bluuebunny/crossref_metadata_2025 huggingface dataset:
Inducible factors with antimicrobial activity after immune challenge in the haemolymph of Red Palm Weevil (Insecta)
Authors: Mastore Maristella , Binda Rossetti Simona , Giovannardi Stefano , Scarì Giorgio , Brivio Maurizio F
Published: August 2014

Insects are capable of innate immune responses elicited after microbial infection. In this process, the receptor-mediated recognition of foreign bodies and the subsequent activation of immunocompetent cells lead to the synthesis ex novo of a peptide pool with antimicrobial activity. We investigated the inducible immune response of a coleopteran, Rhynchophorus ferrugineus, challenged with both Gram-negative and Gram-positive bacteria. After immunization, we evaluated the presence of antimicrobial peptides using either biochemical analyses or microbiological techniques. The antimicrobial properties of the newly synthesized protein pool, detectable in haemolymph fractions of low molecular mass, showed strong antibacterial activity against various bacterial strains ( Escherichia coli, Pseudomonas sp. OX1, Bacillus subtilis and Micrococcus luteus). In addition to the preliminary study of the mechanism of action of the pool of antimicrobial peptides, we also investigated its effects on bacterial cell walls by means of fluorescence microscopy and scanning electron microscopy. The data suggest that the main effects seem to be directed at destabilizing and damaging the bacterial wall. This study provides data that help us to understand some aspects of the inducible innate immunity in a system model that lacks anticipatory responses. However, the weevil has finely tuned its defensive strategies to counteract effectively microbial infection.
A review of anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) impact on major adverse cardiovascular events based on coronary computerized tomography angiography: a 6-year single center review
Authors: Clark Richard A. , Marler Adam T. , Lin Charles K. , McDonough Ryan J. , Prentice Ryan L. , Malik Jamil A. , Villines Todd C. , Hulten Edward A. , Thomas Dustin M. , Slim Ahmad M.
Published: August 2014

Background:

Anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) is a rare finding that is typically found on autopsy in a person with sudden cardiac death or during routine cardiovascular testing. The true prevalence is unknown for this reason. There is also question to the specific anatomy of the anomalies themselves and how best to correct them.

Methods:

We performed a retrospective chart review of all coronary computed tomography angiography (CCTA) studies to evaluate the incidence of all-cause mortality, nonfatal myocardial infarction, stroke and late revascularization (>90 days following CCTA) from January 2005 until July 2012. We describe the origin of the artery, its course, slit-like appearance and treatment in this population.

Results:

We reviewed 1518 CCTA reports and identified 22 patients with ACAOS with an incidence of 1.4% of our original study population over a review period of 6 years with a resultant median follow-up period of 25 months [interquartile range (IQR)25,75 12–34 months]. The indication for CCTA was for chest pain in the majority of patients (73%). We had one patient undergo surgical repair and one with coronary bypass grafting for unrelated symptomatic coronary artery disease.

Conclusion:

ACAOS continues to be a rare but presumed fatal condition in subsets identified to carry high risk features. As the characteristics of the anomalous vessels that increase risk are still debated, over an intermediate to long follow up in a single large center, none of the different anomalous findings with varying degrees of high risk findings were associated with sudden death.
Effect of Local Heating on Postprandial Blood Glucose Excursions Using the InsuPad Device
Authors: Hermanns Norbert , Bitton Gabriel , Reimer André , Krichbaum Michael , Kulzer Bernhard , Haak Thomas
Published: August 2014

Background:

The InsuPad is a medical device to accelerate insulin resorption by applying local heat at the insulin injection site. This crossover study examined the impact of the InsuPad use on postprandial glucose excursions under daily life conditions.

Methods:

In 1 study phase, diabetic patients used the InsuPad when injecting bolus insulin before breakfast and dinner and measured their blood glucose 5 times daily (before breakfast, lunch, and dinner and after breakfast and dinner). In the other study phase, blood glucose measurements were maintained without using the InsuPad. The order of the study phases was randomized.

Results:

Twenty patients with a high insulin demand took part (30% type 1 diabetes, age 53.7 ± 8.9 years, diabetes duration 14.9 ± 7.4 years; HbA1c 8.3 ± 0.8%; total daily insulin demand 0.97 ± 0.32 IU per kg). Postprandial glucose excursion was reduced by 15.4 mg/dl (95% CI 9.7-21.2 mg/dl; P = .011) after breakfast and dinner if InsuPad was used. The mean blood glucose was lower by 8.8 mg/dl (95% CI 0:3-18:0 mg/dl; P = .099) when using the InsuPad. Safety parameters and the percentage of hypoglycemic (< 60 mg/dl) or hyperglycemic (> 300 mg/dl) blood glucose measurements were not negatively affected by InsuPad use (hypoglycemic values 1.4% vs 1.5%, P = .961; hyperglycemic values 2.6% vs 4.0%, P = .098).

Conclusions:

Local heating of the insulin injection site by use of the InsuPad device is an effective and safe method to reduce postprandial blood glucose excursions under daily life conditions without negative side effects on the occurrence of low or high blood glucose values.
Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in patients with ST-elevation myocardial infarction admitted for primary percutaneous coronary intervention: Impact of ventricular fibrillation in STEMI patients
Authors: Demirel Fatma , Rasoul Saman , Elvan Arif , Ottervanger Jan Paul , Dambrink Jan-Henk E , Gosselink AT Marcel , Hoorntje Jan CA , Ramdat Misier Anand R , van ‘t Hof Arnoud WJ
Published: August 2014

Objective:

Pre-hospital life-threatening ventricular tachycardia/fibrillation (VT/VF) is relatively common in the acute phase of ST-elevation myocardial infarction (STEMI). We evaluated the prognostic impact of out-of-hospital cardiac arrest (OHCA) due to VT/VF in non-selected patients with STEMI admitted for primary percutaneous coronary intervention (PCI).

Methods:

Prospective hospital registry was used to collect data of consecutive STEMI patients admitted to our hospital between 2005 and 2010. Patients with OHCA were identified from this registry, and their medical records were reviewed.

Results:

During the study period, 4653 patients were admitted with STEMI. Data regarding OHCA due to VT/VF was available in 4643 patients (99.8%). A total of 326 patients (7.0%) had OHCA due to VT/VF. Patients with OHCA were younger (60.3 ± 11.8 vs. 64.1 ± 12.9 year, p<0.001), less often had diabetes (5.2% vs. 12.4%, p<0.001) but more often presented with signs of heart failure (Killip class >1:17.5% vs. 7.7%, p<0.001) and cardiogenic shock (29.6% vs. 2.5%, p<0.001). Coronary angiography was performed in 97.5% of the patients. Coronary angiography and primary PCI were performed equally in both groups. In patients with OHCA, the left main artery (2.3% vs. 1.0%, p=0.04) and LAD (49.2% vs. 41.2%, p=0.01) were more often the culprit artery. In-hospital mortality was significantly higher among patients with OHCA (13.80% vs. 3.4%, p<0.001). However, in patients who were discharged alive from the hospital, the one-year mortality and the combined incidence of death and appropriate ICD therapy were similar in patients with and without OHCA.

Conclusion:

In a large non-selected STEMI patient population admitted for primary PCI, OHCA due to VT/VF was associated with higher in-hospital mortality but did not affect the long-term prognosis.
Incidental Finding of Renal Cell Carcinoma
Authors: Bellman Nancy L.
Published: August 2014

Renal cell carcinoma, the most common renal neoplasm, often goes undetected since it typically remains asymptomatic. In some cases, renal cell carcinoma invades the renal vein and infiltrates the inferior vena cava. Understanding of this natural history will enable sonographers to evaluate a patient further when a thrombus in the inferior vena cava or renal vein is visualized. This case report presents a renal cell carcinoma that was incidentally detected secondary to a thrombosed inferior vena cava and validates the importance of evaluating the kidneys in such cases.
Characterisation and quantification of cavities in 9Cr martensitic steel for power plants
Authors: Yadav S. D. , Sonderegger B. , Sartory B. , Sommitsch C. , Poletti C.
Published: August 2014

This work focuses on the characterisation of cavities evolution in a P91 steel pipe in three conditions: as received, and after creep at 650°C and 60 MPa for 7000 and 9000 h. A field emission gun scanning electron microscope (FEG-SEM) equipped with focused ion beam (FIB) gun, a conventional scanning electron microscope (SEM) and a light optical microscope (LOM) have been employed for the investigation. This study reveals two types of cavities: the pre-existing cavities, which are rare in this type of heat resistant steels, with a mean diameter of 2·56 μm and the cavities produced during creep with diameters smaller than 0·6 μm. Lath boundaries and precipitates are found to be preferential sites for cavity nucleation. Furthermore, the number density and volume fraction of these small cavities are calculated from 2D measurements and compared to 3D results obtained by FIB serial sectioning.
Effect of microstructure on electrical conductivity of Inconel 718 alloys
Authors: Pereira D. , Clarke T. , Menezes R. , Hirsch T.
Published: August 2014

The microstructural evolution of Inconel 718 during aging processes has been studied through a combination of eddy current testing, X-ray diffraction analysis, and metallography and hardness measurements. Measurements were carried out in samples subjected to eight different heat treatment cycles, between 620 and 1035°C for 1–18 h. Different amounts of secondary precipitates were achieved, reaching 18 of delta phase for samples overaged at 900°C for 18 h. Results show that the different microstructures of Inconel 718 obtained have a distinguishable effect on electrical conductivity when this is measured through an appropriately sensitive technique (i.e. eddy current testing). The lowest conductivity values were observed for under aged samples (1·44 IACS). A clear increase in conductivity values was seen for all aged or overaged conditions, reaching a maximum of 1·63 IACS, when coarsening of intra granular precipitates, associated with an increase in density of globular precipitates at grain boundaries, was identified. The influence of microstructure on conductivity could be shown to be due to the competition between two effects on the scattering of electrons: matrix purification and precipitation characteristics. A combination of hardness values and electrical properties proved to be a fast and practical way of determining the stage of aging of the alloy.
Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects
Authors: Connelly Jon P. , Kwon Erika M. , Gao Yongxing , Trivedi Niraj S. , Elkahloun Abdel G. , Horwitz Marshall S. , Cheng Linzhao , Liu P. Paul
Published: August 2014

Key Points

Successful generation of iPSC lines from FPD patient fibroblasts. Restoration of megakaryopoiesis after RUNX1 mutation correction.
Treatment adherence among new triptan users: a 2-year cohort study in Taiwan
Authors: Chen Ting-Bin , Chen Yung-Tai , Fuh Jong-Ling , Tang Chao-Hsiun , Wang Shuu-Jiun
Published: August 2014

Background

The persistence of triptan use among newly prescribed users is low in the United States and European countries. However, triptan refill patterns in Asian primary care practices have not been well described.

Methods

Data from the National Health Insurance Research Database in Taiwan were used to conduct a retrospective cohort analysis from 2005 to 2008. All participants were followed for 2 years after receiving a new triptan prescription. Refill and 2-year retention rates of newly prescribed triptans were calculated, and predictors of the first triptan refill and 2-year retention were analyzed.

Results

Of the 13,951 participants with a new triptan prescription (99.9% sumatriptan), 67.4% were prescribed by a neurologist, 67.4% were prescribed at least one prophylactic agent for migraine. Of them, 34.3% adhered to the newly prescribed triptan at the first refill, 0.01% switched to another triptan, and 40.9% switched to a non-triptan acute migraine medication. The 2-year retention rate was 4.0%. The frequency of headache-related neurologic visits for 1 year before the index date, first prescription of triptan or other acute medications, first triptan prescription by a neurologist, and prophylactic use were associated with higher first refill rates. The frequency of headache-related neurologic visits 1 year before the index date and first triptan prescription by a neurologist were related to higher 2-year retention rates. Diabetes mellitus and first triptan prescription at a local medical clinic were associated with reduced probability of continued triptan use at the first refill and 2 years.

Conclusions

Similar to Western societies, the refill and 2-year retention rates were low in new users of triptans. Frequency of neurologic visits and triptan prescription by a neurologist were significant predictors of adherence.
Synthesis and self-assembly behavior of a biodegradable and sustainable soybean oil-based copolymer nanomicelle
Authors: Bao Lixia , Bian Longchun , Zhao Mimi , Lei Jingxin , Wang Jiliang
Published: August 2014

Herein, we report a novel amphiphilic biodegradable and sustainable soybean oil-based copolymer (SBC) prepared by grafting hydrophilic and biocompatible hydroxyethyl acrylate (HEA) polymeric segments onto the natural hydrophobic soybean oil chains. FTIR, H1-NMR, and GPC measurements have been used to investigate the molecular structure of the obtained SBC macromolecules. Self-assembly behaviors of the prepared SBC in aqueous solution have also been extensively evaluated by fluorescence spectroscopy and transmission electron microscopy. The prepared SBC nanocarrier with the size range of 40 to 80 nm has a potential application in the biomedical field.
Workable male sterility systems for hybrid rice: Genetics, biochemistry, molecular biology, and utilization
Authors: Huang Jian-Zhong , E Zhi-Guo , Zhang Hua-Li , Shu Qing-Yao
Published: August 2014

The exploitation of male sterility systems has enabled the commercialization of heterosis in rice, with greatly increased yield and total production of this major staple food crop. Hybrid rice, which was adopted in the 1970s, now covers nearly 13.6 million hectares each year in China alone. Various types of cytoplasmic male sterility (CMS) and environment-conditioned genic male sterility (EGMS) systems have been applied in hybrid rice production. In this paper, recent advances in genetics, biochemistry, and molecular biology are reviewed with an emphasis on major male sterility systems in rice: five CMS systems, i.e., BT-, HL-, WA-, LD- and CW- CMS, and two EGMS systems, i.e., photoperiod- and temperature-sensitive genic male sterility (P/TGMS). The interaction of chimeric mitochondrial genes with nuclear genes causes CMS, which may be restored by restorer of fertility (Rf) genes. The PGMS, on the other hand, is conditioned by a non-coding RNA gene. A survey of the various CMS and EGMS lines used in hybrid rice production over the past three decades shows that the two-line system utilizing EGMS lines is playing a steadily larger role and TGMS lines predominate the current two-line system for hybrid rice production. The findings and experience gained during development and application of, and research on male sterility in rice not only advanced our understanding but also shed light on applications to other crops.
An evaluation of seasonal variations in footwear worn by adults with inflammatory arthritis: a cross‐sectional observational study using a web‐based survey
Authors: Brenton‐Rule Angela , Hendry Gordon J , Barr Georgina , Rome Keith
Published: August 2014

Background

Foot problems are common in adults with inflammatory arthritis and therapeutic footwear can be effective in managing arthritic foot problems. Accessing appropriate footwear has been identified as a major barrier, resulting in poor adherence to treatment plans involving footwear. Indeed, previous New Zealand based studies found that many people with rheumatoid arthritis and gout wore inappropriate footwear. However, these studies were conducted in a single teaching hospital during the New Zealand summer therefore the findings may not be representative of footwear styles worn elsewhere in New Zealand, or reflect the potential influence of seasonal climate changes. The aim of the study was to evaluate seasonal variations in footwear habits of people with inflammatory arthritic conditions in New Zealand.

Methods

A cross‐sectional study design using a web‐based survey. The survey questions were designed to elicit demographic and clinical information, features of importance when choosing footwear and seasonal footwear habits, including questions related to the provision of therapeutic footwear/orthoses and footwear experiences.

Results

One‐hundred and ninety‐seven participants responded who were predominantly women of European descent, aged between 46–65 years old, from the North Island of New Zealand. The majority of participants identified with having either rheumatoid arthritis (35%) and/or osteoarthritis (57%) and 68% reported established disease (>5 years duration). 18% of participants had been issued with therapeutic footwear. Walking and athletic shoes were the most frequently reported footwear type worn regardless of the time of year. In the summer, 42% reported wearing sandals most often. Comfort, fit and support were reported most frequently as the footwear features of greatest importance. Many participants reported difficulties with footwear (63%), getting hot feet in the summer (63%) and the need for a sandal which could accommodate a supportive insole (73%).

Conclusions

Athletic and walking shoes were the most popular style of footwear reported regardless of seasonal variation. During the summer season people with inflammatory arthritis may wear sandals more frequently in order to accommodate disease‐related foot deformity. Healthcare professionals and researchers should consider seasonal variation when recommending appropriate footwear, or conducting footwear studies in people with inflammatory arthritis, to reduce non‐adherence to prescribed footwear.
The benefit of specialized team approaches in patients with acute kidney injury undergoing continuous renal replacement therapy: propensity score matched analysis
Authors: Oh Hyung Jung , Lee Mi Jung , Kim Chan Ho , Kim Dae Young , Lee Hye Sun , Park Jung Tak , Na Sungwon , Han Seung Hyeok , Kang Shin-Wook , Koh Shin Ok , Yoo Tae-Hyun
Published: August 2014

Introduction

Continuous renal replacement therapy (CRRT) has been widely used in critically ill acute kidney injury (AKI) patients. Moreover, some centers operate a specialized CRRT team (SCT) composed of physicians and nurses, but few studies have yet determined the superiority of SCT control.

Methods

A total of 334 among 534 patients in the original cohort, who started CRRT for severe AKI between August 2007 and September 2009 in Yonsei University Health System and were matched with a propensity score (PS), were divided into two groups based on SCT application. Moreover, we compared CRRT-related outcomes including down-time per day and lost time per filter-exchange between the two groups. The primary outcomes were 28- and 90-day all-cause mortality, and the secondary outcomes were the rates of renal function recovery at 28- and 90-day.

Results

The down-time per day, lost time per filter-exchange, and red blood cell-transfused numbers during CRRT treatment were significantly lower after SCT approach compared with the group before SCT, while net ultrafiltration rate in the after SCT group was significantly higher compared to the before SCT group. During the study period, the 28- and 90-day all-cause mortality rates were significantly decreased after SCT application. Cox regression analysis revealed that 28- and 90-day all-cause mortality rates were significantly lower under SCT control, after adjusting for primary diagnosis, emergent surgical cases, Charlson Comorbidity Index and biochemical parameters. However, there were no significant differences in the rate of renal function recovery before and after SCT approach in CRRT.

Conclusions

A well-organized CRRT team could be beneficial for clinical outcomes through improving quality of care in AKI patients requiring CRRT treatment in the ICU.
Severe respiratory insufficiency during pandemic H1N1 infection: prognostic value and therapeutic potential of pulmonary surfactant protein A
Authors: Tolosa Monica Fern , Palaniyar Nades
Published: August 2014

For almost two decades, studies have shown collectins to be critical for effective antimicrobial defense of the airways. Members of this protein family, which includes surfactant proteins (SP)-A and D, provide broad-spectrum protection through promoting the aggregation and clearance of pathogens. Interestingly, these proteins may also modulate the immune response, and growing evidence has shown collectins to be protective against several markers of inflammation and injury. In a recent study by Herrera-Ramos and colleagues, genetic variants of collectins were examined in Spanish patients with the pandemic 2009 H1N1 influenza A virus. Comparing genotypes for measures of poor lung function, inflammation, and admission to intensive care, these authors identified three variants of the SP-A gene SFTPA2 that positively correlated with flu severity. Remarkably, they also found the haplotype 1A1 of SFTPA2 to be protective against these indicators, suggesting that targeted therapy with a recombinant form of SP-A2 may improve patient outcome. Although further work is required to confirm the specificity and efficacy of SP-A in therapeutic H1N1 protection, this study is one of the first to suggest a clinical role for SP-A in pandemic influenza.
Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer
Authors: White Nicole M , Cabanski Christopher R , Silva-Fisher Jessica M , Dang Ha X , Govindan Ramaswamy , Maher Christopher A
Published: August 2014

Background

Long intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive.

Results

Here we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation.

Conclusions

Our systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology.
HMBPP-deficientListeriamutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells
Authors: Frencher James T , Shen Hongbo , Yan Lin , Wilson Jessica O , Freitag Nancy E , Rizzo Alicia N , Chen Crystal Y , Chen Zheng W
Published: August 2014

Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactAΔgcpEprfA* mutant. The HMBPP-deficient ΔgcpE mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention.
Phase I Dose-Escalation Study of LCL161, an Oral Inhibitor of Apoptosis Proteins Inhibitor, in Patients With Advanced Solid Tumors
Authors: Infante Jeffrey R. , Dees E. Claire , Olszanski Anthony J. , Dhuria Shyeilla V. , Sen Suman , Cameron Scott , Cohen Roger B.
Published: August 2014

Purpose

LCL161 antagonizes the function of inhibitor of apoptosis proteins (IAPs), thereby promoting cancer cell death. This first-in-human dose-escalation study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of LCL161 in patients with advanced solid tumors. A second part of the study assessed the relative bioavailability of a tablet versus solution formulation.

Patients and Methods

LCL161 was administered orally, once weekly, on a 21-day cycle to adult patients with advanced solid tumors by using an adaptive Bayesian logistic regression model with overdose control–guided dose escalation.

Results

Fifty-three patients received at least one dose of LCL161 (dose range, 10 to 3,000 mg). LCL161 was well tolerated at doses up to 1,800 mg. Cytokine release syndrome (CRS) was the only dose-limiting toxicity (in three [6%] of 53 patients) and was the most common grades 3 to 4 event (in five [9%] of 53 patients). Vomiting, nausea, asthenia/fatigue, and anorexia were common but not severe. Although the MTD was not formally determined, an 1,800-mg dose was selected in compliance with the protocol for additional study, given the dose-limiting CRS at higher doses and pharmacodynamic activity at lower doses. LCL161 was rapidly absorbed, and exposure was generally increased with dose. The tablet formulation of LCL161 was better tolerated than the solution; tablet and solution formulations had similar exposures, and the solution was discontinued. No patient had an objective response. LCL161 induced degradation of cellular IAP1 protein in the blood, skin, and tumor and increased circulating cytokine levels.

Conclusion

The 1,800-mg dose of LCL161, administered as a single agent once weekly, in tablet formulation is the recommended dose for additional study. This combined dose and formulation was well tolerated and had significant pharmacodynamic activity, which warrants additional investigation.
Nanotechnology in Radiation Oncology
Authors: Wang Andrew Z. , Tepper Joel E.
Published: August 2014

Nanotechnology, the manipulation of matter on atomic and molecular scales, is a relatively new branch of science. It has already made a significant impact on clinical medicine, especially in oncology. Nanomaterial has several characteristics that are ideal for oncology applications, including preferential accumulation in tumors, low distribution in normal tissues, biodistribution, pharmacokinetics, and clearance, that differ from those of small molecules. Because these properties are also well suited for applications in radiation oncology, nanomaterials have been used in many different areas of radiation oncology for imaging and treatment planning, as well as for radiosensitization to improve the therapeutic ratio. In this article, we review the unique properties of nanomaterials that are favorable for oncology applications and examine the various applications of nanotechnology in radiation oncology. We also discuss the future directions of nanotechnology within the context of radiation oncology.
Role of Radiation Therapy in Palliative Care of the Patient With Cancer
Authors: Lutz Stephen T. , Jones Joshua , Chow Edward
Published: August 2014

Radiotherapy is a successful, time-efficient, well-tolerated, and cost-effective intervention that is crucial for the appropriate delivery of palliative oncology care. The distinction between curative and palliative goals is blurred in many patients with cancer, requiring that treatments be chosen on the basis of factors related to the patient (ie, poor performance status, advanced age, significant weight loss, severe comorbid disease), the cancer (ie, metastatic disease, aggressive histology), or the treatment (ie, poor response to systemic therapy, previous radiotherapy). Goals may include symptom relief at the site of primary tumor or from metastatic lesions. Attention to a patient's discomfort and transportation limitations requires hypofractionated courses, when feasible. Innovative approaches include rapid response palliative care clinics as well as the formation of palliative radiotherapy specialty services in academic centers. Guidelines are providing better definitions of appropriate palliative radiotherapy interventions, and bone metastases fractionation has become the first radiotherapy quality measure accepted by the National Quality Forum. Further advances in the palliative radiation oncology subspecialty will require integration of education and training between the radiotherapy and palliative care specialties.
Value: A Framework for Radiation Oncology
Authors: Teckie Sewit , McCloskey Susan A. , Steinberg Michael L.
Published: August 2014

In the current health care system, high costs without proportional improvements in quality or outcome have prompted widespread calls for change in how we deliver and pay for care. Value-based health care delivery models have been proposed. Multiple impediments exist to achieving value, including misaligned patient and provider incentives, information asymmetries, convoluted and opaque cost structures, and cultural attitudes toward cancer treatment. Radiation oncology as a specialty has recently become a focus of the value discussion. Escalating costs secondary to rapidly evolving technologies, safety breaches, and variable, nonstandardized structures and processes of delivering care have garnered attention. In response, we present a framework for the value discussion in radiation oncology and identify approaches for attaining value, including economic and structural models, process improvements, outcome measurement, and cost assessment.
Frontiers in Radiotherapy for Early-Stage Invasive Breast Cancer
Authors: Fisher Christine M. , Rabinovitch Rachel
Published: August 2014

The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies.
Impact of Informative Censoring on the Kaplan-Meier Estimate of Progression-Free Survival in Phase II Clinical Trials
Authors: Campigotto Federico , Weller Edie
Published: August 2014

Informative censoring in a progression-free survival (PFS) analysis arises when patients are censored for initiation of an effective anticancer treatment before the protocol-defined progression, and these patients are at a different risk for treatment failure than those who continue on therapy. This may cause bias in the estimated PFS when using the Kaplan-Meier method for analysis. Although there are several articles that discuss this issue from a theoretical perspective or in randomized phase III studies, there are little data to demonstrate the magnitude of the bias on the estimated quantities from a phase II trial. This article describes the issues by using two oncology phase II trials as examples, evaluates the impact of the bias using simulations, and provides recommendations. The two trials were selected because they demonstrate two different reasons for censoring. Simulations show that the magnitude of the bias depends primarily on the proportion of patients who are informatively censored and secondarily on the hazard ratio between the group of patients who remain on study and the group of patients who are informatively censored. Recommendations include using an alternative end point, which includes inadequate response and initial signs of clinical progression as treatment failure, and a competing risk analysis for studies in which competing events preclude or modify the probability of observing the primary event of interest. If informative censoring cannot be avoided, then all patients should be observed until progression, and sensitivity analyses should be used as appropriate.
Generation of catalytic human Ago4 identifies structural elements important for RNA cleavage
Authors: Hauptmann Judith , Kater Lukas , Löffler Patrick , Merkl Rainer , Meister Gunter
Published: August 2014

Argonaute proteins bind small RNAs and mediate cleavage of complementary target RNAs. The human Argonaute protein Ago4 is catalytically inactive, although it is highly similar to catalytic Ago2. Here, we have generated Ago2-Ago4 chimeras and analyzed their cleavage activity in vitro. We identify several specific features that inactivate Ago4: the catalytic center, short sequence elements in the N-terminal domain, and an Ago4-specific insertion in the catalytic domain. In addition, we show that Ago2-mediated cleavage of the noncanonical miR-451 precursor can be carried out by any catalytic human Ago protein. Finally, phylogenetic analyses establish evolutionary distances between the Ago proteins. Interestingly, these distances do not fully correlate with the structural changes inactivating them, suggesting functional adaptations of individual human Ago proteins.
CaMKII binding to GluN2B is important for massed spatial learning in the Morris water maze
Authors: Stein Ivar S. , Donaldson Michaela S. , Hell Johannes W.
Published: August 2014

Learning and memory as well as long-term potentiation (LTP) depend on Ca2+influx through the NMDA-type glutamate receptor (NMDAR) and the resulting activation of the Ca2+and calmodulin-dependent protein kinase (CaMKII). Ca2+influx via the NMDAR triggers CaMKII binding to the NMDAR for enhanced CaMKII accumulation at post-synaptic sites that experience heightened activity as occurring during LTP. Previously, we generated knock-in (KI) mice in which we replaced two residues in the NMDAR GluN2B subunit to impair CaMKII binding to GluN2B. Various forms of LTP at the Schaffer collateral synapses in CA1 are reduced by 50%. Nevertheless, working memory in the win-shift 8 arm maze and learning of the Morris water maze (MWM) task was normal in the KI mice although recall of the task was impaired in these mice during the period of early memory consolidation. We now show that massed training in the MWM task within a single day resulted in impaired learning. However, learning and recall of the Barnes maze task and contextual fear conditioning over one or multiple days were surprisingly unaffected. The differences observed in the MWM compared to the Barnes maze and contextual fear conditioning suggest a differential involvement of CaMKII and the specific interaction with GluN2B, probably depending on varying degrees of stress, cognitive demand or even potentially different plasticity mechanisms associated with the diverse tasks.
Observations on spiny dogfish (Squalus acanthias) captured in late spring in a North Carolina estuary
Authors: Bangley Charles , Rulifson Roger
Published: August 2014

Five spiny dogfish were captured in early-mid May during gillnet and longline sampling targeting juvenile coastal sharks in inshore North Carolina waters.  Dogfish captures were made within Back Sound and Core Sound, North Carolina.  All dogfish were females over the size at maturity, and were caught at stations 1.77-2.74 m in depth, with temperatures 22.9-24.2 °C, 32.8-33.4 ppt salinity, and 6.9-8.0 mg/L dissolved oxygen.  Stations where dogfish were captured were approximately 6.5-15.7 km from the nearest inlet and 43.4-247.1 m from the nearest seagrass bed.  These observations are among the latest in the spring for spiny dogfish in the southeastern U.S. and occurred at higher temperatures than previously recorded for this species.  It is unclear whether late-occurring spiny dogfish in this area represent a cryptic late-migrating or resident segment of the Northwest Atlantic population.
Information technologies for solving problems of certification and licensing of the enterprises of electronic industry, conducting advanced research and analysis of sales
Authors: Ярцев  , Yartsev M. , Чубур  , Chubur K. , Евдокимова  , Evdokimova S. , Анциферова  , Antsiferova V. , Зольников  , Zolnikov Vladimir
Published: August 2014

The paper considers issues of using information technologies for solving problems of certification and licensing of the enterprises of electronic industry, conducting advanced research and analysis of sales. The structure of the database and identify the steps of adding information.
Research of parameters of assessment of human settlements to improve the efficiency of their fire protection on the example of fire department, Voronezh
Authors: Бартенев  , Bartenev A. , Сербулов  , Serbulov Yuriy
Published: August 2014

Methods of research of parameters estimation of territories of settlements. developed generalized method of calculation of parameters estimation of territories of settlements.
Analysis of the functional possibilities CAD SIMETRIX on example of the scheme MOS-transistor
Authors: Лавлинский  , Lavlinskiy V. , Жвад  , Zhvad Akhmed Khashim Khalil
Published: August 2014

In article are compared functional possibilities CAD SIMetrix on base different analysis on example of the equivalent scheme MOS-transistor.
Prediction mathematico-tools stability of a strategic choice at management of the commercial organization
Authors: Лапшина  , Lapshina Marina , Феоктистов  , Feoktistov R.
Published: August 2014

In article the problem of prediction of stability of a strategic choice taking into account interrelations between subjects of the market and definition of the conditions providing stabilization of the market on a basis to model operation of dynamics of transient phenomenons of the market is considered.
Predict how long the strength and stiffness of wood constructional composite material
Authors: Стородубцева  , Storodubtseva Tamara
Published: August 2014

The paper deals with a new method of predicting the durability of wood-construction onnyh composite materials that are used in industrial and transportation facilities, undergoes aggressive influences of different environments. The method is based on experimental studies of creep processes of these materials.
Motivation of the choice of the programming language for realization main element information system of the designing the processes of technological preparing the undertaking of cutting area work
Authors: Юдина  , Yudina N. , Колупаева  , Kolupaeva T.
Published: August 2014

A basis of the choice of the programming language happen to in article for efficient development and debug of applications IS TPPLR not only to account of the use the suitable facilities of the visual designing the forms (presently this not rarity), but also to account, first, high efficiency compiler Borland themselves and, secondly, so named increment to compiling and linkings of the performed module (when recompilation and recomposition are subjected to only that modules, in which were contributed change).
Integrating psychological screening into reviews of patients with COPD
Authors: Hardy Sheila , Smart David , Scanlan Mike , Rogers Stephen
Published: August 2014

Background:

People with chronic obstructive pulmonary disease (COPD) have a high prevalence of anxiety and depression, which can have an impact on their symptoms and the way they manage their condition. Intervention that takes psychological distress into account may lead to better outcomes than simple advice-giving.

Aim:

To explore the feasibility of integrating psychological screening and intervention into nurse-led reviews of patients with COPD.

Method:

Nurses were given training on a pathway developed for patients with COPD. This included screening for depression and anxiety and assessing their severity; providing self-management education by means of a motivational approach; and offering pulmonary rehabilitation.

Results:

The nurses’ level of confidence increased following training. Patients were accepting of the screening process and felt more able and motivated to manage their condition after the intervention. Eleven of the 35 patients that took part in the study period had evidence of anxiety and/or depression. Out of a total of 16 patients eligible for pulmonary rehabilitation, 12 agreed to referral. Of these, three patients were seen by their GP, one was started on antidepressants, and one was referred to the psychology service.

Conclusion:

Training practice nurses to screen for depression and anxiety, and to offer self-management education using a motivational interviewing approach, increased the reported capability and motivation of patients with COPD to manage their condition. It may also improve the uptake of pulmonary rehabilitation. Use of this pathway does not place a burden on other care providers or greatly increase prescribing costs.
Arterialised earlobe capillary blood gases in the COPD population
Authors: Young Jane
Published: August 2014

Arterialised ear lobe capillary blood (ELCB) gas sampling is a widely used clinical procedure undertaken across both primary and secondary care settings. The prevalence of this sampling method has grown among health professionals, coupled with a growing demand for domiciliary oxygen therapy in the UK, in particular for those who have chronic obstructive pulmonary disease (COPD). Research studies supporting arterialised ELCB gas sampling show inconsistencies in technique, and a survey of respiratory nurses’ current practice demonstrated wider inconsistencies. In the absence of national clinical guidelines to direct this practice, and an acknowledged and accepted under-calculation of partial pressure of oxygen, this article investigates the sampling method used to obtain arterialised ELCB gas sampling and consequently questions its reliability in practice.
Decontamination methods for flexible nasal endoscopes
Authors: Javed Faisal , Sood Salil , Banfield Graham
Published: August 2014

A national survey was carried out to investigate the current UK practice for decontaminating flexible nasal endoscopes. A postal questionnaire was sent to Sisters in Charge of 200 ear, nose and throat (ENT) outpatient departments in the UK, with an overall response rate of 60.5%. Decontamination with chlorine dioxide wipes was the most favoured method, used in 58% of the hospitals that participated in this survey. Automated machines were also used in many places (34%). Only a few hospitals used flexible sheaths (7%). Many departments do not use a separate protocol for high-risk patients.
Understanding the concept of the key worker: do focus groups help?
Authors: Hull Ken , Turton Pat
Published: August 2014

The concept of the ‘key-worker role’ within paediatric haematology and oncology services is recognised in the UK through inclusion in published policies and guidance. Such guidance originates from both statutory and voluntary sector organisations. Within the policy direction itself, references are made to both ‘designated’ and ‘non-designated’ key workers, and there remains ongoing confusion within the professional field about the exact nature of the process of ‘key-working’ and how this should operate. This confusion therefore also exists for parents, carers and service users. The project described here aimed to examine the concept of the key-worker role through consultation with users as part of local service development. Focus group discussion was identified as the methodology of choice. Careful planning and delivery ensured that meaningful data emerged. Active participation by those attending the focus group discussion was observed. The focus group was in two sessions, both of which were digitally recorded and transcribed, with contemporaneous notes taken. These were subjected to thematic analysis and clear themes emerged regarding the importance of terminology, communication, skill mix and the use of technology. This local project achieved greater clarity about how to develop the key-worker role to best meet the needs of users through highlighting the need to include both the key-worker role, and the process of key-working. It is concluded that the use of focus groups is both a valid and valuable mechanism of consultation, as user consultation regarding service design and evaluation of care delivered is high on the wider agenda of the NHS.
The Mental Capacity Act 2005: riding the storm of criticism
Authors: Tingle John
Published: August 2014

John Tingle discusses the Government's response to the House of Lords Select Committee report on the Mental Capacity Act 2005 .
Use of a coverlet system for the management of skin microclimate
Authors: Collier Mark , Potts Carol , Shaw Elaine
Published: August 2014

Pressure and shear are the two key extrinsic factors that cause pressure ulcer damage. However, if the resilience of the skin and soft tissue deteriorates, the individual's susceptibility to such pressure damage will increase. The risk is greater if the microclimate at the interface between the skin and the support surface is impaired. This will occur when the skin temperature is elevated and there is excess moisture on the skin surface. Microclimate management therefore plays an important role in pressure ulcer prevention. This article describes how use of a new coverlet system (Skin IQ Microclimate Manager, ArjoHuntleigh) can avoid the accumulation of heat and moisture at the patient/support-surface interface