Assessing a Suitable Radiotherapy Utilisation Benchmark for Older Patients With Head and Neck Cancer.

Aims: To (i) determine the actual radiotherapy utilization (RTU) stratified by age, (ii) develop an age- and co-morbidity adjusted optimal RTU model and (iii) examine the tolerance and toxicity of treatment of older patients with head and neck cancer.

Materials And Methods: A retrospective cohort study based on New South Wales Cancer Registry records (2010-2014) linked to radiotherapy data (2010-2015) and admitted patient data (2008-2015) for patients diagnosed with head and neck cancer. We calculated the actual RTU, defined as the proportion of patients who received at least one course of radiotherapy within a year of diagnosis, by age group, including patients aged 80+ years.

A Comprehensive Bioinformatic Analysis of RNA-seq Datasets Reveals a Differential and Variable Expression of Wildtype and Variant UGT1A Transcripts in Human Tissues and Their Deregulation in Cancers.

The locus generates over 60 different alternatively spliced transcripts and 30 circular RNAs. To date, v2 and v3 transcripts are the only variant UGT1A transcripts that have been functionally characterized. Both v2 and v3 transcripts encode the same inactive variant UGT1A proteins (i2s) that can negatively regulate glucuronidation activity and influence cancer cell metabolism.

Examining the role of child welfare worker characteristics and the substantiation decision.

Background: The role of child welfare workers is twofold, to promote the safety of children and youth and to address their wellbeing. This provincially legislated mandate requires child welfare workers to make decisions across the child welfare service continuum. After a report of child maltreatment is investigated, workers are required to assess the veracity of the allegation through the substantiation decision and to determine whether the child has been victimized, which may impact on families' future involvement with services.

Development of an age- and comorbidity- adjusted optimal radiotherapy utilisation rate for lung, rectal, prostate and cervical cancers.

Introduction: Optimal radiotherapy utilisation (RTU) modelling estimates the proportion of people with cancer who would benefit from radiotherapy. Assessment of comorbidities is an important component of the assessment of suitability for radiotherapy in addition to chronological age and life expectancy. Comorbidities have not been considered in previous optimal RTU models.

Previous antibiotic therapy as independent risk factor for the presence of vancomycin-resistant enterococci in surgical inpatients. Results from a matched case-control study.

Background: Investigation of risk factors for the presence of vancomycin-resistant enterococci (VRE) in inpatients on surgical wards and associated intensive care units of a German tertiary care hospital.

Methods: A single-centre retrospective matched case-control study was performed with surgical inpatients admitted between July 2013 and December 2016. Patients with in-hospital detection of VRE later than 48 h after admission were included and comprised 116 VRE-positive cases and 116 VRE-negative matched controls.

Health Services Research in Brachytherapy: Current Understanding and Future Challenges.

Brachytherapy is an integral component of cancer care. Widespread concerns have been expressed though about the need for greater brachytherapy availability across many jurisdictions. Yet, health services research in brachytherapy has lagged behind that in external beam radiotherapy.

Gender diversity and leadership in Radiation Oncology in Australia and New Zealand.

Introduction: There has been a groundswell of discussion and activism surrounding gender diversity. Given the growing importance of this issue, a working group was established under the Faculty of Radiation Oncology (FRO) of the Royal Australian and New Zealand College of Radiologists' (RANZCR) Economics and Workforce Committee (EWC) to review the current status of gender diversity within radiation oncology (RO) in Australia and New Zealand.

Methods: De-identified data were provided from two recent FRO workforce censuses conducted in 2014 and 2018 with permission from the EWC.

Effects of Myopia and Glaucoma on the Neural Canal and Lamina Cribrosa Using Optical Coherence Tomography.

Prcis: Glaucoma was associated with axial bowing and rotation of Bruchs membrane opening (BMO) and anterior laminar insertion (ALI), skewed neural canal, and deeper anterior lamina cribrosa surface (ALCS). Longer axial length was associated with wider, longer, and more skewed neural canal and flatter ALCS.

