Synthesis of substituted benzooxaborinin-1-ols via palladium-catalysed cyclisation of alkenyl- and alkynyl-boronic acids

Two new palladium-catalysed reactions have been developed for the synthesis of stable 4-substituted benzooxaborinin-1-ols. A palladium-catalysed cyclisation of ortho-alkenylbenzene boronic acids can be used to access 4-chlorobenzooxaborinin-1-ols via a Wacker-type oxidation and chlorination. Alternatively, ortho-alkynylbenzene boronic acids undergo a palladium-catalysed oxyallylation reaction to provide 4-allylbenzooxaborinin-1-ols

NorthStar, a support tool for the design and evaluation of quality improvement interventions in healthcare

Background: The Research-Based Education and Quality Improvement (ReBEQI) European partnership aims to establish a framework and provide practical tools for the selection, implementation, and evaluation of quality improvement (QI) interventions. We describe the development and preliminary evaluation of the software tool NorthStar, a major product of the ReBEQI project. Methods: We focused the content of NorthStar on the design and evaluation of QI interventions. A lead individual from the ReBEQI group drafted each section, and at least two other group members reviewed it. The content is based on published literature, as well as material developed by the ReBEQI group. We developed the software in both a Microsoft Windows HTML help system version and a web-based version. In a preliminary evaluation, we surveyed 33 potential users about the acceptability and perceived utility of NorthStar. Results: NorthStar consists of 18 sections covering the design and evaluation of QI interventions. The major focus of the intervention design sections is on how to identify determinants of practice (factors affecting practice patterns), while the major focus of the intervention evaluation sections is on how to design a cluster randomised trial. The two versions of the software can be transferred by email or CD, and are available for download from the internet. The software offers easy navigation and various functions to access the content. Potential users (55% response rate) reported above-moderate levels of confidence in carrying out QI research related tasks if using NorthStar, particularly when developing a protocol for a cluster randomised trial Conclusion: NorthStar is an integrated, accessible, practical, and acceptable tool to assist developers and evaluators of QI interventions

Complete Genome Sequence of KPC-Producing Klebsiella pneumoniae Strain CAV1193

Carbapenem resistance in Klebsiella pneumoniae, frequently conferred by the blaKPC gene, is a major public health threat. We sequenced a blaKPC-containing strain of K. pneumoniae belonging to the emergent lineage ST941, in order to better understand the evolution of blaKPC within this species

Primed Infusion with Delayed Equilibrium of Gd.DTPA for Enhanced Imaging of Small Pulmonary Metastases.

To use primed infusions of the magnetic resonance imaging (MRI) contrast agent Gd.DTPA (Magnevist), to achieve an equilibrium between blood and tissue (eqMRI). This may increase tumor Gd concentrations as a novel cancer imaging methodology for the enhancement of small tumor nodules within the low signal-to-noise background of the lung

Identification of liver metastases with probe-based confocal laser endomicroscopy at two excitation wavelengths.

BACKGROUND: Metastasis of colorectal cancer to the liver is the most common indication for hepatic resection in a western population. Incomplete excision of malignancy due to residual microscopic disease normally results in worse patient outcome. Therefore, a method aiding in the real time discrimination of normal and malignant tissue on a microscopic level would be of benefit. MATERIAL AND METHODS: The ability of fluorescent probe-based confocal laser endomicroscopy (pCLE) to identify normal and malignant liver tissue was evaluated in an orthotopic murine model of colorectal cancer liver metastasis (CRLM). To maximise information yield, two clinical fluorophores, fluorescein and indocyanine green (ICG) were injected and imaged in a dual wavelength approach (488 and 660 nm, respectively). Visual tissue characteristics on pCLE examination were compared with histological features. Fluorescence intensity in both tissues was statistically analysed to elucidate if this can be used to differentiate between normal and malignant tissue. RESULTS: Fluorescein (488 nm) enabled good visualisation of normal and CRLM tissue, whereas ICG (660 nm) visualisation was limited to normal liver tissue only. Fluorescence intensity in areas of CRLM was typically 53-100% lower than normal hepatic parenchyma. Using general linear mixed modelling and receiver operating characteristic analysis, high fluorescence intensity was found to be statistically more likely in normal hepatic tissue. CONCLUSION: Real time discrimination between normal liver parenchyma and metastatic tissue with pCLE examination of fluorescein and ICG is feasible. Employing two (rather than a single) fluorophores allows a combination of qualitative and quantitative characteristics to be used to distinguish between hepatic parenchyma and CRLM. Lasers Surg. Med. © 2016 Wiley Periodicals, Inc

Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Developing the content of two behavioural interventions : using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #1

Background: Evidence shows that antibiotics have limited effectiveness in the management of upper respiratory tract infection (URTI) yet GPs continue to prescribe antibiotics. Implementation research does not currently provide a strong evidence base to guide the choice of interventions to promote the uptake of such evidence-based practice by health professionals. While systematic reviews demonstrate that interventions to change clinical practice can be effective, heterogeneity between studies hinders generalisation to routine practice. Psychological models of behaviour change that have been used successfully to predict variation in behaviour in the general population can also predict the clinical behaviour of healthcare professionals. The purpose of this study was to design two theoretically-based interventions to promote the management of upper respiratory tract infection (URTI) without prescribing antibiotics. Method: Interventions were developed using a systematic, empirically informed approach in which we: selected theoretical frameworks; identified modifiable behavioural antecedents that predicted GPs intended and actual management of URTI; mapped these target antecedents on to evidence-based behaviour change techniques; and operationalised intervention components in a format suitable for delivery by postal questionnaire. Results: We identified two psychological constructs that predicted GP management of URTI: "Self-efficacy," representing belief in one's capabilities, and "Anticipated consequences," representing beliefs about the consequences of one's actions. Behavioural techniques known to be effective in changing these beliefs were used in the design of two paper-based, interactive interventions. Intervention 1 targeted self-efficacy and required GPs to consider progressively more difficult situations in a "graded task" and to develop an "action plan" of what to do when next presented with one of these situations. Intervention 2 targeted anticipated consequences and required GPs to respond to a "persuasive communication" containing a series of pictures representing the consequences of managing URTI with and without antibiotics. Conclusion: It is feasible to systematically develop theoretically-based interventions to change professional practice. Two interventions were designed that differentially target generalisable constructs predictive of GP management of URTI. Our detailed and scientific rationale for the choice and design of our interventions will provide a basis for understanding any effects identified in their evaluation. Trial registration: Clinicaltrials.gov NCT00376142This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer

A common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study

Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

BACKGROUND: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. METHODS: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2(*) MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg(-1) OXi4503. RESULTS: A significant decrease in SW1222 tumour perfusion was observed (-43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2(*) in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. CONCLUSIONS: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting