Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

Clear cell renal cell carcinoma is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cancer. We find hotspots of point mutations in the 5’-UTR of TERT, targeting a MYC-MAX-MAD1 repressor, that result in telomere lengthening. The commonest structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This occurs in childhood or adolescence, is generally the initiating event, and precedes emergence of the tumor’s most recent common ancestor by years to decades. Similar genomic changes drive inherited kidney cancers. Modelling differences in age-incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Targeting essential genes in deleted regions of chromosome 3p could represent a potential preventative strategy for renal cancer

Acceleration-Based Running Intensities of Professional Rugby League Match-Play

Purpose: To quantify the energetic cost of running and acceleration efforts during rugby league competition to aid in prescription and monitoring of training. Methods: Global positioning system (GPS) data were collected from 37 professional rugby league players across 2 seasons. Peak values for relative distance, average acceleration/deceleration, and metabolic power (P_met) were calculated for 10 different moving-average durations (1–10 min) for each position. A mixed-effects model was used to assess the effect of position for each duration, and individual comparisons were made using a magnitude-based-inference network. Results: There were almost certainly large differences in relative distance and P_met between the 10-min window and all moving averages <5 min in duration (ES = 1.21–1.88). Fullbacks, halves, and hookers covered greater relative distances than outside backs, edge forwards, and middle forwards for moving averages lasting 2–10 min. Acceleration/deceleration demands were greatest in hookers and halves compared with fullbacks, middle forwards, and outside backs. P_met was greatest in hookers, halves, and fullbacks compared with middle forwards and outside backs. Conclusions: Competition running intensities varied by both position and moving-average duration. Hookers exhibited the greatest P_met of all positions, due to high involvement in both attack and defense. Fullbacks also reached high P_met, possibly due to a greater absolute volume of running. This study provides coaches with match data that can be used for the prescription and monitoring of specific training drills

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

Village Water Ozonation System

The Village Water Ozonation System (VWOS) team’s core mission statement is to provide economically sustainable and culturally sensitive drinking water solutions for communities, to empower communities with the ability to properly maintain their drinking water supply, and to transform people’s lives by decreasing the occurrences of waterborne diseases. Currently, the VWOS team is partnering with Friends in Action to design and implement two drinking water treatment systems for the community living on Rama Cay, an island in the Bluefields Lagoon on the eastern coastline of Nicaragua. The wells on the island are contaminated with E. coli and other bacteria and contain high levels of salt that cause the water to be unhealthy, distasteful, and corrosive to metal equipment in the system. The team hopes to design a system that will disinfect the water, remove salinity from the well water with a safe and efficient disposal of all byproducts, and decrease corrosion agents. VWOS is partnering with Forward Edge International for the third time (Nicaragua 2009 and Mexico 2016) to design water treatment systems for communities in Oaxaca, Mexico and Kijabe, Kenya. The system for Oaxaca is ready for implementation and awaits availability to travel. The system for Kijabe is in the initial stage of communicating with the client on specifics for the design.https://mosaic.messiah.edu/engr2021/1018/thumbnail.jp

Fitting a 3D Morphable Model to Edges: A Comparison Between Hard and Soft Correspondences

We propose a fully automatic method for fitting a 3D morphable model to single face images in arbitrary pose and lighting. Our approach relies on geometric features (edges and landmarks) and, inspired by the iterated closest point algorithm, is based on computing hard correspondences between model vertices and edge pixels. We demonstrate that this is superior to previous work that uses soft correspondences to form an edge-derived cost surface that is minimised by nonlinear optimisation.Comment: To appear in ACCV 2016 Workshop on Facial Informatic

Systematic evaluation of spliced alignment programs for RNA-seq data

High-throughput RNA sequencing is an increasingly accessible method for studying gene structure and activity on a genome-wide scale. A critical step in RNA-seq data analysis is the alignment of partial transcript reads to a reference genome sequence. To assess the performance of current mapping software, we invited developers of RNA-seq aligners to process four large human and mouse RNA-seq data sets. In total, we compared 26 mapping protocols based on 11 programs and pipelines and found major performance differences between methods on numerous benchmarks, including alignment yield, basewise accuracy, mismatch and gap placement, exon junction discovery and suitability of alignments for transcript reconstruction. We observed concordant results on real and simulated RNA-seq data, confirming the relevance of the metrics employed. Future developments in RNA-seq alignment methods would benefit from improved placement of multimapped reads, balanced utilization of existing gene annotation and a reduced false discovery rate for splice junctions

American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) joint consensus statement on optimal analgesia within an enhanced recovery pathway for colorectal surgery: part 1-from the preoperative period to PACU

BACKGROUND: Within an enhanced recovery pathway (ERP), the approach to treating pain should be multifaceted and the goal should be to deliver "optimal analgesia," which we define in this paper as a technique that optimizes patient comfort and facilitates functional recovery with the fewest medication side effects. METHODS: With input from a multi-disciplinary, international group of clinicians, and through a structured review of the literature and use of a modified Delphi method, we achieved consensus surrounding the topic of optimal analgesia in the perioperative period for colorectal surgery patients. DISCUSSION: As a part of the first Perioperative Quality Improvement (POQI) workgroup meeting, we sought to develop a consensus document describing a comprehensive, yet rational and practical, approach for developing an evidence-based plan for achieving optimal analgesia, specifically for a colorectal surgery ERP. The goal was two-fold: (a) that application of this process would lead to improved patient outcomes and (b) that investigation of the questions raised would identify knowledge gaps to aid the direction for research into analgesia within ERPs in the years to come. This document details the evidence for a wide range of analgesic components, with particular focus from the preoperative period to the post-anesthesia care unit. The overall conclusion is that the combination of analgesic techniques employed in the perioperative period is not important as long as it is effective in delivering the goal of optimal analgesia as set forth in this document

American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) Joint Consensus Statement on Optimal Analgesia within an Enhanced Recovery Pathway for Colorectal Surgery: Part 2-From PACU to the Transition Home.

BACKGROUND: Within an enhanced recovery pathway (ERP), the approach to treating pain should be multifaceted and the goal should be to deliver "optimal analgesia", which we define in this paper as a technique that optimizes patient comfort and facilitates functional recovery with the fewest medication side effects. METHODS: With input from a multidisciplinary, international group of experts and through a structured review of the literature and use of a modified Delphi method, we achieved consensus surrounding the topic of optimal analgesia in the perioperative period for colorectal surgery patients. DISCUSSION: As a part of the first Perioperative Quality Improvement (POQI) workgroup meeting, we sought to develop a consensus document describing a comprehensive, yet rational and practical, approach for developing an evidence-based plan for achieving optimal analgesia, specifically for a colorectal surgery within an ERP. The goal was twofold: (a) that application of this process would lead to improved patient outcomes and (b) that investigation of the questions raised would identify knowledge gaps to aid the direction for research into analgesia within ERPs in the years to come. This document details the evidence for a wide range of analgesic components, with particular focus on care in the post-anesthesia care unit, general care ward, and transition to home after discharge. The preoperative and operative consensus statement for analgesia was covered in Part 1 of this paper. The overall conclusion is that the combination of analgesic techniques employed in the perioperative period is not important as long as it is effective in delivering the goal of "optimal analgesia" as set forth in this document