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Background Guidance and reporting principles such as CONSORT (for randomised trials) and PRISMA (for systematic reviews) have greatly improved the reporting, discoverability, transparency and consistency of published research. We sought to develop similar guidance for case study evaluations undertaken to explore the influence of context on the processes and outcomes of complex interventions. Methods A range of experts were recruited to an online Delphi panel, sampling for maximum diversity in disciplines (e.g. public health, health services research, organisational studies), settings (e.g. country), and sectors (e.g. academic, policy, third sector). To inform panel deliberations, we prepared background materials based on: [a] a systematic meta-narrative review of empirical and methodological literatures on case study, context and complex interventions; [b] the collective experience of a network of health systems and public health researchers; and [c] the established RAMESES II standards (which cover one kind of case study). We developed a list of topics and issues based on these sources and encouraged panel members to provide free text comments. Their feedback informed development of a set of items in the form of questions for potential inclusion in the reporting principles. We circulated these by email, asking panel members to rank each potential item twice (for relevance and validity) on a 7-point Likert scale. This sequence was repeated twice. Results We recruited 51 panel members from 50 organisations across 12 countries, who brought experience of a range of case study research methods and applications. 26 completed all three Delphi rounds, reaching over 80% consensus on 16 items covering title, abstract, definitions of terms, philosophical assumptions, research question(s), rationale, how context and complexity relates to the intervention, ethical approval, empirical methods, findings, use of theory, generalisability and transferability, researcher perspective and influence, conclusions and recommendations, and funding and conflicts of interest. Conclusion The ‘Triple C’ (Case study, Context, Complex interventions) reporting principles recognise that case studies are undertaken in different ways for different purposes and based on different philosophical assumptions. They are designed to be enabling rather than prescriptive, and to make case study evaluation reporting on context and complex health interventions more comprehensive, accessible and useable.

Case study methodology is widely used in health research, but has had a marginal role in evaluative studies, given it is often assumed that case studies offer little for making causal inferences. We undertook a narrative review of examples of case study research from public health and health services evaluations, with a focus on interventions addressing health inequalities. We identified five types of contribution these case studies made to evidence for causal relationships. These contributions relate to: (1) evidence about system actors’ own theories of causality; (2) demonstrative examples of causal relationships; (3) evidence about causal mechanisms; (4) evidence about the conditions under which causal mechanisms operate; and (5) inference about causality in complex systems. Case studies can and do contribute to understanding causal relationships. More transparency in the reporting of case studies would enhance their discoverability, and aid the development of a robust and pluralistic evidence base for public health and health services interventions. To strengthen the contribution that case studies make to that evidence base, researchers could: draw on wider methods from the political and social sciences, in particular on methods for robust analysis; carefully consider what population their case is a case ‘of’; and explicate the rationale used for making causal inferences.

The ground state of chromonic liquid crystals, as revealed by a number of recent experiments, is quite different from that of ordinary nematic liquid crystals: it istwistedinstead of uniform. The common explanation provided for this state within the classical elastic theory of Frank demands that one Ericksen’s inequality is violated. Since in general such a violation makes Frank’s elastic free-energy functional unbounded below, the question arises as to whether the twisted ground state can be locally stable. We answer this question in theaffirmative. In reaching this conclusion, a central role is played by the specific boundary conditions imposed in the experiments on the boundary of rigid containers and by a general formula that we derive here for the second variation in Frank’s elastic free energy.

Background There is a growing need for methods that acknowledge and successfully capture the dynamic interaction between context and implementation of complex interventions. Case study research has the potential to provide such understanding, enabling in-depth investigation of the particularities of phenomena. However, there is limited guidance on how and when to best use different case study research approaches when evaluating complex interventions. This study aimed to review and synthesise the literature on case study research across relevant disciplines, and determine relevance to the study of contextual influences on complex interventions in health systems and public health research. Methods Systematic meta-narrative review of the literature comprising (i) a scoping review of seminal texts (n = 60) on case study methodology and on context, complexity and interventions, (ii) detailed review of empirical literature on case study, context and complex interventions (n = 71), and (iii) identifying and reviewing ‘hybrid papers’ (n = 8) focused on the merits and challenges of case study in the evaluation of complex interventions. Results We identified four broad (and to some extent overlapping) research traditions, all using case study in a slightly different way and with different goals: 1) developing and testing complex interventions in healthcare; 2) analysing change in organisations; 3) undertaking realist evaluations; 4) studying complex change naturalistically. Each tradition conceptualised context differently—respectively as the backdrop to, or factors impacting on, the intervention; sets of interacting conditions and relationships; circumstances triggering intervention mechanisms; and socially structured practices. Overall, these traditions drew on a small number of case study methodologists and disciplines. Few studies problematised the nature and boundaries of ‘the case’ and ‘context’ or considered the implications of such conceptualisations for methods and knowledge production. Conclusions Case study research on complex interventions in healthcare draws on a number of different research traditions, each with different epistemological and methodological preferences. The approach used and consequences for knowledge produced often remains implicit. This has implications for how researchers, practitioners and decision makers understand, implement and evaluate complex interventions in different settings. Deeper engagement with case study research as a methodology is strongly recommended.

© 2018, The Author(s). Treating care as an effect of material implementations, we use qualitative interviews with people living with HIV in London, most of whom are migrants, to explore care practices linked to clinical treatment delivered as part of the ‘cascade of HIV care’. We consider how HIV care is done, and what HIV care does, drawing on assemblage theory. We ask how is care affected by the situations in which it is enacted? and what contingent forms of care does the HIV care cascade potentiate? A prime actor in the care assemblages revealed in our study is immigration, from which multiple uncertainties flow, including access to vital resources such as housing and income. Yet we also found that clinical HIV care is worked-with in practice to afford multiple forms of care. Here, viral care is translated into matters of vital concern to produce care which extends ‘beyond the virus’. Practices of care beyond the virus afford social protection, including through making-up social relations and networks, and novel modes of sociality. Friendship connections, community organisations and HIV clinics are among the key actors involved. Being attuned to how HIV care is made to matter helps generate new ways of knowing and doing care.

Global Navigation Satellite Systems (GNSS) have become a powerful tool use in surveying and mapping, air and maritime navigation, ionospheric/space weather research and other applications. However, in some cases, its maximum efficiency could not be attained due to some uncorrelated errors associated with the system measurements, which is caused mainly by the dispersive nature of the ionosphere. Ionosphere has been represented using the total number of electrons along the signal path at a particular height known as Total Electron Content (TEC). However, there are many methods to estimate TEC but the outputs are not uniform, which could be due to the peculiarity in characterizing the biases inside the observables (measurements), and sometimes could be associated to the influence of mapping function. The errors in TEC estimation could lead to wrong conclusion and this could be more critical in case of safety-of-life application. This work investigated the performance of Ciraolo’s and Gopi’s GNSS-TEC calibration techniques, during 5 geomagnetic quiet and disturbed conditions in the month of October 2013, at the grid points located in low and middle latitudes. The data used are obtained from the GNSS ground-based receivers located at Borriana in Spain (40 $$^{\circ }$$ N, 0 $$^{\circ }$$ E; mid latitude) and Accra in Ghana (5.50 $$^{\circ }$$ N, −0.20 $$^{\circ }$$ E; low latitude). The results of the calibrated TEC are compared with the TEC obtained from European Geostationary Navigation Overlay System Processing Set (EGNOS PS) TEC algorithm, which is considered as a reference data. The TEC derived from Global Ionospheric Maps (GIM) through International GNSS service (IGS) was also examined at the same grid points. The results obtained in this work showed that Ciraolo’s calibration technique (a calibration technique based on carrier-phase measurements only) estimates TEC better at middle latitude in comparison to Gopi’s technique (a calibration technique based on code and carrier-phase measurements). At the same time, Gopi’s calibration was also found more reliable in low latitude than Ciraolo’s technique. In addition, the TEC derived from IGS GIM seems to be much reliable in middle-latitude than in low-latitude region.

The tick microbiome comprises communities of microorganisms, including viruses, bacteria and eukaryotes, and is being elucidated through modern molecular techniques. The advent of next-generation sequencing (NGS) technologies has enabled the genes and genomes within these microbial communities to be explored in a rapid and cost-effective manner. The advantages of using NGS to investigate microbiomes surpass the traditional non-molecular methods that are limited in their sensitivity, and conventional molecular approaches that are limited in their scalability. In recent years the number of studies using NGS to investigate the microbial diversity and composition of ticks has expanded. Here, we provide a review of NGS strategies for tick microbiome studies and discuss the recent findings from tick NGS investigations, including the bacterial diversity and composition, influential factors, and implications of the tick microbiome.

A Satellite Based Augmentation System (SBAS) is designed to improve Global Navigation Satellite Systems (GNSS) in terms of integrity, accuracy, availability and continuity. The main limitation to SBAS performance optimization is the ionosphere, and this is more critical in low latitude. During geomagnetically disturbed periods the role of storm-time winds is important because they modify the atmospheric composition toward low latitudes. An index of ionospheric disturbance, the relative percentage of deviation of the vertical Total Electron Content (TEC) from the quiet level (DvTEC) at each station was evaluated to study positive and negative phases of the geomagnetic storms. The rate of change of TEC index (ROTI) over all the GNSS stations was estimated to evaluate equatorial ionospheric gradients and irregularities. From the study it is observed that the positive deviations are more frequent than negative ones. The availability map, which is the mean of the combine Vertical Protection Level (VPL) and Horizontal Protection Level (HPL) are used for the SBAS performance. The cases of moderate and minor storms studied during the months of July and October 2013 showed that the SBAS system performance during the disturbed periods depends on the local time in which the storm occurs, geographic longitude and other phenomena that need further study. During the storm-time conditions considered, three out of seven geomagnetic storms indicated good SBAS performance and exceed monthly average of the availability map, three geomagnetic storms reduced the system performance below monthly average while one does not have effect on SBAS system performance in respect to monthly average. The present study indicates ROTI as a better proxy than geomagnetic indices for the assessment of storm-time effects on GNSS-SBAS performance.

Trophoblast cells migrate and invade the decidual stroma in a tightly regulated process to maintain immune homeostasis at the maternal-placental interface during the first weeks of pregnancy. Locally synthesized factors modulate trophoblast cell function and their interaction with maternal leukocytes to promote the silent clearance of apoptotic cells. The vasoactive intestinal peptide (VIP) is a pleiotropic polypeptide with trophic and anti-inflammatory effects in murine pregnancy models. We explored the effect of VIP on two human first trimester trophoblast cell lines, particularly on their migration, invasiveness and interaction with phagocytic cells, and the signalling and regulatory pathways involved. We found that VIP enhanced trophoblast cell migration and invasion through the activation of high affinity VPAC receptors and PKA-CRE signalling pathways. VIP knocked-down trophoblast cells showed reduced migration in basal and leukemic inhibitor factor (LIF)-elicited conditions. In parallel, VIP-silenced trophoblast cells failed to induce the phagocytosis of apoptotic bodies and the expression of immunosuppressant markers by human monocytes. Our results suggest that VIP-mediated autocrine pathways regulate trophoblast cell function and contribute to immune homeostasis maintenance at placentation and may provide new clues for therapeutic intervention in pregnancies complicated by defective deep placentation. Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fátima Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1-142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma.