Carbon Monoxide Screening in Pregnancy: An Evaluation Study of a Plymouth Pilot Intervention

This report provides an analysis and evaluation of a National Institute for Health and Care Excellence (NICE) recommended pilot intervention which was designed to identify pregnant women exposed to carbon monoxide due to cigarette smoke and refers them to local stop smoking services (LSSS). The pilot intervention was carried out by community midwives working in two areas of Plymouth. The city has areas of social and health inequalities and the study drew on populations from a socially deprived neighbourhood and a socially affluent area. The pilot was instigated following new NICE guidance recommending that all women attending initial ante natal booking appointments with their community midwives be offered a Carbon Monoxide (CO) breath analyser screening to determine their smoking status and or exposure to other forms of CO. This evaluation study identifies the benefits and barriers associated with the implementation of the CO screening pilot. In particular, our aims were to explore any detrimental impact on the relationship between women and their community midwives, identify the impact on midwives in terms of time and resources, reveal the responses and acceptability or otherwise of the screening as perceived and experienced by the women being asked to participate during the booking appointment and finally to evaluate the success of the intervention overall in relation to the numbers of referrals made to Plymouth’s LSSS. A further aim was explore any differences in the two socio demographic areas. We adopted a mixed methods approach involving four focus group interviews with 23 midwives, a survey posted to the 258 women who attended initial antenatal booking appointments in the study areas, an online version of the survey to ascertain the views and experiences of pregnant women and new mothers nationally and an interrogation of an internet forum discussion board for mothers. A two page questionnaire consisting of 12 questions was designed and posted to women who attended the booking appointment with the midwife during the three month pilot period and the same survey was made available online. Questions were designed to elicit women’s views about the information given by the midwife in relation to the screening, whether they had agreed to participate in the CO screening process, their experiences and views about offering CO screening to pregnant women and their smoking status and those of other household members. Of the 258 questionnaires posted to women who had attended the clinic during the pilot intervention 40 completed responses were returned representing a 15.5% response rate. Only 4 responses were received from the online survey posting but an additional 484 comments posted on the Mumsnet website discussion board were analysed. Our findings show that in general there was a high degree of acceptability for the intervention. Midwives and their clients were generally in support of the screening being offered to all pregnant women. However, this support was dependent on a number of contextual factors. Women wanted to be properly informed about the screening and midwives wanted to be kept informed about the effects of the intervention on women’s smoking cessation. Initial and ongoing training of midwives in utilising the protocol and in instructing women to correct use the monitor was also very important. Trust was revealed to be a very important aspect of the relationship between women and their midwives. Some women felt that the CO screening was being used just to check whether or not they were smokers and some midwives also worried about the possible negative effects the CO screening may have on their relationships with women

Force and energy dissipation variations in non-contact atomic force spectroscopy on composite carbon nanotube systems

UHV dynamic force and energy dissipation spectroscopy in non-contact atomic force microscopy were used to probe specific interactions with composite systems formed by encapsulating inorganic compounds inside single-walled carbon nanotubes. It is found that forces due to nano-scale van der Waals interaction can be made to decrease by combining an Ag core and a carbon nanotube shell in the Ag@SWNT system. This specific behaviour was attributed to a significantly different effective dielectric function compared to the individual constituents, evaluated using a simple core-shell optical model. Energy dissipation measurements showed that by filling dissipation increases, explained here by softening of C-C bonds resulting in a more deformable nanotube cage. Thus, filled and unfilled nanotubes can be discriminated based on force and dissipation measurements. These findings have two different implications for potential applications: tuning the effective optical properties and tuning the interaction force for molecular absorption by appropriately choosing the filling with respect to the nanotube.Comment: 22 pages, 6 figure

Reconstructing cell cycle and disease progression using deep learning

We show that deep convolutional neural networks combined with nonlinear dimension reduction enable reconstructing biological processes based on raw image data. We demonstrate this by reconstructing the cell cycle of Jurkat cells and disease progression in diabetic retinopathy. In further analysis of Jurkat cells, we detect and separate a subpopulation of dead cells in an unsupervised manner and, in classifying discrete cell cycle stages, we reach a sixfold reduction in error rate compared to a recent approach based on boosting on image features. In contrast to previous methods, deep learning based predictions are fast enough for on-the-fly analysis in an imaging flow cytometer

