Effects of saddle angle on heavy intensity time trial cycling: Implications of the UCI rule 1.3.014

The UCI dictates that during sanctioned events, the saddle of the bicycle may be at angle of no more than 3° of forward rotation, so as to prevent performance advantages (Rule 1.3.014). This research investigates the effect on performance when rotating the saddle beyond the mandated angle during a laboratory 4km time trial (TT). Eleven competitive male cyclists (age 26±6 (mean±SD) yrs, height 179.2±6.7 cm, body mass 72.5±6.7 kg; V̇O2max 70.9±8.6 ml∙kg-1∙min-1) completed laboratory 4km TTs using saddle angles of 0°, 3° and 6°. Completion time and mean power were recorded, in addition to lower appendage kinematics, crank torque kinetics and cardiorespiratory responses. There were no significant changes in TT time, power output, cardiorespiratory variables or crank torque kinetics as a function of saddle angle (P>0.05). There were significant effects on minimum and maximum hip angle and the horizontal displacement of the greater trochanter (P<0.05). At 6° the maximum hip angle and forward displacement of the greater trochanter was greater compared to 0° and 3°. Minimum hip angle was greater at 6° than 3° (P<0.05). In conclusion, contravening UCI rule 1.3.014 by using a saddle angle beyond 3° does not result in performance advantages during a laboratory 4 km. However, tilting the saddle does appear to cause a forward displacement of the pelvis leading to an opening of the hip angle at the top and bottom of the pedal stroke

The effects of forward rotation of posture on heavy intensity cycling: Implications of UCI rule 1.3.013

UCI rule 1.3.013 limits the forward displacement of the nose of the saddle to 5cm rearward of the centre of the bottom-bracket. This study tests the effects of contravening this rule on 4km laboratory time trials and highlights biomechanical and physiological responses that could be of interest to coaches and bike fitters. Ten competitive male cyclists age 26±2 (mean±SD) yrs, height 180±5 cm, body mass 71±6 kg; V̇ O2max 70.9±8.6 ml·kg-1·min-1) completed 4km time trials and heavy intensity bouts. Riding posture was rotated forward where the nose of the saddle was 0, 2, 4, and 6cm to the rear of the bottom bracket (P0, P2, P4 and P6). End time, power, cardiorespiratory responses, lower appendage kinematics and crank torque kinetics were measured. There was no significant effect of position on 4 km time trials completion time or power. During 4 km time trials and heavy intensity bouts, gas exchange variables and lower limb range of motion were unchanged (P>0.05). Trunk lean angle, cardiac output and stroke volume were greater at P6 than other positions (P0.05). Results indicate, contravening rule 1.3.013 does not bring about improvements to 4km laboratory TTs. The rearward shift in peak crank torque most likely occurs as a function of altered muscle activation. Haemodynamic variations are possibly related to changes in peripheral resistance at the most forward position. Further work is necessary to allude to probable improvements in aerodynamics

Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study

Objectives: To investigate geographic variation in guideline-indicated treatments for NSTEMI in the English National Health Service (NHS). Design: Cohort study using registry data from the Myocardial Ischaemia National Audit Project. Setting: All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS. Participants: 357,228 patients with NSTEMI between 1st January, 2003 and 30th June, 2013. Main outcome measure: Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication. Results: The proportion of NSTEMI who received optimal care was low (48,257/357,228; 13.5%) and varied between CCGs (median 12.8%, interquartile range 0.7 to 18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0 to 40.0%) and least for use of an electrocardiogram (96.7%, 92.5 to 98.7%). The highest rates of care were for acute aspirin (median 92.8%, interquartile range 88.6 to 97.1%), and aspirin (90.1%, 85.1 to 93.3%) and statins (86.4%, 82.3 to 91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, interquartile range 8.7 to 16.6%), dietary advice (32.4%, 23.9 to 41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4 to 46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between hospitals differences (median 64.7%, interquartile range 57.4% to 70.0%; between hospital variance: 1.92, 95% confidence interval 1.51 to 2.44; interclass correlation 0.996, 0.976 to 0.999). Conclusions: Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths

Hybrid Societies : Challenges and Perspectives in the Design of Collective Behavior in Self-organizing Systems

Hybrid societies are self-organizing, collective systems, which are composed of different components, for example, natural and artificial parts (bio-hybrid) or human beings interacting with and through technical systems (socio-technical). Many different disciplines investigate methods and systems closely related to the design of hybrid societies. A stronger collaboration between these disciplines could allow for re-use of methods and create significant synergies. We identify three main areas of challenges in the design of self-organizing hybrid societies. First, we identify the formalization challenge. There is an urgent need for a generic model that allows a description and comparison of collective hybrid societies. Second, we identify the system design challenge. Starting from the formal specification of the system, we need to develop an integrated design process. Third, we identify the challenge of interdisciplinarity. Current research on self-organizing hybrid societies stretches over many different fields and hence requires the re-use and synthesis of methods at intersections between disciplines. We then conclude by presenting our perspective for future approaches with high potential in this area

Acute heart failure presentation, management, and outcomes in cancer patients: a national longitudinal study

AIMS: Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). The aim of the study is to investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. METHODS AND RESULTS: This retrospective, population-based cohort study identified 221 953 patients admitted to a hospital in England for HF during 2012–2018 (12 867 with a breast, prostate, colorectal, or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on (i) HF presentation and in-hospital mortality, (ii) place of care, (iii) HF medication prescribing, and (iv) post-discharge survival, using propensity score weighting and model-based adjustment. Heart failure presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward [−2.4% age point difference (ppd) (95% CI −3.3, −1.6)] or were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists (ACEi/ARB) for heart failure with reduced ejection fraction [−2.1 ppd (−3.3, −0.9)] than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). CONCLUSION: Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

BACKGROUND: Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. METHODS: Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. FINDINGS: A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. CONCLUSIONS: In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. TRIAL REGISTRATION NUMBER: EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function

This review bridges functional and evolutionary aspects of plastid chromosome architecture in land plants and their putative ancestors. We provide an overview on the structure and composition of the plastid genome of land plants as well as the functions of its genes in an explicit phylogenetic and evolutionary context. We will discuss the architecture of land plant plastid chromosomes, including gene content and synteny across land plants. Moreover, we will explore the functions and roles of plastid encoded genes in metabolism and their evolutionary importance regarding gene retention and conservation. We suggest that the slow mode at which the plastome typically evolves is likely to be influenced by a combination of different molecular mechanisms. These include the organization of plastid genes in operons, the usually uniparental mode of plastid inheritance, the activity of highly effective repair mechanisms as well as the rarity of plastid fusion. Nevertheless, structurally rearranged plastomes can be found in several unrelated lineages (e.g. ferns, Pinaceae, multiple angiosperm families). Rearrangements and gene losses seem to correlate with an unusual mode of plastid transmission, abundance of repeats, or a heterotrophic lifestyle (parasites or myco-heterotrophs). While only a few functional gene gains and more frequent gene losses have been inferred for land plants, the plastid Ndh complex is one example of multiple independent gene losses and will be discussed in detail. Patterns of ndh-gene loss and functional analyses indicate that these losses are usually found in plant groups with a certain degree of heterotrophy, might rendering plastid encoded Ndh1 subunits dispensable