Physical Confirmation and Mapping of Overlapping Rat Mammary Carcinoma Susceptibility QTLs, Mcs2 and Mcs6

Only a portion of the estimated heritability of breast cancer susceptibility has been explained by individual loci. Comparative genetic approaches that first use an experimental organism to map susceptibility QTLs are unbiased methods to identify human orthologs to target in human population-based genetic association studies. Here, overlapping rat mammary carcinoma susceptibility (Mcs) predicted QTLs, Mcs6 and Mcs2, were physically confirmed and mapped to identify the human orthologous region. To physically confirm Mcs6 and Mcs2, congenic lines were established using the Wistar-Furth (WF) rat strain, which is susceptible to developing mammary carcinomas, as the recipient (genetic background) and either Wistar-Kyoto (WKy, Mcs6) or Copenhagen (COP, Mcs2), which are resistant, as donor strains. By comparing Mcs phenotypes of WF.WKy congenic lines with distinct segments of WKy chromosome 7 we physically confirmed and mapped Mcs6 to ∼33 Mb between markers D7Rat171 and gUwm64-3. The predicted Mcs2 QTL was also physically confirmed using segments of COP chromosome 7 introgressed into a susceptible WF background. The Mcs6 and Mcs2 overlapping genomic regions contain multiple annotated genes, but none have a clear or well established link to breast cancer susceptibility. Igf1 and Socs2 are two of multiple potential candidate genes in Mcs6. The human genomic region orthologous to rat Mcs6 is on chromosome 12 from base positions 71,270,266 to 105,502,699. This region has not shown a genome-wide significant association to breast cancer risk in pun studies of breast cancer susceptibility

Diagnosis, treatment, and outcome of patients with oesophagogastric cancer during the COVID-19 pandemic:national study

Background: The national response to COVID-19 has had a significant impact on cancer services. This study investigated the effect of national lockdown on diagnosis, management, and outcomes of patients with oesophagogastric cancers in Scotland. Methods: This retrospective cohort study included consecutive new patients presenting to regional oesophagogastric cancer multidisciplinary teams in National Health Service Scotland between October 2019 and September 2020. The study interval was divided into before and after lockdown, based on the first UK national lockdown. Electronic health records were reviewed and results compared. Results: Some 958 patients with biopsy-proven oesophagogastric cancer in 3 cancer networks were included: 506 (52.8 per cent) before and 452 (47.2 per cent) after lockdown. Median age was 72 (range 25–95) years and 630 patients (65.7 per cent) were men. There were 693 oesophageal (72.3 per cent) and 265 gastric (27.7 per cent) cancers. Median time to gastroscopy was 15 (range 0–337) days before versus 19 (0–261) days after lockdown (P < 0.001). Patients were more likely to present as an emergency after lockdown (8.5 per cent before versus 12.4 per cent after lockdown; P = 0.005), had poorer Eastern Cooperative Oncology group performance status, were more symptomatic, and presented with a higher stage of disease (stage IV: 49.8 per cent before versus 58.8 per cent after lockdown; P = 0.04). There was a shift to treatment with non-curative intent (64.6 per cent before versus 77.4 per cent after lockdown; P < 0.001). Median overall survival was 9.9 (95 per cent c.i. 8.7 to 11.4) months before and 6.9 (5.9 to 8.3) months after lockdown (HR 1.26, 95 per cent c.i. 1.09 to 1.46; P = 0.002). Conclusion: This national study has highlighted the adverse impact of COVID-19 on oesophagogastric cancer outcomes in Scotland. Patients presented with more advanced disease and a shift towards treatment with non-curative intent was observed, with a subsequent negative impact on overall survival

CO2 saturated brine injected into fractured shale: An X-ray micro-tomography in-situ analysis at reservoir conditions

Fracture morphology and permeability are key factors in enhanced gas recovery (EOR) and Carbon Geo-storage (CCS) in shale gas reservoirs as they determine production and injection rates. However, the exact effect of CO2-saturated (live) brine on shale fracture morphology, and how the permeability changes during live brine injection and exposure is only poorly understood. We thus imaged fractured shale samples before and after live brine injection in-situ at high resolution in 3D via X-ray micro-computed tomography. Clearly, the fractures’ aperture and connectivity increased after live brine injection

Beating the random walk: a performance assessment of long-term interest rate forecasts

