Palladium-templated subcomponent self-assembly of macrocycles, catenanes, and rotaxanes.

The reaction of 2,6-diformylpyridine with diverse amines and Pd(II) ions gave rise to a variety of metallosupramolecular species, in which the Pd(II) ion is observed to template a tridentate bis(imino)pyridine ligand. These species included a mononuclear complex as well as [2+2] and [3+3] macrocycles. The addition of pyridine-containing macrocyclic capping ligands allows for topological complexity to arise, thereby enabling the straightforward preparation of structures that include a [2]catenane, a [2]rotaxane, and a doubly threaded [3]rotaxane.This work was underwritten by the Marie Curie Academic-Industrial Initial Training Network on Dynamic Molecular Nanostructures (DYNAMOL) of the European Union’s Seventh Framework Programme (FP7) and the UK Engineering and Physical Sciences Research Council (EPSRC). We thank the Cambridge Chemistry NMR service for experimental assistance, Diamond Light Source (UK) for synchrotron beamtime on I19 (MT7984), and the EPSRC National Crystallography Service for X-ray data collection.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/anie.20140616

Process evaluation in the field: global learnings from seven implementation research hypertension projects in low-and middle-income countries.

BACKGROUND:Process evaluation is increasingly recognized as an important component of effective implementation research and yet, there has been surprisingly little work to understand what constitutes best practice. Researchers use different methodologies describing causal pathways and understanding barriers and facilitators to implementation of interventions in diverse contexts and settings. We report on challenges and lessons learned from undertaking process evaluation of seven hypertension intervention trials funded through the Global Alliance of Chronic Diseases (GACD). METHODS:Preliminary data collected from the GACD hypertension teams in 2015 were used to inform a template for data collection. Case study themes included: (1) description of the intervention, (2) objectives of the process evaluation, (3) methods including theoretical basis, (4) main findings of the study and the process evaluation, (5) implications for the project, policy and research practice and (6) lessons for future process evaluations. The information was summarized and reported descriptively and narratively and key lessons were identified. RESULTS:The case studies were from low- and middle-income countries and Indigenous communities in Canada. They were implementation research projects with intervention arm. Six theoretical approaches were used but most comprised of mixed-methods approaches. Each of the process evaluations generated findings on whether interventions were implemented with fidelity, the extent of capacity building, contextual factors and the extent to which relationships between researchers and community impacted on intervention implementation. The most important learning was that although process evaluation is time consuming, it enhances understanding of factors affecting implementation of complex interventions. The research highlighted the need to initiate process evaluations early on in the project, to help guide design of the intervention; and the importance of effective communication between researchers responsible for trial implementation, process evaluation and outcome evaluation. CONCLUSION:This research demonstrates the important role of process evaluation in understanding implementation process of complex interventions. This can help to highlight a broad range of system requirements such as new policies and capacity building to support implementation. Process evaluation is crucial in understanding contextual factors that may impact intervention implementation which is important in considering whether or not the intervention can be translated to other contexts

Impact of hiatal hernia on histological pattern of non-erosive reflux disease

BACKGROUND: Hiatus hernia (HH) has major pathophysiological effects favoring gastroesophageal reflux and hence contributing to esophageal mucosa injury, especially in patients with severe gastroesophageal disease. However, prospective studies investigating the impact of HH on the esophageal mucosa in non-erosive reflux disease (NERD) are lacking. This study evaluated the association between the presence of (HH) and the histological findings in symptomatic patients with NERD. METHODS: Fifty consecutive patients with gastroesophageal reflux disease (GERD) were enrolled. After conventional endoscopy, Lugol solution was applied and biopsy specimens were obtained. Histological parameters including basal zone hyperplasia, papillary length and cellular infiltration were evaluated. The chi-square test with Yates' correlation was used for comparing discrete parameters between groups. However, Fisher's exact probability test was used where the expected frequencies were lower than 5. Wilcoxon's test for unpaired samples was preferred in cases of semi-quantitative parameters. RESULTS: The presence of HH along with more severe findings (0.01 <P < 0.05) was confirmed in 18 patients. NERD was observed in 29 (58%) patients. Basal zone hyperplasia and loss of glycogen accompanied HH in all cases, and the correlation was significant in NERD (P < 0.001). The remaining histological patterns were similar between erosive reflux disease and NERD in the presence of HH. CONCLUSION: The presence of HH is correlated with more severe endoscopy findings, and predisposes for severe histological abnormality in cases of NERD

Peer support to improve diabetes care: an implementation evaluation of the Australasian Peers for Progress Diabetes Program.

BACKGROUND: Several studies have now demonstrated the benefits of peer support in promoting diabetes control. The aim of this study is to evaluate the implementation of a cluster randomised controlled trial of a group-based, peer support program to improve diabetes self-management and thereby, diabetes control in people with Type 2 Diabetes in Victoria, Australia. METHODS: The intervention program was designed to address four key peer support functions i.e. 1) assistance in daily management, 2) social and emotional support, 3) regular linkage to clinical care, and 4) ongoing and sustained support to assist with the lifelong needs of diabetes self-care management. The intervention participants attended monthly group meetings facilitated by a trained peer leader for 12 months. Data was collected on the intervention's reach, participation, implementation fidelity, groups' effectiveness and participants' perceived support and satisfaction with the intervention. The RE-AIM and PIPE frameworks were used to guide this evaluation. RESULTS: The trial reached a high proportion (79%) of its target population through mailed invitations. Out of a total of 441 eligible individuals, 273 (61.9%) were willing to participate. The intervention fidelity was high (92.7%). The proportion of successful participants who demonstrated a reduction in 5 years cardiovascular disease risk score was 65.1 and 44.8% in the intervention and control arm respectively. Ninety-four percent (94%) of the intervention participants stated that the program helped them manage their diabetes on a day to day basis. Overall, attending monthly group meetings provided 'a lot of support' to 57% and 'moderate' support to 34% of the participants. CONCLUSION: Peer support programs are feasible, acceptable and can be used to supplement treatment for patients motivated to improve behaviours related to diabetes. However, program planners need to focus on the participation component in designing future programs. The use of two evaluation frameworks allowed a comprehensive evaluation of the trial from the provider-, participant- and public health perspective. The learnings gained from this evaluation will guide and improve future implementation by improving program feasibility for adoption and acceptability among participants, and will ultimately increase the likelihood of program effectiveness for the participants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 . Registered 16 June 2009

Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T.

Purpose To determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.Materials and methods Ten patients with newly diagnosed locally advanced HNSCC underwent two magnetic resonance imaging (MRI) scans between 24 and 168 hours apart prior to chemoradiotherapy treatment. A multiple gradient echo sequence was used to calculate T2* maps. A quadratic function was used to model the blood transverse relaxation rate as a function of blood oxygenation. A set of published coefficients measured at 3T were incorporated to account for tissue hematocrit levels and used to plot the dependence of fractional blood oxygenation (Y) on T2* values, together with the corresponding repeatability range. Repeatability of T2* using Bland-Altman analysis, and calculation of limits of agreement (LoA), was used to assess the sensitivity, defined as the minimum difference in fractional blood oxygenation that can be confidently detected.Results T2* LoA for 22 outlined tumor volumes were 13%. The T2* dependence of fractional blood oxygenation increases monotonically, resulting in increasing sensitivity of the method with increasing blood oxygenation. For fractional blood oxygenation values above 0.11, changes in T2* were sufficient to detect differences in blood oxygenation greater than 10% (Δ T2* > LoA for ΔY > 0.1).Conclusion Quantitation of T2* at 3T can detect clinically relevant changes in tumor oxygenation within a wide range of blood volumes and oxygen tensions, including levels reported in HNSCC. J. Magn. Reson. Imaging 2016;44:72-80

The scope of the crustacean immune system for disease control

The culture or wild capture of marine and freshwater shellfish, including crustaceans, is without doubt a key source of protein for a burgeoning world population. Historically the expansion of aquaculture has, however, been accompanied by the increased incidence of economically significant diseases, most notably of viral and bacterial origin. Since the late 1970s great progress has been made in our understanding of the generalized protostome innate immune system. Distinct pathways, pathogen receptor proteins and effector molecules have since been identified that are not ancestral or homologous to those of the deuterostomes, including vertebrates. Within the past decade progress has accelerated with the rapid characterisation of new classes of recognition proteins, immune effectors and regulatory pathways. This paper provides a broad overview of our current understanding of invertebrate immunology, taking the crustacean decapod immune system as its focus. Recent developments in the field are described briefly and their implications and potential considered. These advances offer fundamental new insights in our efforts to understand disease in cultured populations and also to develop knowledge of environmental effects on host/pathogen interactions within a fishery context. Of course, challenges do remain, including the lack of an immortal cell line and the limited publically-available genomic resources. These are considered in this review as priorities for future research effort. With the continued application of more insightful technologies, coupled with associated investment, it is expected that the speed at which some of these issues are resolved will accelerate

Interpreting changes in measles genotype: the contribution of chance, migration and vaccine coverage

<p>Abstract</p> <p>Background</p> <p>In some populations, complete shifts in the genotype of the strain of measles circulating in the population have been observed, with given genotypes being replaced by new genotypes. Studies have postulated that such shifts may be attributable to differences between the fitness of the new and the old genotypes.</p> <p>Methods</p> <p>We developed a stochastic model of the transmission dynamics of measles, simulating the effects of different levels of migration, vaccination coverage and importation of new genotypes on patterns in the persistence and replacement of indigenous genotypes.</p> <p>Results</p> <p>The analyses illustrate that complete replacement in the genotype of the strain circulating in populations may occur because of chance. This occurred in >50% of model simulations, for levels of vaccination coverage and numbers of imported cases per year which are compatible with those observed in several Western European populations (>80% and >3 per million per year respectively) and for the given assumptions in the model.</p> <p>Conclusion</p> <p>The interpretation of genotypic data, which are increasingly being collected in surveillance programmes, needs to take account of the underlying vaccination coverage and the level of the importation rate of measles cases into the population.</p

Longitudinal stroke recovery associated with dysregulation of complement system - A proteomics pathway analysis

Currently the longitudinal proteomic profile of post-ischemic stroke recovery is relativelyunknown with few well-accepted biomarkers or understanding of the biological systemsthat underpin recovery. We aimed to characterize plasma derived biological pathwaysassociated with recovery during the first year post event using a discovery proteomicsworkflow coupled with a topological pathway systems biology approach. Blood samples(n = 180, ethylenediaminetetraacetic acid plasma) were collected from a subgroup of60 first episode stroke survivors from the Australian START study at 3 timepoints: 3–7days (T1), 3-months (T2) and 12-months (T3) post-stroke. Samples were analyzed byliquid chromatography mass spectrometry using label-free quantification (data availableat ProteomeXchange with identifier PXD015006). Differential expression analysis revealedthat 29 proteins between T1 and T2, and 33 proteins between T1 and T3 weresignificantly different, with 18 proteins commonly differentially expressed across thetwo time periods. Pathway analysis was conducted using Gene Graph EnrichmentAnalysis on both the Kyoto Encyclopedia of Genes and Genomes and Reactomedatabases. Pathway analysis revealed that the significantly differentiated proteinsbetween T1 and T2 were consistently found to belong to the complement pathway.Further correlational analyses utilized to examine the changes in regulatory effects ofproteins over time identified significant inhibitory regulation of clusterin on complementcomponent 9. Longitudinal post-stroke blood proteomics profiles suggest that thealternative pathway of complement activation remains in a state of higher activation from3-7 days to 3 months post-stroke, while simultaneously being regulated by clusterin andvitronectin. These findings also suggest that post-stroke induced sterile inflammation andimmunosuppression could inhibit recovery within the 3-month window post-stroke