Feedback control architecture and the bacterial chemotaxis network.

PMCID: PMC3088647This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

Cost Effectiveness of Strategies for Caring for Critically Ill Patients with COVID-19 in Tanzania.

BACKGROUND: The resources for critical care are limited in many settings, exacerbating the significant morbidity and mortality associated with critical illness. Budget constraints can lead to choices between investing in advanced critical care (e.g. mechanical ventilators in intensive care units) or more basic critical care such as Essential Emergency and Critical Care (EECC; e.g. vital signs monitoring, oxygen therapy, and intravenous fluids). METHODS: We investigated the cost effectiveness of providing EECC and advanced critical care in Tanzania in comparison with providing 'no critical care' or 'district hospital-level critical care' using coronavirus disease 2019 (COVID-19) as a tracer condition. We developed an open-source Markov model ( https://github.com/EECCnetwork/POETIC_CEA ) to estimate costs and disability-adjusted life-years (DALYs) averted, using a provider perspective, a 28-day time horizon, patient outcomes obtained from an elicitation method involving a seven-member expert group, a normative costing study, and published literature. We performed a univariate and probabilistic sensitivity analysis to assess the robustness of our results. , RESULTS: EECC is cost effective 94% and 99% of the time when compared with no critical care (incremental cost-effectiveness ratio [ICER] $37 [-$9 to $790] per DALY averted) and district hospital-level critical care (ICER$14 [-$200 to$263] per DALY averted), respectively, relative to the lowest identified estimate of the willingness-to-pay threshold for Tanzania ($101 per DALY averted). Advanced critical care is cost effective 27% and 40% of the time, when compared with the no critical care or district hospital-level critical care scenarios, respectively. CONCLUSION: For settings where there is limited or no critical care delivery, implementation of EECC could be a highly cost-effective investment. It could reduce mortality and morbidity for critically ill COVID-19 patients, and its cost effectiveness falls within the range considered 'highly cost effective'. Further research is needed to explore the potential of EECC to generate even greater benefits and value for money when patients with diagnoses other than COVID-19 are accounted for

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, \u3c160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks\u27 gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.)

Reservoirs and vectors of emerging viruses

Wildlife, especially mammals and birds, are hosts to an enormous number of viruses, most of which we have absolutely no knowledge about even though we know these viruses circulate readily in their specific niches. More often than not, these viruses are silent or asymptomatic in their natural hosts. In some instances, they can infect other species, and in rare cases, this cross-species transmission might lead to human infection. There are also instances where we know the reservoir hosts of zoonotic viruses that can and do infect humans. Studies of these animal hosts, the reservoirs of the viruses, provide us with the knowledge of the types of virus circulating in wildlife species, their incidence, pathogenicity for their host, and in some instances, the potential for transmission to other hosts. This paper describes examples of some of the viruses that have been detected in wildlife, and the reservoir hosts from which they have been detected. It also briefly explores the spread of arthropod-borne viruses and their diseases through the movement and establishment of vectors in new habitats

A national-scale assessment of climate change impacts on species: assessing the balance of risks and opportunities for multiple taxa

It is important for conservationists to be able to assess the risks that climate change poses to species, in order to inform decision making. Using standardised and repeatable methods, we present a national-scale assessment of the risks of range loss and opportunities for range expansion, that climate change could pose for over 3,000 plants and animals that occur in England. A basic risk assessment that compared projected future changes in potential range with recently observed changes classified 21% of species as being at high risk and 6% at medium risk of range loss under a B1 climate change scenario. A greater number of species were classified as having a medium (16%) or high (38%) opportunity to potentially expand their distribution. A more comprehensive assessment, incorporating additional ecological information, including potentially confounding and exacerbating factors, was applied to 402 species, of which 35 % were at risk of range loss and 42 % may expand their range extent. This study covers a temperate region with a significant proportion of species at their poleward range limit. The balance of risks and opportunities from climate change may be different elsewhere. The outcome of both risk assessments varied between taxonomic groups, with bryophytes and vascular plants containing the greatest proportion of species at risk from climate change. Upland habitats contained more species at risk than other habitats. Whilst the overall pattern was clear, confidence was generally low for individual assessments, with the exception of well-studied taxa such as birds. In response to climate change, nature conservation needs to plan for changing species distributions and increasing uncertainty of the future

The time scale of recombination rate evolution in great apes

We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- And between-species genome-wide recombination rate variation in several close relatives

Bilingualism for the Minor or the Major? An Evaluative Analysis of Parallel Conceptions in China

This paper is an analysis of two conceptions of bilingualism that exist in parallel in China. One is traditional bilingualism referring to the use of a native minority language and standard Chinese by minority groups and the other, seen as bilingualism with modern characteristics, is a modern-day phenomenon in which the majority Han group aspire to produce bilinguals with a strong competence in mother tongue Chinese and a foreign language, primarily English, by using Chinese and the foreign language as mediums of instruction in teaching school subjects. The focus of the analysis is on the latter for the simple reason that current literature on the new phenomenon is mostly available only in Chinese. An equally important aim of this paper is to explore the impact of the new phenomenon on minority education and to examine the reason why this impact is largely ignored in bilingualism discussions, despite obvious consequences with respect to ethnic identity, personality development and academic performance of minority students. Thus, the traditional conception is briefly reviewed at the start

The measurement of bilingual abilities: central challenges

In this handbook chapter I analyse the concept of bilingual abilities. Bilinguals vary widely in what they can do with their languages or in the ways in which they use their languages on a daily basis. This means that there is a great deal of variability in what the term covers. While many researchers subscribe to the holistic view of bilingualism, in the academic literature bilinguals are still often described in negative terms as having a "deficit" in one or another subsystem of their languages. The key aim of this chapter is to identify what makes individuals with bilingual abilities unique speaker-hearers in their own right, avoiding the fractional view of bilingualism, and how these abilities can be measured

ESPEN Guideline: Clinical Nutrition in inflammatory bowel disease

Introduction: The ESPEN guideline presents a multidisciplinary focus on clinical nutrition in inflammatory bowel disease (IBD). Methodology: The guideline is based on extensive systematic review of the literature, but relies on expert opinion when objective data were lacking or inconclusive. The conclusions and 64 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. Results: IBD is increasingly common and potential dietary factors in its aetiology are briefly reviewed. Malnutrition is highly prevalent in IBD – especially in Crohn's disease. Increased energy and protein requirements are observed in some patients. The management of malnu-trition in IBD is considered within the general context of support for malnourished patients. Treatment of iron deficiency (parenterally if necessary) is strongly recommended. Routine provision of a special diet in IBD is not however supported. Parenteral nutrition is indicated only when enteral nutrition has failed or is impossible. The recommended perioperative man-agement of patients with IBD undergoing surgery accords with general ESPEN guidance for patients having abdominal surgery. Probiotics may be helpful in UC but not Crohn's disease. Primary therapy using nutrition to treat IBD is not supported in ulcerative colitis, but is mod-erately well supported in Crohn's disease, especially in children where the adverse conse-quences of steroid therapy are proportionally greater. However, exclusion diets are generally not recommended and there is little evidence to support any particular formula feed when nutritional regimens are constructed. Conclusions: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 64 recommendations, of which 9 are very strong recom-mendations (grade A), 22 are strong recommendations (grade B) and 12 are based only on sparse evidence (grade 0); 21 recommendations are good practice points (GPP)