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Δευτέρα 27 Φεβρουαρίου 2017
Point-of-care monitoring for the management of trauma-induced bleeding.
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Late latent mucinous syphilis mimicking connective tissue disease
Abstract
As evidenced by the CDC statistics, syphilis is yet again on the rise. It is known as the great mimicker because of its variable symptoms and how frequently it can be confused with other diseases. The different stages of syphilis (primary, secondary, latent, late latent and tertiary) are discussed. We describe a new histopathologic pattern of syphilis, one that mimics connective tissue disease and can represent a diagnostic pitfall. In this time and age when syphilis is rising especially among the men who have sex with men subgroup, it is important to keep a high index of suspicion of syphilis even when clinically and histopathologically the findings on first glance may not appear characteristic.
http://ift.tt/2m6k2Mf
Hazards and Incidents: Detection and Learning in Radiation Medicine, A Comparison of Two Educational Interventions
Publication date: Available online 27 February 2017
Source:Practical Radiation Oncology
Author(s): Robert Thompson, Yilan Lu, Marc Potvin, Jordan Holmes, Lisa Di Prospero, Brian Keller, Ewa Szumacher, Brian Liszewski, Pamela Catton, Meredith Giuliani, Bethany Pitcher, Melania Pintilie, Jean-Pierre Bissonnette
PurposeInter-professional, educational live simulations were compared to group discussion-based exercises in terms of their ability to improve Radiation Medicine trainees` ability to detect hazards and incidents and understand behaviors that may prevent them.Methods and MaterialsTrainees and recent graduates of Radiation Therapy, Medical Physics, and Radiation Oncology programs were recruited and randomized to either a simulation-based or group discussion-based training intervention. Participants engaged in hazard and incident detection, analysis, as well as a discussion of potential preventive measures and the concept of the "highly reliable team". A video examination tool modeled on actual incidents, using five-minute videos created by faculty, students, and volunteers, was created to test hazard and incident recognition ability before and after training. Hazard and incident detection sensitivity and specificity analyses were conducted and a survey of the participants' and facilitators' perceptions was conducted.ResultsTwenty-seven participants were assigned to the simulation (n=15) or discussion group (n=12). Hazard and incident-detection sensitivity ranged from 0.04–0.56 before and 0.04–0.35 after training for the discussion and simulation groups, respectively. The pre- and post-training difference in sensitivity between groups was 0.03 (p=0.75) for the minimum and 0.33 (p=0.034) for the maximum reaction time. Participant perceptions of the training's educational value in a variety of domains ranged from a mean score of 6.58–8.17 and 7–8.07 for the discussion and simulation groups, respectively. Differences were not statistically significant. Twenty-six of the 27 participants indicated that they would recommend this event to a colleague.ConclusionsParticipants' ability to detect hazard and incidents as portrayed in 5-minute videos in this study was low both before and after training and simulation-based training was not superior to discussion-based training. However, levels of satisfaction and perceptions of the training's educational value were high, especially with simulation-based training.
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Intraoperative dermoscopic features of onychomatricoma: a review of 10 cases
Summary
Background
Amelanotic nail tumours are difficult to diagnose. Dermoscopy is an accessible tool successfully used in diagnosis of amelanotic or melanotic skin tumours. We have previously shown the usefulness of dermoscopy in the preoperative diagnosis of onychomatricoma (OM). In this study, we completed this work by identifying additional intraoperative criteria to better establish the initial diagnosis of this tumour.
Aims
Evaluation of intraoperative dermoscopy in a small series of OM cases in order to define relevant diagnostic criteria.
Methods
In total, 10 patients with OM diagnosed in our centre were enrolled in the study. Six trained dermoscopists individually evaluated each criterion, then the data were compared and a consensus reached after discussion between the observers. For each criterion, we analysed its frequency and its interobserver accordance. We defined three architectural criteria (the 'Sagrada Familia' sign, digitations and the 'mirror sign'), and three vascular criteria (sagittal vessels, dotted vessels and irregular vessels).
Results
The Sagrada Familia sign, digitations and mirror sign were found in 100%, 90% and 70% of the cases, respectively, with high interobserver agreement. The vascular criteria were less regularly observed: sagittal, dotted and irregular vessels were respectively found in 80%, 70% and 50% of the OM cases, and were more difficult to assess, as shown by the lower interobserver agreement rates.
Conclusion
Intraoperative dermoscopy of the nail matrix and bed offers useful information for the diagnosis and management of OM. Larger comparative studies should be performed to evaluate the true benefit of this approach.
http://ift.tt/2lty1IC
Multiple pilomatrixomas in children: the need for long-term follow-up and aesthetically sensitive incisions
Summary
Pilomatrixomas are benign, calcified epitheliomas of the hair follicle, predominately affecting children and commonly presenting in the head and neck region. The current literature is almost unanimous in recommending surgical excision. Reconstruction of these defects may require the need for a skin graft, resulting in poor cosmetic outcome and donor site morbidity. We present two cases demonstrating the benefits of minimal access incisions for pilomatrixomas in children. We recommend that multiple or recurrent lesions should prompt referral to a specialist for management and long-term follow-up.
http://ift.tt/2ltngG3
Intraoperative dermoscopic features of onychomatricoma: a review of 10 cases
Summary
Background
Amelanotic nail tumours are difficult to diagnose. Dermoscopy is an accessible tool successfully used in diagnosis of amelanotic or melanotic skin tumours. We have previously shown the usefulness of dermoscopy in the preoperative diagnosis of onychomatricoma (OM). In this study, we completed this work by identifying additional intraoperative criteria to better establish the initial diagnosis of this tumour.
Aims
Evaluation of intraoperative dermoscopy in a small series of OM cases in order to define relevant diagnostic criteria.
Methods
In total, 10 patients with OM diagnosed in our centre were enrolled in the study. Six trained dermoscopists individually evaluated each criterion, then the data were compared and a consensus reached after discussion between the observers. For each criterion, we analysed its frequency and its interobserver accordance. We defined three architectural criteria (the 'Sagrada Familia' sign, digitations and the 'mirror sign'), and three vascular criteria (sagittal vessels, dotted vessels and irregular vessels).
Results
The Sagrada Familia sign, digitations and mirror sign were found in 100%, 90% and 70% of the cases, respectively, with high interobserver agreement. The vascular criteria were less regularly observed: sagittal, dotted and irregular vessels were respectively found in 80%, 70% and 50% of the OM cases, and were more difficult to assess, as shown by the lower interobserver agreement rates.
Conclusion
Intraoperative dermoscopy of the nail matrix and bed offers useful information for the diagnosis and management of OM. Larger comparative studies should be performed to evaluate the true benefit of this approach.
http://ift.tt/2lty1IC
Multiple pilomatrixomas in children: the need for long-term follow-up and aesthetically sensitive incisions
Summary
Pilomatrixomas are benign, calcified epitheliomas of the hair follicle, predominately affecting children and commonly presenting in the head and neck region. The current literature is almost unanimous in recommending surgical excision. Reconstruction of these defects may require the need for a skin graft, resulting in poor cosmetic outcome and donor site morbidity. We present two cases demonstrating the benefits of minimal access incisions for pilomatrixomas in children. We recommend that multiple or recurrent lesions should prompt referral to a specialist for management and long-term follow-up.
http://ift.tt/2ltngG3
The value of systematic contouring of the bowel for treatment plan optimization in image-guided cervical cancer high-dose-rate brachytherapy
Source:Brachytherapy
Author(s): Antonio L. Damato, Ivan Buzurovic, Mandar S. Bhagwat, Robert A. Cormack, Phillip M. Devlin, Scott Friesen, Jorgen Hansen, Larissa J. Lee, Matthias M. Manuel, Linda P. Cho, Desmond O'Farrell, Akila N. Viswanathan
PurposeTo investigate the dose–volume histogram metrics and optimization results of the contoured bowel in cervical cancer brachytherapy.Methods and MaterialsTreatment plans of cervical cancer patients treated with image-guided high dose rate were retrospectively analyzed with institutional review board approval. In addition to the clinical target volume, rectum, bladder, and sigmoid, the bowel was contoured at the time of planning (Group 1) or at the time of this analysis (Group 2).ResultsThirty-two patients treated with 145 insertions were included. Before optimization, mean ± 1 standard deviation overall bowel minimum dose to the most irradiated 2 cm3 volume of an organ (D2cc) was 67.8 Gyα/β3 ± 13.7 Gyα/β3 (Group 1: 72.6 ± 13.2 Gyα/β3; Group 2: 57.3 ± 8.0 Gyα/β3). Before optimization, one patient in Group 1 presented a bowel D2cc metric exceeding 100 Gyα/β3. After optimization, bowel D2cc mean ± 1 standard deviation was 59.4 ± 6.7 Gyα/β3 (Group 1: 61.4 ± 6.0 Gyα/β3, p < 0.001; Group 2: 55.2 ± 6.5 Gyα/β3, p = 0.026).ConclusionsGiven the potentially high doses and the benefit of optimization in reducing dose to the organs at risk, we recommend consideration of systematic contouring of the bowel when bowel is present in the pelvis.
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Microwave ablation in the spleen versus partial splenic artery embolisation: A new technique for hypersplenism in cirrhosis
Publication date: Available online 28 February 2017
Source:Arab Journal of Gastroenterology
Author(s): Fathia Assal, Mohamed El Kassas, Eslam Esmail, Amr A. Elbadry, Sabry Abousaif, Reem Mahdy, Asem Elfert
Background and study aimsSplenectomy has been associated with high perioperative morbidity and mortality. Partial splenic artery embolisation (PSE) was found to be an effective and safer method but with numerous complications. Local thermal ablative techniques such as microwave ablation (MWA) have been tried and were found to be safe and effective alternatives. This randomised controlled study aimed to compare the efficacy and safety of MWA versus PSE in the treatment of hypersplenism in patients with post-hepatitis C cirrhosis.Patients and methodsIn total, 40 patients with post-hepatitis C cirrhosis complicated with hypersplenism were randomised into two groups: Group I: 20 patients treated with percutaneous MWA of splenic parenchyma under ultrasound guidance and Group II: 20 patients treated with PSE using Embosphere.ResultsThere was a significant increase in haemoglobin levels in group I compared with group II after 3months of follow-up. However, White blood cell (WBC) count and platelets significantly increased more in group II than in group I after 1month. Postprocedure significant hyperbilirubinaemia, hypoalbuminaemia, decreased prothrombin concentration, and increased creatinine levels were encountered in group II only. There was a significant increase in postoperative complications in group II compared to group I, and a single case of mortality was reported in group II.ConclusionMWA and PSE were comparably effective; however, MWA was safer than PSE, which caused serious adverse events and mortality. MWA appears to be a good alternative for the treatment of hypersplenism in patients with cirrhosis and portal hypertension.
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Schwannoma of the psoas: An unusual cause of abdominal pain
Publication date: Available online 28 February 2017
Source:Arab Journal of Gastroenterology
Author(s): Elias Makhoul, Ralph Kamel, Naim Hanna
Schwannomas are usually benign tumours arising from Schwann cells of peripheral nerve sheath. Retroperitoneal location is extremely rare compromising 0.5–5% of all schwannomas, except in patients having von Recklinghausen's disease, in whom retroperitoneal location is more frequent and malignant cases are known to occur. Complete surgical excision with negative margins is the definitive treatment on which the diagnosis is usually made due to nonspecific radiologic appearance.In this article we would like to present an unusual cause of recurrent, abdominal pain in an eighty-six-year-old male.
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Expression of Rab5a correlates with tumor progression in pancreatic carcinoma
Abstract
Rab family protein Rab5a has been implicated in cancer progression. To date, its expression pattern in human pancreatic cancer has not been investigated. This study aims to examine clinical significance, biological role, and potential mechanism of action of mRab5a in human pancreatic cancer. We analyzed Rab5a protein in cancer tissue of 111 cases of pancreatic cancer using immunohistochemistry. The results show that Rab5a overexpression correlates with high T stage, positive nodal status, and advanced TNM stage. We performed knockdown of Rab5a through transfection of Rab5a-specific siRNA in the Capan-2 cell line, which shows high endogenous expression, and of Rab5a plasmid in the CFPAC-1 cell line, which shows low endogenous expression. Rab5a knockdown inhibited cell proliferation and invasion while its overexpression promoted cell proliferation and invasion. In addition, overexpression of Rab5a induced resistance to 5-FU and gemcitabine while its knockdown reduced resistance to 5-FU and gemcitabine. Furthermore, our results show that Rab5a overexpression upregulates Wnt signaling and expression of Wnt target genes including c-myc and MMP7. Blocking Wnt signaling abolished the effects of Rab5a on Wnt targets and on cancer cell proliferation. In summary, our results show that Rab5a is overexpressed in pancreatic cancer and promotes aggressive biological behavior through regulation of the Wnt/β-catenin signaling pathway.
http://ift.tt/2m0O1oD
Adsorption behavior and mechanism of ibuprofen onto BiOCl microspheres with exposed {001} facets
Abstract
BiOCl microspheres with exposed {001} facets have been synthesized through a simple solvothermal method. The adsorption and photocatalytic activities of BiOCl microspheres were evaluated by removal of ibuprofen (IBP) as the model reaction. Parameters including IBP concentration, BiOCl dosage, and inorganic ions were investigated to reveal the role of adsorption in BiOCl-based photocatalysis. We found that the high IBP removal rate by BiOCl is not due to photocatalytic oxidation but to surface adsorption. The combination of ICP/MS, IC, XPS, and FT-IR results directly proved that anion exchange between dissociated IBP and Cl accompanied by the formation of surface complex (O–Bi–OOC–C12H17) onto the BiOCl surface is the main adsorption mechanism. In addition, we also demonstrated that organic compounds with carboxyl group (–COOH) such as diclofenac, benzoic acid, and p-phthalic acid can be adsorbed by BiOCl while organic compounds without carboxyl group such as carbamazepine, nitrobenzene, and p-chloronitrobenzene cannot be adsorbed. We believe that the BiOCl adsorption behavior and mechanism should be considered when discussing its photocatalytic mechanism.
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Heavy metal accumulation in some aquatic insects (Coleoptera: Hydrophilidae) and tissues of Chondrostoma regium (Heckel, 1843) relevant to their concentration in water and sediments from Karasu River, Erzurum, Turkey
Abstract
The objectives of this research were to determine and compare the heavy element concentrations in two study areas in Erzurum, Turkey (Aşkale and Dumlu sites). Assessment of some heavy elements in sediment, water, fish (Chondrostoma regium) tissues, and some aquatic insects (Coleoptera: Hydrophilidae) were carried out in June to August 2014. Heavy element levels in aquatic insect samples and their associated water and sediment were analyzed by energy dispersive X-ray fluorescence (EDXRF) spectrometer. Fish tissues, from the same habitat, were measured by inductively coupled plasma mass spectrometry (ICP-MS). Eleven elements (Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Hg, Pb) were measured in fish tissues, and 14 elements (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Br, Pb) were measured in insects. According to the results, it can be said that insects were contaminated by water and sediment, thus accumulated higher concentration of some elements than their environment. The fish, which was caught from Aşkale station, accumulates significantly higher level of heavy metals than Dumlu station's fish. The results were compared with national and international standards. The values of some heavy elements were found at higher concentration than the acceptable limits. The possible consequences of these results are briefly discussed from the point of potential hazards to ecology and human health. Element concentrations in fish tissue are below the limits, which are proposed by Turkish Food Codex, FAO/WHO, and EC, and safe for human consumption in the edible parts of fish species in the regions.
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Effects of epiphytic algae on biomass and physiology of Myriophyllum spicatum L. with the increase of nitrogen and phosphorus availability in the water body
Abstract
The disappearance of submerged vascular macrophytes in shallow eutrophic lakes is a common phenomenon in the world. To explore the mechanism of the decline in submerged macrophyte abundance due to the growth of epiphytic algae along a nutrient gradient in eutrophic water, a 2 × 3 factorial experiment was performed over 4 weeks with the submerged macrophyte (Myriophyllum spicatum L.) by determining the plant's biomass and some physiological indexes, such as chlorophyll (Chl) content, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity in the leaves of M. spicatum L. on days 7, 14, 21, and 28, which are based on three groups of nitrogen and phosphorus levels in the water body (N-P [mg L−1]: NP1 0.5–0.05, NP2 2.5–0.25, NP3 4.5–0.45) and two levels of epiphytic algae (the epiphytic algae group and the control group). Epiphytic algal biomass was also assayed. The results indicated that epiphytic algal biomass remarkably enhanced in the course of the experiment with elevated levels of nitrogen and phosphorus in the water. Under the same level of nutrient condition, plants' biomass accumulation and Chl content were higher in the control group than that in the epiphytic algae group, respectively, while MDA content and SOD activity in the former were lower than that in the latter. The influences of epiphytic algae on the biomass accumulation and Chl content and MDA content became greater and greater with elevated levels of nutrients. In general, in this experiment, water nutrients promoted the growth of both epiphytic algae and submerged plants, while the growth of epiphytic algae hindered submerged macrophytes' growth by reducing Chl content and promoting peroxidation of membrane lipids in plants.
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Editorial Board
Publication date: April 2017
Source:Medical Image Analysis, Volume 37
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Dual Discriminative Local Coding for Tissue Aging Analysis
Publication date: Available online 27 February 2017
Source:Medical Image Analysis
Author(s): Yang Song, Qing Li, Fan Zhang, Heng Huang, Dagan Feng, Yue Wang, Mei Chen, Weidong Cai
In aging research, morphological age of tissue helps to characterize the effects of aging on different individuals. While currently manual evaluations are used to estimate morphological ages under microscopy, such operation is difficult and subjective due to the complex visual characteristics of tissue images. In this paper, we propose an automated method to quantify mor- phological ages of tissues from microscopy images. We design a new sparse representation method, namely dual discriminative local coding (DDLC), that classifies the tissue images into different chronological ages. DDLC in- corporates discriminative distance learning and dual-level local coding into the basis model of locality-constrained linear coding thus achieves higher discriminative capability. The morphological age is then computed based on the classification scores. We conducted our study using the publicly avail- able terminal bulb aging database that has been commonly used in existing microscopy imaging research. To represent these images, we also design a highly descriptive descriptor that combines several complementary texture features extracted at two scales. Experimental results show that our method achieves significant improvement in age classification when compared to the existing approaches and other popular classifiers. We also present promising results in quantification of morphological ages.
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Facile control of ZnO nanostructures by varying molar concentration of zinc acetate
Publication date: June 2017
Source:Materials Research Bulletin, Volume 90
Author(s): H.R. Guzmán-Carrillo, E.M. Rivera-Muñoz, N. Cayetano-Castro, R. Herrera-Basurto, Z. Barquera-Bibiano, F. Mercader-Trejo, A. Manzano-Ramírez
This paper reports the synthesis of ZnO nanostructures (nano-bullets, nanorods, nanospheres) by a facile and novel modified polyol method without surfactants, varying only the molar concentration of precursor salt (Zinc acetate dihydrate) using ethylene glycol and deionized water. At a constant temperature of 160°C, nano-bullets were obtained at a concentration of 0.6M, whereas at 0.8M nanorods were observed while at 1.0M only nanospheres appear. X-ray Diffraction, Scanning Electron Microscopy, High-Resolution Transmission Electron Microscopy and Room-Temperature Photoluminescence properties were used to characterize the nanostructures. Based on the results it is suggested a high dependence between morphology and molar concentration of the precursor salt as well as a mechanism of crystallization of the different nanostructures. The nanostructures may be used to produce optoelectronic devices.
Graphical abstract
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Effect of biochar on cadmium bioavailability and uptake in wheat (Triticum aestivum L.) grown in a soil with aged contamination
Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Tahir Abbas, Muhammad Rizwan, Shafaqat Ali, Muhammad Zia-ur-Rehman, Muhammad Farooq Qayyum, Farhat Abbas, Fakhir Hannan, Jörg Rinklebe, Yong Sik Ok
Cadmium (Cd) is a well-known and widespread toxic heavy metal while the effects of biochar (BC) on Cd bioavailability and toxicity in wheat, especially in soils with aged contamination are largely unknown. In the present study, the effect of rice straw BC on Cd immobilization in soil and uptake by wheat in an agricultural contaminated-soil was investigated. Different levels of rice straw BC (0%, 1.5%, 3.0% and 5% w/w) were incorporated into the soil and incubated for two weeks. After this, wheat plants were grown in the amended soil until maturity. The results show that the BC treatments increased the soil and soil solution pH and silicon contents in the plant tissues and in the soil solution while decreased the bioavailable Cd in soil. The BC application increased the plant-height, spike-length, shoot and root dry mass and grain yield in a dose additive manner when compared with control treatment. As compared to control, BC application increased the photosynthetic pigments and gas exchange parameters in leaves. Biochar treatments decreased the oxidative stress while increased the activities of antioxidant enzymes in shoots compared to the control. The BC treatments decreased the Cd and Ni while increased Zn and Mn concentrations in shoots, roots, and grains of wheat compared to the control. As compared to the control, Cd concentration in wheat grains decreased by 26%, 42%, and 57% after the application of 1.5%, 3.0%, and 5.0% BC respectively. Overall, the application of rice straw BC might be effective in immobilization of metal in the soil and reducing its uptake and translocation to grains.
Graphical abstract
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U-Pb geochronology and petrogenesis of intrusive rocks: Constraints on the mode of genesis and timing of Cu mineralization in SWSK area, Lut Block
Publication date: June 2017
Source:Journal of Geochemical Exploration, Volume 177
Author(s): A. Hosseinkhani, M.H. Karimpour, A. Malekzadeh Shafaroudi, J.F. Santos
The South-West Sorkh-Kuh (SWSK) area, part of the Tertiary volcanic-plutonic rocks in the Lut Block, eastern Iran, comprises volcanic rocks intruded by intrusive rocks of hornblende diorite and biotite quartz monzonite compositions. Biotite quartz monzonite has been intensively affected by quartz-sericite-pyrite, argillic and silicification alterations and hornblende diorite shows weak propylitic and carbonate alterations. Disseminated, stockwork and vein-type styles of mineralization are associated with intrusive rocks. The vein-type mineralization with NW-SE trend is hosted by hornblende diorite. The ore in vein-type mineralization consist of quartz, chalcopyrite, pyrite, and secondary Cu-Fe minerals. Disseminated and stockwork mineralizations consist of quartz, pyrite, chalcopyrite, and secondary minerals replacing biotite quartz monzonite and hornblende diorite intrusive rocks. The highest grades in terms of Cu (3%), As (1.3%), Mo (150ppm), Pb (362ppm), Zn (743ppm), and Au (278ppb) are associated with vein-type mineralization. Intrusive rocks causing mineralization, are of metaluminous to peraluminous types with calc-alkaline to high-K calc-alkaline affinity formed in a volcanic arc setting. The enrichment of LILE (Ba, K, Cs, Sr), depletion of HFSE (Nb, P, Ti) and enrichment of LREE relative to HREE indicate the formation of source magmas above a subduction zone. The results of zircon U–Pb dating give constraints on the timing of emplacement of biotite quartz monzonite and hornblende diorite bodies at 40.16±0.72 and 20.1±2.1Ma, respectively. The younger date extends the time span of mineralizations in the Lut Block from Middle Eocene to Early Oligocene (42–33Ma.) reported by previous researchers to more recent Early Miocene times. The initial 87Sr/86Sr ratios and εNd values of both biotite quartz monzonite and hornblende diorite reside in the restricted ranges of 0.7055–0.7066 and −0.33 to +1.88, respectively, consistent with an origin above a subduction zone followed by crustal contaminations of the initial magma compositions, especially with regard to biotite quartz monzonite. The zircon U-Pb ages as well as geochemical and radiogenic isotope data for the intrusive bodies associated with mineralization in this study are in accordance with previous studies on intrusive bodies related to porphyry copper deposits in the Lut Block. In contrast to previous studies, this study further extends the span of mineralization events to at least Early Miocene times.
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Grain structure modification of Cu-Sn IMCs by applying Cu-Zn UBM on transient liquid-phase bonding in novel 3D-IC technologies
Publication date: June 2017
Source:Intermetallics, Volume 85
Author(s): Wei-Yu Chen, Rui-Wen Song, Jenq-Gong Duh
This study focuses on the formation mechanism of impinged-grain of Cu6Sn5 and interfolded-grain of Cu6(Sn,Zn)5 in Cu/Sn-3.5Ag/Cu and Cu/Sn-3.5Ag/Cu-15Zn (wt %) transient liquid-phase (TLP) bonding after reflow, respectively. Due to the application of TLP process in 3D-IC technology, the Cu-Sn intermetallic compounds (IMCs) rapidly form from the Cu pads and occupy the entire joint. These Cu-Sn IMCs with large volume fraction weaken the bond reliability resulting from its homogeneous grain structure and brittleness. It is demonstrated that doping Zn into one of the Cu substrates effectively modify the homogeneous grain structure into interfolded structure. The interfolded grain structure of Cu6(Sn,Zn)5 acts as a barrier for crack propagation and therefore enhances the bond reliability. The mechanisms involved are explained in details using thermodynamic related theories, First-principle simulation, FE-SEM observation and electron backscatter diffraction (EBSD) analyses. Owing to the effective modification of grain structure, Cu/Sn-3.5Ag/Cu-15Zn TLP bonding is potentially useful in strengthening the interconnections for novel 3D-IC technologies.
Graphical abstract
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Effects of chronic waterborne cadmium and zinc interactions on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas)
Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Melissa K. Driessnack, Ankur Jamwal, Som Niyogi
The present study was designed to evaluate the interactive effects of chronic waterborne cadmium (Cd) and zinc (Zn) on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas). Trios (1 male: 2 female; n=6–7) of fish were exposed for 21 days to: (i) control (no added Cd or Zn), (ii) waterborne Cd (7µg/L), (iii) waterborne Zn (170µg/L), and (iv) Cd and Zn in mixture (7 and 170µg/L, respectively). Exposure to Cd or Zn alone did not elicit any significant effect on reproductive output (cumulative egg production) relative to the control, however exposure to Cd and Zn in mixture resulted in a ~50% decrease in fish fecundity. Plasma estradiol in females was reduced by Cd and Zn exposures, both individually and in mixture, with the maximum reduction in the metal mixture exposure. The expression of hepatic estrogen receptor genes (ER-α and ER-β) in females was affected by exposure to Zn, alone and in mixture with Cd, but not to Cd alone, whereas hepatic vitellogenin gene expression was downregulated across all treatments. Increased follicular atresia in the ovary was also recorded, but only in fish exposed to Cd and Zn in mixture. The interactions of Cd and Zn in mixture decreased Cd accumulation in tissues (gill and liver), however no reciprocal reduction in tissue Zn accumulation was observed. In addition, the expression of the hepatic metallothionein gene was upregulated following exposure to Zn, alone and in combination with Cd, with no additive effects in the latter treatment. Overall, our findings suggest that chronic exposure to waterborne Cd and Zn in mixture may induce additive reproductive toxicity, essentially by disrupting estrogen-mediated functions in fish.
http://ift.tt/2m0Ihva
Effects of bamboo charcoal on antibiotic resistance genes during chicken manure composting
Publication date: June 2017
Source:Ecotoxicology and Environmental Safety, Volume 140
Author(s): Haichao Li, Manli Duan, Jie Gu, Yajun Zhang, Xun Qian, Jun Ma, Ranran Zhang, Xiaojuan Wang
Composting is widely used for animal waste disposal, and bamboo charcoal (BC) can be used for nitrogen conservation during composting. However, the effects of BC on antibiotic resistance genes (ARGs) during chicken manure composting are still unclear. This study investigated the effects on ARGs of adding different proportions of BC (0%, 5%, 10%, and 20% w/w) to chicken manure compost. After 26 days, the relative abundances (RAs) of most ARGs (tetC, tetG, tetW, tetX, sul2, drfA1, drfA7, ermB, ermF, ermQ, and ermX) and intI1 declined by 21.6–99.5%, whereas sul1 increased by 7.5–17.7 times. The average RAs reductions with 0%, 5%, 10%, and 20% BC were 0.85, 1.05, 1.08, and 1.15 logs, respectively. The most important environmental factor for the ARG profiles was temperature according to redundancy analysis. Furthermore, BC significantly decreased the bio-Cu and bio-Zn levels, thereby reducing the co-selection pressure from heavy metals. Different proportions of BC had no significant effects on the removal of tetG, tetW, tetX, sul2, drfA1, and ermB. Supplementation with 10% BC was more effective at removing tetC and drfA7 compared with the other treatments. The results suggested that 10% BC supplementation is appropriate for reducing ARGs in chicken manure compost.
Graphical abstract
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Zinc complexed chitosan/TPP nanoparticles: A promising micronutrient nanocarrier suited for foliar application
Publication date: 1 June 2017
Source:Carbohydrate Polymers, Volume 165
Author(s): Paresh Deshpande, Ashwin Dapkekar, Manoj D. Oak, Kishore M. Paknikar, Jyutika M. Rajwade
Cultivation of cereals in zinc deficient soils leads to declined nutritional quality of grain. Zinc deficiency in humans is a consequence of consumption of micronutrient deficient cereals as staple food. To achieve an increase in zinc density in grain, we evaluated zinc complexed chitosan nanoparticles (Zn-CNP) as a potential 'nanocarrier' suited for foliar fertilization. Zn-CNP were synthesized using tri-polyphosphate as a cross-linker. Spherical Zn-CNP (diameter 250–300nm) were positively charged (zeta potential, +42.34mV) and contained ∼20mg Zn/g (w/w). Plant growth in zinc deficient sand media, followed by foliar application of Zn-CNP (twice-a-week, for 5 weeks) after anthesis resulted in 27 and 42% increase in grain zinc content of MACS 3125 and UC1114 (durum wheat cultivars) respectively. Translocation of zinc ions from foliar applied Zn-CNP into the leaf and seed tissue was demonstrated using zinquin and dithizone stains, respectively. The study indicates the suitability of chitosan-based nanocarriers in agronomic biofortification.
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Editorial Board
Publication date: March 2017
Source:Pathology - Research and Practice, Volume 213, Issue 3
http://ift.tt/2l700l5
Usefulness of the Continuous-Wave Doppler-Derived Pulmonary Arterial–Right Ventricular Pressure Gradient Just before Atrial Contraction for the Estimation of Pulmonary Arterial Diastolic and Wedge Pressures
Source:Ultrasound in Medicine & Biology
Author(s): Michito Murayama, Taisei Mikami, Sanae Kaga, Kazunori Okada, Takuma Hioka, Nobuo Masauzi, Masahiro Nakabachi, Hisao Nishino, Shinobu Yokoyama, Mutsumi Nishida, Hiroyuki Iwano, Mamoru Sakakibara, Satoshi Yamada, Hiroyuki Tsutsui
In our new echocardiographic method, pulmonary regurgitant velocity immediately before right atrial (RA) contraction is used to estimate pulmonary artery diastolic pressure (PADP) and mean PA wedge pressure (MPAWP). Our aim here was to compare the usefulness of this new method with that of the conventional method, which uses pulmonary regurgitant velocity at end diastole. We studied 55 consecutive patients who underwent echocardiography and right-sided heart catheterization. The pulmonary regurgitant velocities just before RA contraction and at end diastole were measured to obtain echocardiographic estimates of PADP (EPADPpreA and EPADPED, respectively) by adding the pressure gradients to the echocardiographically estimated RA pressure. Compared with EPADPED, EPADPpreA correlated better with PADP (r = 0.87) and MPAWP (r = 0.80), and direct fixed biases were detected for EPADPED but not for EPADPpreA. The area under the receiver operating characteristic curve distinguishing patients with MPAWP ≥18 mm Hg was greater for EPADPpreA (0.97) than for E/e′ (0.94) and E/A (0.83). EPADPpreA is thus useful in estimating PADP and MPAWP in patients with heart disease.
http://ift.tt/2liJKbY
What Help Could Ultrasound Elastography Give to the Diagnosis of Breast Papillary Lesions?
Source:Ultrasound in Medicine & Biology
Author(s): Lu-Jing Li, Ji-Yi Yao, Xin-Chuan Zhou, Xin-Bao Zhao, Wen-Jing Zhong, Bing Ou, Bao-Ming Luo, Shao-Yun Hao, Hui Zhi
On the basis of results of our previous studies and the findings of other scholars, the most common histologic type of false-positive diagnosis with strain elastography (SE) was papilloma. The objectives of our study were to evaluate whether SE could contribute to conventional ultrasound differentiation between benign and malignant papillary lesions and between papillary lesions and other common benign breast lesions. Data on 89 papillary lesions at our hospital, including 74 benign and 15 malignant papillary lesions, were included in our study. In addition, 198 non-papillary benign tumors were selected as the control group, including 126 fibroadenomas and 72 cases of fibrocystic mastopathy. All patients gave written informed consent. All patients with breast lesions underwent conventional ultrasound and SE examination. Breast Imaging Recording and Data System (BI-RADS) category and SE score were compared with respect to sensitivity, specificity and accuracy in differentiating between benign and malignant papillary lesions. We then explored the possibility of using BI-RADS combined with SE to differentiate papillary lesions from non-papillary benign tumors. For differentiating between benign and malignant papillary lesions, the area under the receiver operating characteristic curve (AUC) of BI-RADS was 0.568, whereas the AUC values of SE score, strain ratio and BI-RADS combined with SE were 0.517, 0.584 and 0.509, respectively (p > 0.05). For differentiating between papillary lesions and non-papillary benign lesions, the AUC of BI-RADS combined with SE was 0.835, which was higher than the values for BI-RADS (0.775) and SE (SE score: 0.648, strain ratio: 0.661) (p < 0.001). The specificity and accuracy of BI-RADS combined with SE were significantly higher than those for BI-RADS alone without a decrease in sensitivity (p < 0.05). SE could not improve the diagnostic efficiency of BI-RADS in differentiating between benign and malignant papillary lesions. However, BI-RADS combined with SE could improve the specificity of BI-RADS without decrease in sensitivity for differentiating breast papillary lesions from non-papillary benign lesions.
http://ift.tt/2mohoC8
Inhibition of CDK4 sensitizes multidrug resistant ovarian cancer cells to paclitaxel by increasing apoptosiss
Abstract
Purpose
Overexpression of cyclin-dependent kinase (CDK) 4 has been observed in a variety of cancers and has been found to contribute to tumor cell growth and proliferation. However, the effect of inhibition of CDK4 in ovarian cancer is unknown. We investigated the therapeutic effect of the CDK4 inhibitor palbociclib in combination with paclitaxel in ovarian cancer cells.
Methods
Cell viabilities were determined by MTT assay after exposure to different dosages of palbociclib and/or paclitaxel. Western blot, immunofluorescence, and Calcein AM assays were conducted to determine the mechanisms underlying the cytotoxic effects of palbociclib in combination with paclitaxel. CDK4 siRNA was used to validate the outcome of targeting CDK4 by palbociclib in ovarian cancer cells.
Results
We found that combinations of palbociclib and paclitaxel significantly enhanced drug sensitivity in both Rb-positive (SKOV3TR) and Rb-negative (OVCAR8TR) ovarian cancer-derived cells. When combined with paclitaxel, palbociclib induced apoptosis in both SKOV3TR and OVCAR8TR cells. We also found that palbociclib inhibited the activity of P-glycoprotein (Pgp), and that siRNA-mediated CDK4 knockdown sensitized multidrug resistant (MDR) SKOV3TR and OVCAR8TR cells to paclitaxel.
Conclusions
Inhibition of CDK4 by palbociclib can enhance paclitaxel sensitivity in both Rb-positive and Rb-negative MDR ovarian cancer cells by increasing apoptosis. CDK4 may serve as a promising target in the treatment of ovarian cancer.
http://ift.tt/2mxzqi9
Targeting NK-cell checkpoints for cancer immunotherapy
Aura Muntasell | Maria C Ochoa | Luna Cordeiro | Pedro Berraondo | Ascension López-Díaz de Cerio | Mariona Cabo | Miguel López-Botet | Ignacio Melero
http://ift.tt/2mEyqYP
Editorial Board
Source:Free Radical Biology and Medicine, Volume 104
http://ift.tt/2mof12p
Cryptosporidium-contaminated water disinfection by a novel Fenton process
Publication date: May 2017
Source:Free Radical Biology and Medicine, Volume 106
Author(s): Sina Matavos-Aramyan, Mohsen Moussavi, Hedieh Matavos-Aramyan, Sara Roozkhosh
Three novel modified advanced oxidation process systems including ascorbic acid-, pro-oxidants- and ascorbic acid-pro-oxidants-modified Fenton system were utilized to study the disinfection efficiency on Cryptosporidium-contaminated drinking water samples. Different concentrations of divalent and trivalent iron ions, hydrogen peroxide, ascorbic acid and pro-oxidants at different exposure times were investigated. These novel systems were also compared to the classic Fenton system and to the control system which comprised of only hydrogen peroxide. The complete in vitro mechanism of the mentioned modified Fenton systems are also provided. The results pointed out that by considering the optimal parameter limitations, the ascorbic acid-modified Fenton system decreased the Cryptosporidium oocytes viability to 3.91%, while the pro-oxidant-modified and ascorbic acid-pro-oxidant-modified Fenton system achieved an oocytes viability equal to 1.66% and 0%, respectively. The efficiency of the classic Fenton at optimal condition was observed to be 20.12% of oocytes viability. The control system achieved 86.14% of oocytes viability. The optimum values of the operational parameters during this study are found to be 80mgL−1 for the divalent iron, 30mgL−1 for ascorbic acid, 30mmol for hydrogen peroxide, 25mgL−1 for pro-oxidants and an exposure time equal to 5min. The ascorbic acid-pro-oxidants-modified Fenton system achieved a promising complete water disinfection (0% viability) at the optimal conditions, leaving this method a feasible process for water disinfection or decontamination, even at industrial scales.
Graphical abstract
http://ift.tt/2mo26xk
Effect of shear stress on structure and function of polyplex micelles from poly(ethylene glycol)-poly(l-lysine) block copolymers as systemic gene delivery carrier
Source:Biomaterials, Volume 126
Author(s): Kaori M. Takeda, Yuichi Yamasaki, Anjaneyulu Dirisala, Sorato Ikeda, Theofilus A. Tockary, Kazuko Toh, Kensuke Osada, Kazunori Kataoka
Structural stability of polyplex micelles (PMs), prepared from plasmid DNA (pDNA) and poly(ethylene glycol)-b-poly(l-lysine) block catiomer (PEG−PLys), was evaluated in terms of their resistance against shear stress. When exposed to shear stress at magnitudes typically present in the blood stream, structural deterioration was observed in PMs owing to the partial removal of PEG−PLys strands. Eventually, impaired PEG coverage of the polyplex core led to accelerated degradation by nucleases, implying that structural deterioration by shear stress in blood stream may be a major cause of rapid clearance of PMs from blood circulation. To address this issue, introduction of disulfide crosslinking into the PM core was shown to be an efficient strategy, which successfully mitigated unfavorable effects of shear stress. Furthermore, improved in vivo blood retention profile and subsequently enhanced antitumor efficacy in systemic treatment of pancreatic adenocarcinoma were confirmed for the crosslinked PMs loaded with pDNA encoding an anti-angiogenic protein, suggesting that high stability under the shear stress during blood circulation may be a critical factor in systemically applicable gene delivery systems.
http://ift.tt/2mo248G
Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis
Abstract
Psoriasis is a common disease, which has a considerable impact on the healthcare system. Therefore, appropriate use of therapeutic resources is very important. Management of psoriasis in daily clinical practice is highly variable because many issues are still debated and not definitely addressed by the evidence-based medicine. Moreover, the different availability and reimbursability of drugs in each country justifies national guidelines. Expert consensus can provide helpful guidelines for optimizing patient care. A total of 20 dermatologists from different areas of Italy and with large experience in the treatment of psoriasis agreed to participate in the guidelines expert panel who aimed to reach consensus on the factors influencing psoriasis severity, the indications for systemic treatments, the parameters to be considered in the choice of treatment, and the factors to be considered in the choice of biological treatment. The recommendations for the use, screening and monitoring of systemic therapies were based on the 2015 S3 European Dermatology Forum/European Academy of Dermatology and Venereology psoriasis guidelines. Recommendations on the treatment of psoriasis in special patient populations were also agreed. The final document was discussed in a meeting moderated by a facilitator with participation of the entire group and adopting a nominal group technique to reach consensus. A statement was regarded as consented when agreement was achieved by at least 75% of the voting experts according to the Delphi procedure.
http://ift.tt/2myyry6
The treatment of vulval lichen sclerosus in prepubertal girls: a critically appraised topic
Summary
Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life.
http://ift.tt/2m5x5h0
APOE e4 status and poor glycaemic control predict white matter hyperintensity growth from 73-76 years
Publication date: Available online 27 February 2017
Source:Neurobiology of Aging
Author(s): Simon R. Cox, Stuart J. Ritchie, David Alexander Dickie, Alison Pattie, Natalie A. Royle, Janie Corley, Benjamin S. Aribisala, Sarah E. Harris, Maria Valdés Hernández, Alan J. Gow, Susana Muñoz Maniega, John M. Starr, Mark E. Bastin, Joanna M. Wardlaw, Ian J. Deary
We examined whether APOE status interacts with vascular risk factors (VRFs) to predict progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking and hypercholesterolemia, and via objective measures of blood HbA1c, Body Mass Index, diastolic and systolic blood pressure, and blood HDL ratio. APOE e4 allele was coded as either present or absent. WMH progression was measured on MRI over 3 years in 434 older adults, in a same-year-of-birth cohort. APOE e4 carriers with either a self-reported diagnosis of diabetes (β = 0.160, p = 0.002) or higher glycated haemoglobin levels (β = 0.114, p = 0.014) exhibited greater WMH progression, and the former survived correction for multiple testing. All other APOE-VRF interactions were non-significant (βinteraction < 0.056, p > 0.228). The results suggest that carrying the APOE 'risk' e4 allele increases the risk of greater age-related WMH progression over the early part of the eighth decade of life, when combined with poorer glycaemic control. The interaction effect was robust to co-occurring VRFs, suggesting a possible target for mitigating brain and cognitive ageing at this age.
http://ift.tt/2m0s60I
Enhancing Mitofusin/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies
Publication date: Available online 27 February 2017
Source:Neurobiology of Aging
Author(s): Bilal Khalil, Marie-Jeanne Cabirol-Pol, Laetitia Miguel, Alexander J. Whitworth, Magalie Lecourtois, Jean-Charles Liévens
TAR DNA-binding protein 43 kDa (TDP-43) is considered a major pathological protein in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The precise mechanisms by which TDP-43 dysregulation leads to toxicity in neurons are not fully understood. Using TDP-43-expressing Drosophila, we examined whether mitochondrial dysfunction is a central determinant in TDP-43 pathogenesis. Expression of human wild-type TDP-43 in Drosophila neurons results in abnormally small mitochondria. The mitochondrial fragmentation is correlated with a specific decrease in the mRNA and protein levels of the Drosophila pro-fusion gene mitofusin/marf. Importantly, overexpression of Marf ameliorates defects in spontaneous walking activity and startle-induced climbing response of TDP-43-expressing flies. Partial inactivation of the mitochondrial pro-fission factor, DRP1, also mitigates TDP-43-induced locomotor deficits. Expression of TDP-43 impairs neuromuscular junction transmission upon repetitive stimulation of the giant fiber circuit that controls flight muscles, which is also ameliorated by Marf overexpression. We show here for the first time that enhancing the pro-fusion gene mitofusin/marf is beneficial in an in vivo model of TDP-43 proteinopathies, serving as a potential therapeutic target.
http://ift.tt/2myvj5l
Plain language summaries in Simplified Chinese
Linked Article: Thandar et al. Br J Dermatol 2017; 176:330–343.
Linked Article: Køster et al. Br J Dermatol 2017; 176:446–456.
Linked Article: Mohanty et al. Br J Dermatol 2017; 176:403–412.
Linked Article: Steinke et al. Br J Dermatol 2017; 176:363–370.
Linked Article: Kohl et al. Br J Dermatol 2017; 176:352–362.
http://ift.tt/2m5GB3J
The treatment of vulval lichen sclerosus in prepubertal girls: a critically appraised topic
Summary
Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life.
http://ift.tt/2m5x5h0
Plain language summaries in Simplified Chinese
Linked Article: Thandar et al. Br J Dermatol 2017; 176:330–343.
Linked Article: Køster et al. Br J Dermatol 2017; 176:446–456.
Linked Article: Mohanty et al. Br J Dermatol 2017; 176:403–412.
Linked Article: Steinke et al. Br J Dermatol 2017; 176:363–370.
Linked Article: Kohl et al. Br J Dermatol 2017; 176:352–362.
http://ift.tt/2m5GB3J
Imaging of the endolymphatic space in patients with Ménière’s disease
Source:Auris Nasus Larynx
Author(s): Tadao Yoshida, Satofumi Sugimoto, Masaaki Teranishi, Hironao Otake, Masahiro Yamazaki, Shinji Naganawa, Tsutomu Nakashima, Michihiko Sone
ObjectiveTo examine endolymphatic hydrops (EH) using magnetic resonance imaging (MRI) in patients with definite Ménière's disease (MD) and those with nonotological diseases.MethodsWe studied 32 patients with unilateral MD, 10 patients with bilateral MD and 21 patients with control ears who had other benign diseases not associated with hearing or vestibular dysfunction. The mean age of the subjects was 54.0 years (range 27–74) in the MD group and 56.1 years (range 24–79) in the control group. Using MRI, the degree of EH was classified as none, mild and significant in the cochlea and vestibule separately. The ratio of the area of endolymphatic space to the vestibular fluid space was calculated for the vestibule. The duration of MD was defined as the months between the first attack of MD and the MRI study.ResultsEH was present in the cochlea of 45/52 affected ears of patients with MD (87%) and in 16/42 control ears (38%). Significant cochlear hydrops was present in 37/52 affected ears (71%) and in 4/42 control ears (10%). EH in the vestibule was present in 49/52 affected ears (94%) and in 3/42 control ears (7%). Significant vestibular hydrops was present in 40/52 affected ears (77%) and in none of the 42 control ears. There was no relationship between the degree of EH and its duration. Using a cut off value for the relative size of EH in the vestibule of 41.9%, the test had a sensitivity of 88.5% and a specificity of 100% to diagnose definite MD.ConclusionCochlear EH was occasionally observed in control ears on MRI, as in normal temporal bone specimens. The presence or absence and degree of vestibular EH were significantly different between ears with MD and control ears. EH in the vestibule might be a specific predictor of definite MD.
http://ift.tt/2l6RZwF
Not All Probabilities Are Equivalent: Evidence From Orientation Versus Spatial Probability Learning.
Author: Jabar, Syaheed B.; Anderson, Britt
DOI: 10.1037/xhp0000354
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017
http://ift.tt/2m5my5I
Weighted Integration Suggests That Visual and Tactile Signals Provide Independent Estimates About Duration.
Author: Ball, Danny M.; Arnold, Derek H.; Yarrow, Kielan
DOI: 10.1037/xhp0000368
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017
http://ift.tt/2mEXEGD
The Onset and Time Course of Semantic Priming During Rapid Recognition of Visual Words.
Author: Hoedemaker, Renske S.; Gordon, Peter C.
DOI: 10.1037/xhp0000377
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017
http://ift.tt/2m5crgY
Anticipation in Manual Tracking With Multiple Delays.
Author: Stepp, Nigel; Turvey, Michael T.
DOI: 10.1037/xhp0000393
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017
http://ift.tt/2mEZaIB
Contextual Cueing Improves Attentional Guidance, Even When Guidance Is Supposedly Optimal.
Author: Harris, Anthony M.; Remington, Roger W.
DOI: 10.1037/xhp0000394
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017
http://ift.tt/2m5AXP1
Detecting Target Changes in Multiple Object Tracking With Peripheral Vision: More Pronounced Eccentricity Effects for Changes in Form Than in Motion.
Author: Vater, Christian; Kredel, Ralf; Hossner, Ernst-Joachim
DOI: 10.1037/xhp0000376
Publication Date: POST AUTHOR CORRECTIONS, 23 February 2017
http://ift.tt/2mERBlq
Hand hygiene compliance: Social cohesion and role modeling
Source:American Journal of Infection Control
Author(s): Deepak Asudani
http://ift.tt/2ltisk3
Classification of aliphatic-butylene terephthalate copolyesters in relation to aliphatic/aromatic ratio
Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Malgorzata Wojtczak, Slawomir Dutkiewicz, Andrzej Galeski, Agnieszka Gutowska
Aliphatic-aromatic copolyesters containing: butylene terephthalate ester and a mixture of butylene esters: adipate, succinate and glutarate, (PBASGT), were synthesized and classified according to their chemical composition and physical performance. Several such mixtures of aliphatic dimethyl esters are available on the market. Structures and properties of PBASGTs were characterized by various techniques including 1H NMR spectrometry, calorimetry, x-ray scattering and diffraction, dynamic mechanical analysis and tensile testing. All copolyesters were nearly random copolymers. Surprisingly, only the aromatic component is able to crystallize in the form characteristic for poly (butylene terephtalate). The increase of aromatic units content did not change the crystallographic form, however, a stronger crystallinity develops. The dramatic changes of thermal and mechanical properties of PBASGT were observed with the increase of aliphatic units content, e.g. from brittle to tough behavior. Copolyesters with aromatic content of 30% and below exhibit single relaxation peak of aliphatic rich amorphous components. At the concentration of 40% and above the aromatic component is segregated while the amorphous aliphatic units form joint pools. A partial segmental miscibility of aromatic and aliphatic components is suggested. It was shown that PBASGT with 40% of aromatic units is biodegradable.
Graphical abstract
http://ift.tt/2myxiqv
Block copolymer compatibilized polymer: fullerene blend morphology and properties
Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Y. Sun, P. Pitliya, C. Liu, X. Gong, D. Raghavan, A. Karim
Recent studies have shown the role of block copolymer as compatibilizer in tuning the phase separated morphology of the active layer so as to improve the overall photovoltaic efficiency of organic photovoltaic (OPV) devices. Here, we substantiate this observation by investigating the role of a rod-coil block copolymer poly-(3-hexylthiophene)-b-polystyrene (P3HT-b-PS) as compatibilizer in influencing the blend morphology and device performance of several polymer:fullerene blend systems. Fullerene derivatives N-(3-methoxypropyl)-2-(carboxyethyl)-5-(4-cyanophenyl) fulleropyrrolidine (NCPF) and N-(3-methoxypropyl)-2-(carboxyethyl)-5-(5, 5-difluorobenzo-dioxole) fulleropyrrolidine (FFNCPF) were synthesized using Prato reaction, while P3HT-b-PS copolymer was synthesized using the combination of Grignard metathesis, ATRP, and click chemistry. The addition of P3HT-b-PS in P3HT:PCBM blend led to the formation of more homogenous structure compared to the pure P3HT:PCBM blend. Also, a reduction in domain size was observed in P3HT: FFNCPF system upon P3HT-b-PS addition which can be attributed to the compatibilization effect of BCP. Incorporation of P3HT-b-PS block copolymer was found to effectively alter the thin film nanostructure of polymer/fullerene derivative blends and polymer crystalline structure. Maximum enhancement in power conversion efficiency (PCE) of compatabilized P3HT:PCBM blend system was noticed followed by P3HT:FFNCPF and P3HT:NCPF. The moderate improvement in photovoltaic properties can be correlated with face-on orientation of P3HT crystallites and the segregation of the fullerene domains at the bulk heterojunction (BHJ) cathode interface which facilitates the efficient charge collection as respective electrodes.
Graphical abstract
http://ift.tt/2myu7PM
Nano-voids in epoxy resins: Role in the transport of light gases
Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): David Roilo, Pushkar N. Patil, Roberto S. Brusa, Antonio Miotello, Riccardo Checchetto
Epoxy membranes with same chemical structure but different free volumes were prepared using aliphatic epoxide and polyether diamines as cross-linking agents. Their fractional free volume fh(T) was previously evaluated as a function of temperature and cross-linking density [P. N. Patil et al., PhysChemChemPhys18 (2016) 3817–3824]. Original H2 permeation measurements were performed changing sample temperature and network structure and compared with CO2 and N2 transport data. Modelling gas permeability Φ in the framework of the free volume theory we observe that the Arrhenius-type behavior of Φ for test gases is consequence of the fh(T) linear increase with temperature and that at equal fh value membranes exhibit increasing Φ values by decreasing the cross-linking density. Analysis of permeability data on this set of test molecules with different size and condensation properties suggests that increasing the cross-linking between polymer chains limits their thermal fluctuations and the redistribution of the free volume elements where diffusional jumps of penetrant molecules occur.
Graphical abstract
http://ift.tt/2myCg6E
Correlation between viscoelastic behavior and morphology of nanocomposites based on SR/EPDM blends compatibilized by maleic anhydride
Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Leila Bazli, Alireza Khavandi, Mohammad Ali Boutorabi, Mohammad Karrabi
Silicone rubber (SR)/ethylene-propylene-diene monomer (EPDM)/nanoclay (Cloisite15 A) nanocomposites with various compositions were prepared via melt compounding using a two-roll mill. The maleic anhydride grafted ethylene-propylene-diene monomer (MAH-g-EPDM) was used as a compatibilizer in this immiscible system. The effect of adding the nanoclay and MAH-g-EPDM on the oscillatory shear rheological properties, dynamic mechanical performance, relaxation behavior and morphology of the nanocomposites were studied. Cole-Cole, Van Gurp-Palmen and Han plots revealed a good dispersion of the filler in EPDM and an agglomeration of it in SR, which were also presented in XRD analysis. Furthermore, it was observed that MAH can have a compatibilizing effect on the nanocomposites only in the presence of the nanoclay, which was in agreement with the DMTA results. Based on SEM observations, spherical and elongated droplet structures were observed for the rubber blends and nanocomposites, respectively. In addition, droplets in MAH and the nanoclay-containing samples were more regular than the MAH-free ones, which asserts the synergistic effect of these two components. Moreover, interfacial tensions between the matrix and dispersed phase calculated from the Palierne model provided a good insight for the obtained results.
Graphical abstract
http://ift.tt/2myun13
Novel electrochromic copolymers based on 3-3′-dibromo-2-2′-bithiophene and 3,4 ethylene dioxythiophene
Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Buket Bezgin Carbas
A novel electrochromic material of poly(3-3′-dibromo-2-2′-bithiophene) (P(DBT)) and new electrochromic copolymers of 3,4-ethylenedioxythiophene and 3-3′-dibromo-2-2′-bithiophene prepared from different monomer feed ratios were synthesized by using electroanalytical methods. Homopolymerization and copolymerization were achieved in the medium of 0.1 M LiClO4/ACN solvent-electrolyte couple. Cyclic voltammetry (CV), atomic force microscopy (AFM), fourier transform infrared spectroscopy and ultraviolet and visible (UV-Vis) absorption spectroscopy were used to characterize corresponding homopolymer and copolymers. Electrochemical, morphological and optical properties of copolymers were alternated depending on changing the monomer feed ratio in the copolymer structure. Furthermore, electrochromic properties of the all polymers were also investigated.
Graphical abstract
http://ift.tt/2myhCDA
Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies
Abstract
Purpose
Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters.
Methods
Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated.
Results
Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was <10 ms at all time points. There was no relevant relationship between change in QTcF and alectinib plasma concentrations. Alectinib treatment resulted in a generally asymptomatic exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1–2.
Conclusions
Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.
http://ift.tt/2lNnaMj
Overexpression of ANLN contributed to poor prognosis of anthracycline-based chemotherapy in breast cancer patients
Abstract
Purpose
To investigate the associations of ANLN expression with prognosis of breast cancer and clinical outcome of anthracycline-based chemotherapy.
Methods
This study enrolled 308 breast cancer patients in which 264 of them received anthracycline-based chemotherapy. Immunohistochemistry was used to detect ANLN expression level of the patients. Clinical characteristics of the patients were collected, and associations of ANLN expression with prognosis were analyzed.
Results
Our results showed that ANLN expression was associated with survival of breast cancer patients, and it was also related to clinical outcome of patients received anthracycline-based chemotherapy. Breast cancer patients with high expression of ANLN would have poor prognosis and poor clinical outcome to anthracycline-based chemotherapy.
Conclusion
ANLN could be an independent prognosis predictor for breast cancer, and its expression might be used to predict the anthracycline-based chemotherapy clinical outcome in breast cancer patients.
http://ift.tt/2moaIUu
An allometric pharmacokinetic/pharmacodynamics model for BI 893923, a novel IGF-1 receptor inhibitor
Abstract
Purpose
BI 893923 is a novel IGF1R/INSR inhibitor with promising anti-tumor efficacy. Dose-limiting hyperglycemia has been observed for other IGF1R/INSR inhibitors in clinical trials. To counterbalance anti-tumor efficacy with the risk of hyperglycemia and to determine the therapeutic window, we aimed to develop a translational pharmacokinetic/pharmacodynamics model for BI 893923. This aimed to translate pharmacokinetics and pharmacodynamics from animals to humans by an allometrically scaled semi-mechanistic model.
Methods
Model development was based on a previously published PK/PD model for BI 893923 in mice (Titze et al., Cancer Chemother Pharmacol 77:1303–1314, 13). PK and blood glucose parameters were scaled by allometric principles using body weight as a scaling factor along with an estimation of the parameter exponents. Biomarker and tumor growth parameters were extrapolated from mouse to human using the body weight ratio as scaling factor.
Results
The allometric PK/PD model successfully described BI 893923 pharmacokinetics and blood glucose across mouse, rat, dog, minipig, and monkey. BI 893923 human exposure as well as blood glucose and tumor growth were predicted and compared for different dosing scenarios. A comprehensive risk–benefit analysis was conducted by determining the net clinical benefit for each schedule. An oral dose of 2750 mg BI 893923 divided in three evenly distributed doses was identified as the optimal human dosing regimen, predicting a tumor growth inhibition of 90.4% without associated hyperglycemia.
Conclusion
Our model supported human therapeutic dose estimation by rationalizing the optimal efficacious dosing regimen with minimal undesired effects. This modeling approach may be useful for PK/PD scaling of other IGF1R/INSR inhibitors.
http://ift.tt/2lsfb4v
Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main and Multivessel Coronary Artery Disease: Do We Have the Evidence?.
Author: Gersh, Bernard J. MB, ChB, DPhil; Stone, Gregg W. MD; Bhatt, Deepak L. MD, MPH
Page: 819-821
http://ift.tt/2l6KXYD
Why NOBLE and EXCEL Are Consistent With Each Other and With Previous Trials.
Author: Ruel, Marc MD, MPH; Farkouh, Michael E. MD, MSc
Page: 822-824
http://ift.tt/2lQ7OVv
Role of Diastolic Stress Testing in the Evaluation for Heart Failure With Preserved Ejection Fraction: A Simultaneous Invasive-Echocardiographic Study.
Author: Obokata, Masaru MD, PhD; Kane, Garvan C. MD, PhD; Reddy, Yogesh N. V. MD; Olson, Thomas P. PhD; Melenovsky, Vojtech MD, PhD; Borlaug, Barry A. MD
Page: 825-838
http://ift.tt/2l6C7dn
High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.
Author: Ellingsen, Oyvind MD, PhD; Halle, Martin MD; Conraads, Viviane MD, PhD; Stoylen, Asbjorn MD, PhD; Dalen, Havard MD, PhD; Delagardelle, Charles MD; Larsen, Alf-Inge MD, PhD; Hole, Torstein MD, PhD; Mezzani, Alessandro MD, PhD; Van Craenenbroeck, Emeline M. MD, PhD; Videm, Vibeke MD, PhD; Beckers, Paul PhD; Christle, Jeffrey W. PhD; Winzer, Ephraim MD, PhD; Mangner, Norman MD; Woitek, Felix MD; Hollriegel, Robert MD; Pressler, Axel MD; Monk-Hansen, Tea MD, PhD; Snoer, Martin MD, PhD; Feiereisen, Patrick PhD; Valborgland, Torstein MD; Kjekshus, John MD, PhD; Hambrecht, Rainer MD; Gielen, Stephan MD; Karlsen, Trine PhD; Prescott, Eva MD, DMSc; Linke, Axel MD; For the SMARTEX Heart Failure Study (Study of Myocardial Recovery After Exercise Training in Heart Failure) Group
Page: 839-849
http://ift.tt/2lQgkUN
Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis.
Author: Mariscalco, Giovanni MD, PhD; Wozniak, Marcin J. PhD; Dawson, Alan G. MB ChB, BSc; Serraino, Giuseppe F. MD; Porter, Richard MB ChB; Nath, Mintu MSc; Klersy, Catherine MD, MSc; Kumar, Tracy BSc; Murphy, Gavin J. MD
Page: 850-863
http://ift.tt/2l6Rfrs
An Apparent Obesity Paradox in Cardiac Surgery.
Author: Carnethon, Mercedes R. PhD; Khan, Sadiya S. MD, MS
Page: 864-866
http://ift.tt/2lQbCpO
Brain Emboli After Left Ventricular Endocardial Ablation.
Author: Whitman, Isaac R. MD; Gladstone, Rachel A. BA; Badhwar, Nitish MD; Hsia, Henry H. MD; Lee, Byron K. MD; Josephson, S. Andrew MD; Meisel, Karl M. MD; Dillon, William P. Jr. MD; Hess, Christopher P. MD, PhD; Gerstenfeld, Edward P. MD; Marcus, Gregory M. MD, MAS
Page: 867-877
http://ift.tt/2l6OoPd
The Sound of Silence: How Much Noise Should We Make About Postablation Silent Strokes?.
Author: Zei, Paul C. MD, PhD; Vora, Nirali MD
Page: 878-880
http://ift.tt/2lQ5IF5
Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure.
Author: Abu-Taha, Issam H. PhD; Heijman, Jordi PhD; Hippe, Hans-Jorg MD; Wolf, Nadine M. PhD; El-Armouche, Ali MD; Nikolaev, Viacheslav O. PhD; Schafer, Marina MSc; Wurtz, Christina M. PhD; Neef, Stefan MD; Voigt, Niels MD; Baczko, Istvan MD, PhD; Varro, Andras MD, PhD, DSc; Muller, Marion MSc; Meder, Benjamin MD; Katus, Hugo A. MD; Spiger, Katharina PhD; Vettel, Christiane PhD; Lehmann, Lorenz H. MD; Backs, Johannes MD; Skolnik, Edward Y. MD; Lutz, Susanne PhD; Dobrev, Dobromir MD; Wieland, Thomas PhD
Page: 881-897
http://ift.tt/2l6KWE8
Meal Timing and Frequency: Implications for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association.
Author: St-Onge, Marie-Pierre PhD, FAHA, Chair; Ard, Jamy MD; Baskin, Monica L. PhD; Chiuve, Stephanie E. ScD; Johnson, Heather M. MD, FAHA; Kris-Etherton, Penny PhD, RD, FAHA; Varady, Krista PhD; On behalf of the American Heart Association Obesity Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; and Stroke Council
Page: e96-e121
http://ift.tt/2lQ7wxY
ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Author: Chan, Wiley V. MD, Co-Chair; Pearson, Thomas A. MD, MPH, PhD, FAHA, Co-Chair; Bennett, Glen C. MPH; Cushman, William C. MD, FAHA; Gaziano, Thomas A. MD, MSc; Gorman, Paul N. MD, PhD; Handler, Joel MD; Krumholz, Harlan M. MD, ScM, FACC, FAHA; Kushner, Robert F. MD; MacKenzie, Thomas D. MD, MSPH; Sacco, Ralph L. MD, FAHA; Smith, Sidney C. Jr MD, FACC, FAHA; Stevens, Victor J. PhD; Wells, Barbara L. PhD; Castillo, Graciela MPH; Heil, Susan K.R. PhD; Stephens, Jennifer MPH; Vann, Julie C. Jacobson PhD, MS, RN
Page: e122-e137
http://ift.tt/2l6SlUb
Wide Complex Tachycardia on Telemetry: What Is the Diagnosis?.
Author: Padala, Santosh K. MD; Kalahasty, Gautham MD; Ellenbogen, Kenneth A. MD
Page: 904-906
http://ift.tt/2l6KUvX
In Vivo Study of Electromagnetic Interference With Pacemakers Caused by Everyday Electric and Magnetic Fields.
Author: Stunder, Dominik MSc; Seckler, Tobias MSc; Joosten, Stephan PhD; Zink, Matthias Daniel MD; Driessen, Sarah PhD; Kraus, Thomas MD; Marx, Nikolaus MD; Napp, Andreas MD
Page: 907-909
http://ift.tt/2lQalPC
Letter by Nadir Regarding Article, "Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting)".
Author: Nadir, M. Adnan MD, MBBS, MRCP
Page: e138-e139
http://ift.tt/2l6KzcW
Letter by Vallurupalli and Uretsky Regarding Article, "Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting)".
Author: Vallurupalli, Srikanth MD; Uretsky, Barry F. MD
Page: e140-e141
http://ift.tt/2lQ08Tu
Response by Meneveau and Ecarnot to Letter Regarding Article, "Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients With Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting)".
Author: Meneveau, Nicolas MD, PhD; Ecarnot, Fiona MSc
Page: e142-e143
http://ift.tt/2l6EgWM
Letter by Crossley Regarding Article, "What I Wish Clinicians Knew About Industry [horizontal ellipsis] and Vice Versa".
Author: Crossley, George H. MD
Page: e144
http://ift.tt/2l6KUfr
Correction to: Apoptosis of Endothelial Cells Precedes Myocyte Cell Apoptosis in Ischemia/Reperfusion Injury.
Author:
Page: e145
http://ift.tt/2lQajHu
A Rare Case of Stroke Secondary to Iron Deficiency Anemia in a Young Female Patient
Ischemic strokes occur when there is a sudden obstruction of an artery supplying blood flow to an area of the brain, leading to a focal neurological deficit. Strokes can be thrombotic or embolic in etiology and are associated with underlying conditions such as hypertension and atherosclerosis. Possible etiologies of strokes include cardioembolic disease, hematologic disorders, connective tissue disorders, and substance abuse or can be cryptogenic. Most stroke cases are seen in patients over 65 years of age. However, about one-fourth of strokes occur in young adults. Iron deficiency anemia (IDA) has been described as a known cause for strokes in children, but very few case reports describe this association in adults. We describe a 20-year-old female who presented with sudden onset left side weakness. Magnetic Resonance Imaging (MRI) of the brain demonstrated ischemic infarctions. Patient was also found to be severely anemic. Patient had a thorough work-up including Magnetic Resonance Angiography (MRA) of the brain, echocardiogram, and an extensive screen for thrombophilia disorders. This, however, did not demonstrate a clear etiology. As it has been suggested that IDA is a potential cause for stroke, it is possible the stroke in this young patient was attributable to severe IDA.
http://ift.tt/2m5dL3x
Gene therapy for primary immune deficiencies: a Canadian perspective
The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term...
http://ift.tt/2ltarvt
Gene therapy for primary immune deficiencies: a Canadian perspective
The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term...
http://ift.tt/2ltarvt
Factors Associated with Early Mortality Among Patients with De Novo Metastatic Breast Cancer: A Population-Based Study
Background.
Although improvements in survival have been achieved for patients with metastatic breast cancer, some patients experience early death after diagnosis.
Patients and Methods.Using Surveillance, Epidemiology, and End Results data, we identified 26,538 patients with de novo metastatic breast cancer diagnosed between January 1, 2000 and June 30, 2011. We evaluated time trends for deaths at 1 and 6 months after diagnosis. We then restricted the cohort to patients diagnosed between 2010 and 2011 (n = 3,317), when human epidermal growth factor receptor 2 was routinely collected, and examined factors associated with early death.
Results.In 2000, 15.9% of patients died within 1 month of diagnosis and 33.2% within 6 months. In 2011, the proportion of women dying within 1 month decreased to 13.4% and 26.3% within 6 months (p < .001). Older age and uninsured status were associated with early death (at both time points, age ≥70 [versus age <40] had >8.5 higher odds of dying, and uninsured [versus insured] patients had >2.5 higher odds of death). In addition, in some subgroups (e.g., no insurance and triple negative disease), more than half of patients died within 6 months. Region was also associated with early death.
Conclusion.Although we observed improvements in the proportion of patients experiencing early death, one quarter of patients with de novo metastatic disease diagnosed in 2011 died within 6 months of diagnosis. In addition to tumor factors and older age, geography and uninsured status were associated with early death. Our findings highlight the need for focused interventions for metastatic patients at highest risk for poor outcomes. The Oncologist 2017;22:1–8
Implications for Practice: With nearly one quarter of patients in our dataset diagnosed in 2011 dying within 6 months of diagnosis, our findings highlight the persistent and critical need of further characterization and identification of patients who are risk for poor outcomes in order to optimize care, impact change, and improve outcomes for all women with metastatic breast cancer. Our data also emphasize the need for interventions among those at highest risk for early death. These interventions would likely promote immediate referral for clinical trial participation, early palliative care referrals, and additional supportive services, optimizing equitable patient access to cancer treatment and care.
http://ift.tt/2liuLiv
Survival Gains from First-Line Systemic Therapy in Metastatic Non-Small Cell Lung Cancer in the U.S., 1990-2015: Progress and Opportunities
Background.
Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients.
Materials and Methods.We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990–2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use.
Results.From 1990–2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively.
Conclusion.Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:1–7
Implications for Practice: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990–2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care.
http://ift.tt/2mo4FQ1
Response to Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasia with 8p11 Translocation and CEP110-FGFR1 Rearrangement
This brief communication reports on a patient with an exceedingly rare "8p11 (eight-p-eleven) myeloproliferative syndrome" (EMS) with CEP110-FGFR1 rearrangement who responded to treatment with the multi-tyrosine kinase inhibitor (TKI) dasatinib. Dasatinib improved quality of life substantially by increasing blood counts and reducing the need for transfusions. This report demonstrates that the second-generation TKI may provide a therapeutic option for elderly and frail EMS patients who cannot be offered aggressive therapy, including allogeneic hematopoietic cell transplantation. The Oncologist 2017;22:1–4
http://ift.tt/2limqLG
Stomach curvature is generated by left-right asymmetric gut morphogenesis [RESEARCH ARTICLE]
Adam Davis, Nirav M. Amin, Caroline Johnson, Kristen Bagley, H. Troy Ghashghaei, and Nanette Nascone-Yoder
http://ift.tt/2l6EWeF
Left-right (LR) asymmetry is a fundamental feature of internal anatomy, yet the emergence of morphological asymmetry remains one of the least understood phases of organogenesis. Asymmetric rotation of the intestine is directed by forces outside of the gut, but the morphogenetic events that generate anatomical asymmetry in other regions of the digestive tract remain unknown. Here we show that the mechanisms that drive the curvature of the stomach are intrinsic to the gut tube itself. The left wall of the primitive stomach expands more than the right wall, as the left epithelium becomes more polarized and undergoes radial rearrangement. These asymmetries exist across species, and are dependent on LR patterning genes, including FoxJ1, Nodal and Pitx2. Our findings have implications for how LR patterning manifests distinct types of morphological asymmetries in different contexts.
http://ift.tt/2l6EWeF
Notch signalling restricts inflammation and serpine1 in the dynamic endocardium of the regenerating zebrafish heart [RESEARCH ARTICLE]
Juliane Münch, Dimitrios Grivas, Alvaro Gonzalez-Rajal, Rebeca Torregrosa-Carrion, and Jose Luis de la Pompa
http://ift.tt/2lQ9RJv
The zebrafish heart regenerates after ventricular damage through a process involving inflammation, fibrotic tissue deposition/removal and myocardial regeneration. Using 3D whole-mount imaging, we reveal a highly dynamic endocardium during cardiac regeneration, including changes in cell morphology, behaviour and gene expression. These events lay the foundation for an initial expansion of the endocardium that matures to form a coherent endocardial structure within the injury site. We studied two important endocardial molecules, Serpine1 and Notch, which are implicated in different aspects of endocardial regeneration. Notch signalling regulates developmental gene expression and features of endocardial maturation. Also, Notch manipulation interferes with the attenuation of the inflammatory response and cardiomyocyte proliferation and dedifferentiation. Serpine1 is strongly expressed very early in the wound endocardium with decreasing expression at later time points. Serpine1 expression persists in Notch-abrogated hearts, in what appears to be a conserved mechanism. Functional inhibition studies show that Serpine1 controls endocardial maturation and proliferation and cardiomyocyte proliferation. Thus, we describe a highly dynamic endocardium in the regenerating heart and two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.
http://ift.tt/2lQ9RJv
Function of Nerfin-1 in preventing medulla neurons dedifferentiation requires its inhibition of Notch activity [RESEARCH ARTICLE]
Jiajun Xu, Xue Hao, Meng-Xin Yin, Yi Lu, Yunyun Jin, Jinjin Xu, Ling Ge, Wenqing Wu, Margaret Ho, Yingzi Yang, Yun Zhao, and Lei Zhang
http://ift.tt/2l6yVPd
Drosophila larval central nervous system comprises the central brain, ventral nerve cord and optic lobe. In these regions, neuroblasts divide asymmetrically to self-renew and generate differentiated neurons or glia. To date, mechanisms of preventing neuron dedifferentiation is still unclear, especially in the optic lobe. Here we show that the zinc finger transcription factor Nerfin-1 is expressed in early stage of medulla neurons and essential for maintaining their differentiation. Loss of Nerfin-1 activates Notch signaling, which promotes neuron-to-NB reversion. Repressing Notch signaling largely rescues dedifferentiation in nerfin-1 mutant clones. Thus, we conclude that Nerfin-1 represses Notch activity in medulla neurons and prevents them from dedifferentiation.
http://ift.tt/2l6yVPd
FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step EMT [RESEARCH ARTICLE]
Hana Goto, Samuel C. Kimmey, Richard H. Row, David Q. Matus, and Benjamin L. Martin
http://ift.tt/2lQ7feh
Mesoderm induction begins during gastrulation. Recent evidence from several vertebrate species indicates mesoderm induction continues after gastrulation in neuromesodermal progenitor cells (NMPs) within the posterior-most embryonic structure called the tailbud. It is unclear to what extent the molecular mechanisms of mesoderm induction are conserved between gastrula and post-gastrula stages of development. Fibroblast growth factor (FGF) signaling is required for mesoderm induction during gastrulation through positive transcriptional regulation of the t-box transcription factor brachyury (ntla in zebrafish). We find that FGF is continuously required for paraxial mesoderm (PM) induction in post-gastrula NMPs, but has the opposite effect on brachyury expression. FGF signaling represses brachyury and the NMP marker sox2 through regulation of tbx16 and msgn1, thereby committing cells to a PM fate. FGF mediated PM induction in NMPs functions in tight coordination with canonical Wnt signaling during the epithelial to mesenchymal transition from NMP to mesodermal progenitor. Wnt signaling initiates the EMT, while FGF signaling terminates this event. Our results indicate that germ layer induction in the tailbud is not a simple continuation of gastrulation events.
http://ift.tt/2lQ7feh
The role of variant histone H2AV in D. melanogaster larval hematopoiesis [RESEARCH ARTICLE]
Melina Grigorian, Heather DeBruhl, and Joseph S. Lipsick
http://ift.tt/2l6vHLj
Replication-independent histone variants can replace the canonical replication-dependent histones. Vertebrates have multiple H2A variant histones, including H2AZ and H2AX that are present in most eukaryotes. H2AZ regulates transcriptional activation as well as maintenance of gene silencing, while H2AX is important in DNA damage repair. The fruit fly Drosophila melanogaster has only one histone H2A variant (H2AV), which is a chimera of H2AZ and H2AX. In this study we found that lack of H2AV led to the formation of black melanotic masses in the third instar larvae of Drosophila. The formation of these masses was found in conjunction with a loss of a majority of the primary lymph gland lobes. Interestingly, the cells of the posterior signaling center were preserved in these mutants. Reduction of H2AV levels by RNAi knockdown caused a milder phenotype that preserved the lymph gland structure, but that included precocious differentiation of the prohemocytes located within the medullary zone and secondary lobes of the lymph gland. Mutant rescue experiments suggest that the H2AZ-like rather than the H2AX-like function of H2AV is primarily required for normal hematopoiesis.
http://ift.tt/2l6vHLj
Amyloid and tau PET demonstrate region-specific associations in normal older people
Source:NeuroImage, Volume 150
Author(s): Samuel N. Lockhart, Michael Schöll, Suzanne L. Baker, Nagehan Ayakta, Kaitlin N. Swinnerton, Rachel K. Bell, Taylor J. Mellinger, Vyoma D. Shah, James P. O'Neil, Mustafa Janabi, William J. Jagust
β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB—AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p<.01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates.
http://ift.tt/2l6A2OA
Cross-cultural consistency and diversity in intrinsic functional organization of Broca's Region
Source:NeuroImage, Volume 150
Author(s): Yu Zhang, Lingzhong Fan, Svenja Caspers, Stefan Heim, Ming Song, Cirong Liu, Yin Mo, Simon B. Eickhoff, Katrin Amunts, Tianzi Jiang
As a core language area, Broca's region was consistently activated in a variety of language studies even across different language systems. Moreover, a high degree of structural and functional heterogeneity in Broca's region has been reported in many studies. This raised the issue of how the intrinsic organization of Broca's region effects by different language experiences in light of its subdivisions. To address this question, we used multi-center resting-state fMRI data to explore the cross-cultural consistency and diversity of Broca's region in terms of its subdivisions, connectivity patterns and modularity organization in Chinese and German speakers. A consistent topological organization of the 13 subdivisions within the extended Broca's region was revealed on the basis of a new in-vivo parcellation map, which corresponded well to the previously reported receptorarchitectonic map. Based on this parcellation map, consistent functional connectivity patterns and modularity organization of these subdivisions were found. Some cultural difference in the functional connectivity patterns was also found, for instance stronger connectivity in Chinese subjects between area 6v2 and the motor hand area, as well as higher correlations between area 45p and middle frontal gyrus. Our study suggests that a generally invariant organization of Broca's region, together with certain regulations of different language experiences on functional connectivity, might exists to support language processing in human brain.
http://ift.tt/2lPV1SY
On the neural basis of sensory weighting: Alpha, beta and gamma modulations during complex movements
Source:NeuroImage, Volume 150
Author(s): Nicolas Lebar, Jérémy Danna, Simon Moré, Laurence Mouchnino, Jean Blouin
Previous studies have revealed that visual and somatosensory information is processed as a function of its relevance during movement execution. We thus performed spectral decompositions of ongoing neural activities within the somatosensory and visual areas while human participants performed a complex visuomotor task. In this task, participants followed the outline of irregular polygons with a pen-controlled cursor. At unpredictable times, the motion of the cursor deviated 120° with respect to the actual pen position creating an incongruence between visual and somatosensory inputs, thus increasing the importance of visual feedback to control the movement as suggested in previous studies. We found that alpha and beta power significantly decreased in the visual cortex during sensory incongruence when compared to unperturbed conditions. This result is in line with an increased gain of visual inputs during sensory incongruence. In parallel, we also found a simultaneous decrease of gamma and beta power in sensorimotor areas which has not been reported previously. The gamma desynchronization suggests a reduced integration of somatosensory inputs for controlling movements with sensory incongruence while beta ERD could be more specifically linked to sensorimotor adaptation processes.
http://ift.tt/2lQ11LH
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