This article assesses the performance of a number of long-term interest rate forecast approaches, namely time series models, structural economic models, expert forecasts and combinations thereof. The predictive performance of these approaches is compared using outside sample forecast errors, where a random walk forecast acts as benchmark. It is found that for five major Organization for Economic Co-operation and Development (OECD) countries, namely the US, Germany, UK, The Netherlands and Japan, the other forecasting approaches do not outperform the random walk on a 3-month forecast horizon. On a 12-month forecast horizon, the random walk model is outperformed by a model that combines economic data and expert forecasts. Several methods of combination are considered: equal weights, optimized weights and weights based on the forecast error. It seems that the additional information contents of the structural models and expert knowledge adds considerably to the performance of forecasting 12 months ahead. © 2013 Taylor & Francis

Grounding Word Learning in Space

Humans and objects, and thus social interactions about objects, exist within space. Words direct listeners' attention to specific regions of space. Thus, a strong correspondence exists between where one looks, one's bodily orientation, and what one sees. This leads to further correspondence with what one remembers. Here, we present data suggesting that children use associations between space and objects and space and words to link words and objects—space binds labels to their referents. We tested this claim in four experiments, showing that the spatial consistency of where objects are presented affects children's word learning. Next, we demonstrate that a process model that grounds word learning in the known neural dynamics of spatial attention, spatial memory, and associative learning can capture the suite of results reported here. This model also predicts that space is special, a prediction supported in a fifth experiment that shows children do not use color as a cue to bind words and objects. In a final experiment, we ask whether spatial consistency affects word learning in naturalistic word learning contexts. Children of parents who spontaneously keep objects in a consistent spatial location during naming interactions learn words more effectively. Together, the model and data show that space is a powerful tool that can effectively ground word learning in social contexts

Laboratory models for studying ectopic pregnancy

PURPOSE OF REVIEW: Understanding of the aetiology of tubal ectopic pregnancy (tEP) remains incomplete. We aim to summarize the latest advances in laboratory models of tEP that we believe will, ultimately, contribute to improving the diagnosis and management of the condition. RECENT FINDINGS: Progress in proteome pre-fractionation and multidimensional protein identification technology has proved particularly effective in identifying novel biomarkers of tEP. These, and related global proteomic and genomic approaches, have as yet to be fully exploited in this context but do have substantial potential to inform future hypothesis driven studies. The majority of data generated since 2009 to explain the aetiology of tEP continues to derive from descriptive human ex-vivo studies. In-vitro models of Fallopian tube ciliary and smooth muscle function have improved to a limited degree, on the back of continuing advances in imaging and data acquisition. We believe that the recent development of a primary human Fallopian tube epithelium culture system represents the most significant recent advance in laboratory models for studying ectopic pregnancy. There remain no good animal models of tEP. SUMMARY: The establishment of a viable animal model of tEP remains the key obstacle to a complete understanding the aetiology of the condition

The Novel Object and Unusual Name (NOUN) database: a collection of novel images for use in experimental research

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects’ novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects’ colors. Results from a similarity sorting task (and subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprise both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in language, categorization, perception, visual memory and related domains

Surviving pediatric intensive care: physical outcome after 3 months

Objective: This study investigated the prevalence and nature of physical and neurocognitive sequelae in pediatric intensive care unit ( PICU) survivors. Design and setting: Prospective follow-up study 3 months after discharge from a 14-bed tertiary PICU in The Netherlands. Patients and participants: The families of 250 previously healthy children unexpectedly admitted to the PICU were invited to visit the outpatient follow-up clinic for structured medical examination of the child 3 months after discharge; 186 patients were evaluated. Measurements and results: Pediatric Cerebral Performance Category ( PCPC) and Pediatric Overall Performance Category ( POPC) values were determined at PICU discharge, at the outpatient follow-up clinic, and retrospectively before admission to the PICU. We found that 69% of children had physical sequelae. In 30% of cases these were caused by a previously unknown illness and in 39% by acquired morbidity. In 8% of the children the acquired morbidity was related to complications from PICU procedures. Three months after discharge 77% of the children had normal PCPC scores and 31% had normal POPC scores. Conclusions: Our results indicate that PICU survival may be associated with substantial physical sequelae. Structured follow-up research, preferably by multicenter studies, is warranted in PICU survivor

The role of lifestyle changes in the management of chronic liver disease

The prevalence of obesity worldwide has dramatically increased during the last three decades. With obesity comes a variety of adverse health outcomes which are grouped under the umbrella of metabolic syndrome. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several liver conditions which are directly affected by overweight and obese status, including non-alcoholic fatty liver disease, chronic infection with hepatitis C virus and post-liver transplant status. The deleterious effects of obesity on liver disease and overall health can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting non-pharmacological, lifestyle interventions that lead to weight reduction, improved physical activity and better nutrition as part of the management and treatment of these liver conditions