Waveforms of molecular oscillations reveal circadian timekeeping mechanisms

Circadian clocks play a pivotal role in orchestrating numerous physiological and developmental events. Waveform shapes of the oscillations of protein abundances can be informative about the underlying biochemical processes of circadian clocks. We derive a mathematical framework where waveforms do reveal hidden biochemical mechanisms of circadian timekeeping. We find that the cost of synthesizing proteins with particular waveforms can be substantially reduced by rhythmic protein half-lives over time, as supported by previous plant and mammalian data, as well as our own seedling experiment. We also find that previously-enigmatic, cyclic expression of positive arm components within the mammalian and insect clocks allows both a broad range of peak time differences between protein waveforms and the symmetries of the waveforms about the peak times. Such various peak-time differences may facilitate tissue-specific or developmental stage-specific multicellular processes. Our waveform-guided approach can be extended to various biological oscillators, including cell-cycle and synthetic genetic oscillators.Comment: Supplementary material is available at the journal websit

Dewis Choice::A Welsh Initiative promoting justice for older victim-survivors of domestic abuse

In 2002, the World Health Organization (WHO) brought global attention to elder abuse and the need for prevention in issuing the Toronto Declaration. With the rise in the proportion of people aged 60 and over, but also the spectacular demographic projections for people aged 80 years and older (globally the number of persons aged 80 and over is expected to triple by 2050), how we age, and how well we age is of great concern. Furthermore, there will be a growing need to protect the most vulnerable older people from harm. For the development of policies and interventions, more insight into this complex phenomenon is required. Therefore, the current chapter examines the effect of abuse on the quality of life of older women, and more specifically, the moderating effect of coping on the relationship between abuse and quality of life.Daphne, 201

Survival After In-Hospital Cardiopulmonary Resuscitation: A Meta-Analysis

OBJECTIVE: To determine the rates of immediate survival and survival to discharge for adult patients undergoing in-hospital cardiopulmonary resuscitation, and to identify demographic and clinical variables associated with these outcomes. MEASUREMENTS AND MAIN RESULTS: The MEDLARS database of the National Library of Medicine was searched. In addition, the authors' extensive personal files and the bibliography of each identified study were searched for further studies. Two sets of inclusion criteria were used, minimal (any study of adults undergoing in-hospital cardiopulmonary resuscitation) and strict (included only patients from general ward and intensive care units, and adequately defined cardiopulmonary arrest and resuscitation). Each study was independently reviewed and abstracted in a nonblinded fashion by two reviewers. The data abstracted were compared, and any discrepancies were resolved by consensus discussion. For the subset of studies meeting the strict criteria, the overall rate of immediate survival was 40.7% and the rate of survival to discharge was 13.4%. The following variables were associated with failure to survive to discharge: sepsis on the day prior to resuscitation (odds ratio [OR] 31.3; 95% confidence interval [CI] 1.9, 515), metastatic cancer (OR 3.9; 95% CI 1.2, 12.6), dementia (OR 3.1; 95% CI 1.1, 8.8), African-American race (OR 2.8; 95% CI 1.4, 5.6), serum creatinine level at a cutpoint of 1.5 mg/dL (OR 2.2; 95% CI 1.2, 3.8), cancer (OR 1.9; 95% CI 1.2, 3.0), coronary artery disease (OR 0.55; 95% CI 0.4, 0.8), and location of resuscitation in the intensive care unit (OR 0.51; 95% CI 0.4, 0.8). CONCLUSIONS: When talking with patients, physicians can describe the overall likelihood of surviving discharge as 1 in 8 for patients who undergo cardiopulmonary resuscitation and 1 in 3 for patients who survive cardiopulmonary resuscitation