Phosphorylation of PRH/HHEX by Protein Kinase CK2 Regulates Cell Proliferation and Cell Migration in Diverse Cell Types

Disruption of the regulatory mechanisms that control cell proliferation and cell migration results in multiple disease states including cancer and leukemia. The Proline-Rich Homeodomain protein (PRH)/haematopoietically expressed homeobox protein (HHEX) is a transcription factor that controls cell proliferation and cell migration in a variety of tissues in the adult and in the embryo. Phosphorylation of PRH by Protein Kinase CK2 (Casein Kinase II) stops PRH from binding to DNA and regulating the transcription of its direct target genes. In leukaemic cells phosphorylation also results in the production of a transdominant-negative truncated PRH phosphoprotein by the proteasome. Phosphorylation of PRH is increased in breast and prostate cancer cells and the consequent loss of PRH activity increases cell proliferation and migration. PRH also regulates the proliferation of vascular smooth muscle cells and CK2-dependent phosphorylation of PRH in these cells accompanies increased cell proliferation during intimal thickening. Thus the ability of PRH to regulate cell behaviour and the control of PRH by CK2 is not limited to a specific cell type or tissue. This raises the possibility that the PRH-CK2 axis could be targeted in a variety of disease states ranging from multiple cancers to the intimal thickening that occurs in vein bypass graft failure and restenosis

An improved database of coastal flooding in the United Kingdom from 1915 to 2016

Coastal flooding caused by extreme sea levels can produce devastating and wide-ranging consequences. The ‘SurgeWatch’ v1.0 database systematically documents and assesses the consequences of historical coastal flood events around the UK. The original database was inevitably biased due to the inconsistent spatial and temporal coverage of sea-level observations utilised. Therefore, we present an improved version integrating a variety of ‘soft’ data such as journal papers, newspapers, weather reports, and social media. SurgeWatch2.0 identifies 329 coastal flooding events from 1915 to 2016, a more than fivefold increase compared to the 59 events in v1.0. Moreover, each flood event is now ranked using a multi-level categorisation based on inundation, transport disruption, costs, and fatalities: from 1 (Nuisance) to 6 (Disaster). For the 53 most severe events ranked Category 3 and above, an accompanying event description based upon the Source-Pathway-Receptor-Consequence framework was produced. Thus, SurgeWatch v2.0 provides the most comprehensive and coherent historical record of UK coastal flooding. It is designed to be a resource for research, planning, management and education

Spatial and temporal analysis of extreme sea level and storm surge events around the coastline of the UK

In this paper we analyse the spatial footprint and temporal clustering of extreme sea level and skew surge events around the UK coast over the last 100 years (1915-2014). The vast majority of the extreme sea level events are generated by moderate, rather than extreme skew surges, combined with spring astronomical high tides. We distinguish four broad categories of spatial footprints of events and the distinct storm tracks that generated them. There have been rare events when extreme levels have occurred along two unconnected coastal regions during the same storm. The events that occur in closest succession (< 4 days) typically impact different stretches of coastline. The spring/neap tidal cycle prevents successive extreme sea level events from happening within 4-8 days. Finally, the 2013/14 season was highly unusual in the context of the last 100 years from an extreme sea level perspective

A user-friendly database of coastal flooding in the United Kingdom from 1915–2014

Coastal flooding caused by extreme sea levels can be devastating, with long-lasting and diverse consequences. Historically, the UK has suffered major flooding events, and at present 2.5 million properties and £150 billion of assets are potentially exposed to coastal flooding. However, no formal system is in place to catalogue which storms and high sea level events progress to coastal flooding. Furthermore, information on the extent of flooding and associated damages is not systematically documented nationwide. Here we present a database and online tool called ‘SurgeWatch’, which provides a systematic UK-wide record of high sea level and coastal flood events over the last 100 years (1915-2014). Using records from the National Tide Gauge Network, with a dataset of exceedance probabilities and meteorological fields, SurgeWatch captures information of 96 storms during this period, the highest sea levels they produced, and the occurrence and severity of coastal flooding. The data are presented to be easily assessable and understandable to a range of users including, scientists, coastal engineers, managers and planners and concerned citizens

What doesn’t kill me ... : adversity-related experiences are vital in the development of superior Olympic performance

Objectives: Recent research suggests that experiencing some adversity can have beneficial outcomes for human growth and development. The purpose of this paper was to explore the adversities that the world’s best athletes encounter and the perceived role that these experiences play in their psychological and performance development. Design: A qualitative design was employed because detailed information of rich quality was required to better understand adversity-related experiences in the world’s best athletes. Method: Semi-structured interviews were conducted with 10 Olympic gold medalists from a variety of sports. Inductive thematic analysis was used to analyze the data. Results: The findings indicate that the participants encountered a range of sport- and non-sport adversities that they considered were essential for winning their gold medals, including repeated non-selection, significant sporting failure, serious injury, political unrest, and the death of a family member. The participants described the role that these experiences played in their psychological and performance development, specifically focusing on their resultant trauma, motivation, and learning. Conclusions: Adversity-related experiences were deemed to be vital in the psychological and performance development of Olympic champions. In the future, researchers should conduct more in-depth comparative studies of Olympic athletes’ adversity- and growth-related experiences, and draw on existing and alternative theoretical explanations of the growth-performance relationship. For professional practitioners, adversity-related experiences offer potential developmental opportunities if they are carefully and purposely harnessed

Understanding key constraints and practice design in Rugby Union place kicking : experiential knowledge of professional kickers and experienced coaches

Place kicks present valuable opportunities to score points in Rugby Union, which are typically performed under varying constraints in competitive performance environments. Previous quantitative studies suggest these interacting constraints can influence fluctuations in place kick success. To further the understanding of how fluctuations in place kicking success emerge, our aim was twofold: i) to explore and identify the key constraints that professional place kickers and experienced place kicking coaches perceive to influence the difficulty of a place kick and ii) to understand the level to which current place kicking practice environments represent these key constraints experienced in performance environments. Six professional place kickers and six experienced place kicking coaches were interviewed. Using a deductive thematic analysis, 11 key constraints were identified: individual constraints of expectation for success and fatigue, task constraints of angle and distance to goalposts, environmental constraints of wind, weather, pitch, and crowd, and situational constraints of previous kicking performance, time remaining and current score margin. Place kicking is typically practised individually or with a small number of place kickers in isolation from team sessions. Where possible, coaches should be encouraged to include place kicking in simulated game scenarios during practice to represent key constraints from performance environments. Our study demonstrates how experiential knowledge can enrich the understanding of sport performance and inform the design of practice environments which simulate relevant constraints of competitive performance to enhance skill adaptation of athletes

A comparison of the 31 January–1 February 1953 and 5–6 December 2013 coastal flood events around the UK

A North Sea storm surge during 31 January–1 February 1953 caused Northwest Europe's most severe coastal floods in living memory. This event killed more than 2000 people on the coasts of England, the Netherlands, and Belgium. In the UK, where this study focuses, this event was a pivotal influence for flood risk management. Subsequent progress included a national tide gauge network, a storm surge forecasting and warning service, and major defense upgrades such as the Thames Barrier. Almost 60-years later, on 5–6 December 2013 Storm “Xaver” generated a surge event of similar magnitude. This paper describes a detailed comparison of these two events in the UK in terms of: (1) the meteorological conditions; (2) the observed high sea levels; and (3) the coastal flooding and impacts. The 1953 storm had a more southerly track and generated bigger waves due to the north-northwesterly onshore winds off East Anglia. The 2013 storm had a more west-to-east path from the north Atlantic to Scandinavia. Consequently, the 1953 high waters were more extreme in the southern North Sea. However, the 2013 event coincided with larger astronomical tides, resulting in a larger spatial “footprint”. The extreme sea levels impacted communities on the west, east, and south coasts, with 2800 properties flooded during the 2013 event, compared to 24,000 properties (mainly between the Humber and Thames) in 1953. The 1953 floods remain a benchmark in the UK as an event which included failed defenses, damaged property and infrastructure and loss of life. Measures taken after 1953 greatly reduced the consequences of the 5–6 December 2013 storm. Continued monitoring of extreme sea levels and their consequences is important to inform a realistic perspective on future planning and resilience

What orthopaedic surgery residents need to know about the hand and wrist?

<p>Abstract</p> <p>Background</p> <p>To develop a Core Curriculum for Orthopaedic Surgery; and to conduct a national survey to assess the importance of curriculum items as judged by orthopaedic surgeons with primary affiliation non-academic. Attention for this manuscript was focused on determining the importance of topics pertaining to adult hand and wrist reconstruction.</p> <p>Methods</p> <p>A 281-item questionnaire was developed and consisted of three sections: 1) Validated Musculoskeletal Core Curriculum; 2) Royal College of Physician and Surgeons of Canada (RCPSC) Specialty Objectives and; 3) A procedure list. A random group of 131 [out of 156] orthopaedic surgeons completed the questionnaire. Data were analyzed descriptively and quantitatively using histograms, a Modified Hotel ling's T²-statistic <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> with p-value determined by a permutation test, and the Benjamini-Hochberg/Yekutieli procedure</p> <p>Results</p> <p>131/156 (84%) orthopaedic surgeons participated in this study. 27/32 items received an average mean score of at least 3.0/4.0 by all respondents thus suggesting that 84% of the items are either "probably important" or "important" to know by the end of residency (SD range 0.007–0.228). The Benjamini-Hochberg procedure demonstrated that for 80% of the 32 × 31/2 = 496 possible pairs of hand and wrist questions did not appear to demonstrate the same distribution of ratings given that one question was different from that of another question.</p> <p>Conclusion</p> <p>This study demonstrates with reliable statistical evidence, agreement on the importance of 27/32 items pertaining to hand and wrist reconstruction is included in a Core Curriculum for Orthopaedic Surgery. Residency training programs need ensure that educational opportunities focusing on the ability to perform with proficiency procedures pertaining to the hand and wrist is taught and evaluated in their respective programs.</p

Scaling Peak Oxygen Consumption for Body Size and Composition in People With a Fontan Circulation

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND: Peak oxygen consumption (peak ̇ VO2) is traditionally divided (“ratio- scaled”) by body mass (BM) for clinical interpretation. Yet, it is unknown whether ratio- scaling to BM can produce a valid size- independent expression of peak VO2 in people with a Fontan circulation. Furthermore, people with a Fontan circulation have deficits in lean mass, and it is unexplored whether using different measures of body composition may improve scaling validity. The objective was to assess the validity of different scaling denominators (BM, stature, body surface area, fat- free mass, lean mass, and appendicular lean mass using ratio and allometric scaling). ̇ METHODS AND RESULTS: Eighty- nine participants (age: 23.3±6.7 years; 53% female) with a Fontan circulation had their cardiorespiratory fitness and body composition measured by cardiopulmonary exercise testing and dual- energy x- ray absorptiometry. Ratio and allometric (log- linear regression) scaling was performed and Pearson correlations assessed scaling validity. Scaling denominators BM (r=−0.25, P=0.02), stature (r=0.46, P<0.001), and body surface area (0.23, P=0.03) were significantly correlated with their respective ratio- scaled expressions of peak ̇ VO2, but fat- free mass, lean mass, or appendicular Downloaded from http://ahajournals.org by on December 14, 2022 lean mass were not (r≤0.11; R2=1%). Allometrically expressed peak denominator (r=≤0.23; R2=≤4%). ̇ ̇ VO2 resulted in no significant correlation with any scaling CONCLUSIONS: The traditional and accepted method of ratio- scaling to BM is invalid because it fails to create a size- independent expression of peak VO2 in people with a Fontan circulation. However, ratio- scaling to measures of body composition (fat- free mass, lean mass, and appendicular lean mass) and allometric techniques can produce size- independent expressions of peak ̇ VO2 in people with a Fontan circulation.Canon Medical Systems UK Ltd.University of ExeterMedical Research Future Fun