The use of lower resolution viewing devices for mammographic interpretation: implications for education and training.

Aims: To establish whether lower resolution, lower cost viewing devices have the potential to deliver mammographic interpretation training.

Methods: On three occasions over eight months, fourteen consultant radiologists and reporting radiographers read forty challenging digital mammography screening cases on three different displays: a digital mammography workstation, a standard LCD monitor, and a smartphone. Standard image manipulation software was available for use on all three devices.

Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer.

Purpose: Aromatase inhibitors (AIs) have an established role in the treatment of breast cancer. Response rates are only 50% to 70% in the neoadjuvant setting and lower in advanced disease. Accurate biomarkers are urgently needed to predict response in these settings and to determine which individuals will benefit from adjuvant AI therapy.

Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3.

A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing.

A national survey of marine biotoxins in wild-caught abalone in Australia.

The first national survey of Australian wild-caught abalone was conducted between September 2012 and December 2013. The aim of the survey was to determine the presence of paralytic shellfish toxins (PSTs), amnesic shellfish toxins (ASTs), and diarrhetic shellfish toxins (DSTs) in wild-caught abalone at levels above the current Codex marine biotoxin limits during the 2013 fishing season. Abalone (n = 190) were collected from 68 abalone-fishing blocks for which the combined annual harvest accounts for 80 % of Australian production.

Angle-closure glaucoma on long-haul flights.

Importance: Unlike other modes of long-distance travel, long-haul flights delay urgent, specialist medical treatment until the destination is reached or the plane is diverted. Angle-closure glaucoma (ACG) occurring during those flights results in considerable morbidity and may cause permanent visual loss. It is preventable in patients with risk factors but may be an underrecognized and underreported phenomenon on long-haul flights.

Corrosion pitting and environmentally assisted small crack growth.

In many applications, corrosion pits act as precursors to cracking, but qualitative and quantitative prediction of damage evolution has been hampered by lack of insights into the process by which a crack develops from a pit. An overview is given of recent breakthroughs in characterization and understanding of the pit-to-crack transition using advanced three-dimensional imaging techniques such as X-ray computed tomography and focused ion beam machining with scanning electron microscopy. These techniques provided novel insights with respect to the location of crack development from a pit, supported by finite-element analysis.

A quality improvement project sustainably decreased time to onset of active physical therapy intervention in patients with acute lung injury.

Rationale: Rehabilitation started early during an intensive care unit (ICU) stay is associated with improved outcomes and is the basis for many quality improvement (QI) projects showing important changes in practice. However, little evidence exists regarding whether such changes are sustainable in real-world practice.

Objectives: To evaluate the sustained effect of a quality improvement project on the timing of initiation of active physical therapy intervention in patients with acute lung injury (ALI).

Cardiomyocyte-specific loss of diacylglycerol acyltransferase 1 (DGAT1) reproduces the abnormalities in lipids found in severe heart failure.

Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides.

Tokamak operation with safety factor q95 < 2 via control of MHD stability.

Magnetic feedback control of the resistive-wall mode has enabled the DIII-D tokamak to access stable operation at safety factor q(95) = 1.9 in divertor plasmas for 150 instability growth times. Magnetohydrodynamic stability sets a hard, disruptive limit on the minimum edge safety factor achievable in a tokamak, or on the maximum plasma current at a given toroidal magnetic field.

Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer.

The phosphatidylinositol-3-kinase pathway plays an important role in proliferation, migration and survival in breast cancer and may play a role in resistance to endocrine therapy. Pathway activation occurs as a result of mutations in PIK3CA or loss of functional PTEN. Matched primary and recurrent samples from 120 breast cancer patients treated with endocrine therapy were profiled with a qPCR-based mutation assay covering eight mutational hotspots in PIK3CA.

Molecular changes in lobular breast cancers in response to endocrine therapy.

Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray.

Intellectual and developmental disabilities in Kinshasa, Democratic Republic of the Congo: causality and implications for resilience and support.

This article reports results of a 7-month qualitative study on intellectual and related developmental disabilities in Kinshasa, Democratic Republic of the Congo, particularly as they relate to the causes and meaning of intellectual and developmental disabilities (IDD). This study raises important questions related to the understanding of resilience of persons affected by IDD and the nature and purpose of support they use or desire.

