A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging.

We demonstrate diffraction limited multiphoton imaging in a massively parallel, fully addressable time-resolved multi-beam multiphoton microscope capable of producing fluorescence lifetime images with sub-50ps temporal resolution. This imaging platform offers a significant improvement in acquisition speed over single-beam laser scanning FLIM by a factor of 64 without compromising in either the temporal or spatial resolutions of the system. We demonstrate FLIM acquisition at 500 ms with live cells expressing green fluorescent protein.

Effect of phosphorylation on EGFR dimer stability probed by single-molecule dynamics and FRET/FLIM.

Deregulation of epidermal growth factor receptor (EGFR) signaling has been correlated with the development of a variety of human carcinomas. EGF-induced receptor dimerization and consequent trans- auto-phosphorylation are among the earliest events in signal transduction. Binding of EGF is thought to induce a conformational change that consequently unfolds an ectodomain loop required for dimerization indirectly.

Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion.

Background And Purpose: Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK-tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population.

Methods: TNK-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK-tissue-type plasminogen activator dose-escalation, safety, and feasibility trial.

Randomized assessment of rapid endovascular treatment of ischemic stroke.

Background: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation.

Methods: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group).

Endovascular therapy for ischemic stroke with perfusion-imaging selection.

Background: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes.

Methods: We randomly assigned patients with ischemic stroke who were receiving 0.

Diffuse pleural thickening following heart failure-related pleural effusions in an asbestos exposed patient.

Diffuse pleural thickening (DPT) is a well-recognized consequence of asbestos exposure and often follows a benign asbestos-related pleural effusion. At our tertiary center, in the North West of England where the prevalence of asbestos-related pleural disease is high, we have encountered a series of patients that have had led us to consider a new hypothesis in DPT. We postulate that non-asbestos-related pleural effusions, particularly transudative pleural effusions, caused by heart failure can trigger the development of DPT.

The Stroke Riskometer(TM) App: validation of a data collection tool and stroke risk predictor.

Background: The greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the 'mass' approach), the 'high risk' approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise.

A study of patients with isolated mediastinal and hilar lymphadenopathy undergoing EBUS-TBNA.

Background: Isolated mediastinal and/or hilar lymphadenopathy (IMHL) may be caused by benign and malignant disorders or be 'reactive'. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a reported low negative predictive value (NPV) in IMHL, necessitating mediastinoscopy in selected patients. The aim of this study was to examine the NPV of EBUS-TBNA in an IMHL population and determine whether clinical variables differentiate between pathological and reactive IMHL.

Imaging tumour heterogeneity of the consequences of a PKCα-substrate interaction in breast cancer patients.

Breast cancer heterogeneity demands that prognostic models must be biologically driven and recent clinical evidence indicates that future prognostic signatures need evaluation in the context of early compared with late metastatic risk prediction. In pre-clinical studies, we and others have shown that various protein-protein interactions, pertaining to the actin microfilament-associated proteins, ezrin and cofilin, mediate breast cancer cell migration, a prerequisite for cancer metastasis. Moreover, as a direct substrate for protein kinase Cα, ezrin has been shown to be a determinant of cancer metastasis for a variety of tumour types, besides breast cancer; and has been described as a pivotal regulator of metastasis by linking the plasma membrane to the actin cytoskeleton.

Nodal staging in lung cancer: a risk stratification model for lymph nodes classified as negative by EBUS-TBNA.

Background: Over the last 10 years, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become established as the first-line nodal staging procedure of choice for lung cancer patients. However, the pathway for patients following a negative EBUS-TBNA has not been clearly defined. The primary aim of this study was to develop and validate a risk stratification model to categorize lymph nodes deemed negative by EBUS-TBNA into "low-risk" and "high-risk" groups, where "risk" refers to the risk of false negative sampling.

The mediation of social influences on smoking cessation and awareness of the early signs of lung cancer.

Background: Whilst there has been no clear consensus on the potential for earlier diagnosis of lung cancer, recent research has suggested that the time between symptom onset and consultation can be long enough to plausibly affect prognosis. In this article, we present findings from a qualitative study involving in-depth interviews with patients who had been diagnosed with lung cancer (n = 11), and people who were at heightened risk of developing the disease (n = 14).

Methods: A grounded theory methodology was drawn upon to conduct thematic and narrative based approaches to analysis.

Absolute cardiovascular risk and GP decision making in TIA and minor stroke.

Background: Transient ischaemic attacks (TIA) and minor strokes (TIAMS) have the same pathophysiological mechanism as stroke and carry a high risk of recurrent ischaemic events. Diagnosis of TIAMS can be challenging and often occurs in general practice. Absolute cardiovascular risk (ACVR) is recommended as the basis for vascular risk management.

Structural clues to UO₂²⁺/VO₂⁺ competition in seawater extraction using amidoxime-based extractants.

Here we present the first structural comparison of amidoxime complexes of UO2(2+) and VO2(+) (the main competitor in the extraction of uranium from seawater using amidoxime-based sorbents) using a 4,5-di(amidoxime)-functionalized imidazole ligand. The amidoxime groups resist tautomerization in both cases and quite different coordination modes (chelating vs. bridging) are observed.

Can computed tomography characteristics predict outcomes in patients undergoing radial endobronchial ultrasound-guided biopsy of peripheral lung lesions?

Introduction: Percutaneous computed tomography (CT)-guided lung biopsy is a standard minimally invasive technique for sampling peripheral lung lesions. Radial endobronchial ultrasound (EBUS) offers an alternative approach but it has yet to be defined which patients are most suited to this procedure. The primary aim of this study was to investigate whether CT characteristics could predict the success of radial EBUS-guided sampling.

Development and characterization of a novel, antimicrobial, sterile hydrogel dressing for burn wounds: single-step production with gamma irradiation creates silver nanoparticles and radical polymerization.

Patients with burn wounds are susceptible to wound infection and sepsis. This research introduces a novel burn wound dressing that contains silver nanoparticles (SNPs) to treat infection in a 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS-Na(+) ) hydrogel. Silver nitrate was dissolved in AMPS-Na(+) solution and then exposed to gamma irradiation to form SNP-infused hydrogels.

A template-based procedure for determining white matter integrity in the internal capsule early after stroke.

The integrity of descending white matter pathways, measured by fractional anisotropy from DW-MRI, is a key prognostic indicator of motor recovery after stroke. Barriers to translation of fractional anisotropy measures into routine clinical practice include the time required for manually delineating volumes of interest (VOIs), and inter-examiner variability in this process. This study investigated whether registering and then editing template volumes of interest 'as required' would improve inter-examiner reliability compared with manual delineation, without compromising validity.

Emergency and stroke physician combined consensus statement on thrombolysis for acute stroke.

The New Zealand Faculty of the Australasian College for Emergency Medicine (ACEM) is the professional body representing the specialist emergency medicine physicians who work in and lead emergency departments of New Zealand. The National Stroke Network Leadership Group represents New Zealand stroke clinicians including stroke physicians and neurologists who work within and lead district health board (DHB) stroke services. In an effort to promote their shared goal of ensuring patient safety while striving to achieve improved stroke outcomes, the two communities have set up a consensus group to develop this combined emergency physician and neurologist/stroke physician consensus statement on the use of intravenous alteplase in stroke ('stroke thrombolysis').

Nonaborane and decaborane cluster anions can enhance the ignition delay in hypergolic ionic liquids and induce hypergolicity in molecular solvents.

The dissolution of nido-decaborane, B10H14, in ionic liquids that are hypergolic (fuels that spontaneously ignite upon contact with an appropriate oxidizer), 1-butyl-3-methylimidazolium dicyanamide, 1-methyl-4-amino-1,2,4-triazolium dicyanamide, and 1-allyl-3-methylimidazolium dicyanamide, led to the in situ generation of a nonaborane cluster anion, [B9H14](-), and reductions in ignition delays for the ionic liquids suggesting salts of borane anions could enhance hypergolic properties of ionic liquids. To explore these results, four salts based on [B10H13](-) and [B9H14](-), triethylammonium nido-decaborane, tetraethylammonium nido-decaborane, 1-ethyl-3-methylimidazolium arachno-nonaborane, and N-butyl-N-methyl-pyrrolidinium arachano-nonaborane were synthesized from nido-decaborane by reaction of triethylamine or tetraethylammonium hydroxide with nido-decaborane in the case of salts containing the decaborane anion or via metathesis reactions between sodium nonaborane (Na[B9H14]) and the corresponding organic chloride in the case of the salts containing the nonaborane anion. These borane cluster anion salts form stable solutions in some combustible polar aprotic solvents such as tetrahydrofuran and ethyl acetate and trigger hypergolic reactivity of these solutions.

Antagonism of EGFR and HER3 enhances the response to inhibitors of the PI3K-Akt pathway in triple-negative breast cancer.

Both abundant epidermal growth factor receptor (EGFR or ErbB1) and high activity of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway are common and therapeutically targeted in triple-negative breast cancer (TNBC). However, activation of another EGFR family member [human epidermal growth factor receptor 3 (HER3) (or ErbB3)] may limit the antitumor effects of these drugs. We found that TNBC cell lines cultured with the EGFR or HER3 ligand EGF or heregulin, respectively, and treated with either an Akt inhibitor (GDC-0068) or a PI3K inhibitor (GDC-0941) had increased abundance and phosphorylation of HER3.

Intravenous thrombolysis is unsafe in stroke due to infective endocarditis.

Embolic stroke is the most common neurological complication of infective endocarditis and a major source of morbidity and mortality. Septic embolism is considered a contraindication to intravenous thrombolysis in patients with ischaemic stroke because of concerns over an increased risk of intracranial haemorrhage. We describe a patient with occult endocarditis who was treated with thrombolysis for acute stroke and review other cases reported in the literature.

EBUS-TBNA in elderly patients with lung cancer: safety and performance outcomes.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) enables minimally invasive lymph node sampling during bronchoscopy under conscious sedation. The primary purpose of this study was to investigate the safety profile of EBUS-TBNA in an elderly population. The secondary aim was to assess the efficacy of EBUS-TBNA for nodal staging and pathological diagnosis in elderly patients with primary lung cancer.

Real waiting times for surgery. Proposal for an improved system for their management.

Objectives: In Spain, official information on waiting times for surgery is based on the interval between the indication for surgery and its performance. We aimed to estimate total waiting times for surgical procedures, including outpatient visits and diagnostic tests prior to surgery. In addition, we propose an alternative system to manage total waiting times that reduces variability and maximum waiting times without increasing the use of health care resources.