Auxin-regulated reversible inhibition of TMK1 signaling by MAKR2 modulates the dynamics of root gravitropism

Plants are able to orient their growth according to gravity, which ultimately controls both shoot and root architecture.1 Gravitropism is a dynamic process whereby gravistimulation induces the asymmetric distribution of the plant hormone auxin, leading to asymmetric growth, organ bending, and subsequent reset of auxin distribution back to the original pre-gravistimulation situation.1, 2, 3 Differential auxin accumulation during the gravitropic response depends on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.1, 2, 3, 4 In particular, the timing of this dynamic response is regulated by PIN2,5,6 but the underlying molecular mechanisms are poorly understood. Here, we show that MEMBRANE ASSOCIATED KINASE REGULATOR2 (MAKR2) controls the pace of the root gravitropic response. We found that MAKR2 is required for the PIN2 asymmetry during gravitropism by acting as a negative regulator of the cell-surface signaling mediated by the receptor-like kinase TRANSMEMBRANE KINASE1 (TMK1).2,7, 8, 9, 10 Furthermore, we show that the MAKR2 inhibitory effect on TMK1 signaling is antagonized by auxin itself, which triggers rapid MAKR2 membrane dissociation in a TMK1-dependent manner. Our findings suggest that the timing of the root gravitropic response is orchestrated by the reversible inhibition of the TMK1 signaling pathway at the cell surface

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life

Changes in physical activity during the retirement transition: a series of novel n-of-1 natural experiments.

BACKGROUND: Existing evidence about the impact of retirement on physical activity (PA) has primarily focused on the average change in PA level after retirement in group-based studies. It is unclear whether findings regarding the direction of PA change after retirement from group-based studies apply to individuals. This study aimed to explore changes in PA, PA determinants and their inter-relationships during the retirement transition at the individual level. METHODS: A series of n-of-1 natural experiments were conducted with seven individuals who were aged 55-76 years and approaching retirement. PA was measured by tri-axial accelerometry. Twice-daily self-report and ecological momentary assessments of evidence- and theory-based determinants of PA (e.g. sleep length/quality, happiness, tiredness, stress, time pressure, pain, intention, perceived behavioural control, priority, goal conflict and goal facilitation) were collected via a questionnaire for a period of between 3 and 7 months, which included time before and after the participant's retirement date. A personalised PA determinant was also identified by each participant and measured daily for the duration of the study. Dynamic regression models for discrete time binary data were used to analyse data for each individual participant. RESULTS: Two participants showed a statistically significant increase in the probability of engaging in PA bouts after retirement and two participants showed a significant time trend for a decrease and increase in PA bouts over time during the pre- to post-retirement period, respectively. There was no statistically significant change in PA after retirement for the remaining participants. Most of the daily questionnaire variables were significantly associated with PA for one or more participants but there were no consistent pattern of PA predictors across participants. For some participants, the relationship between questionnaire variables and PA changed from pre- to post-retirement. CONCLUSIONS: The findings from this study demonstrate the impact of retirement on individual PA trajectories. Using n-of-1 methods can provide information about unique patterns and determinants of individual behaviour over time, which has been obscured in previous research. N-of-1 methods can be used as a tool to inform personalised PA interventions for individuals within the retirement transition

Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans.

BACKGROUND: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. METHODS: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. RESULTS: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. CONCLUSION: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely

Physical activity levels in adults and older adults 3–4 years after pedometer-based walking interventions: Long-term follow-up of participants from two randomised controlled trials in UK primary care

Background Physical inactivity is an important cause of noncommunicable diseases. Interventions can increase short-term physical activity (PA), but health benefits require maintenance. Few interventions have evaluated PA objectively beyond 12 months. We followed up two pedometer interventions with positive 12-month effects to examine objective PA levels at 3–4 years. Methods and findings Long-term follow-up of two completed trials: Pedometer And Consultation Evaluation-UP (PACE-UP) 3-arm (postal, nurse support, control) at 3 years and Pedometer Accelerometer Consultation Evaluation-Lift (PACE-Lift) 2-arm (nurse support, control) at 4 years post-baseline. Randomly selected patients from 10 United Kingdom primary care practices were recruited (PACE-UP: 45–75 years, PACE-Lift: 60–75 years). Intervention arms received 12-week walking programmes (pedometer, handbooks, PA diaries) postally (PACE-UP) or with nurse support (PACE-UP, PACE-Lift). Main outcomes were changes in 7-day accelerometer average daily step counts and weekly time in moderate-to-vigorous PA (MVPA) in ≥10-minute bouts in intervention versus control groups, between baseline and 3 years (PACE-UP) and 4 years (PACE-Lift). PACE-UP 3-year follow-up was 67% (681/1,023) (mean age: 59, 64% female), and PACE-Lift 4-year follow-up was 76% (225/298) (mean age: 67, 53% female). PACE-UP 3-year intervention versus control comparisons were as follows: additional steps/day postal +627 (95% CI: 198–1,056), p = 0.004, nurse +670 (95% CI: 237–1,102), p = 0.002; total weekly MVPA in bouts (minutes/week) postal +28 (95% CI: 7–49), p = 0.009, nurse +24 (95% CI: 3–45), p = 0.03. PACE-Lift 4-year intervention versus control comparisons were: +407 (95% CI: −177–992), p = 0.17 steps/day, and +32 (95% CI: 5–60), p = 0.02 minutes/week MVPA in bouts. Neither trial showed sedentary or wear-time differences. Main study limitation was incomplete follow-up; however, results were robust to missing data sensitivity analyses. Conclusions Intervention participants followed up from both trials demonstrated higher levels of objectively measured PA at 3–4 years than controls, similar to previously reported 12-month trial effects. Pedometer interventions, delivered by post or with nurse support, can help address the public health physical inactivity challenge

Measuring change in trials of physical activity interventions: a comparison of self-report questionnaire and accelerometry within the PACE-UP trial

Background: Few trials have compared estimates of change in physical activity (PA) levels using self-reported and objective PA measures when evaluating trial outcomes. The PACE-UP trial offered the opportunity to assess this, using the self-administered International Physical Activity Questionnaire (IPAQ) and waist-worn accelerometry. Methods: The PACE-UP trial (N=1023) compared usual care (n=338) with two pedometer-based walking interventions, by post (n=339) or with nurse support (n=346). Participants wore an accelerometer at baseline and 12months and completed IPAQ for the same 7-day periods. Main outcomes were weekly minutes, all in ≥10min bouts as per UK PA guidelines of: i) accelerometer moderate-to-vigorous PA (Acc-MVPA) ii) IPAQ moderate+vigorous PA (IPAQ-MVPA) and iii) IPAQ walking (IPAQ-Walk). For each outcome, 12month values were regressed on baseline to estimate change. Results: Analyses were restricted to 655 (64%) participants who provided data on all outcomes at baseline and 12 months. Both intervention groups significantly increased their accelerometry MVPA minutes/week compared with control: postal group 42 (95% CI 22, 61), nurse group 43 (95% CI 24, 63). IPAQ-Walk minutes/week also increased: postal 57 (95% CI 2, 112), nurse 43 (95% CI -11, 97) but IPAQ-MVPA minutes/week showed non-significant decreases: postal -11 (95% CI -65, 42), nurse -34 (95% CI -87, 19). Conclusions: Our results demonstrate the necessity of using a questionnaire focussing on the activities being altered, as with IPAQ-Walk questions. Even then, the change in PA was estimated with far less precision than with accelerometry. Accelerometry is preferred to self-report measurement, minimising bias and improving precision when assessing effects of a walking intervention

Effectiveness of a lifestyle physical activity intervention in a women's organization

Objective: The objective of the present study was to evaluate the effectiveness of a minimal contact physical activity intervention that was maximally integrated into the existing structures of a women's organization.status: publishe