The impact of sport participation on bone mass and geometry in adolescent males

Exercise is an effective approach for developing bone mass and adolescence is a key period to optimize bone health. However, sports specific training may have different effects on bone outcomes. This study examined the differences on bone outcomes between osteogenic (football) and non-osteogenic (swimming and cycling) sports and a control group in adolescent males. Methods: One hundred twenty one males (13.1±0.1 years) were measured: 41 swimmers, 37 footballers, 29 cyclists and 14 controls. Dual energy X-ray absorptiometry measured bone mineral density (BMD) and content (BMC) at lumbar spine, right and left hip and total body. Hip structural analysis evaluated bone geometry at the femoral neck. Quantitative ultrasound evaluated bone stiffness at both feet. Results: Footballers had significantly higher BMD at total body less head (7-9%), total hip (12-2%) and legs (7-11%) compared to all groups and significantly higher BMD at the femoral neck than controls (14%). Cyclists had higher BMD at the trochanter (10%) and BMC at the arms (10%) compared to controls. Geometrical analysis showed that footballers had significantly higher cross-sectional area (8-19%) compared to all groups, cross-sectional moment of inertia (17 %) compared to controls and section modulus compared to cyclists (11%) and controls (21%). Footballers had significantly higher bone stiffness compared to all groups (10-20%) at the dominant foot and (12-13%) at the nondominant foot compared to swimmers and controls. Conclusions: Adolescent male footballers exhibited higher bone density, geometry and stiffness compared to swimmers, cyclists and controls. Although swimmers and cyclists had higher bone outcomes compared to controls, these differences were not significant.The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007-2013] under grant agreement n°. PCIG13-GA-2013-618496

Determinants of bone outcomes in adolescent athletes at baseline: the PRO-BONE study

This is the author accepted manuscript. The final version is available from the American College of Sports Medicine (ACSM) via the DOI in this record.Purpose: The determinants of areal bone mineral density (aBMD) and hip geometry 26 estimates in adolescent athletes are poorly understood. This study aimed to identify the 27 determinants of aBMD and hip geometry estimates in adolescent male athletes. Methods: 28 One hundred twenty one males (13.1±0.1 years) were measured: 41 swimmers, 37 29 footballers, 29 cyclists and 14 controls. Dual energy X-ray absorptiometry (DXA) measured 30 aBMD at lumbar spine, femoral neck (FN) and total body. Hip structural analysis evaluated 31 hip geometry estimates at the FN. Multiple linear regression examined the contribution of the 32 sports practised, stature, lean and fat mass, serum calcium and vitamin D, moderate to 33 vigorous physical activity (MVPA), vertical jump and cardiorespiratory fitness (CRF) with 34 aBMD and hip geometry estimates. Results: Region specific lean mass was the strongest 35 positive predictor of aBMD (β = 0.614 - 0.931) and football participation was the next 36 strongest predictor (β = 0.304 - 0.579). Stature (β = 0.235 - 0.380), fat mass (β = 0.189), 37 serum calcium (β = 0.103), serum vitamin D (β = 0.104 - 0.139) and vertical jump (β = 0.146 38 - 0.203) were associated with aBMD across various specific sites. All hip geometry estimates 39 were associated with lean mass (β = 0.370 - 0.568) and stature (β = 0.338 - 0.430). Football 40 participation was associated with hip cross-sectional area (β = 0.322) and MVPA (β = 0.140 - 41 0.142). CRF (β = 0.183 - 0.207) was associated with section modulus and cross-sectional 42 moment of inertia. Conclusions: Region specific lean mass is the strongest determinant of 43 aBMD and hip geometry estimates in adolescent male athletes. Football participation and 44 stature were important determinants for aBMD and hip geometry estimates while the 45 contribution of the other predictors was site specific.The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007-2013] under grant agreement n°. PCIG13-GA-2013-61849

Low estimated glomerular filtration rate and pneumonia in stroke patients: findings from a prospective stroke registry in the East of England

Priya Vart,1,2 Joao H Bettencourt-Silva,3,4 Anthony K Metcalf,3,4 Kristian M Bowles,3,4 John F Potter,3,4 Phyo K Myint1,3,4 1Ageing Clinical and Experimental Research, Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK; 2Radboud Institute for Health Sciences, Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands; 3Stroke Research Group, Norfolk and Norwich University Hospital, Norwich, UK; 4Norwich Medical School, University of East Anglia, Norwich, UK Purpose: Low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2) is a recognized risk factor for pneumonia in general population. While pneumonia is common after stroke, the association between levels of eGFR and pneumonia in stroke patient population has not yet been examined thoroughly. Patients and methods: Using data of 10,329 patients from the Norfolk and Norwich Stroke Registry between January 2003 and April 2015, we examined the association of poststroke pneumonia (in-hospital and after discharge) with low eGFR and when eGFR is divided into the complete spectrum of clinically relevant categories; (≥90) (ref.), 60–89, 45–59, 30–44, 15–30, and <15 mL/min/1.73 m2). Results: In all, 1,519 (14.7%) developed in-hospital pneumonia and 1,037 (12.9%) developed pneumonia after hospital discharge. In age- and sex-adjusted model, low eGFR was associated with in-hospital pneumonia (subdistribution hazard ratio (sHR): 1.13; 95% CI: 1.01–1.25) and pneumonia after discharge (sHR: 1.20; 95% CI: 1.07–1.38). In fully adjusted model, association remained significant for pneumonia after hospital discharge. When eGFR was categorized in all clinically relevant categories, association with in-hospital pneumonia tended to be “U” shaped (eg, compared to eGFR ≥90, sHR for 60–89 was 0.78; 95% CI: 0.62–0.99 and for <15 was 1.06; 95% CI: 0.71–1.60) and association with pneumonia after discharge tended to increase with decline in eGFR level such that risk was almost two fold higher at eGFR <15 (sHR: 1.85; 95% CI: 1.01–3.51). Association for in-hospital pneumonia was driven mainly by aspiration pneumonia, whereas association in stroke survivors was predominantly for nonaspiration pneumonia. Conclusion: In stroke patients, low eGFR at admission was associated with pneumonia, particularly severely reduced eGFR with nonaspiration pneumonia after hospital discharge. eGFR could form the basis for identifying patients at high risk of poststroke pneumonia. Keywords: stroke, eGFR, prognosis, epidemiolog

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of “emergency” granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis

Integrating Extrinsic and Intrinsic Cues into a Minimal Model of Lineage Commitment for Hematopoietic Progenitors

Autoregulation of transcription factors and cross-antagonism between lineage-specific transcription factors are a recurrent theme in cell differentiation. An equally prevalent event that is frequently overlooked in lineage commitment models is the upregulation of lineage-specific receptors, often through lineage-specific transcription factors. Here, we use a minimal model that combines cell-extrinsic and cell-intrinsic elements of regulation in order to understand how both instructive and stochastic events can inform cell commitment decisions in hematopoiesis. Our results suggest that cytokine-mediated positive receptor feedback can induce a “switch-like” response to external stimuli during multilineage differentiation by providing robustness to both bipotent and committed states while protecting progenitors from noise-induced differentiation or decommitment. Our model provides support to both the instructive and stochastic theories of commitment: cell fates are ultimately driven by lineage-specific transcription factors, but cytokine signaling can strongly bias lineage commitment by regulating these inherently noisy cell-fate decisions with complex, pertinent behaviors such as ligand-mediated ultrasensitivity and robust multistability. The simulations further suggest that the kinetics of differentiation to a mature cell state can depend on the starting progenitor state as well as on the route of commitment that is chosen. Lastly, our model shows good agreement with lineage-specific receptor expression kinetics from microarray experiments and provides a computational framework that can integrate both classical and alternative commitment paths in hematopoiesis that have been observed experimentally

The link between volcanism and plutonism in epizonal magma systems; high-precision U–Pb zircon geochronology from the Organ Mountains caldera and batholith, New Mexico

The Organ Mountains caldera and batholith expose the volcanic and epizonal plutonic record of an Eocene caldera complex. The caldera and batholith are well exposed, and extensive previous mapping and geochemical analyses have suggested a clear link between the volcanic and plutonic sections, making this an ideal location to study magmatic processes associated with caldera volcanism. Here we present high-precision thermal ionization mass spectrometry U–Pb zircon dates from throughout the caldera and batholith, and use these dates to test and improve existing petrogenetic models. The new dates indicate that Eocene volcanic and plutonic rocks in the Organ Mountains formed from ~44 to 34 Ma. The three largest caldera-related tuff units yielded weighted mean [superscript 206]Pb/[superscript 238]U dates of 36.441 ± 0.020 Ma (Cueva Tuff), 36.259 ± 0.016 Ma (Achenback Park tuff), and 36.215 ± 0.016 Ma (Squaw Mountain tuff). An alkali feldspar granite, which is chemically similar to the erupted tuffs, yielded a synchronous weighted mean [superscript 206]Pb/[superscript 238]U date of 36.259 ± 0.021 Ma. Weighted mean [superscript 206]Pb/[superscript 238]U dates from the larger volume syenitic phase of the underlying Organ Needle pluton range from 36.130 ± 0.031 to 36.071 ± 0.012 Ma, and the youngest sample is 144 ± 20 to 188 ± 20 ka younger than the Squaw Mountain and Achenback Park tuffs, respectively. Younger plutonism in the batholith continued through at least 34.051 ± 0.029 Ma. We propose that the Achenback Park tuff, Squaw Mountain tuff, alkali feldspar granite and Organ Needle pluton formed from a single, long-lived magma chamber/mush zone. Early silicic magmas generated by partial melting of the lower crust rose to form an epizonal magma chamber. Underplating of the resulting mush zone led to partial melting and generation of a high-silica alkali feldspar granite cap, which erupted to form the tuffs. The deeper parts of the chamber underwent continued recharge and crystallization for 144 ± 20 ka after the final eruption. Calculated magmatic fluxes for the Organ Needle pluton range from 0.0006 to 0.0030 km3/year, in agreement with estimates from other well-studied plutons. The petrogenetic evolution proposed here may be common to many small-volume silicic volcanic systems

Immune Boosting Explains Regime-Shifts in Prevaccine-Era Pertussis Dynamics

Understanding the biological mechanisms underlying episodic outbreaks of infectious diseases is one of mathematical epidemiology’s major goals. Historic records are an invaluable source of information in this enterprise. Pertussis (whooping cough) is a re-emerging infection whose intermittent bouts of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. It has been suggested that recent increases in pertussis incidence and shifts in the age-distribution of cases may be due to diminished natural immune boosting. Here we show that a model that incorporates this mechanism can account for a unique set of pre-vaccine-era data from Copenhagen. Under this model, immune boosting induces transient bursts of large amplitude outbreaks. In the face of mass vaccination, the boosting model predicts larger and more frequent outbreaks than do models with permanent or passively-waning immunity. Our results emphasize the importance of understanding the mechanisms responsible for maintaining immune memory fo