Age and decisions to limit life support for patients with acute lung injury: a prospective cohort study.

Introduction: The proportion of elderly Americans admitted to the intensive care unit (ICU) in the last month of life is rising. Hence, challenging decisions regarding the appropriate use of life support are increasingly common. The objective of this study was to estimate the association between patient age and the rate of new limitations in the use of life support, independent of daily organ dysfunction status, following acute lung injury (ALI) onset.

Quantification of tumour budding, lymphatic vessel density and invasion through image analysis in colorectal cancer.

Background: Tumour budding (TB), lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) have shown promise as prognostic factors in colorectal cancer (CRC) but reproducibility using conventional histopathology is challenging. We demonstrate image analysis methodology to quantify the histopathological features which could permit standardisation across institutes and aid risk stratification of Dukes B patients.

Methods: Multiplexed immunofluorescence of pan-cytokeratin, D2-40 and DAPI identified epithelium, lymphatic vessels and all nuclei respectively in tissue sections from 50 patients diagnosed with Dukes A (n = 13), Dukes B (n = 29) and Dukes C (n = 8) CRC.

A case of congenital central hypoventilation syndrome in a three-generation family with non-polyalanine repeat PHOX2B mutation.

We describe a three generation family in whom multiple individuals are variably affected due to a PHOX2B non-polyalanine repeat mutation. This family demonstrates extreme phenotypic variability and autosomal dominant transmission over three generations not previously reported in the wider literature. Novel findings also inclue a history of recurrent second trimester miscarriage.

Empiric combination therapy for gram-negative bacteremia.

Background: Empirical combination antibiotic regimens consisting of a β-lactam and an aminoglycoside are frequently employed in the pediatric population. Data to demonstrate the comparative benefit of empirical β-lactam combination therapy relative to monotherapy for culture-proven Gram-negative bacteremia are lacking in the pediatric population.

Methods: We conducted a retrospective cohort study of children treated for Gram-negative bacteremia at The Johns Hopkins Hospital from 2004 through 2012.

Identification of novel HSP90α/β isoform selective inhibitors using structure-based drug design. demonstration of potential utility in treating CNS disorders such as Huntington's disease.

A structure-based drug design strategy was used to optimize a novel benzolactam series of HSP90α/β inhibitors to achieve >1000-fold selectivity versus the HSP90 endoplasmic reticulum and mitochondrial isoforms (GRP94 and TRAP1, respectively). Selective HSP90α/β inhibitors were found to be equipotent to pan-HSP90 inhibitors in promoting the clearance of mutant huntingtin protein (mHtt) in vitro, however with less cellular toxicity. Improved tolerability profiles may enable the use of HSP90α/β selective inhibitors in treating chronic neurodegenerative indications such as Huntington's disease (HD).

Saturated gain spectrum of VECSELs determined by transient measurement of lasing onset.

We describe time-resolved measurements of the evolution of the spectrum of radiation emitted by an optically-pumped continuous-wave InGaAs-GaAs quantum well laser, recorded as lasing builds up from noise to steady state. We extract a fitting parameter corresponding to the gain dispersion of the parabolic spectrum equal to -79 ± 30 fs2 and -36 ± 6 fs2 for a resonant and anti-resonant structure, respectively. Furthermore the recorded evolution of the spectrum allows for the calculation of an effective FWHM gain bandwidth for each structure, of 11 nm and 18 nm, respectively.

Video recording of ophthalmic surgery--ethical and legal considerations.

Video documenting is increasingly used in ophthalmic training and research, with many ophthalmologists routinely recording their surgical cases. Although this modality represents an excellent means of improving technique and advancing knowledge, there are major ethical and legal considerations with its use. Informed consent to record is required in most situations.

A scenario-based, randomized trial of patient values and functional prognosis on intensivist intent to discuss withdrawing life support.

Objectives: To evaluate the effect of 1) patient values as expressed by family members and 2) a requirement to document patients' functional prognosis on intensivists' intention to discuss withdrawal of life support in a hypothetical family meeting.

Design: A three-armed, randomized trial.

Setting: One hundred seventy-nine U.