Digital representation of historical globes : methods to make 3D and pseudo-3D models of sixteenth century Mercator globes

In this paper, the construction of digital representations of a terrestrial and celestial globe will be discussed. Virtual digital (3D) models play an important role in recent research and publications on cultural heritage. The globes discussed in this paper were made by Gerardus Mercator (1512-1594) in 1541 and 1551. Four techniques for the digital representation are discussed and analysed, all using high-resolution photographs of the globes. These photographs were taken under studio conditions in order to get equal lighting and to avoid unwanted light spots. These lighting conditions are important, since the globes have a highly reflective varnish covering. Processing these images using structure from motion, georeferencing of separate scenes and the combination of the photographs with terrestrial laser scanning data results in true 3D representations of the globes. Besides, pseudo-3D models of these globes were generated using dynamic imaging, which is an extensively used technique for visualisations over the Internet. The four techniques and the consequent results are compared on geometric and radiometric quality, with a special focus on their usefulness for distribution and visualisation during an exhibition in honour of the five hundredth birthday of Gerardus Mercator

General practitioners' wellbeing during the COVID-19 pandemic: Novel methods with social media data

Background: It is difficult to engage busy healthcare professionals in research. Yet during the COVID-19 pandemic, gaining their perspectives has never been more important.// Objective: To explore social media data for insights into the wellbeing of UK General Practitioners (GPs) during the Covid-19 pandemic.// Methods: We used a combination of search approaches to identify 381 practising UK NHS GPs on Twitter. Using a two stage social media analysis, we firstly searched for key themes from 91,034 retrieved tweets (before and during the pandemic). Following this we used qualitative content analysis to provide in-depth insights from 7145 tweets related to wellbeing.// Results: Social media proved a useful tool to identify a cohort of UK GPs; following their tweets longitudinally to explore key themes and trends in issues related to GP wellbeing during the pandemic. These predominately related to support, resources and public perceptions and fluctuations were identified at key timepoints during the pandemic, all achieved without burdening busy GPs.// Conclusion: Social media data can be searched to identify a cohort of GPs to explore their wellbeing and changes over time

The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081

The human enteropathogen, Yersinia enterocolitica, is a significant link in the range of Yersinia pathologies extending from mild gastroenteritis to bubonic plague. Comparison at the genomic level is a key step in our understanding of the genetic basis for this pathogenicity spectrum. Here we report the genome of Y. enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray data relating to the genetic diversity of the Y. enterocolitica species. Our analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork of horizontally acquired genetic loci, including a plasticity zone of 199 kb containing an extraordinarily high density of virulence genes. Microarray analysis has provided insights into species-specific Y. enterocolitica gene functions and the intraspecies differences between the high, low, and nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence analysis we provide new information on the evolution of the Yersinia. We identify numerous loci that represent ancestral clusters of genes potentially important in enteric survival and pathogenesis, which have been lost or are in the process of being lost, in the other sequenced Yersinia lineages. Our analysis also highlights large metabolic operons in Y. enterocolitica that are absent in the related enteropathogen, Yersinia pseudotuberculosis, indicating major differences in niche and nutrients used within the mammalian gut. These include clusters directing, the production of hydrogenases, tetrathionate respiration, cobalamin synthesis, and propanediol utilisation. Along with ancestral gene clusters, the genome of Y. enterocolitica has revealed species-specific and enteropathogen-specific loci. This has provided important insights into the pathology of this bacterium and, more broadly, into the evolution of the genus. Moreover, wider investigations looking at the patterns of gene loss and gain in the Yersinia have highlighted common themes in the genome evolution of other human enteropathogens

Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial

Objective: To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. Background: The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Methods: Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. Results: A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). Conclusion: In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity

APRI: A simple bedside marker for advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH

Background. Non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. The NASH fibrosis score (NFS) has proven to be a reliable, non-invasive marker for prediction of advanced fibrosis. Aspartate aminotransferase-to-platelet ratio index (APRI) is a simpler calculation than NFS, but has never been studied in patients with non-alcoholic fatty liver disease (NAFLD). Aim. To validate APRI as a non-invasive marker of liver fibrosis in subjects with NAFLD to be used in clinical practice. Design/Methods. The cohort consisted of 111 patients with histological diagnoses of NAFLD. The biopsy samples were staged and graded according to the NASH clinical research network (CRN) criteria. These were grouped into fatty liver disease (FLD), NASH, no/mild fibrosis, and advanced fibrosis. The sensitivity and specificity of APRI were compared with NFS and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio. Results. The APRI was significantly higher in the advanced fibrosis group. The area under receiver operating characteristic (ROC) curve for APRI was 0.85 with an optimal cut-off of 0.98, giving a sensitivity of 75% and a specificity of 86%. The NFS was significantly lower in the advanced fibrosis group. The ROC for NFS gave an area under curve (AUC) of 0.77 and a cut-off value of -1.3 with a sensitivity of 76% and specificity of 69%. The positive predictive value for APRI was 54% as opposed to 34% for NFS. The negative predictive value was 93% for APRI and 94% for NFS. Conclusion. APRI compared favourably to NFS and was superior to AST/ALT for the prediction of advanced fibrosis. We therefore propose the use of APRI in a new algorithm for the detection of advanced fibrosis

Validation of the prognostic performance of Breast Cancer Index (BCI) in hormone receptor-positive (HR+) postmenopausal breast cancer patients in the TEAM trial

Purpose: Early-stage HR+ breast cancer patients face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is significantly prognostic for overall (0-10 years) and late (5-10 years) distant recurrence risk (DR) in N0 and N1 patients. Here, BCI prognostic performance was evaluated in HR+ postmenopausal women from the TEAM trial.Experimental Design: 3544 patients were included in the analysis (N=1519 N0, N=2025 N+). BCI risk groups were calculated using pre-specified cut-points. Kaplan-Meier analyses and logranktests were used to assess the prognostic significance of BCI risk groups based on DR. Hazard ratios (HR) and confidence intervals (CI) were calculated using Cox models with and without clinical covariates.Results: For overall 10-year DR, BCI was significantly prognostic in N0 (N=1196) and N1 (N=1234) patients who did not receive prior chemotherapy (p<0.001). In patients who were DRfree for 5 years, 10-year late DR rates for low- and high-risk groups were 5.4% and 9.3% (N0 cohort, N=1285) and 4.8% and 12.2% (N1 cohort, N=1625) with multivariate HRs of 2.25 (95% CI: 1.30-3.88; p=0.004) and 2.67 (95% CI: 1.53-4.63; p=<0.001), respectively. Late DR performance was substantially improved using previously optimized cut-points, identifying BCIlow-risk groups with even lower 10-year late DR rates of 3.8% and 2.7% in N0 and N1 patients, respectively.Conclusions: The TEAM trial represents the largest prognostic validation study for BCI to date and provides a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ early-stage breast cancer patients

A cross‐sectional study of α‐synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function

IntroductionAlzheimer's disease (AD) pathology is defined by β-amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; ?-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed.MethodsA validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk-factors, genetics, and cognitive trajectories.ResultsSAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aβ burden but lower CSF p-tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early-AD who were already AD biomarker positive.DiscussionSAA is a sensitive, specific marker for LB-pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α-synuclein co-pathology in understanding AD's nature and progression.HighlightsSAA shows 79% sensitivity, 97% specificity for LB-pathology detection in AD. SAA positivity prevalence increases with disease stage and age. Higher Aβ burden, lower CSF p-tau181 linked with higher SAA+ rates in dementia. SAA+ impacts cognitive impairment in early disease stages. Study underpins need for wider LB-pathology screening in AD treatment