Physiology of exercise in health and disease, with special reference to effort intolerance, training and thermoregulation in man

1. Davies, C.T.M., (1968) Limitdtions to the prediction of maximum oxygen intake from cardiac frequency measurements. J. Appl. Physiol. 24, 700 -706 || 2. Cotes, J.E., Davies, C.T.M., Edholm, G G., Healy, M.J.R., and Tanner, J.M., (1969). Factors relating to the aerobic capacity of 46 healthy British males and females, ages 18 -28 years. Proc. Roy. Soc. Lond. B 174, 91 -114 || 3. Davies, C.T.M., Tuxworth, W., and Young, J.M., (1970). Physiological effects of repeated exercise. Clin. Sci. 39, 247 -258 || 4. Di Prampero, P.E., Davies, C.T.M., Cerretelli, P., and Margaria R., (1970) An analysis of 02 debt contracted in submaximal exercise. J. Appl. Physiol. 29, 547 -551 || 5. Godfrey, S., and Davies, C.T.M., (1970) Estimates of arterial PCO2 and their effect on the calculated values of cardiac output and deadspace in exercise tests. Clin. Sci. 39, 529 -537 || 6. Davies, C.T.M., Kitchin, A.H., Knibbs, A.V., and Neilson, J.M., (1971) Computer Quantitation of ST segment response to graded exercise in untrained and trained normal subjects. Cardiovascular Research, 5, 201 -209 || 7. Godfrey, S., Davies, C.T.M., Wozniak, E., and Barnes, Carolyn A., (1971) Cardio -respiratory response to exercise in normal children. Clin. Sci. 40, 419 -431 || 8. Davies, C.T.M., (1972). The oxygen transporting system in relation to age. Clin. Sci. 42, 1 -13 || 9. Davies, C.T.M., Di Prampero, P.E., and Ceretelli, P., (1972) Kinetics of cardiac output and respiratory gas exchange during exercise and recovery. J. Appl. Physiol. 32, 618 -625 || 10. Edwards, R.H.T., Denison, D.M., Jones, G., Davies, C.T.M., and Campbell, E.J.M., (1972) Changes in mixed venous gas tensions at the start of exercise in man. J. Appl. Physiol. 32, 165 -169 || 11. Davies, C.T.M., and Barnes, Carolyn A., (1972) Plasma FFA in relation to maximum power output in man. Int. Z. Angew Physiol. 30, 247-257 || 12. Davies, C.T.M., Barnes Carolyn A., Fox, R.H., Ojikutu, R., Ola and Samueloff A.S., (1972). Ethnic difference in physical work capacity. J. Appl. Physiol. 33, 726 -732 || 13. Davies, C.T.M., (1973) Relationship of maximum aerobic power output to productivity and absenteeism of East African sugar cane workers. Brit. J. Ind. Med. 30, 146 -154 || 14. Davies, C.T.M., Chukweumeka, A.C., and Van Haaren, J.P.M., (1973) Iron deficiency anaemia: its effect on maximum aerobic power and responses to exercise in African males, aged 17 -40 years. Clin. Sci. 44, 555 -566 || 15. Cotes, J.E., Berry, G., Burkinshaw, L., Davies, C.T.M., Hall, A.M., Jones, P.R.M., and Knibbs, A.V., (1973). Cardiac frequency during submaximal exercise in young adults: relation to lean body mass, total body potassium and amount of leg muscle. Q.J.Expl.Physiol. 58, 239 -250 || 16. Davies, C.T.M., and Van Haaren, J.P.M., (1973) The effect of treatment the physiological responses to exercise in East African Industrial workers with iron deficiency anaemia. Brit. J. Ind. Med. 30, 335 -340. || 17. Sargeant, A.J., and Davies, C.T.M., (1973). Perceived exertion during rhythmic exercise involving different muscle masses. Human Ergology, 2, 3 -11 || 18. Davies, C.T.M., Sargeant, A.J., and Smith, B., (1974). The physiological responses to running downhill. Europ. J. Appl. Physiol. 32, 187 -194 || 19. Davies, C.T.M., and Sargeant, A.J., (1974) Physiological responses to standardised arm work. Ergonomics 17, 41 -49 || 20. Davies, C.T.M., and Sargeant, A.J., (1974). Exercise performance with one and two -legs breathing air and 45% oxygen. J. Appl. Physiol. 36, 142 -148 || 21. Davies, C.T.M., Few J.D., Foster, K.G., and Sargeant, A.J., (1974). Plasma catecholamine concentration during dynamic exercise involving different muscle groups. Eur. J. Appl. Physiol. 32, 195 -206 || 22. Davies, C.T.M., and Sargeant, A.J., (1974). Indirect determination of maximal aerobic power during work with one or two limbs. Europ. J. Appl. Physiol. 32, 207 -215 || 23. Davies, C.T.M., and Sargeant, A.J., (1974). Effects of hypoxic training on normoxic maximal aerobic power output. Europ. J. Appl. Physiol. 33, 227 -236 || 24. Davies, C.T.M., and Sargeant, A.J., (1975) Changes in physiological performance of the lower limb after fracture and subsequent rehabilitation Clin. Sci. & Mol. Med. 48, 107 -114 || 25. Davies, C.T.M., and Sargeant, A.J., (1975) physiological responses to 1 and 2 leg 377 -381 || 26. Davies, C.T.M., and Sargeant, A.J., (1975). exercise in patients following fracture J. Rehab. Med. 7, 45 -50. Effects of training on the work. J. Appl. Physiol. 38, Physiological responses to of the lower limb. Scand. || 27. Davies, C.T.M., Godfrey, S., Light, M., Sargeant, A.J., and Zeidifard, E.,. (1975) Cardiopulmonary responses to exercise in obese girls and young women. J. Appl. Physiol. 38, 373 -376 || 28. Davies, C.T.M., and Sargeant, A.J., (1975) Circadian variation in physiological responses to exercise on a stationary bicycle ergometer Brit. J. Ind. Med. 32, 110 -114 || 29. Collins, K.J. Brotherhood, J.R., Davies, C.T.M., Dore, Caroline, Hackett, J., Imms, F.J., Musgrove, J., Weiner, J.S., Amin, M.A., El Karim, M., Ismail, H11.M., Omer A.J.S., and Sukkar, M.Y., (1976). Physiological performance and work capacity of Sudanese can cutters with Schistosoma mansoni infection. Amer. J. Trop. Med. & Hyg. 25, 401,421 || 30. Nielsen, B., and Davies, C.T.M., (1976). Temperature regulation during exercise in water and air. Acta Physiol. Scand. 98, 500 -508 || 31. Davies, C.T.M., Brotherhood, J.R., Few,J.D., and Zeidifard, E., (1976) Effects of ß blockade and atropinisation on plasma catecholamine concentration during exercise. Eur. J. Appl. Physiol. 36, 49 -56 || 32. Davies, C.T.M., Brotherhood, J.R., and Zeidifard, E., (1976). Temperature regulation during severe exercise with some observations on the effects of skin wetting. J. Appl. Physiol. 41, 772 -776 || 33. Sargeant, A.J., Davies, C.T.M., Edwards, R.H.T., Maunder, C., and Young A., (1977). Functional and structural changes after disuse of human muscle. Clin. Sci. & Mol. Med. 52,337 -342 || 34. Sargeant, A.J., and Davies, C.T.M., (1977). Forces applied to cranks of a bicycle ergometer during one and two leg cycling. J. Appl. Physiol. 42, 514 -518 || 35. Sargeant, A.J., & Davies, C.T.M., (1977). The effect of disuse muscular atrophy on the forces generated in dynamic exercise. Clin. Sci. & Mol. Med. 53, 182 -188 || 36. Fohlin, L., Freyschuss, E., Bjarke, B., Davies, C.T.M., and Thoren, C., (1978). Function and Dimensions of the circulatory system in anorexia nervosa. Acta. Paed. Scand. 67, 11 -16 || 37. Davies, C.T.M., Von Dobeln, W. Fohlin, L., Freyschuss u., and Thoren, C., (1978). Total body potassium, fat free weight and maximal aerobic power in children with Anorexia Nervosa. Acta. Pediatr. Scand. 67, 229 -334 || 38. Davies, C.T.M., Brotherhood, J.P., and ZeidiFard, E., (1978). Effects of Atropine and (3-Blockade on Temperature Regulation and Performance during Prolonged Exercise. Europ. J. Appl. Physiol. 38, 225 -232 || 39. Zeidifard, E., and Davies, C.T.M., (1978). An Assessment of a N20 Rebreathing Method for the Estimation of Cardiac Output During Severe Exercise. Ergonomics, 21, 567 -572 || 40. Sargeant,A.J., Crawley, M.A., and Davies, C.T.M., (1979). Physiological Responses to Exercise in Myocardial Infarction Patients Following Residential Rehabilitation. Arch. Phys. Med. Rehabil. 60, 121 -125 || 41. Davies, C.T.M., (1979). The effects of different levels of heat production induced by diathermy and eccentric work on thermoregulation during exercise at a given skin temperature. Eur. J. Appl. Physiol. 40, 171 -180 || 42. Davies, C.T.M., and Thompson, M.W., (1979). Aerobic Performance of Female Marathon and Male Ultra- marathon Athletes. Eur. J. Appl. Physiol. 41, 233 -245 || 43. Davies, C.T.M., (1979). Thermoregulation during exercise in relation to sex and age. Eur. J. Appl. Physiol. 42, 71 -79 || 44. Davies, C.T.M., (1979). Influence of skin temperature on sweating and aerobic performance during severe work. J. Appl. Physiol. 47, 770 -777 || 45. Davies, C.T.M., and Sargeant, A.J., (1979). The effects of atropine and Practolol on the perception of exertion during treadmill exercise. Ergonomics 22, 1141 -1146 || 46. C.T.M., Fohlen L., and Temperature regulation in Anorexia nervosa patients during prolonged exercise. Acta. Med. Scand. 205, 257 -262 || 47. Davies, C.T.M., (1980) Influence of air flow and skin temperature on sweating during and following exercise. Ergonomics. 23, 559 -569 || 48. Davies, C.T.M., Fohlen L., and Thoren C., (1979) The effects of wind resistance on the forward motion of a runner. J. Appl. Physiol. 48, 702 -709 || 49. Davies, C.T.M., (1980) Metabolic cost of exercise and physical performance in children with some observations on external loading. Eur. J. Appl. 45, 95 -102 || 50. Davies, C.T.M., (1980) Effect of air resistance on the metabolic cost and performance of cycling. Eur. J. Appl. Physiol. 45, 245 -254

An empirical study of assurance in the UK government major projects portfolio: from data to recommendations, to action or inaction

© 2020, Emerald Publishing Limited. Purpose: Effective and robust governance of major projects and programmes in the public sector is crucial to the accountability of the state and the transparency of state spending. The theoretical discourse on governance, in the context of projects and programmes, is not fully mature, although is now sufficiently well developed to warrant an increased scholarly focus on practice. This paper aims to contribute to the empirical literature through a study of assurance routines in the UK Government Major Projects Portfolio (GMPP). Design/methodology/approach: A framework analysis approach to the evaluation of a subset of GMPP database generates original insights into (1) the framing of assurance review recommendations, (2) the treatment of assurance review data and (3) the subsequent tracking of the implementation of actions arising from the assurance review process. Findings: The analysis reveals that the “delivery confidence” of the major projects and programmes included in this study improves during the time that they are assured on the GMPP. This would suggest that “enhanced” governance routines are desirable in programmes and projects that exhibit high degrees of complexity and scale. Originality/value: The research findings contribute to the wider conversations in this journal and elsewhere on project governance routines and governance-as-practice in the context of government and public services

Index selection in terminal sires improves lamb performance at finishing

Lamb meat is often perceived by consumers as fatty, and consumption has decreased in recent decades. A lean growth index was developed in the UK for terminal sire breeds to increase carcass lean content and constrain fat content at a constant age end point. The purposes of this study were 1) to evaluate the effects of index selection of terminal sires on their crossbred offspring at finishing and 2) to evaluate its effectiveness within terminal sire breeds. Approximately 70% of lambs marketed in the UK have been sired by rams of breeds typically thought of as specialized terminal sires. The most widely used are Charollais, Suffolk, and Texel. These breeds participated in sire referencing schemes from the early 1990s by sharing rams among flocks selected on the lean growth index. From 1999 to 2002 approximately 15 “high” and 15 “low” lean growth index score rams were selected from within their sire referencing schemes and mated to Welsh and Scottish Mule ewes. Their crossbred offspring were commercially reared on 3 farms in the UK. Lambs were finished to an estimated 11% subcutaneous fat by visual evaluation. At finishing, lambs were weighed, ultrasonically scanned, and assessed for condition score and conformation. Records were obtained for 6,356 lambs on finishing BW (FWT), ultrasonic muscle depth (UMD), ultrasonic fat depth, overall condition score (OCS), and conformation of gigot, loin, and shoulder. Ultrasonic fat depth was log transformed (logUFD) to approach normality. High-index-sired lambs were heavier at finishing (1.2 ± 0.2 kg) with thicker UMD (0.7 ± 0.2 mm) and less logUFD (0.08 ± 0.01 mm; P \u3c 0.05). There were no differences in OCS or conformation based on the sire index or breed (P \u3e 0.08). Suffolk-sired lambs were heavier than Charollais (1.0 ± 0.3 kg), which were heavier than Texel (0.9 ± 0.3 kg; P \u3c 0.001). Texel-sired lambs had thicker UMD than Charollais (0.7 ± 0.2 mm; P \u3c 0.001) but were not different than Suffolk. Charollais-sired lambs had greater logUFD than both Texel (0.098 ± 0.016 mm) and Suffolk (0.061 ± 0.017 mm) sired lambs (P \u3c 0.001). Within a breed, high- and low-index-sired lambs differed in performance with the exceptions of FWT and UMD in Suffolks. Index selection produced heavier and leaner lambs at finishing. Producers have flexibility in choosing the terminal sire that best fits their production system

Genetic evaluation of days to harvest in crossbred lambs

Days to harvest (DTH) is the number of days a lamb is fed before reaching a target level of fatness. Although economically relevant, this trait has not been thoroughly evaluated in sheep. Most lambs harvested in the United Kingdom are crossbreds sired by purebred terminal sires, with Charollais, Suffolk, and Texel most commonly used. Sires from these breeds were selected on an index designed to increase lean growth while constraining fat. The purpose of this research was to 1) evaluate the effects of index selection in terminal sires on DTH and 2) evaluate the feasibility of incorporating DTH into genetic evaluation programs. Charollais, Suffolk, and Texel sheep had participated in sire referencing schemes where genetic links among flocks were established by sharing rams. Rams with high or low index scores were chosen from these schemes and mated to crossbred ewes at 3 farms in the United Kingdom. Lambs were harvested at a target 11% subcutaneous fat. Records on DTH from 6,350 lambs were analyzed in 2 ways: 1) as time to harvest fitting a survival model and 2) as a normally distributed variable in a bivariate analysis with weight at harvest. The survival analysis was stratified by rearing type (single or twin). In both approaches, sires were fitted using a multivariate normal distribution with a relationship matrix. Regardless of model fitted, sire index did not affect DTH (P \u3e 0.10). However, Texel-sired lambs reached harvest faster (P \u3c 0.01) than either Charollais- or Suffolk-sired lambs although DTH in those 2 breed types did not differ (P \u3e 0.1). Ewe lambs reached harvest faster than wethers (P \u3c 0.01). Lambs from older ewes were harvested faster (P \u3c 0.001). The heritability of DTH was 0.21 from the survival model and 0.20 from the bivariate model. Rank correlation of sire EBV between methods was 0.9, suggesting strong agreement. The use of high or low index sires did not extend DTH in lambs harvested at a target fatness. Importantly, there is no antagonism between improving carcass merit and extending the grazing season. Furthermore, DTH is moderately heritable. If economically justified within a breeding program, it could be reduced through genetic selection

Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis

Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.01 ml/g; n = 47). Six, 24 and 48 h later, we used confocal imaging in vivo to assess cerebral mitochondrial redox potential and cortical oxygenation in response to changes in inspired oxygen. The fraction of inspired oxygen (FiO2) at which the cortical redox potential changed was compared between groups. In a subset of animals, spontaneous hypothermia was maintained or controlled hypothermia induced during imaging. Decreasing FiO2 resulted in a more reduced cerebral redox state around veins, but preserved oxidation around arteries. This pattern appeared at a higher FiO2 in LPS-injected animals, suggesting an increased sensitivity of cortical mitochondria to hypoxemia. This increased sensitivity was accompanied by a decrease in cortical oxygenation, but was attenuated by hypothermia. These results suggest that systemic endotoxemia influences cortical oxygenation and mitochondrial function, and that therapeutic hypothermia can be protective

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist