Minimally Complex Nucleic Acid Feedback Control Systems for First Experimental Implementations

Chemical reaction networks based on catalysis, degradation, and annihilation may be used as building blocks to construct a variety of dynamical and feedback control systems in Synthetic Biology. DNA strand-displacement, which is based on DNA hybridisation programmed using Watson-Crick base pairing, is an effective primitive to implement such reactions experimentally. However, experimental construction, validation and scale-up of nucleic acid control systems is still significantly lagging theoretical developments, due to several technical challenges, such as leakage, crosstalk, and toehold sequence design. To help the progress towards experimental implementation, we provide here designs representing two fundamental classes of reference tracking control circuits (integral and state-feedback control), for which the complexity of the chemical reactions required for implementation has been minimised. The supplied 'minimally complex' control circuits should be ideal candidates for first experimental validations of nucleic acid controllers.</p

The consistency between planned and actually given nursing care in long-terminstitutional care

Continuous information exchange between healthcare professionals is facilitated by individualized care plans. Compliance with the planned care as documented in care plans is important to provide person-centered care which contributes to the continuity of care and quality of care outcomes. Using the Nursing Interventions Classification, this study examined the consistency between documented and actually provided interventions by type of nursing staff with 150 residents in long-term institutional care. The consistency was especially high for basic (93%) and complex (79%) physiological care. To a lesser extent for interventions in the behavioral domain (66%). Except for the safety domain, the probability that documented interventions were provided was high for all domains (≥ 91%, p > 0.05). NAs generally provided the interventions as documented. Findings suggest that HCAs worked beyond there scope of practice. The results may have implications for the deployment of nursing staff and are of importance to managers

Short- and long-term effects of a physical activity counselling programme in COPD:A randomized controlled trial

SummaryBackgroundWe were interested in the effects of a physical activity (PA) counselling programme in three groups of COPD patients from general practice (primary care), outpatient clinic (secondary care) and pulmonary rehabilitation (PR).MethodsIn this randomized controlled trial 155 COPD patients, 102 males, median (IQR) age 62 (54–69) y, FEV1predicted 60 (40–75) % were assigned to a 12-weeks' physical activity counselling programme or usual care. Physical activity (pedometer (Yamax SW200) and metabolic equivalents), exercise capacity (6-min walking distance) and quality of life (Chronic Respiratory Questionnaire and Clinical COPD Questionnaire) were assessed at baseline, after three and 15 months.ResultsA significant difference between the counselling and usual care group in daily steps (803 steps, p = 0.001) and daily physical activity (2214 steps + equivalents, p = 0.001)) from 0 to 3 months was found in the total group, as well as in the outpatient (1816 steps, 2616 steps + equivalents, both p = 0.007) and PR (758 steps, 2151 steps + equivalents, both p = 0.03) subgroups. From 0 to 15 months no differences were found in physical activity. However, when patients with baseline physical activity>10,000 steps per day (n = 8), who are already sufficiently active, were excluded, a significant long-term effect of the counselling programme on daily physical activity existed in the total group (p = 0.02). Differences in exercise capacity and quality of life were found only from 0 to 3 months, in the outpatient subgroup.ConclusionOur PA counselling programme effectively enhances PA level in COPD patients after three months. Sedentary patients at baseline still benefit after 15 months.ClinicalTrials.gov: registration number NCT00614796

Orvieto, Angiolo

Objective. Although regular physical activity is an effective secondary prevention strategy for patients with a chronic disease, it is unclear whether patients change their daily physical activity after being diagnosed. Therefore, the aims of this study were to (1) describe changes in levels of physical activity in middle-aged women before and after diagnosis with a chronic disease (heart disease, diabetes, asthma, breast cancer, arthritis, depression); and to (2) examine whether diagnosis with a chronic disease affects levels of physical activity in these women. Methods. Data from 5 surveys (1998-2010) of the Australian Longitudinal Study on Women's Health (ALSWH) were used. Participants (N = 4840, born 1946-1951) completed surveys every three years, with questions about diseases and leisure time physical activity. The main outcome measure was physical activity, categorized as: nil/sedentary, low active, moderately active, highly active. Results. At each survey approximately half the middle-aged women did not meet the recommended level of physical activity. Between consecutive surveys, 41%-46% of the women did not change, 24%-30% decreased, and 24%-31% increased their physical activity level. These proportions of change were similar directly after diagnosis with a chronic disease, and in the years before or after diagnosis. Generalized estimating equations showed that there was no statistically significant effect of diagnosis with a chronic disease on levels of physical activity in women. Conclusion. Despite the importance of physical activity for the management of chronic diseases, most women did not increase their physical activity after diagnosis. This illustrates a need for tailored interventions to enhance physical activity in newly diagnosed patients. (C) 2015 Elsevier Inc. All rights reserved

Implementation and evaluation of a physical activity counselling programme in primary care among cancer survivors:SoDA study protocol

INTRODUCTION: Physical activity (PA) favourably affects various health outcomes in cancer survivors, but little is known about how to implement a PA programme in primary care. We therefore aim to implement and evaluate such a programme for cancer survivors in general practice. METHODS AND ANALYSES: The Stimulation of Daily Activity study is an implementation study with a single-arm longitudinal design in 15 Dutch general practices. Patients aged ≥18 years who finished cancer treatment more than 6 months ago will be eligible for inclusion. The intervention will comprise six coaching sessions with the practice nurse in 9 months, seeking to increase PA in daily activities and using an activity tracker for goal setting and feedback. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will be used to evaluate implementation in terms of the health outcomes, extent of implementation and barriers and facilitators to implementation, using a mixed methods approach. Descriptive analyses and linear mixed model analyses will be performed on the quantitative data, while qualitative data from focus groups and interviews will be analysed by thematic analyses. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee of the University Medical Centre Groningen, the Netherlands, concluded that this study was not subject to the Dutch Medical Research Involving Human Subjects Act (registration number: 201900586). The study results will be made available to patients and general practitioners via (inter)national publications and conferences, newsletters, public summaries and via (social) media

Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial

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Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt