The International Classification of Functioning Disability and Health Framework (ICF): a new approach to enhance sport and physical activity participation among people with disabilities in Scotland.

This research provides a pilot study of the International Classification of Functioning Disability and Health Framework (ICF) involving persons with disabilities (PWD) with and without lived experience of sport participation in Scotland. National surveys in Scotland provide limited information on the nature of individual disability restricting the understanding of the relationship between disability and sport and physical activity participation. The ICF is a framework that aims to describe and classify functioning and thus can be used as a tool to provide a more detailed description of impairment for PWDs beyond their clinical condition. This knowledge has the potential to enhance the development of policies to increase the participation levels in this group. The ICF has also been used to inform the current IPC classification system at a competitive and elite level. As part of a larger study, 450 participants aged between 12 and 70 years completed an online questionnaire examining attitudes to, and participation in, sport and physical activity as well as completing the structural and functional components of the ICF. Subsequently, 18 people participated in focus groups aged between 13 and 61 years. The focus groups examined four meta-theme areas: physical, social, psychological, and sport-specific factors. The results confirm that the ICF provided a more detailed indicator of the key impairments that could have an impact on sport and physical activity participation. There was a clear lack of awareness of the links between the ICF and the classification system for competitive parasport. We concluded that a modified ICF-based assessment tool, incorporating social and environmental factors, has the potential to predict the likelihood of participation and offers a more comprehensive picture of both individual and national disability characteristics. This allows for the development of targeted policies and strategies to assist those with a disability to participate in sport. The overall framework presents a shift in thinking, in policy terms, for those in public health and in sport governance and delivery. The significance of this work is especially concerned with public health and wellbeing and sport development policy as pathways from recreational sport user to elite athlete parasport classification and performance.

Slow Relaxation and Diffusion in Holographic Quantum Critical Phases.

The dissipative dynamics of strongly interacting systems are often characterized by the timescale set by the inverse temperature τ_{P}∼ℏ/(k_{B}T). We show that near a class of strongly interacting quantum critical points that arise in the infrared limit of translationally invariant holographic theories, there is a collective excitation (a quasinormal mode of the dual black hole spacetime) whose lifetime τ_{eq} is parametrically longer than τ_{P}: τ_{eq}≫T^{-1}. The lifetime is enhanced due to its dependence on a dangerously irrelevant coupling that breaks the particle-hole symmetry and the invariance under Lorentz boosts of the quantum critical point. The thermal diffusivity (in units of the butterfly velocity) is anomalously large near the quantum critical point and is governed by τ_{eq} rather than τ_{P}. We conjecture that there exists a long-lived, propagating collective mode with velocity v_{s}, and in this case the relation D=v_{s}^{2}τ_{eq} holds exactly in the limit Tτ_{eq}≫1. While scale invariance is broken, a generalized scaling theory still holds provided that the dependence of observables on the dangerously irrelevant coupling is incorporated. Our work further underlines the connection between dangerously irrelevant deformations and slow equilibration.

Hydrodynamic theory of thermoelectric transport and negative magnetoresistance in Weyl semimetals.

We present a theory of thermoelectric transport in weakly disordered Weyl semimetals where the electron-electron scattering time is faster than the electron-impurity scattering time. Our hydrodynamic theory consists of relativistic fluids at each Weyl node, coupled together by perturbatively small intervalley scattering, and long-range Coulomb interactions. The conductivity matrix of our theory is Onsager reciprocal and positive semidefinite. In addition to the usual axial anomaly, we account for the effects of a distinct, axial-gravitational anomaly expected to be present in Weyl semimetals. Negative thermal magnetoresistance is a sharp, experimentally accessible signature of this axial-gravitational anomaly, even beyond the hydrodynamic limit.

Managing blood glucose during and after exercise in Type 1 diabetes: reproducibility of glucose response and a trial of a structured algorithm adjusting insulin and carbohydrate intake.

AIMS AND OBJECTIVES: To enable people with Type 1 diabetes to exercise safely by investigating the reproducibility of the glucose response to an algorithm for carbohydrate and insulin adjustment during and after exercise compared to their self-management strategies. BACKGROUND: Difficulties in managing blood glucose levels in Type 1 diabetes whilst exercising is known to deter people from exercise. Currently there is a limited evidence base to aid health care professionals enable people with diabetes to exercise safely. This study seeks to address this gap. DESIGN: A quasi-experimental study was undertaken amongst people with Type 1 diabetes. METHODS: Over 14 days, 14 participants undertook four exercise sessions (40 minutes at 50%VO2max). Two sessions were undertaken in week 1 self-managing their diabetes and two sessions in week 2 using an algorithm for carbohydrate and insulin adjustment. RESULTS: The mean reduction of glucose levels detected by Continuous Glucose Monitoring during exercise was 3·1 (SD 2·03) mmol/l. Time spent within the range of 4-9 mmol/l during exercise was not significantly different between the self-managed and the algorithm weeks (-3-22·4 min). The mean reduction of blood glucose for each individual over all four exercise sessions ranged between 0·8-5·95 mmol/l. The technical error between days one and two was 2·4 mmol/l (CV=33·2%) and between days 3-4 the technical error was 2·7 mmol/l (CV=33·7%). CONCLUSIONS: The results provide useful data about the reproducibility of the blood glucose response to moderate intensity exercise, despite the variability of individual responses 40 minutes of moderate intensity exercise decreases Continuous Glucose Monitoring glucose by 3 mmol/l with or without a 30% decrease of insulin before exercise. RELEVANCE TO CLINICAL PRACTICE: This information provides valuable baseline information for people with diabetes and health care professionals who wish to encourage physical activity and undertake further research in this area.

Indoor 16.1-km time-trial performance in cyclists aged 25- 63 years.

In this study, we assessed age-related changes in indoor 16.1-km cycling time-trial performance in 40 competitive male cyclists aged 25-63 years. Participants completed two tests: (1) a maximal ramped Kingcycle ergometer test, with maximal ramped minute power (RMPmax, W) recorded as the highest mean external power during any 60 s and maximal heart rate (HRmax, beats min(-1)) as the highest value during the test; and (2) an indoor Kingcycle 16.1-km time-trial with mean external power output (W), heart rate (beats min(-1)), and pedal cadence (rev min(-1)) recorded throughout the event. Results revealed age-related declines (P < 0.05) in absolute and relative time-trial external power output [(24 W (7.0%) per decade], heart rate [7 beats min(-1) (3.87%) per decade], and cadence [3 rev min(-1) (3.1%) per decade]. No relationships (P > 0.05) were observed for mean power output and heart rate recorded during the time-trial versus age when expressed relative to maximal ramped minute power and maximal heart rate respectively. Strong relationships (P < 0.05) were observed for maximal ramped minute power and time-trial power (r= 0.95) and for maximal heart rate and time-trial heart rate (r= 0.95). Our results show that indoor 16.1-km time-trial performance declines with age but relative exercise intensity (%RMPmax and %HRmax) does not change.

Effect of age on 16.1-km time-trial performance.

In this study, we assessed the performance of trained senior (n = 6) and veteran (n = 6) cyclists (mean age 28 years, s = 3 and 57 years, s = 4 respectively). Each competitor completed two cycling tests, a ramped peak aerobic test and an indoor 16.1-km time-trial. The tests were performed using a Kingcycle ergometer with the cyclists riding their own bicycle fitted with an SRM powermeter. Power output, heart rate, and gas exchange variables were recorded continuously and blood lactate concentration [HLa] was assessed 3 min after the peak ramped test and at 2.5-min intervals during the time-trial. Peak values for power output (RMP(max)), heart rate (HR(peak)), oxygen uptake (VO2(peak)), and ventilation (V(Epeak)) attained during the ramped test were higher in the senior group (P < 0.05), whereas [HLa](peak), RER(peak), V(E): VO2(peak), and economy(peak) were similar between groups (P > 0.05). Time-trial values (mean for duration of race) for power output (W(TT)), heart rate (HR(TT)), VO2 (VO(2TT)), and V(E) (V(ETT)) were higher in the seniors (P < 0.05), but [HLa](TT), RER(TT), V(ETT): VO2(TT), and economy(TT) were similar between the groups (P > 0.05). Time-trial exercise intensity, expressed as %RMP(max), %HR(peak), % VO2(peak), and % V(Epeak), was similar (P > 0.05) for seniors and veterans (W(TT): 81%, s = 2 vs. 78%, s = 8; HR(TT): 96%, s = 4 vs. 94%, s = 4; VO2(TT): 92%, s = 4 vs. 95%, s = 10; V(ETT): 89%, s = 8 vs. 85%, s = 8, respectively). Overall, seniors attained higher absolute values for power output, heart rate, VO2, and V(E) but not blood lactate concentration, respiratory exchange ratio (RER), V(E): VO2, and economy. Veterans did not accommodate age-related declines in time trial performance by maintaining higher relative exercise intensity.

Effect of cell cycle inhibition on Cisplatin-induced cytotoxicity.

Pharmacological inhibitors of cyclin-dependent kinase (CDK)2 are currently in preclinical and clinical development. The purpose of our work was to evaluate a series of guanine derivatives for their ability to inhibit CDK2, affect cell cycle progression, and enhance the cytotoxic and apoptotic effects of cisplatin. A panel of guanine derivatives, including O(6)-benzylguanine (O(6)-BG), S(6)-benzyl-6-thioguanine (S(6)-BG), S(6)-[(cyclohexyl)methyl]-6-thioguanine (S(6)-CMG), O(6)-[(cyclohexyl)methyl]guanine (O(6)-CMG), O(6)-benzyl-9-methylguanine (9-CH(3)-BG), O(6)-[(cyclohexyl)methyl]-9-methyl-guanine (9-CH(3)-CMG), and 7-benzylguanine (N7-BG), exhibited varying degrees of CDK2 inhibition with O(6)-CMG being the most potent and 9-CH(3)-BG, 9-CH(3)-CMG, and N7-BG the least potent compounds. Treatment with S(6)-CMG and O(6)-CMG significantly decreased the percentage of cells in S phase. In SQ20b and SCC61 head and neck cancer cell lines, the most potent CDK2 inhibitor, O(6)-CMG, was also the most effective at enhancing cisplatin-induced cytotoxicity and apoptosis. Cisplatin-induced DNA platination increased in SQ20b cells pretreated with S(6)-BG, S(6)-CMG, and O(6)-CMG. Treatment with both O(6)-BG and trichostatin A, an indirect cell cycle inhibitor, demonstrated additive effects on cisplatin-induced cytotoxicity. In summary, we have identified a group of guanine derivatives that were effective modulators of cisplatin-induced cytotoxicity and apoptosis.

Resistance-modifying agents. 11.(1) Pyrimido[5,4-d]pyrimidine modulators of antitumor drug activity. Synthesis and structure-activity relationships for nucleoside transport inhibition and binding to alpha1-acid glycoprotein.

The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, alpha(1)-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of (3)H-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4'-methoxybenzylamino, 3',4'-dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.

Caffeine lowers perceptual response and increases power output during high-intensity cycling.

The aim of this study was to determine the effects of caffeine ingestion on a 'preloaded' protocol that involved cycling for 2 min at a constant rate of 100% maximal power output immediately followed by a 1-min 'all-out' effort. Eleven male cyclists completed a ramp test to measure maximal power output. On two other occasions, the participants ingested caffeine (5 mg. kg(-1)) or placebo in a randomized, double-blind procedure. All tests were conducted on the participants' own bicycles using a Kingcycle test rig. Ratings of perceived exertion (RPE; 6-20 Borg scale) were lower in the caffeine trial by approximately 1 RPE point at 30, 60 and 120 s during the constant rate phase of the preloaded test (P <0.05). The mean power output during the all-out effort was increased following caffeine ingestion compared with placebo (794+/-164 vs 750+/-163 W; P=0.05). Blood lactate concentration 4, 5 and 6 min after exercise was also significantly higher by approximately 1 mmol. l(-1) in the caffeine trial (P <0.05). These results suggest that high-intensity cycling performance can be increased following moderate caffeine ingestion and that this improvement may be related to a reduction in RPE and an elevation in blood lactate concentration.

Science and cycling: current knowledge and future directions for research.

In this holistic review of cycling science, the objectives are: (1) to identify the various human and environmental factors that influence cycling power output and velocity; (2) to discuss, with the aid of a schematic model, the often complex interrelationships between these factors; and (3) to suggest future directions for research to help clarify how cycling performance can be optimized, given different race disciplines, environments and riders. Most successful cyclists, irrespective of the race discipline, have a high maximal aerobic power output measured from an incremental test, and an ability to work at relatively high power outputs for long periods. The relationship between these characteristics and inherent physiological factors such as muscle capilliarization and muscle fibre type is complicated by inter-individual differences in selecting cadence for different race conditions. More research is needed on high-class professional riders, since they probably represent the pinnacle of natural selection for, and physiological adaptation to, endurance exercise. Recent advances in mathematical modelling and bicycle-mounted strain gauges, which can measure power directly in races, are starting to help unravel the interrelationships between the various resistive forces on the bicycle (e.g. air and rolling resistance, gravity). Interventions on rider position to optimize aerodynamics should also consider the impact on power output of the rider. All-terrain bicycle (ATB) racing is a neglected discipline in terms of the characterization of power outputs in race conditions and the modelling of the effects of the different design of bicycle frame and components on the magnitude of resistive forces. A direct application of mathematical models of cycling velocity has been in identifying optimal pacing strategies for different race conditions. Such data should, nevertheless, be considered alongside physiological optimization of power output in a race. An even distribution of power output is both physiologically and biophysically optimal for longer ( > 4 km) time-trials held in conditions of unvarying wind and gradient. For shorter races (e.g. a 1 km time-trial), an 'all out' effort from the start is advised to 'save' time during the initial phase that contributes most to total race time and to optimize the contribution of kinetic energy to race velocity. From a biophysical standpoint, the optimum pacing strategy for road time-trials may involve increasing power in headwinds and uphill sections and decreasing power in tailwinds and when travelling downhill. More research, using models and direct power measurement, is needed to elucidate fully how much such a pacing strategy might save time in a real race and how much a variable power output can be tolerated by a rider. The cyclist's diet is a multifactorial issue in itself and many researchers have tried to examine aspects of cycling nutrition (e.g. timing, amount, composition) in isolation. Only recently have researchers attempted to analyse interrelationships between dietary factors (e.g. the link between pre-race and in-race dietary effects on performance). The thermal environment is a mediating factor in choice of diet, since there may be competing interests of replacing lost fluid and depleted glycogen during and after a race. Given the prevalence of stage racing in professional cycling, more research into the influence of nutrition on repeated bouts of exercise performance and training is required.

Sodium bicarbonate ingestion does not alter the slow component of oxygen uptake kinetics in professional cyclists.

We examined the effects of pre-exercise sodium bicarbonate (NaHCO3) ingestion on the slow component of oxygen uptake (VO2) kinetics in seven professional road cyclists during intense exercise. One hour after ingesting either a placebo or NaHCO3 (0.3 g x kg body mass(-1)), each cyclist (age, 25 +/- 2 years; VO2max, 74.7 +/- 5.9 ml x kg(-1) x min(-1); mean +/- s) performed two bouts of 6 min duration at an intensity of 90% VO2max interspersed by 8 min of active recovery. Gas exchange and blood data (pH, blood lactate concentration and [HCO3-]) were collected during the tests. In both bouts, the slow component of VO2 was defined as the difference between end-exercise VO2 and the VO2 at the end of the third minute. No significant difference was found in the slow component of VO2 between conditions in the first (NaHCO3, 210 +/- 69 ml; placebo, 239 +/- 105 ml) or second trial (NaHCO3, 123 +/- 88 ml; placebo, 197 +/- 101 ml). In conclusion, pre-exercise NaHCO3 ingestion did not significantly attenuate the VO2 slow component of professional road cyclists during high-intensity exercise.