Opening Lecture The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition?

Awareness of the ancestral human diet might advance traditional nutrition science. The human genome has hardly changed since the emergence of behaviourally-modern humans in East Africa 100-50 · 10 3 years ago; genetically, man remains adapted for the foods consumed then. The best available estimates suggest that those ancestors obtained about 35 % of their dietary energy from fats, 35 % from carbohydrates and 30 % from protein. Saturated fats contributed approximately 7 . 5 % total energy and harmful trans-fatty acids contributed negligible amounts. Polyunsaturated fat intake was high, with n-6:n-3 approaching 2 :1 (v. 10 : 1 today). Cholesterol consumption was substantial, perhaps 480 mg/d. Carbohydrate came from uncultivated fruits and vegetables, approximately 50 % energy intake as compared with the present level of 16 % energy intake for Americans. High fruit and vegetable intake and minimal grain and dairy consumption made ancestral diets base-yielding, unlike today's acid-producing pattern. Honey comprised 2-3% energy intake as compared with the 15 % added sugars contribute currently. Fibre consumption was high, perhaps 100 g/d, but phytate content was minimal. Vitamin, mineral and (probably) phytochemical intake was typically 1 . 5 to eight times that of today except for that of Na, generally <1000 mg/d, i.e. much less than that of K. The field of nutrition science suffers from the absence of a unifying hypothesis on which to build a dietary strategy for prevention; there is no Kuhnian paradigm, which some researchers believe to be a prerequisite for progress in any scientific discipline. An understanding of human evolutionary experience and its relevance to contemporary nutritional requirements may address this critical deficiency

Application of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development

The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF) and extinction (EXT)) of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing.L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0-75 microM) and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points) were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and time to reach change points) showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration.Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent manner. The most noticeable effect on growth occurred during early larval stages: L2 and L3. This study supports the utility of the C. elegans growth assay and mathematical modeling in determining the effects of potentially toxic substances in an alternative model organism using high-throughput technologies

The implementation of medical revalidation: an assessment using normalisation process theory

Abstract Background Medical revalidation is the process by which all licensed doctors are legally required to demonstrate that they are up to date and fit to practise in order to maintain their licence. Revalidation was introduced in the United Kingdom (UK) in 2012, constituting significant change in the regulation of doctors. The governing body, the General Medical Council (GMC), envisages that revalidation will improve patient care and safety. This potential however is, in part, dependent upon how successfully revalidation is embedded into routine practice. The aim of this study was to use Normalisation Process Theory (NPT) to explore issues contributing to or impeding the implementation of revalidation in practice. Methods We conducted seventy-one interviews with sixty UK policymakers and senior leaders at different points during the development and implementation of revalidation: in 2011 (n = 31), 2013 (n = 26) and 2015 (n = 14). We selected interviewees using purposeful sampling. NPT was used as a framework to enable systematic analysis across the interview sets. Results Initial lack of consensus over revalidation’s purpose, and scepticism about its value, decreased over time as participants recognised the benefits it brought to their practice (coherence category of NPT). Though acceptance increased across time, revalidation was not seen as a legitimate part of their role by all doctors. Key individuals, notably the Responsible Officer (RO), were vital for the successful implementation of revalidation in organisations (cognitive participation category). The ease with which revalidation could be integrated into working practices varied greatly depending on the type of role a doctor held and the organisation they work for and the provision of resources was a significant variable in this (collective action category). Formal evaluation of revalidation in organisations was lacking but informal evaluation was taking place. Revalidation had not yet reached the stage where feedback was being used for improvement (reflexive monitoring category). Conclusions Requiring all organisations to use the same revalidation model made revalidation easy to integrate into existing work for some but problematic for others. In order for revalidation to be fully embedded and successful, impeding factors, such as a lack of resources, need to be addressed

Power-constrained intermittent control

In this article, input power, as opposed to the usual input amplitude, constraints are introduced in the context of intermittent control. They are shown to result in a combination of quadratic optimisation and quadratic constraints. The main motivation for considering input power constraints is its similarity with semi-active control. Such methods are commonly used to provide damping in mechanical systems and structures. It is shown that semi-active control can be re-expressed and generalised as control with power constraints and can thus be implemented as power-constrained intermittent control. The method is illustrated using simulations of resonant mechanical systems and the constrained nature of the power flow is represented using power-phase-plane plots. We believe the approach we present will be useful for the control design of both semi-active and low-power vibration suppression systems

Spots, plages, and flares on lambda Andromedae and II Pegasi

We present the results of a contemporaneous photometric and spectroscopic monitoring of lambda And and II Peg aimed at investigating the behavior of surface inhomogeneities in the atmospheres of these active stars which have nearly the same temperature but different gravity. The light curves and the modulation of the surface temperature, as recovered from LDRs, are used to map the photospheric spots, while the H-alpha emission has been used as an indicator of chromospheric inhomogeneities. The spot temperatures and sizes were derived from a spot model applied to the contemporaneous light and temperature curves. We find larger and cooler spots on II Peg (T_sp ~ 3600 K) compared to lambda And (T_sp ~ 3900 K); this could be the result of both the different gravity and the higher activity level of the former. Moreover, we find a clear anti-correlation between the H-alpha emission and the photospheric diagnostics. We have also detected a modulation of the intensity of the HeI D_3 line with the star rotation. A rough reconstruction of the 3D structure of their atmospheres has been also performed by applying a spot/plage model to the light and temperature curves and to the H-alpha flux modulation. A close spatial association of photospheric and chromospheric active regions has been found in both stars. Larger and cooler spots have been found on II Peg, the system with the active component of higher gravity and higher activity level. The area ratio of plages to spots seems to decrease when the spots get bigger. Moreover, with the present and literature data, a correlation between the temperature difference Delta_T = T_ph - T_sp and the surface gravity has been also suggested. In addition, a strong flare affecting the H-alpha, the HeI D_3, and the cores of NaI D_1,2 lines has been observed on II Peg.Comment: Accepted for publication in A&A (7 November 2007) 12 Pages, 7 Figure

Report 13: Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries

Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe is now experiencing large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, widescale social distancing including local and national lockdowns. In this report, we use a semi-mechanistic Bayesian hierarchical model to attempt to infer the impact of these interventions across 11 European countries. Our methods assume that changes in the reproductive number – a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from the deaths observed over time to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. One of the key assumptions of the model is that each intervention has the same effect on the reproduction number across countries and over time. This allows us to leverage a greater amount of data across Europe to estimate these effects. It also means that our results are driven strongly by the data from countries with more advanced epidemics, and earlier interventions, such as Italy and Spain. We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact of interventions implemented several weeks earlier. In Italy, we estimate that the effective reproduction number, Rt, dropped to close to 1 around the time of lockdown (11th March), although with a high level of uncertainty. Overall, we estimate that countries have managed to reduce their reproduction number. Our estimates have wide credible intervals and contain 1 for countries that have implemented all interventions considered in our analysis. This means that the reproduction number may be above or below this value. With current interventions remaining in place to at least the end of March, we estimate that interventions across all 11 countries will have averted 59,000 deaths up to 31 March [95% credible interval 21,000-120,000]. Many more deaths will be averted through ensuring that interventions remain in place until transmission drops to low levels. We estimate that, across all 11 countries between 7 and 43 million individuals have been infected with SARS-CoV-2 up to 28th March, representing between 1.88% and 11.43% of the population. The proportion of the population infected to date – the attack rate - is estimated to be highest in Spain followed by Italy and lowest in Germany and Norway, reflecting the relative stages of the epidemics. Given the lag of 2-3 weeks between when transmission changes occur and when their impact can be observed in trends in mortality, for most of the countries considered here it remains too early to be certain that recent interventions have been effective. If interventions in countries at earlier stages of their epidemic, such as Germany or the UK, are more or less effective than they were in the countries with advanced epidemics, on which our estimates are largely based, or if interventions have improved or worsened over time, then our estimates of the reproduction number and deaths averted would change accordingly. It is therefore critical that the current interventions remain in place and trends in cases and deaths are closely monitored in the coming days and weeks to provide reassurance that transmission of SARS-Cov-2 is slowing

Cellular therapies for treating pain associated with spinal cord injury

Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing

Who will care for the women?

Over 20 million people today, including children, working-age disabled, and elderly persons, require some sort of assistance to live safely. Largely because women live longer than men, well into the ages when the probability of needing care increases, 70 percent of elderly people who need long-term care are women. Furthermore, most long-term care is provided by women, mainly as unpaid care in the home, or as low-paid care in institutions and community settings (Stone & Weiner 2001). The United States faces a severe long-term care crisis because of the nation\u27s inability to plan for the changing demographic balance. The crisis in long term care has two problems: a) that we are putting too many resources into institutional care relative to home- and community-based care and relying too heavily on unpaid care in the home to meet the real needs of the aging population, and b) that we do not, and increasingly will not, have enough people to provide for the volume of care that will be needed in the coming decades. This chapter begins with a description of the long-term care system in the United States – what long-term care is, who needs it, in what settings it is provided, and who pays for it. Using the author\u27s analysis of a national survey of caregivers conducted by the National Alliance for Caregiving and the AARP in 2003 along with other sources, this section shows that a substantial portion of the people who need long-term care rely on unpaid care from family and friends, mainly women. When people do receive paid care, almost half – mostly women -- receive it in institutional settings. The discussion demonstrates that women are far more likely to end up in institutions than men, even controlling for age and level of impairment. It then argues that, for a number of reasons, states and the federal government will have to respond to the preferences of consumers for home- and community-based care

Gene Expression Modifications by Temperature-Toxicants Interactions in Caenorhabditis elegans

Although organophosphorus pesticides (OP) share a common mode of action, there is increased awareness that they elicit a diverse range of gene expression responses. As yet however, there is no clear understanding of these responses and how they interact with ambient environmental conditions. In the present study, we investigated genome-wide gene expression profiles in the nematode Caenorhabditis elegans exposed to two OP, chlorpyrifos and diazinon, in single and combined treatments at different temperatures. Our results show that chlorpyrifos and diazinon induced expression of different genes and that temperature affected the response of detoxification genes to the pesticides. The analysis of transcriptional responses to a combination of chlorpyrifos and diazinon shows interactions between toxicants that affect gene expression. Furthermore, our combined analysis of the transcriptional responses to OP at different temperatures suggests that the combination of OP and high temperatures affect detoxification genes and modified the toxic levels of the pesticides