Adiabatic perturbation theory and geometry of periodically-driven systems

We give a systematic review of the adiabatic theorem and the leading non-adiabatic corrections in periodically-driven (Floquet) systems. These corrections have a two-fold origin: (i) conventional ones originating from the gradually changing Floquet Hamiltonian and (ii) corrections originating from changing the micro-motion operator. These corrections conspire to give a Hall-type linear response for non-stroboscopic (time-averaged) observables allowing one to measure the Berry curvature and the Chern number related to the Floquet Hamiltonian, thus extending these concepts to periodically-driven many-body systems. The non-zero Floquet Chern number allows one to realize a Thouless energy pump, where one can adiabatically add energy to the system in discrete units of the driving frequency. We discuss the validity of Floquet Adiabatic Perturbation Theory (FAPT) using five different models covering linear and non-linear few and many-particle systems. We argue that in interacting systems, even in the stable high-frequency regimes, FAPT breaks down at ultra slow ramp rates due to avoided crossings of photon resonances, not captured by the inverse-frequency expansion, leading to a counter-intuitive stronger heating at slower ramp rates. Nevertheless, large windows in the ramp rate are shown to exist for which the physics of interacting driven systems is well captured by FAPT.The authors would like to thank M. Aidelsburger, M. Atala, E. Dalla Torre, N. Goldman, M. Heyl, D. Huse, G. Jotzu, C. Kennedy, M. Lohse, T. Mori, L. Pollet, M. Rudner, A. Russomanno, and C. Schweizer for fruitful discussions. This work was supported by AFOSR FA9550-16-1-0334, NSF DMR-1506340, ARO W911NF1410540, and the Hungarian research grant OTKA Nos. K101244, K105149. M. K. was supported by Laboratory Directed Research and Development (LDRD) funding from Berkeley Lab, provided by the Director, Office of Science, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The authors are pleased to acknowledge that the computational work reported in this paper was performed on the Shared Computing Cluster which is administered by Boston University's Research Computing Services. The authors also acknowledge the Research Computing Services group for providing consulting support which has contributed to the results reported within this paper. The study of the driven non-integrable transverse-field Ising model was carried out using QuSpin [185] - an open-source state-of-the-art Python package for dynamics and exact diagonalization of quantum many body systems, available to download here. (FA9550-16-1-0334 - AFOSR; DMR-1506340 - NSF; W911NF1410540 - ARO; K101244 - Hungarian research grant OTKA; K105149 - Hungarian research grant OTKA; DE-AC02-05CH11231 - Laboratory Directed Research and Development (LDRD) funding from Berkeley Lab)https://arxiv.org/pdf/1606.02229.pd

HORYZONS trial: protocol for a randomised controlled trial of a moderated online social therapy to maintain treatment effects from first-episode psychosis services.

INTRODUCTION: Specialised early intervention services have demonstrated improved outcomes in first-episode psychosis (FEP); however, clinical gains may not be sustained after patients are transferred to regular care. Moreover, many patients with FEP remain socially isolated with poor functional outcomes. To address this, our multidisciplinary team has developed a moderated online social media therapy (HORYZONS) designed to enhance social functioning and maintain clinical gains from specialist FEP services. HORYZONS merges: (1) peer-to-peer social networking; (2) tailored therapeutic interventions; (3) expert and peer-moderation; and (4) new models of psychological therapy (strengths and mindfulness-based interventions) targeting social functioning. The aim of this trial is to determine whether following 2 years of specialised support and 18-month online social media-based intervention (HORYZONS) is superior to 18 months of regular care. METHODS AND ANALYSIS: This study is a single-blind randomised controlled trial. The treatment conditions include HORYZONS plus treatment as usual (TAU) or TAU alone. We recruited 170 young people with FEP, aged 16-27 years, in clinical remission and nearing discharge from Early Psychosis Prevention and Intervention Centre, Melbourne. The study includes four assessment time points, namely, baseline, 6-month, 12-month and 18-month follow-up. The study is due for completion in July 2018 and included a 40-month recruitment period and an 18-month treatment phase. The primary outcome is social functioning at 18 months. Secondary outcome measures include rate of hospital admissions, cost-effectiveness, vocational status, depression, social support, loneliness, self-esteem, self-efficacy, anxiety, psychological well-being, satisfaction with life, quality of life, positive and negative psychotic symptoms and substance use. Social functioning will be also assessed in real time through our Smartphone Ecological Momentary Assessment tool. ETHICS AND DISSEMINATION: Melbourne Health Human Research Ethics Committee (2013.146) provided ethics approval for this study. Findings will be made available through scientific journals and forums and to the public via social media and the Orygen website. TRIAL REGISTRATION NUMBER: ACTRN12614000009617; Pre-results

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Left ventricular T2 distribution in Duchenne Muscular Dystrophy

<p>Abstract</p> <p>Background</p> <p>Although previous studies have helped define the natural history of Duchenne Muscular Dystrophy (DMD)-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known.</p> <p>The objective of this study was to assess the distribution of transverse relaxation time (T2) in the left ventricle (LV) of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26) and normal control subjects (n = 13) were studied by Cardiovascular Magnetic Resonance (CMR). DMD subject data was stratified based on subject age and LV Ejection Fraction (EF) into the following groups: A (<12 years old, n = 12); B (≥12 years old, EF ≤ 55%, n = 8) and C (≥12 years old, EF = 55%, n = 6). Controls were also stratified by age into Groups N1 (<12 years, n = 6) and N2 (>12 years, n = 5). LV mid-slice circumferential myocardial strain (ε_cc) was calculated using tagged CMR imaging. T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The Full Width at Half Maximum (<it>FWHM</it>) was calculated from a histogram of LV T2 distribution constructed for each subject.</p> <p>Results</p> <p>In DMD subject groups, <it>FWHM </it>of the T2 histogram rose progressively with age and decreasing EF (Group A <it>FWHM</it>= 25.3 ± 3.8 ms; Group B <it>FWHM</it>= 30.9 ± 5.3 ms; Group C <it>FWHM</it>= 33.0 ± 6.4 ms). Further, <it>FWHM </it>was significantly higher in those with reduced circumferential strain (|ε_cc| ≤ 12%) (Group B, and C) than those with |ε_cc| > 12% (Group A). Group A <it>FWHM </it>was not different from the two normal groups (N1 <it>FWHM </it>= 25.3 ± 3.5 ms; N2 <it>FWHM</it>= 24.0 ± 7.3 ms).</p> <p>Conclusion</p> <p>Reduced EF and ε_cccorrelates well with increased T2 heterogeneity quantified by <it>FWHM</it>, indicating that subclinical functional impairments could be associated with pre-existing abnormalities in tissue structure in young DMD patients.</p

Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension

Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis

Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand) variability manifests itself as dramatic differences in the time between ligand exposure and the sudden activation of the effector caspases that kill cells. However, the contribution of individual proteins to phenotypic variability has not been explored in detail. In this paper we use feature-based sensitivity analysis as a means to estimate the impact of variation in key apoptosis regulators on variability in the dynamics of cell death. We use Monte Carlo sampling from measured protein concentration distributions in combination with a previously validated ordinary differential equation model of apoptosis to simulate the dynamics of receptor-mediated apoptosis. We find that variation in the concentrations of some proteins matters much more than variation in others and that precisely which proteins matter depends both on the concentrations of other proteins and on whether correlations in protein levels are taken into account. A prediction from simulation that we confirm experimentally is that variability in fate is sensitive to even small increases in the levels of Bcl-2. We also show that sensitivity to Bcl-2 levels is itself sensitive to the levels of interacting proteins. The contextual dependency is implicit in the mathematical formulation of sensitivity, but our data show that it is also important for biologically relevant parameter values. Our work provides a conceptual and practical means to study and understand the impact of cell-to-cell variability in protein expression levels on cell fate using deterministic models and sampling from parameter distributions

Culture Adaptation Alters Transcriptional Hierarchies among Single Human Embryonic Stem Cells Reflecting Altered Patterns of Differentiation

We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal (‘Culture Adapted’) human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation