Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence

OBJECTIVE: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness and the acute BP response to exercise in a large birth cohort of adolescents. METHODS: 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8±0.4 years, 38.5% male) completed a submaximal exercise step-test that allowed fitness (VO2 max ) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. RESULTS: Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, height, smoking and socioeconomic status (standardized β: -1.80, 95%CI: -2.64, -0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). CONCLUSION: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realised with more-favourable body composition

Polygenic risk scores for coronary artery disease and subsequent event risk amongst established cases

BACKGROUND: There is growing evidence that polygenic risk scores (PRS) can identify individuals with elevated lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify risk of subsequent events among those surviving a first CAD event remains uncertain, with possible biological differences between CAD onset and progression, and the potential for index event bias. METHODS: Using two baseline subsamples of UK Biobank; prevalent CAD cases (N = 10 287) and individuals without CAD (N = 393 108), we evaluated associations between a CAD PRS and incident cardiovascular and fatal outcomes. RESULTS: A 1 S.D. higher PRS was associated with increased risk of incident MI in participants without CAD (OR 1.33; 95% C.I. 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% C.I. 1.06, 1.25); heterogeneity P = 0.0012. Additionally, among prevalent CAD cases, we found evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% C.I. 0.85, 0.98) compared to those without CAD (OR 1.01; 95% C.I. 0.99, 1.03); heterogeneity P = 0.0041. A similar inverse association was found for ischaemic stroke (Prevalent CAD (OR 0.78; 95% C.I. 0.67, 0.90); without CAD (OR 1.09; 95% C.I. 1.04, 1.15), heterogeneity P < 0.001). CONCLUSIONS: Bias induced by case stratification and survival into UK Biobank may distort associations of polygenic risk scores derived from case-control studies or populations initially free of disease. Differentiating between effects of possible biases and genuine biological heterogeneity is a major challenge in disease progression research

Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: Cross-sectional association with cardiac structure in adolescents

Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment

Contact Manifolds, Contact Instantons, and Twistor Geometry

Recently, Kallen and Zabzine computed the partition function of a twisted supersymmetric Yang-Mills theory on the five-dimensional sphere using localisation techniques. Key to their construction is a five-dimensional generalisation of the instanton equation to which they refer as the contact instanton equation. Subject of this article is the twistor construction of this equation when formulated on K-contact manifolds and the discussion of its integrability properties. We also present certain extensions to higher dimensions and supersymmetric generalisations.Comment: v3: 28 pages, clarifications and references added, version to appear in JHE

Early expansion of CD38+ICOS+ GC Tfh in draining lymph nodes during influenza vaccination immune response

T follicular helper (Tfh) cells provide critical help to B cells during the germinal center (GC) reaction to facilitate generation of protective humoral immunity. Accessing the human lymph node (LN) to study the commitment of CD4 T cells to GC Tfh cell differentiation during in vivo vaccine responses is difficult. We used ultrasound guided fine needle biopsy to monitor recall responses in axillary LNs to seasonal influenza vaccination in healthy volunteers. Specific expansion of GC cell subsets occurred exclusively within draining LNs five days postvaccination. Draining LN GC Tfh and precursor-Tfh cells express higher levels of CD38, ICOS, and Ki67, indicating they were significantly more activated, motile, and proliferating, compared to contralateral LN cells. These observations provide insight into the early expansion phase of the human Tfh lineage within LNs during a vaccine induced memory response and highlights early LN immune responses may not be reflected in the periphery

Arthroscopic treatment of a medial meniscal cyst using a posterior trans-septal approach: a case report

Arthroscopic partial menisectomy followed by cyst decompression is currently recommended for treatment of a meniscal cyst. However, it is doubtful whether partial menisectomy should be performed on cysts communicating with the joint in cases without a meniscal tear on its surface since meniscal function will be sacrificed. In this report, a meniscal cyst arising from the posterior horn of the medial meniscus without meniscal tear on its surface was resected using an arthroscopic posterior trans-septal approach. A 59 year-old male presented to our hospital with popliteal pain when standing up after squatting down. Magnetic resonance imaging revealed a multilobulated meniscal cyst arising from the posterior horn of the medial meniscus extending to the posterior septum with a grade 2 meniscal tear by Mink's classification. The medial meniscus was intact on the surface on arthroscopic examination. The meniscal cyst and posterior septum were successfully resected using a posterior trans-septal approach without harming the meniscus. This is the first report on a meniscal cyst being resected using an arthroscopic posterior trans-septal approach with a 9-month follow-up period

Metabolic profiles of socio-economic position: a multi-cohort analysis

Background: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. Methods: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in 30 000 adults and 4000 children across 10 UK and Finnish cohort studies. Results: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. Conclusions: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities

Bounds on 4D Conformal and Superconformal Field Theories

We derive general bounds on operator dimensions, central charges, and OPE coefficients in 4D conformal and N=1 superconformal field theories. In any CFT containing a scalar primary phi of dimension d we show that crossing symmetry of implies a completely general lower bound on the central charge c >= f_c(d). Similarly, in CFTs containing a complex scalar charged under global symmetries, we bound a combination of symmetry current two-point function coefficients tau^{IJ} and flavor charges. We extend these bounds to N=1 superconformal theories by deriving the superconformal block expansions for four-point functions of a chiral superfield Phi and its conjugate. In this case we derive bounds on the OPE coefficients of scalar operators appearing in the Phi x Phi* OPE, and show that there is an upper bound on the dimension of Phi* Phi when dim(Phi) is close to 1. We also present even more stringent bounds on c and tau^{IJ}. In supersymmetric gauge theories believed to flow to superconformal fixed points one can use anomaly matching to explicitly check whether these bounds are satisfied.Comment: 47 pages, 9 figures; V2: small corrections and clarification