Purpose: Investigate the effects of myopia and glaucoma in the prelaminar neural canal and anterior lamina cribrosa using 1060-nm swept-source optical coherence tomography.

The Somatic Mutation Landscape of UDP-Glycosyltransferase () Genes in Human Cancers.

The human UDP-glycosyltransferase (UGTs) superfamily has a critical role in the metabolism of anticancer drugs and numerous pro/anti-cancer molecules (e.g., steroids, lipids, fatty acids, bile acids and carcinogens).

Radiotherapy utilisation rates for patients with cancer as a function of age: A systematic review.

Introduction: There is an increasing incidence of cancer in older people, but limited data on radiotherapy uptake, and in particular, radiotherapy utilisation (RTU) rates. The RTU rate for older adults with cancer may be lower than recommended due to lower tolerance for radiotherapy as well as additional comorbidities, reduced life expectancy and travel for treatment. Radiotherapy use must be aligned with best available, age-specific evidence to ensure older adults with cancer receive optimal benefit without harms.

Development of an age- and comorbidity adjusted- optimal radiotherapy utilisation rate for women with breast cancer.

Introduction: Optimal radiotherapy utilisation (RTU) modelling estimates the proportion of people with cancer who would benefit from radiotherapy. Older adults with cancer may have comorbidities that can impact physiological reserve and affect radiotherapy recommendations. These have not been considered in previous models.

Use of a Baculovirus-Mammalian Cell Expression-System for Expression of Drug-Metabolizing Enzymes: Optimization of Infection With a Focus on Cytochrome P450 3A4.

Heterologous expression systems are important for analyzing the effects of genetic factors including single nucleotide polymorphisms on the functions of drug-metabolizing enzymes. In this study, we focused on a baculovirus-mammalian cell (Bac-Mam) expression system as a safer and more efficient approach for this purpose. The baculovirus-insect cell expression system is widely utilized in large-scale protein expression.

Regulation of human UDP-glycosyltransferase () genes by miRNAs.

The human gene superfamily is divided into four subfamilies (, , and ) that encodes 22 functional enzymes. UGTs are critical for the metabolism and clearance of numerous endogenous and exogenous compounds, including steroid hormones, bile acids, bilirubin, fatty acids, carcinogens, and therapeutic drugs. Therefore, the expression and activities of UGTs are tightly regulated by multiple processes at the transcriptional, post-transcriptional and post-translational levels.

The Expression Profiles and Deregulation of UDP-Glycosyltransferase () Genes in Human Cancers and Their Association with Clinical Outcomes.

The human UDP-glycosyltransferase (UGTs) superfamily has 22 functional enzymes that play a critical role in the metabolism of small lipophilic compounds, including carcinogens, drugs, steroids, lipids, fatty acids, and bile acids. The expression profiles of genes in human cancers and their impact on cancer patient survival remains to be systematically investigated. In the present study, a comprehensive analysis of the RNAseq and clinical datasets of 9514 patients from 33 different TCGA (the Genome Cancer Atlas) cancers demonstrated cancer-specific UGT expression profiles with high interindividual variability among and within individual cancers.

Diagnostic accuracy of point of care faecal immunochemical testing using a portable high-speed quantitative analyser for diagnosis in 2-week wait patients.

Aim: Laboratory-based faecal immunochemical testing (FIT) is the gold standard for detecting the presence of blood in the stool. The aim was to perform a diagnostic accuracy study to confirm if a point of care (POC) analyser for FIT could be safely used as an adjunct in the triage and management of 2-week wait (TWW) colorectal patients.

Methods: The Point of Care Faecal Immunochemical Testing (POC FIT) prospective observational cohort study was designed for TWW patients at a regional referral centre.

Circular RNAs of UDP-Glycosyltransferase () Genes Expand the Complexity and Diversity of the UGT Transcriptome.

The human UDP-glycosyltransferase () gene superfamily generates 22 canonical transcripts coding for functional enzymes and also produces nearly 150 variant UGT transcripts through alternative splicing and intergenic splicing. In the present study, our analysis of circRNA databases identified backsplicing events that predicted 85 circRNAs from genes, with 33, 11, and 19 circRNAs from , , , respectively. Most of these UGT circRNAs were reported by one database and had low abundance in cell- or tissue-specific contexts.

Factors affecting radiotherapy utilisation in geriatric oncology patients in NSW, Australia.

Background And Purpose: Large non-age-specific radiotherapy utilisation rate (RTU) studies have demonstrated that actual RTU is below the optimal recommended utilisation rate for both curative and palliative intent radiotherapy indications. The optimal utilisation rate for the geriatric oncology cohort of patients has not yet been determined. The purpose of this research was to examine the actual RTU for patients treated in New South Wales (NSW), Australia as a function of increasing age, and the relationship between RTU and tumour site, travelling distance and socio-economic status.

The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes.

ADME genes are a group of genes that are involved in drug absorption, distribution, metabolism, and excretion (ADME). The expression profiles of ADME genes within tumours is proposed to impact on cancer patient survival; however, this has not been systematically examined. In this study, our comprehensive analyses of pan-cancer datasets from the Cancer Genome Atlas (TCGA) revealed differential intratumoral expression profiles for ADME genes in 21 different cancer types.

Adoption of faecal immunochemical testing for 2-week-wait colorectal patients during the COVID-19 pandemic: an observational cohort study reporting a new service at a regional centre.

Aim: The COVID-19 pandemic has resulted in the near-complete loss of routine endoscopy services. We describe a major reorganization of service at a regional referral centre (Royal Surrey NHS Foundation Trust) to manage the crisis. Faecal immunochemical testing (FIT) was implemented for triage to make optimum use of limited diagnostic resources.

The carboxyl-terminal di-lysine motif is essential for catalytic activity of UDP-glucuronosyltransferase 1A9.

UDP-Glucuronosyltransferase (UGT) is a type I membrane protein localized to the endoplasmic reticulum (ER). UGT has a di-lysine motif (KKXX/KXKXX) in its cytoplasmic domain, which is defined as an ER retention signal. However, our previous study has revealed that UGT2B7, one of the major UGT isoform in human, localizes to the ER in a manner that is independent of this motif.

Hetero-oligomer formation of mouse UDP-glucuronosyltransferase (UGT) 2b1 and 1a1 results in the gain of glucuronidation activity towards morphine, an activity which is absent in homo-oligomers of either UGT.

UDP-Glucuronosyltransferase (UGT, Ugt) is a major drug metabolizing enzyme family involved in the glucuronidation and subsequent elimination of drugs and small lipophilic molecules. UGT forms homo- and hetero-oligomers that enhance or suppress UGT activity. In our previous study, we characterized mouse Ugt1a1 and all the Ugt isoform belonging to the Ugt2b subfamily and revealed that mouse Ugt2b1 and Ugt1a1 cannot metabolize morphine.

The two-week rule colorectal cancer pathway: an update on recent practice, the unsustainable burden on diagnostics and the role of faecal immunochemical testing.

Introduction: Survival for colorectal cancer is improved by earlier detection. Rapid assessment and diagnostic demand have created a surge in two-week rule referrals and have subsequently placed a greater burden on endoscopy services. Between 2009 and 2014, a mean of 709 patients annually were referred to Royal Surrey County Hospital with a detection rate of 53 cancers per year giving a positive predictive value for these patients of 7.

Exascale applications: skin in the game.

As noted in Wikipedia, refers to having 'incurred risk by being involved in achieving a goal', where ' is a synecdoche for the person involved, and is the metaphor for actions on the field of play under discussion'. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with the being exascale applications and the being delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare.