Evidence that both G + C rich and G + C poor isochores are replicated early and late in the cell cycle

Since the G + C content of a gene is correlated to that of the isochore in which it resides, and early replicating isochores are thought to be relatively G + C rich, early replicating genes should also be rich in G + C. This hypothesis is tested on a sample of 44 mammalian genes for which replication time data and sequence information are available. Early replicating genes do not appear to be more G + C rich than late replicating genes, instead there is considerable variation in the G + C content of genes replicated during both halves of S phase. These results show that both G + C rich and poor fractions of the genome are replicated early and late in the cell cycle, and suggest that isochores are not maintained by the replication of DNA sequences in compositionally biased free nucleotide pools

How much of the variation in the mutation rate along the human genome can be explained?

It has been claimed recently that it may be possible to predict the rate of de novo mutation of each site in the human genome with a high degree of accuracy [Michaelson et al. (2012), Cell 151: 143121442]. We show that this claim is unwarranted. By considering the correlation between the rate of de novo mutation and the predictions from the model of Michaelson et al., we show there could be substantial unexplained variance in the mutation rate. We investigate whether the model of Michaelson et al. captures variation at the single nucleotide level that is not due to simple context. We show that the model captures a substantial fraction of this variation at CpG dinucleotides but fails to explain much of the variation at non-CpG sites

Cryptic Variation in the Human Mutation Rate

The mutation rate is known to vary between adjacent sites within the human genome as a consequence of context, the most well-studied example being the influence of CpG dinucelotides. We investigated whether there is additional variation by testing whether there is an excess of sites at which both humans and chimpanzees have a single-nucleotide polymorphism ( SNP). We found a highly significant excess of such sites, and we demonstrated that this excess is not due to neighbouring nucleotide effects, ancestral polymorphism, or natural selection. We therefore infer that there is cryptic variation in the mutation rate. However, although this variation in the mutation rate is not associated with the adjacent nucleotides, we show that there are highly nonrandom patterns of nucleotides that extend similar to 80 base pairs on either side of sites with coincident SNPs, suggesting that there are extensive and complex context effects. Finally, we estimate the level of variation needed to produce the excess of coincident SNPs and show that there is a similar, or higher, level of variation in the mutation rate associated with this cryptic process than there is associated with adjacent nucleotides, including the CpG effect. We conclude that there is substantial variation in the mutation that has, until now, been hidden from view

The impact of fire suppression tasks on firefighter hydration: A critical review with consideration of the utility of reported hydration measures

BACKGROUND: Firefighting is a highly stressful occupation with unique physical challenges, apparel and environments that increase the potential for dehydration. Dehydration leaves the firefighter at risk of harm to their health, safety and performance. The purpose of this review was to critically analyse the current literature investigating the impact of fighting ‘live’ fires on firefighter hydration. METHODS: A systematic search was performed of four electronic databases for relevant published studies investigating the impact of live fire suppression on firefighter hydration. Study eligibility was assessed using strict inclusion and exclusion criteria. The included studies were critically appraised using the Downs and Black protocol and graded according to the Kennelly grading system. RESULTS: Ten studies met the eligibility criteria for this review. The average score for methodological quality was 55 %, ranging from 50 % (‘fair’ quality) to 61 % (‘good’ quality) with a ‘substantial agreement’ between raters (k = .772). Wildfire suppression was considered in five studies and structural fire suppression in five studies. Results varied across the studies, reflecting variations in outcome measures, hydration protocols and interventions. Three studies reported significant indicators of dehydration resulting from structural fire suppression, while two studies found mixed results, with some measures indicating dehydration and other measures an unchanged hydration status. Three studies found non-significant changes in hydration resulting from wildfire firefighting and two studies found significant improvements in markers of hydration. Ad libitum fluid intake was a common factor across the studies finding no, or less severe, dehydration. CONCLUSIONS: The evidence confirms that structural and wildfire firefighting can cause dehydration. Ad libitum drinking may be sufficient to maintain hydration in many wildfire environments but possibly not during intense, longer duration, hot structural fire operations. Future high quality research better quantifying the effects of these influences on the degree of dehydration is required to inform policies and procedures that ensure firefighter health and safety

Visualising Network Traffic Data From AirTraffic Control Radio Systems

In recent years the aviation industry has begun to embrace digital technology forAir Traffic Control (ATC) radio systems. This change has created challenges not onlyfor the industry but also for personnel. However, this implementation offers manyimprovements over older systems; more precise control, straightforward integrationwith other ATC systems and a more efficient way to provide software updates. Thechallenge for personnel is to develop a new skillset enabling a learning transitionfrom analogue to digital systems, with a specific emphasis on computer networkingskills.This project was undertaken in collaboration between the University of Lincoln(UoL) and Park Air Systems (PAS), an industry-leading provider of Air-Space com-munication solutions. A system has been developed to find a mechanism to monitorand visualise network traffic. The use of graphs provides a direct interface for theend-users, enabling a mechanism for identifying performance issues to meet thetransitional challenges from analogue to digital. An easy to use interface has beendesigned, which will enable non-technical users to interact effectively with the sys-tem.Considerable testing was undertaken to investigate the system usability concern-ing the practical application for users with limited networking experience. A surveyprovided a range of quantitative and qualitative data which was further analysed toscrutinize user perspectives on system usability. This involved engineers from PASand postgraduate students from UoL to compare results between direct industrypersonnel and unaffiliated participants

Player Discipline in the NFL: Arbitration or Arbitrary?

Since the Houston Texans drafted him in 2017, Deshaun Watson has statistically been one of the best quarterbacks in the National Football League (“NFL”). Watson led the Texans to the playoffs in both the 2018 and 2019 seasons before internal organizational issues led to Watson requesting a trade after the 2020 season. By the end of March 2021, twenty-one women had filed civil lawsuits alleging Watson of sexual assault and sexual misconduct. Watson did not immediately face any discipline from the NFL, but the Texans made Watson inactive for every week of the 2021 season in light of the accusations and the rift between the organization and the quarterback. In June 2022, a twenty-fourth woman filed a lawsuit against Watson. By August 2022, Watson has settled twenty-three of the twenty-four lawsuits, and a Texas grand jury declined to criminally indict Watson

A Hoard of Unpaid Invoices: Dissecting Economies & Private Market Forces To Solve B2B Late Payments

The average small-to-medium-size business in the United States keeps just enough of a cash buffer to last 27 days worth of normal operational costs, but in 2016 81% of all B2B invoices were delayed at least 30 days or more past the due date of payment. Furthermore, in 2016, the average SMB held roughly $84,000 in unpaid accounts receivables, with that number also varying across industries. As an example, the average IT SMB held roughly$163k in unpaid accounts receivables, while the average transportation company held roughly $102k in the same. Yet we wonder why 50% of all SMBs close shop in under 5 years of their existence. Late business-to-business (B2B) payments are symbolic of rampant trade credit. The conditions surrounding the need, use, exploitation, and the legal protections to curb trade credit vary significantly across nations and business cultures. However, while cultural practices do have a way of impacting commerce, the various instances of late payments across the world have several other universal factors in common as well. In this paper, we take a look at some global economies and the particularities of practices influencing late payments within their borders. We then dissect their public policies in an effort to gauge the pressure points which they hope to address - as well as any noticeable impact such policies may have had on future payment practices. We then juxtapose our lessons from public policy against the impact of private market solutions and technologies aimed at resolving late payments, and use those contrasting images to better understand the various factors that may have been left unanswered in public policy. Finally, I use my experience dissecting and studying the impact of public legislation to craft and put forth policy proposals of my own - aimed at resolving the most common imbalances and exploits observed during the course of my study