Lag, lock, sync, slip: the many 'phases' of coupled flagella

This is the final version of the article. Available from the Royal Society via the DOI in this recordIn a multitude of life's processes, cilia and flagella are found indispensable. Recently, the biflagellated chlorophyte alga Chlamydomonas has become a model organism for the study of ciliary motility and synchronization. Here, we use high-speed, high-resolution imaging of single pipette-held cells to quantify the rich dynamics exhibited by their flagella. Underlying this variability in behaviour are biological dissimilarities between the two flagella—termed cis and trans, with respect to a unique eyespot. With emphasis on the wild-type, we derive limit cycles and phase parametrizations for self-sustained flagellar oscillations from digitally tracked flagellar waveforms. Characterizing interflagellar phase synchrony via a simple model of coupled oscillators with noise, we find that during the canonical swimming breaststroke the cis flagellum is consistently phase-lagged relative to, while remaining robustly phase-locked with, the trans flagellum. Transient loss of synchrony, or phase slippage, may be triggered stochastically, in which the trans flagellum transitions to a second mode of beating with attenuated beat envelope and increased frequency. Further, exploiting this alga's ability for flagellar regeneration, we mechanically induced removal of one or the other flagellum of the same cell to reveal a striking disparity between the beatings of the cis and trans flagella, in isolation. These results are evaluated in the context of the dynamic coordination of Chlamydomonas flagella.Financial support is acknowledged from the EPSRC, ERC Advanced Investigator Grant 247333, and a Senior Investigator Award from the Wellcome Trust (R.E.G.)

Association of estimated glomerular filtration rate and urine albumin-to-creatinine ratio with incidence of cardiovascular diseases and mortality in chinese patients with type 2 diabetes mellitus – a population-based retrospective cohort study

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Statin use reduces cardiovascular events and all-cause mortality amongst Chinese patients with type 2 diabetes mellitus: a 5-year cohort study

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Effect of metformin monotherapy on cardiovascular diseases and mortality: a retrospective cohort study on Chinese type 2 diabetes mellitus patients

Background: Many factors influence whether the first-line oral anti-diabetic drug, metformin, should be initiated to a patient with type 2 diabetes mellitus (T2DM) early in the course of management in addition to lifestyle modifications. This study aims to evaluate the net effects of metformin monotherapy (MM) on the all-cause mortality and cardiovascular disease (CVD) events. Methods: A retrospective 5-year follow-up cohort study was conducted on Chinese adult patients with T2DM and without any CVD history under public primary care. Cox proportional hazard regressions were performed to compare the risk of all-cause mortality and CVD events (CHD, stroke, heart failure) between patients receiving lifestyle modifications plus MM (MM groups) and those with lifestyle modifications alone (control groups). Results: 3400 pairs of matched patients were compared. MM group had an incidence rate of 7.5 deaths and 11.3 CVD events per 1000 person-years during a median follow-up period of 62.5 months whereas control group had 11.1 deaths and 16.3 per 1000 person-years during a median follow-up period of 43.5–44.5 months. MM group showed a 29.5 and 30–35 % risk reduction of all-cause mortality and CVD events (except heart failure) than control group (P < 0.001). MM group was more prone to progress to chronic kidney disease but this was not statistically significant. Conclusions: Type 2 diabetic patients who were started on metformin monotherapy showed improvement in many of the clinical parameters and a reduction in all-cause mortality and CVD events than lifestyle modifications alone. If there is no contraindication and if tolerated, diabetic patients should be prescribed with metformin early in the course of the diabetic management to minimize their risk of having the cardiovascular events and mortality in the long run.published_or_final_versio

Evaluation of the quality of care of a haemodialysis public-private partnership programme for patients with end-stage renal disease

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Effect of a structured diabetes education programme in primary care on hospitalizations and emergency department visits among people with Type 2 diabetes mellitus: results from the Patient Empowerment Programme

AIM: To assess whether a structured diabetes education programme, the Patient Empowerment Programme, was associated with a lower rate of all-cause hospitalization and emergency department visits in a population-based cohort of patients with Type 2 diabetes mellitus in primary care. METHODS: A cohort of 24 250 patients was evaluated using a linked administrative database during 2009-2013. We selected 12 125 patients with Type 2 diabetes who had at least one Patient Empowerment Programme session attendance. Patients who did not participate in the Patient Empowerment Programme were matched one-to-one with patients who did, using the propensity score method. Hospitalization events and emergency department visits were the events of interest. Cox proportional hazard and negative binomial regressions were performed to estimate the hazard ratios for the initial event, and incidence rate ratios for the number of events. RESULTS: During a median 30.5 months of follow-up, participants in the Patient Empowerment Programme had a lower incidence of an initial hospitalization event (22.1 vs 25.2%; hazard ratio 0.879; P<0.001) and emergency department visit (40.5 vs 44%; hazard ratio 0.901; P<0.001) than those who did not participate in the Patient Empowerment Programme. Participation in the Patient Empowerment Programme was associated with a significantly lower number of emergency department visits (incidence rate ratio 0.903; P<0.001): 40.4 visits per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 36.2 per 100 patients annually in those who did. There were significantly fewer hospitalization episodes (incidence rate ratio 0.854; P<0.001): 200 hospitalizations per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 16.9 hospitalizations per 100 patients annually in those who did. CONCLUSIONS: Among patients with Type 2 diabetes, the Patient Empowerment Programme was shown to be effective in delaying the initial hospitalization event and in reducing their frequency. This article is protected by copyright. All rights reserved.postprin

Evaluation of the Effectiveness of Nurse-Led Continence Care Treatments for Chinese Primary Care Patients with Lower Urinary Tract Symptoms

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Antiphase Synchronization in a Flagellar-Dominance Mutant of Chlamydomonas

This is the final version. Available on open access from American Physical Society via the DOI in this record. Groups of beating flagella or cilia often synchronize so that neighboring filaments have identical frequencies and phases. A prime example is provided by the unicellular biflagellate Chlamydomonas reinhardtii, which typically displays synchronous in-phase beating in a low-Reynolds number version of breaststroke swimming. We report the discovery that ptx1, a flagellar-dominance mutant of C. reinhardtii, can exhibit synchronization in precise antiphase, as in the freestyle swimming stroke. High-speed imaging shows that ptx1 flagella switch stochastically between in-phase and antiphase states, and that the latter has a distinct waveform and significantly higher frequency, both of which are strikingly similar to those found during phase slips that stochastically interrupt in-phase beating of the wild-type. Possible mechanisms underlying these observations are discussed.Spanish Ministerio de Ciencia y InnovaciónEngineering and Physical Sciences Research Council (EPSRC)Biotechnology and Biological Sciences Research Council (BBSRC)European Research CouncilWellcome Trus

Prediction of new onset of end stage renal disease in Chinese patients with type 2 diabetes mellitus – a population-based retrospective cohort study

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Effect of Multifactorial Treatment Targets and Relative Importance of Hemoglobin A1c, Blood Pressure, and Low‐Density Lipoprotein‐Cholesterol on Cardiovascular Diseases in Chinese Primary Care Patients With Type 2 Diabetes Mellitus: A Population‐Based Retrospective Cohort Study

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