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Propofol is rapidly acting intravenous agent used for induction in general anaesthesia.It causes pain while administering,being uncomfortable to patients .So an observational study was done to compare the effects of different time duration of venous occlusion on pretreatment with injection Ketamine for prevention of pain at injection site. After approval of ethical committee and written informed consent,ASA grade I and II,60 patients of either gender, aged between 18-60 years were assigned to three groups of 20 each under GA and divided as GROUP K20,K40,and K60 according to venous occlusion duration of 20,40,and 60 seconds respectively on administration of ketamine(0.2mg/kg)as pretreatment for propofol injection pain.Following injection of ketamine ,25% dose of propofol was given and patient was asked for any sensation of pain at the site of injection and graded accordingly. Haemodynamics were compared in all the three groups. All 60 patients were reviewed for propofol pain and haemodynamics were recorded before pretreatment with ketamine and after pretreatment for 5 minutes and results evaluated through chi square test.P value was significant for 20 seconds (p value

Background Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies. Methods This multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided. Results Among 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P Conclusions Patients with advanced ECC have low rates of molecular profiling, possibly in part because of insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

Purpose:To study the clinical profile of patients of snake venom ophthalmia presenting to the tertiary health care centre. Methods:This was a prospective observational study that involved25 patients with snake venom ophthalmia complaining of pain, diminution of vision, photophobia, conjunctival congestion , chemosis, corneal edema, corneal erosions and anterior chamber reaction. Results:There were 18 males and 7 females and the age group taken was 30 to 75 years. Most common presentation in snake venom ophthalmia patients is pain in 92% patients followed bydiminution of vision in 90% patients,conjunctival congestion in 88% patients, photophobia in 84% patients, chemosis in 80% patients, corneal edema in 65% patients, corneal erosions in 55% patients and anterior chamber reaction in 35% patients. Conclusion:Snake venom ophthalmia due tovenom spitting is a reflex mechanism aimed at ejecting venom forcefully into the eyes of the victims.Snake venom may contain a mixture of neurotoxins, cytotoxins, phospholipases and cardiotoxins. The ocular effects of the venom depend on duration of contact of ocular surface with venom. Snake venom ophthalmia is rare form of envenoming which presents as intensely painful blurred vision associated with photophobia, conjunctival congestion, chemosis, corneal epithelial defects and anterior chamber reaction. &nbsp

Purpose:To study the ocular pathology of hyperopic patients presenting to the tertiary health care centre. Methods:This was a retrospective observational study that involved 60 eyes of 30 patients with hypermetropia complaining of diminution of vision with asthenopic symptoms like tiredness of eyes, frontal or frontotemporal headache, watering and mild photophobia. There were three groups based on the criteria of age, i.e, Results:There were 15 males and 15 females. The common hypermetropiarelated findings in patients varying between age of 0-20 years was strabismus and amblyopia. Recurrent styes, recurrent blepharitis infection, recurrent chalazion were seen in equal proportions in all age groups. Primary open angle glaucoma and angle closure glaucoma were reported more in adults ranging between 20-40 years and 40-60 years.Fundus examination in high hypermetropic patients revealed a small optic disc with ill defined margins simulating papillitis which is pseudopapillitis because there is no swelling of the disc and the retina shines due to greater brilliance of light reflections giving shot silk appearance of retina. Conclusion:Hyperopia also termedhypermetropiaorfarsightedness, is a commonrefractive errorin children and adults. Its effect on an individual and the symptoms produced varies greatly, depending on the magnitude ofhyperopia, the age of the individual, the status of the accommodative and convergence system, and the demands placed on the visual system. Individuals with uncorrected hyperopia may experience symptoms such as blurred vision, asthenopia (e.g., headaches and eyestrain) while reading, accommodative/binocular dysfunction,amblyopia, and/or strabismus. Furthermore, uncorrected amblyopia in case of adults can lead to various complications like open angle or angle closure glaucoma, uveal effusion syndrome, non arteritic anterior ischemic optic neuropathy, central serous chorioretinopathy, age related macular degeneration, etc. &nbsp

Purpose:To study the clinical profile and relationship between time of presentation andvisual outcome in patients with central serous chorioretinopathy . Material and Method:Total 100 eyes of 50 patients were selected for the study who presented with complaints of blurring and or sudden painless loss of vision ,out of which 10 eyes of 5 patients were excluded due to corneal opacity, diabetic retinopathy, hypertensive retinopathy ,cataract and retinal detachment, retinitis pigmentosa. Total 90 eyes of 45 patients were included in the study and divided into two groups according to the time of presentation :1) Group 1-Within 15 days of onset of symptoms.2) Group 2 -After 2 months of onset of symptoms. Result:Group 1 patients showed the better visual outcome(BCVA 6/36-6/9) than the group 2 patients(BCVA 6/36-6/24). Conclusion:The time of presentation to the tertiary care centre was the major factors influence the visual outcome in patients with CSR.

Numerous public health hurdles, including pandemics such as COVID-19, have led to concerns about community health practices in relation, necessitating the application of an ethical perspective. International research ethics guidelines are only used in a restricted range of contexts of public health. As a result, a variety of frameworks have been established to assist ethical analysis of public health concerns. In this study, we have used the Nancy Kass framework for analyzing COVID-19 surveillance in Karnataka state of India, which is a six-step approach that can assist public health practitioners in evaluating the ethical consequences of interventions, policy initiatives, services, and so on. In order to supervise the compliance of home quarantine, the government of Karnataka mandated uploading selfies as a digital tracking surveillance measure for the COVID-19 outbreak. However, these measures raised several ethical questions, especially related to an individual’s privacy, confidentiality, autonomy, and liberty. An established state surveillance mechanism with includes enforced measures for data security along with the moral duty of an individual to protect the health of the community can probably balance the principles of ethics.

Purpose -To study the clinical profile of patients of panophthalmitis presenting to the tertiary health care centre. Methods-This was a prospective observational study that involved25 patients with panophthalmitis complaining of blurring of vision, redness, pain, purulent discharge, photophobia and eyelid swelling. Results-There were 18 males and 7 females and the age group taken was 30 to 75 years.14 patients belonged to the age group of 30 to 45 years, out of which 10 were males and 4 were females. 7 patients belonged to age group of 46 to 60 years, out of which 5 were males and 2 were females. 4 patients belonged to the age group of 61 to 75 years, out of which 3 were males and 1 was female. Most common presentation in panophthalmitis patients is loss of vision in 88% patients followed by redness in 76% patients, pain in 72% patients, purulent discharge in 68% patients,photophobia in 55% patients and eyelid swelling in 48% patients. Majority of patients belong to low socioeconomic class. The most common cause was post traumatic followed by post operative and some endogenous infections spread through hematogenous route. Of the 25 cases of culture-positive panophthalmitis, 18 cases (75%) had bacterial growth and 7 cases (25%) had fungal growth. In post-traumaticpanophthalmitis, Gram-positive bacteria were the predominant species, followed by Gram-negative bacteria and fungi. In endogenous panophthalmitis, Gram-negative bacteria were the predominant species, followed by fungi and Gram-positive bacteria. In postsurgical panophthalmitis, all infections were bacterial. Conclusion-Panophthalmitis is a dreaded ocular disease and tends to occur more commonly in males of 30 to 45 years agegroup. Most common presentation of panophthalmitis is loss of vision followed by redness, pain, purulent discharge, photophobia and eyelid swelling and signs include eyelid edema, hypopyon, circumcilliary congestion, corneal haze and ulcer and vitreous haze. Most common cause of panophthalmitis was post traumatic with gram positive bacteria followed by endogenous causes with gram negative bacteria and post operative cases with gram positive bacteria isolated. &nbsp

Patients with CCA withThree hundred seventy-seven patients with CCA were identified, and 95 hadCCA with

OBJECTIVES:We examined the trends in the rate of Henoch-Schönlein purpura (HSP) hospitalizations and the associated resource use among children in the United States from 2006 through 2014.METHODS:Pediatric hospitalizations with HSP were identified by using International Classification of Diseases, Ninth Revision, code 287.0 from the National Inpatient Sample. HSP hospitalization rate was calculated by using the US population as the denominator. Resource use was determined by length of stay (LOS) and hospital cost. We used linear regression for trend analysis.RESULTS:A total of 16 865 HSP hospitalizations were identified, and the HSP hospitalization rate varied by age, sex, and race. The overall HSP hospitalization rate was 2.4 per 100 000 children, and there was no trend during the study period. LOS remained stable at 2.8 days, but inflation-adjusted hospital cost increased from $2802.20 in 2006 to $3254.70 in 2014 (P < .001).CONCLUSIONS:HSP hospitalization rate in the United States remained stable from 2006 to 2014. Despite no increase in LOS, inflation-adjusted hospital cost increased. Further studies are needed to identify the drivers of increased hospitalization cost and to develop cost-effective management strategies.

One of the prime commodities in modern civilization is energy. The amount of energy consumption has become the indicator for the standard of living and the degree of industrialization. People use fossil fuels to meet nearly all of their energy needs, such as powering vehicles, producing electricity for light and heat and running factories, thus greatly exhausting the fossil fuel reserves along with polluting the environment with greenhouse gases. Renewable energy sources are viable alternatives, and among the various types of renewable energy sources available, wind energy is the sector which has a lot of untapped potential. Our objective is to improve the efficiency of a Savonius-type vertical-axis wind turbine (VAWT) which currently has the least efficiency among existing wind turbine designs. Savonius turbines have a very compact structure and can run at low wind speeds which are desirable characteristics for commercial-scale power production. This research paper focuses on improving the efficiency of Savonius wind turbine. Since Savonius-type wind turbines are drag-based wind turbines, we need to reduce the impulsive force acting on the negative face in order to increase the drag difference between the positive and negative side of the rotor blades thereby improving the efficiency of the turbine. Our proposition for attaining higher efficiency is by incorporating the concept of dimples (inspired from golf ball) on the negative side of the rotor blade and tubercles (inspired from whales) on the leading edge of the rotor blade. Dimples reduce the amount of wake region in the case of golf ball by increasing turbulence which is one of the desirable characteristics in the case of Savonius wind turbine. Tubercles help in reducing the wake region behind the rotor blades by increasing the turbulence of air near the surface of the rotor thereby improving the efficiency of the turbine.

Purpose FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown. Patients and Methods Patients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher’s exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis. Results Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 ( P = .04) and CDKN2A/B ( P = .04) were correlated with a shorter OS. Conclusion CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.

Streaming media companies have changed how contents are consumed, produced, and delivered. This research develops a theoretical model on optimal content policies for streaming media companies in order to maximize customer engagement. We have the following interesting findings. First, in contrast to the results in prior literature that firms produce just enough products without overlapping product coverage intervals, we show that overlapping coverage intervals and placing products closer can be a better policy for engagement-based firms. Second, engagement-based model produces more contents when the value of the contents is large to the customers or the profit margin in selling content is less than a certain threshold. Third, on learning a general customers’ distribution, the media firm will always overlap product coverage intervals and place programs closer when the distribution density is larger. Additionally, in facing the tradeoffs of content quality and quantity, the firm should use a higher-quality and low-variety policy for high density clusters but a lower-quality and high-variety policy for low density clusters. Furthermore, when customers consume multiple shows in a period, a better policy is to film TV shows or series with multiple episodes rather than individual movies. Our research contributes to the literature on digital media, and the results provide interesting and insightful implications for streaming companies.

We model a supply chain consisting of a supplier and multiple retailers facing deterministic demand. We denote some retailers as strategic in the sense that given the supplier inventory information, they will implement the optimal stocking policy by incorporating such information. On the other hand some retailers are denoted as naive in the sense that they ignore supply information and resort to a simplistic ordering policy. Naive retailers learn the optimal policy over time and adjust their orders accordingly. We study the dynamics of this game and investigate the impact of such strategic and naive retailers on the cost, ordering pattern and stocking policies of all parties. We analyze the supply chain under two scenarios: the centralized supply chain where the objective is to minimize the total supply chain cost, and the decentralized supply chain where each self-interested player minimizes its own cost in a Stackelberg game setting. We fully characterize the optimal policies under both centralized and decentralized scenarios and show that, surprisingly, the supply chain might be better off by virtue of naive retailers. The result is driven by the fact that strategic and naive players’ decisions shift the positioning of inventory in the supply chain with its final impact being determined by the relative costs of different retailer-types. Our results also offer managerial insights into how access to supply information can improve supply chain performance. This article is protected by copyright. All rights reserved.

BACKGROUND Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit. METHODS Hybrid capture–based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients. Clinical variables, detected mutations, and administered therapies were correlated with overall survival (OS) in a Cox regression model. RESULTS The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA. Fibroblast growth factor receptor (FGFR; 11%) and IDH mutations (20%) were mostly limited to IHCCA but appeared to be mutually exclusive. In the IHCCA group, TP53 and KRAS mutations were associated significantly with poor OS, whereas FGFR2 mutations were associated with improved OS (P = .001), a younger age at onset, and female sex. IDH1/2 mutations were not prognostic. In a multivariate model, the effects of TP53 and FGFR GAs remained significant (P

Background Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance. Methods Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS). Results When genes with an incidence > 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached. Conclusions In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.

Challenges and resolution approaches of fiber coupling to and from optical devices will be discussed. Particular emphasis will be paid to hermetic and ruggedized assemblies.

We analyze a model of rental and return process where limited inventory of a product is rented to two customer classes that differ in their return behavior and penalty costs. The rental demand is a decreasing function of time. We consider two cases: where a demand that is not met is lost and where an unmet demand returns. We show that to minimize penalty cost, the optimal allocation policy may give priority to different classes at different points in time and may decline lower-class demand for some time. Computational results show the benefit of the optimal allocation policy over a priority scheme reportedly used in practice.

Packaging solutions developed for Luxmux's BeST SLED family of sources will be discussed along with their applications. In particular, a narrow linewidth ( 20mW output power from a compact fiber-coupled butterfly package will be presented.

In an attempt to provide a humble 100W electricity for a DC powered home in an incessant manner, this work deals with the design and implementation of a solar PV based home with uninterrupted power supply. The back-up power is supplied by the power grid and battery. In order to keep output voltage constant, the solar PV is cascaded with a buck converter which has a PWM modulator circuit in its feedback. A Proportional controller adjusts the Kp value which maintains the output voltage at a constant level by appropriately varying the duty ratio of the buck converter. The output of this buck converter is connected to a common DC bus. When solar DC power is unavailable, a reduced voltage 1Φ AC power grid (of 90V) supplies the home through a rectifier and a buck converter which maintains a constant 13.6V DC output. Battery also supplies power in cases when the other two sources are unavailable. Battery is charged either from solar PV or from the rectified AC. A microcontroller design ensures that this 100W DC home is supplied power for maximum amount of time at the minimum possible cost. The proposed scheme has been modeled and simulated in the MATLAB/SIMULINK environment. The test results show that the proposed design exhibits an excellent performance.

Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 ( IDH1 ), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients.

Biliary tract cancers are relatively uncommon, have an aggressive disease course and a dismal clinical outcome. Until recently, there have been very few clinical advances in the management of these patients and gemcitabine-based chemotherapy has been the only widely accepted systemic therapy. The advent of next generation sequencing technologies can potentially change the treatment paradigm of this disease. Targeted therapy directed against actionable mutations and identification of molecular subsets with distinct prognostic significance is now feasible in clinical practice. Mutation profiling has highlighted the genomic differences between the intra, extrahepatic cholangiocarcinoma, and gallbladder cancer. The mutational spectrum of intrahepatic cholangiocarcinoma differs according to geographic location and ethnicity. There is a higher incidence of chromatin modulating gene mutations in Western patients as compared with Asian patients with liver fluke-associated cholangiocarcinoma. KRAS and p53 mutations are associated with an aggressive disease prognosis while FGFR mutations may signify a relatively indolent disease course of intrahepatic cholangiocarcinoma. FGFR and IDH mutations have promising agents in clinical trials at this time. An estimated 15 % of gallbladder cancers have Her2/neu amplification and can be targeted by trastuzumab. On the other hand, an estimated 10-15 % of cholangiocarcinomas have DNA repair mutations and may be candidates for immune therapies with checkpoint inhibitors. The promise of targeted therapies for biliary tract cancers can be fulfilled with well-designed, prospective, and multi-center clinical trials.

Background: BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. Methods: The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. Results: Twenty-two cases of BAP1 -mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. Conclusions: BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1 -targeted therapies need to be investigated.

Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).When genes with an incidence 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached.In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.

In this work, a novel 4-terminal perovskite / SiC-based rear contact silicon tandem device has been proposed for long-term cost reduction and higher efficiency. The novel tandem device proposed in this work shows ultra-high power conversion efficiency (PCE) of 27.6 % and 22.7 % with 300 μm and 10 μm thick rear contact Si solar cell, respectively. The realistic TCAD simulation has been performed for Methylammonium lead triiodide perovskite cell. To simulate and predict the realistic behavior of the device, all the fundamental recombination mechanisms have been included in CH3NH3Pbl3 film during the simulation. The perovskite device which is used as top cell shows PCE of 19.9% which is almost equivalent to experimentally available record efficiency of 20.1% The charge carrier decay constants for CH3NH3PM3 used in the simulation have been obtained from experimentally available data.

Background Recently released American College of Cardiology/American Heart Association (ACC/AHA) guideline recommends the Pooled Cohort equations for evaluating atherosclerotic cardiovascular risk of individuals. The impact of the clinical input variable uncertainties on the estimates of ten-year cardiovascular risk based on ACC/AHA guidelines is not known. Methods Using a publicly available the National Health and Nutrition Examination Survey dataset (2005–2010), we computed maximum and minimum ten-year cardiovascular risks by assuming clinically relevant variations/uncertainties in input of age (0–1 year) and ±10 % variation in total-cholesterol, high density lipoprotein- cholesterol, and systolic blood pressure and by assuming uniform distribution of the variance of each variable. We analyzed the changes in risk category compared to the actual inputs at 5 % and 7.5 % risk limits as these limits define the thresholds for consideration of drug therapy in the new guidelines. The new-pooled cohort equations for risk estimation were implemented in a custom software package. Results Based on our input variances, changes in risk category were possible in up to 24 % of the population cohort at both 5 % and 7.5 % risk boundary limits. This trend was consistently noted across all subgroups except in African American males where most of the cohort had ≥7.5 % baseline risk regardless of the variation in the variables. Conclusions The uncertainties in the input variables can alter the risk categorization. The impact of these variances on the ten-year risk needs to be incorporated into the patient/clinician discussion and clinical decision making. Incorporating good clinical practices for the measurement of critical clinical variables and robust standardization of laboratory parameters to more stringent reference standards is extremely important for successful implementation of the new guidelines. Furthermore, ability to customize the risk calculator inputs to better represent unique clinical circumstances specific to individual needs would be highly desirable in the future versions of the risk calculator. Electronic supplementary material The online version of this article (doi:10.1186/s12872-016-0352-x) contains supplementary material, which is available to authorized users.

Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit.Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients. Clinical variables, detected mutations, and administered therapies were correlated with overall survival (OS) in a Cox regression model.The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA. Fibroblast growth factor receptor (FGFR; 11%) and IDH mutations (20%) were mostly limited to IHCCA but appeared to be mutually exclusive. In the IHCCA group, TP53 and KRAS mutations were associated significantly with poor OS, whereas FGFR2 mutations were associated with improved OS (P = .001), a younger age at onset, and female sex. IDH1/2 mutations were not prognostic. In a multivariate model, the effects of TP53 and FGFR GAs remained significant (P .05). Patients with FGFR GAs had superior OS with FGFR-targeted therapy versus standard regimens (P = .006). Targeted therapy in IHCCA was associated with a numerical OS improvement (P = .07).This is the largest clinically annotated data set of BTC cases with CGP and indicates the potential of CGP for improving outcomes. CGP should be strongly considered in the management of BTC patients. Cancer 2016;122:3838-3847. © 2016 American Cancer Society.

Mobile ad-hoc network is an agglomeration of mobile nodes that can communicate without the presence of a fix infrastructure; this lack of infrastructure makes it at risk and open to various attacks. The black hole attack is one of the perilous security risks that increases the network overhead and interrupt the standard functioning of the network, TAODV routing protocol is preferable under such circumstances. In this analysis, TAODV (Trust Based Ad-hoc Network) is used under different traffic patterns like CBR, Exponential and Pareto. As a propagation environment, indoor shadowing environment is used and observe different Quality of Services (QoS).

Gallbladder cancer (GBC) is an aggressive malignancy. Although surgical resection may be curable, most patients are diagnosed at an advanced unresectable disease stage. Cholelithiasis is the major risk factor; however the pathogenesis of the disease, from gallstone cholecystitis to cancer, is still not understood. To understand the molecular genetic underpinnings of this cancer and explore novel therapeutic targets for GBC, we examined the key genes and pathways involved in GBC using RNA sequencing. We performed gene expression analysis of 32 cases of surgically-resected GBC along with normal gallbladder tissue controls. We observed that 519 genes were differentially expressed between GBC and normal GB mucosal controls. The liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR) /RXR pathways were the top canonical pathways involved in GBC. Key genes in these pathways, including SERPINB3 and KLK1, were overexpressed in GBC, especially in female GBC patients. Additionally, ApoA1 gene expression suppressed in GBC as compared with normal control tissues. LXR and FXR genes, known to be important in lipid metabolism also function as tumor suppressors and their down regulation appears to be critical for GBC pathogenesis. LXR agonists may have therapeutic value and as potential therapeutic targets.

Analysis of the impact of input variable variations in categorizing subjects based on ten-year risk threshold of 5Â % (with Hispanics). (DOCX 14Â kb)

Analysis of the impact of input variable variations in categorizing subjects based on ten-year risk threshold of 7.5Â % (with Hispanics). (DOCX 15Â kb)

4076 Background: Gallbladder carcinoma (GBC) is commonly diagnosed at an advanced, unresectable disease stage and has a poor prognosis. Comprehensive genomic profiling (CGP) has a developing role in guiding systemic, precision anti-cancer therapy. Methods: We performed hybrid capture-based CGP on FFPE samples for 491 consecutive advanced GBCs. Mean coverage depth was >550X for up to 315 cancer-related genes plus 37 introns from 28 genes frequently rearranged in cancer. All 4 classes of genomic alterations (GA) were detected. Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA. Results: Median age was 64 (range 25-88) and 69% (337/491) of patients were female. 96% (470), 2.9% (14), and 1.4% (7) of GBC patients had the diagnosis of adenocarcinoma, adenosquamous, or carcinoma not specified (NOS), respectively. Commonly altered genes were TP53 (62%), CDNK2A (31%), ARID1A (18%), and SMAD4 (15%), and most of the genetic aberrations (GA) were short variants. Potentially targetable SCNAs (including ERBB genes, MET, FGFRs, and the CCND1-FGF3/4/19 11q13 amplicon) were identified in 21% of cases (Table). Oncogenic BRAF, ALK, or FGFR2/3 rearrangements were found in 7 cases (1.4%). Moreover, 7.8% of cases had BRCA2 or ATM GA, and 0.8% had INI1loss suggesting benefit from PARP or EZH2 inhibitors, respectively. TMB was low; the 25th, 50th, and 75th percentiles were 2.5, 3.8 and 6.3 mutations/Mb, respectively. Less than 1% of cases had microsatellite instability. Radiological response to TKIs and immunotherapy was noted. Conclusions: In addition to the significant opportunity for anti-HER targeted therapies, other subsets of GBC cases harbored kinase GA (particularly SCNA), the 11q13 amplicon, or BRCA2/ ATM/ INI1mutations that are linked to therapeutic benefit. How the frequency of both driver SCNA and DNA repair alterations in GBC can be linked with inflammation awaits additional investigation. [Table: see text]

4086 Background: Mutations in DNA repair pathway were identified in 13% of Biliary Tract Cancers (BTC) [ Cancer2016;122:3838–3847]. High TMB tumors including melanoma, lung cancer and those with microsatellite instability (MSI-H) are associated with susceptibility to immune blockade using checkpoint inhibitors. TMB data in BTC is limited and its association with actionable somatic mutation (mut) profiles in BTC is unknown. Methods: Comprehensive genomic profiling (CGP) of 309 FFPE tissue blocks of BTC pts with a hybrid capture of all coding exons of 236 cancer-related genes and 47 introns of 19 genes rearranged in cancer was done using FoundationOne. Base substitutions, indels, gene fusion/rearrangements, TMB, and MSI status were assessed. TMB was calculated by counting mutations across a 1.25Mb region and classified into high (TMBH; ≥20 mut/Mb), intermediate (TMBI; 6 - 19mut/Mb) and low (TMBL; < 6mut/Mb). MSI high (MSIH) and Stable (MSS) status was assigned by a computational algorithm examining 114 intronic homopolymer loci. Patients with TMB ≥6 mut/Mb (N = 60) were included in the clinical correlative portion of this study. Results: Sixty patients with TMB ≥6 mut were identified out of 309 pts of which 9 (15%) were TMBH and 51 (85%) were TMBI. These included 3 (5%) MSIH and 18 (30 %) MSS. The median age was 59 years (range: 29-86), 35 (58%) were females, majority were intrahepatic cholangiocarcinoma (n = 31; 52%) and 28 (47%) presented with advanced disease at diagnosis. Twenty three (38%) pts had received radiation therapy, 28 (47%) surgery and 3 (5%) received immunotherapy. Most frequent co-existing mut seen was TP53 (N = 35; 58%). APC mut was seen in 7 (12%) pts. DNA repair pathway muts ( MSH6, BRCA1, BRCA2, ATM, MLH1, or MSH2 genes) were identified in 78% of TMBH versus 16% in TMBI cases (p < 0.0001). Frequency of PIK3CA mut differed significantly between TMBH and TMBI (44% vs 10%, p < 0.0001). Pts with TMBI had a significantly better median OS (110 weeks) as compared to TMBH (43 weeks) (p = 0.003). Conclusions: DNA repair pathway and PIK3CA mut maybe associated with TMBH in BTC. A better understanding of TMB and associated actionable mutations in BTC may be of value for the management of BTC patients with targeted agents and immunotherapy.

428 Background: Acute cholangitis due to malignant biliary obstruction is frequent in patients with pancreatic and hepatobiliary cancers. Recurrent cholangitis (RC) results in repeated hospitalization and delayed cancer care. The risk factors associated with RC are not yet defined. Methods: A pilot review was done on 146 patients admitted with a diagnosis of cholangitis from 2005 to 2014. We included demographics, cancer stage, details of first admission (FA) and interventions. Univariate and multivariate Fine-Gray models were used for statistical analysis. Results: The mean age at FA was 62 yrs, 84 (58%) were males and 99 (68%) were white. Most common cancer was pancreatic 100(69%) and 27(19%) pts had primary cholangitis at FA. During FA, interventions were performed in 114(78%), of whom 51 (45%) had percutaneous drainage (PTBD) and 63 (55%) had endoscopic drainage (ED). Readmission with cholangitis was noted in 35 (24%) cases. Univariate analysis did not show a difference between PTBD and ED. However, subgroup analysis showed external only PTBD and covered metallic stent ED had lower risk of RC. These variables remained significant on multivariate analysis (Subdistribution HR= 0.00, p

240 Background: As seen in lung cancer, young patients with cancer can have different risk factors, presentation, and tumor genotype than older patients with the same disease. The clinical and molecular features of young patients with CCA have yet to be well characterized. Methods: Retrospective chart review was performed on patients with intrahepatic (ICC) or extrahepatic cholangiocarcinoma (ECC) across 5 institutions. Data on demographics, risk factors, treatments, pathology, and overall survival (OS) were collected. Tumor genotyping results from MGH SNaPShot and Foundation Medicine were analyzed. Log-rank tests and Kaplan-Meier survival curves were used for statistical analysis. Results: Of 567 patients analyzed, 134 (23.6%) were < 50 years old (yo) and 455 (80.2%) had ICC. When assessed for risk factors, younger patients ( < 50yo) were more likely to have primary sclerosing cholangitis (PSC) (p < 0.001) and less likely to have diabetes (p = 0.05), compared to older patients ( ≥ 50yo). Surgical resection rates were similar in younger vs older patients (41.9 vs 42.6%, p = 0.890), but younger patients had larger tumors (median size 7.1 vs 5.3cm p = 0.012). Younger patients were also more likely to receive palliative systemic chemotherapy (p < 0.001) and more lines of therapy (median, 2 vs 1 line, p < 0.001). Frequency of treatment with liver directed therapy did not differ between the two groups. Molecular testing was performed on 222/567 (39.1%) patients of which 84/134 (62.7%) were younger patients and 138/433 (31.9%) were older patients. FGFR aberrations were more common in younger patients versus older patients (17.6 vs. 5.7%, p = 0.002). Targeted therapy was given to 15/84 (17.9%) younger and 28/138 (20.3%) older patients based on results of mutational profiling. Finally, no significant difference was seen in OS between younger and older patients (22.9 vs 22.7 months, p = 0.89). Conclusions: Younger patients with CCA may have different risk factors, tumor biology, and tolerance of systemic therapy compared to older patients. Further study is needed as referral patterns to tertiary care centers and motivation of younger patients to seek tertiary care may impact these results.

109Background: FGFR pathway genetic aberrations (GAs) occur in an estimated 10% of intrahepatic cholangiocarcinomas (IHCCA). The most common are FGFR2 mutations (mut). The advent of FGFR targeted inhibitors may alter the outcome of this disease subtype. The natural history of FGFR mutant CCA and prognostic role of co-existing mut is unknown. Methods: We reviewed the records of CCA patients (pts) with FGFR pathway GAs identified on next generation sequencing (NGS). Data reviewed included demographics, treatments, progression-free survival (PFS) with first-line chemotherapy, overall survival (OS) and mut data (Foundation Medicine or Institutional NGS). KM plots and log rank tests were used for statistical analysis. Results: A total of 54 pts with FGFR pathway GAs were identified from our database of 321 biliary cancer pts who had NGS. These included: 32 FGFR2 mut, which occurred almost exclusively in IHCCA (except 1 GB cancer pt). Of these, FGFR fusions occurred in 27. Most common FGFR fusion was FGFR2-BICC...

4079Background: BTC are uncommon and associated with a dismal prognosis. Gemcitabine and platinum-combinations (GP) form the standard approach for treating advanced BTC with a modest improvement in...

287 Background: aBTC is uncommon and has a dismal prognosis with limited therapeutic options. First-line therapy for untreated aBTC is GC, with no approved therapies in the refractory setting. To assess for tumor-specific genetic variants that affect outcomes in patients (pts) who received GC in aBTC, we performed NGS in pts treated with who received GC as first-line therapy. Methods: Archival formalin-fixed, paraffin-embedded samples from pts with mBTC from Ohio State University and MD Anderson Cancer Center who received GC in the first-line and underwent NGS as part of routine care. 315 cancer-related genes plus select introns from 28 genes altered in solid tumors were included in the NGS panel. Univariate Cox regression model was used to determine the association between gene mutations with progression free survival (PFS) and (OS). Results: 80 evaluable pts with aBTC treated with first-line GC chemotherapy underwent successful genomic profiling. A total of 414 cancer-specific mutations were identified, where 49 (12%) genes had mutations with > 5% frequency. 17 of the 49 were known mutations. From the comprehensive analysis, somatic mutations in IDH1 (11 of 80 pts; 13%) (HR 0.31; p = 0.035) was associated with improved overall survival (OS) and progression free survival (PFS). Pts wild type for IDH1 had a median OS of 17.7 months and PFS of 4.5 months, while those with an IDH1 mutation had a median OS that was not reached and an improved PFS of 5.7 months. Conclusions: Somatic mutations in IDH1 were associated with improved clinical outcomes in pts with aBTC who received GC as first-line therapy which is consistent with other solid tumor malignancies. IDH1 is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive utility and its relevance in pt outcomes in aBTC.

244 Background: Biliary tract cancers (BTC) exhibit a diverse and high frequency of actionable mutations detectable using next generation sequencing (NGS). The Breast Cancer Linkage Consortium reported that BRCA2 mutation carriers are at increased risk for BTC with estimated relative risk of 4.97, (95% CI = 1. 50-16.52). The purpose of this study was to evaluate the clinical characteristics of germline/somatic BRCA1/2mutations in CCA patients. Methods: Multi-center retrospective analysis of patients with germline/somatic BRCA1/2- associated CCA diagnosed between January 2000 and December 2013. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures and systemic chemotherapy or radiation were extracted from patient records. Results: Overall, we identified 18 cases including 5 carriers of germline BRCA1/2 mutations (4 BRCA2; 1 BRCA1) and 13 harboring somatic mutations (7 BRCA1; 6 BRCA2) using a NGS panel testing tumor for 'actionable' mutations. One patient presented with two different somatic mutations in the BRCA2gene. Mean age at diagnosis was 60 years (range 36-75), male: females (61.2% vs 38.8%, respectively). Stage at diagnosis: I (n = 4), II (n = 3), III (n = 3) and IV (n = 8). Six patients had extrahepatic CAA; twelve patients had intrahepatic CCA. Prior therapy in 13 patients included platinum-based therapy with one patient receiving prior olaparib. Median overall survival for patients with stage I/II is 34.7 months (95% CI, 7.06-62.9) and for stages III/IV is 25 months (95% CI, 12.02-35.84). Conclusions: BRCA associated CCA may have an enhanced therapeutic sensitivity to DNA damaging agents. This needs confirmation in a larger cohort of patients.