantify the associated risk factors

Macromolecular interactions during gelatinisation and retrogradation in starch-whey systems as studied by rapid visco-analyser

Gelatinisation and retrogradation of starch-whey mixtures were studied in water (pH 7) using the Rapid Visco-Analyser (RVA). The starch:whey ratios ranged from 0:100 - 100:0. Wheat starch, and whey protein concentrate (about 80% solids basis) and isolate (about 96% solids basis) were used. Mixtures with whey isolates were generally more viscous than those with whey concentrates, and this was attributed to fewer non-protein milk components in the former. Whey protein concentrates and isolates reduced the peak, trough and final viscosities of the mixtures, but the breakdown and setback ratios of the mixtures were increased. The gelatinisation temperature increased with whey substitutions indicating that whey protein delayed starch gelatinisation. The temperature of fastest viscosity development decreased as the amount of whey was increased. Whey protein isolate generally exercised a lesser effect than the concentrate. At between 40 - 50% whey substitutions, the dominant phase changed from starch to protein irrespective of the source of the whey protein. An additive law poorly defined selected RVA parameters. Both macromolecules interacted to define the viscosity of the mixture, and an exponential model predicted the viscosity better than the additive law. The results obtained in this study are discussed to assist the understanding of extrusion processing of starch-whey systems as models for whey-fortified snack and ready-to-eat foods. Copyright ©2006 The Berkeley Electronic Press. All rights reserved

Numerical study of strength mismatch in cross-weld tensile testing

The strength mismatch effect on the deformation behaviour of defect-free cross-weld tensile specimens, where there is a variation in strength along the length of the specimen, was investigated through 2D finite element analysis. A simple bi-material model, which is generally used in current engineering assessments (e.g. R6 “Assessment of the integrity of structures containing defects”) to examine the strength mismatch effect on the deformation and fracture behaviour of a weld which actually includes a heat-affected-zone, could lead to non- conservative or overly conservative predictions. In fusion welded components, one would generally observe that there is a heat-affected zone where the material properties are different from the weld and base material, and there is a continuous gradient of properties between the two. The material properties in HAZ are generally assigned discretely; however, in our multi-material model these properties are successfully assigned continuously by embedding subroutines into finite element model. This multi-material approach was used to examine the effect of strength mismatch on the local and global deformation behavior of fusion welds. It has been found that the bi-material modeling, by ignoring the HAZ, and multi-material discrete HAZ modeling of the cross-weld specimens leads to unrealistically biaxial stresses at the interfaces where there is an abrupt variation of the material properties. However, multi- material continuous HAZ modeling eliminates unrealistic stress biaxiality and enables to examine the local deformation more accurately. It was also found that the global stress-strain behaviour obtained using the bi- material and multi-material modeling is different

BRCA1 5382insC mutation in sporadic and familial breast and ovarian carcinoma in Scotland.

A restriction site-generating polymerase chain reaction (RG-PCR) assay was developed to detect the BRCA1 5382insC mutation that has been reported in multiple, apparently unrelated breast/ovarian carcinoma families. The assay has been used to screen tumour DNA from 250 breast cancer patients (aged 19-86 years) and from 80 ovarian cancer patients (aged 25-90 years) in a local population of patients with no known family history. Altogether, 0/80 (0%) ovarian and 1/250 (0.4%) breast tumour DNAs were found to have the 5382insC mutation. The sole positive case was a 26-year-old woman (BC185) with no known family history. One of the reasons for carrying out this analysis was that the 5382insC mutation had previously been shown to segregate with the disease in a very large Scottish 'West Lothian' kindred having breast/ovarian carcinoma. To investigate whether this apparently isolated case and the known family might be related, haplotypes for the markers D17S855, D17S1322, D17S1323 and D17S1327 were analysed. The mutant haplotype in the large kindred was identical to that reported in all other 5382insC mutation families for all markers with the exception of D17S1327. This implies that there has been a recombination event at the telomeric end of common ancestral haplotype in this family. Since the isolated case we identified carries the 'complete' common haplotype, it is unlikely that she is closely related to the West Lothian family

Risk factors for carriage of Neisseria meningitidis during an outbreak in Wales.

In a school outbreak of meningococcal disease in Wales, we compared risk factors for the carriage of Neisseria meningitidis B15 P1.16 with carriage of any meningococci. Students had throat swabs and completed a questionnaire. Sixty (7.9%) carried meningococci; risk for carriage was higher in those >14 years of age

Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods

Background: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. Objectives: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. Design: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level–dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). Results: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. Conclusion: Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438

Risk of death in England following a positive SARS-CoV-2 test: A retrospective national cohort study (March 2020 to September 2022)

Copyright: \ua9 2024 Bauer-Staeb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. BACKGROUND: We aimed to estimate the relative risk of mortality following a first positive SARS-CoV-2 test during the first, second, and third waves of the COVID-19pandemic in England by age, sex, and vaccination status, taking into account pre-existing health conditions and lifestyle factors. METHODS: We conducted a retrospective cohort study of all individuals registered with the National Health Service (NHS) in England from 1 March 2020 to September 2022. Data for all individuals were obtained and linked including primary care records, hospital admission episodes, SARS-CoV-2 test results, vaccinations, and death registrations. We fitted Cox Proportional Hazards models with time dependent covariates for confirmed SARS-CoV-2 infection to model the risk of subsequent mortality. RESULTS: The hazard ratio for death after testing positive for subsequent, compared with those not testing positive, amongst unvaccinated individuals, ranged from 11 to 89 by age and sex, in the first four weeks following a positive test in wave one and reduced to 14 to 50 in wave three. This hazard was further reduced amongst those who had three vaccines to between 1.4 and 7 in wave three. CONCLUSIONS: This study provides robust estimates of increased mortality risk among those who tested positive over the first three waves of the COVID-19 pandemic in England. The estimates show the impact of various factors affecting the risk of mortality from COVID-19. The results provide the first step towards estimating the magnitude and pattern of mortality displacement due to COVID-19, which is essential to understanding subsequent mortality rates in England

Deep optical observations of the central X-ray source in the Puppis A supernova remnant

X-ray observations reveiled a group of radio-silent isolated neutron stars (INSs) at the centre of young supernova remnants (SNRs), dubbed central compact objects or CCOs, with properties different from those of classical rotation-powered pulsars. In at least three cases, evidence points towards CCOs being low-magnetized INSs, born with slow rotation periods, and possibly accreting from a debris disc of material formed out of the supernova event. Understanding the origin of the diversity of the CCOs can shed light on supernova explosion and neutron star formation models. Optical/infrared (IR) observations are crucial to test different CCO interpretations. The aim of our work is to perform a deep optical investigation of the CCO RX J0822.0-4300 in the Puppis A SNR, one of the most poorly understood in the CCO family. By using as a reference the Chandra X-ray coordinates of RX J0822.0-4300, we performed deep optical observations in the B, V and I bands with the Very Large Telescope (VLT). We found no candidate optical counterpart within 3 sigma of the computed Chandra X-ray position down to 5 sigma limits of B~27.2, V~26.9, and I~25.6, the deepest obtained in the optical band for this source. These limits confirm the non-detection of a companion brighter than an M5 dwarf. At the same time, they do not constrain optical emission from the neutron star surface, while emission from the magnetosphere would require a spectral break in the optical/IR.Comment: 4 pages, 2 figures, Astronomy and Astrophysics, accepte