The waiting time paradox: population based retrospective study of treatment delay and survival of women with endometrial cancer in Scotland

No abstract available

Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults: the Midspan family study surveys of parents and offspring

<b>Objective</b>: To estimate trends between 1972-6 and 1996 in the prevalences of asthma and hay fever in adults. Design: Two epidemiological surveys 20 years apart. Identical questions were asked about asthma, hay fever, and respiratory symptoms at each survey. Setting: Renfrew and Paisley, two towns in the west of Scotland. <b>Subjects</b>: 1477 married couples aged 45-64 participated in a general population survey in 1972-6; and 2338 offspring aged 30-59 participated in a 1996 survey. Prevalences were compared in 1708 parents and 1124 offspring aged 45-54. <b>Main outcome measures</b>: Prevalences of asthma, hay fever, and respiratory symptoms. Results: In never smokers, age and sex standardised prevalences of asthma and hay fever were 3.0% and 5.8% respectively in 1972-6, and 8.2% and 19.9% in 1996. In ever smokers, the corresponding values were 1.6% and 5.4% in 1972-6 and 5.3% and 15.5% in 1996. In both generations, the prevalence of asthma was higher in those who reported hay fever (atopic asthma). In never smokers, reports of wheeze not labelled as asthma were about 10 times more common in 1972-6 than in 1996. With a broader definition of asthma (asthma and/or wheeze), to minimise diagnostic bias, the overall prevalence of asthma changed little. However, diagnostic bias mainly affected non-atopic asthma. Atopic asthma increased more than twofold (prevalence ratio 2.52 (95% confidence interval 1.01 to 6.28)) whereas the prevalence of non-atopic asthma did not change (1.00 (0.53 to 1.90)). <b>Conclusion</b>: The prevalence of asthma in adults has increased more than twofold in 20 years, largely in association with trends in atopy, as measured indirectly by the prevalence of hay fever. No evidence was found for an increase in diagnostic awareness being responsible for the trend in atopic asthma, but increased awareness may account for trends in non-atopic asthma

Performance of novel VUV-sensitive Silicon Photo-Multipliers for nEXO

Liquid xenon time projection chambers are promising detectors to search for neutrinoless double beta decay (0$\nu \beta \beta$), due to their response uniformity, monolithic sensitive volume, scalability to large target masses, and suitability for extremely low background operations. The nEXO collaboration has designed a tonne-scale time projection chamber that aims to search for 0$\nu \beta \beta$ of \ce{^{136}Xe} with projected half-life sensitivity of $1.35\times 10^{28}$~yr. To reach this sensitivity, the design goal for nEXO is $\leq$1\% energy resolution at the decay $Q$-value ($2458.07\pm 0.31$~keV). Reaching this resolution requires the efficient collection of both the ionization and scintillation produced in the detector. The nEXO design employs Silicon Photo-Multipliers (SiPMs) to detect the vacuum ultra-violet, 175 nm scintillation light of liquid xenon. This paper reports on the characterization of the newest vacuum ultra-violet sensitive Fondazione Bruno Kessler VUVHD3 SiPMs specifically designed for nEXO, as well as new measurements on new test samples of previously characterised Hamamatsu VUV4 Multi Pixel Photon Counters (MPPCs). Various SiPM and MPPC parameters, such as dark noise, gain, direct crosstalk, correlated avalanches and photon detection efficiency were measured as a function of the applied over voltage and wavelength at liquid xenon temperature (163~K). The results from this study are used to provide updated estimates of the achievable energy resolution at the decay $Q$-value for the nEXO design

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Comparative cellular analysis of motor cortex in human, marmoset and mouse

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals(1). Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.Cardiovascular Aspects of Radiolog

Axillary recurrence in breast cancer

Aim: To determine whether axillary recurrence reflects inadequate axillary treatment or adverse pathological features. Methods: The case-records were reviewed of 2122 women aged under 75 years, treated for invasive breast cancer during the time-period 1/1/86–31/12/91 in a geographically defined area. Data were abstracted on operations performed, pathological features, post-operative treatments and details of axillary recurrence. The risk of axillary recurrence was examined by pathological, treatment and patient factors. Results: Axillary recurrence was more than twice as likely after inadequate compared to adequate treatment of the axilla (adequate staging or axillary radiotherapy or clearance). Delayed treatment of the axilla was not as successful as adequate primary treatment: multiple axillary recurrences were twice as common, one third of which were uncontrolled at time of death. Inadequate surgical treatment was associated with increased rates of recurrence despite endocrine therapy, chemotherapy or radiotherapy. Lymphoedema was twice as common if axillary radiotherapy was combined with any axillary surgical procedure. Conclusions: Axillary recurrence is more common in tumours with adverse pathology but may also result from inadequate axillary treatment. In order to minimise axillary recurrence, optimal treatment of the axilla entails adequate staging (sampling of four or more nodes) and treatment (axillary clearance or radiotherapy and endocrine therapy) in all women