Search

Engineering schools and higher education institutions need to rethink their curricula in light of these findings. With the current curriculum challenges, the report suggests new measures that will aid education development. Goals, analysis, content, policy, content, evaluation methods, and implementation are all part of the investigation. Using a craft knowledge approach, this article shows how instructors' theories and beliefs are connected to their actual teaching practices while also accounting for local and cultural differences. According to a study, policy making and implementation are inconsistent in the Indian education sector.

Smart Agriculture (SA) incorporates low cost and low energy consuming sensors and devices to enhance quantitative and qualitative agricultural production. However, these devices uses an open channel i.e., Internet and generates large amount of data in real-time and thus, has the potential to be misused. As a consequence, the major concern in the implementation of SA is minimizing the risk of security and data privacy violation (e.g., adversaries performing inference attacks). To address these challenges, we propose PEFL, a deep privacy-encoding based Federated Learning (FL) framework that adopts a perturbation-based encoding and Long-Short Term Memory-AutoEncoder (LSTM-AE) technique to achieve the target of privacy. Then a FL-based Gated Recurrent Unit Neural Network algorithm (FedGRU) is designed using the encoded data for intrusion detection. The experiment results based on ToN-IoT dataset reveals that the PEFL can efficiently identify normal and attack patterns after transformation over other non-FL and FL methods.

Background & Aims Retreatment with glecaprevir/pibrentasvir (G/P) resulted in a rate of sustained virologic response 12 weeks after treatment completion (SVR12) of >90% in HCV genotype 1 (GT1) patients who previously failed a regimen of sofosbuvir plus an NS5A inhibitor (NS5Ai). This study investigated the prevalence and impact of baseline NS3 and NS5A resistance-associated substitutions (RASs) on the efficacy of G/P in prior GT1 sofosbuvir+NS5Ai failures and the persistence of treatment-emergent RASs. Methods Longitudinal samples from 177 patients enrolled in a phase IIIb, randomized pragmatic clinical trial were analyzed. Patients without cirrhosis were randomized to 12 or 16 weeks of G/P, and patients with compensated cirrhosis were randomized to G/P and ribavirin for 12 weeks or G/P for 16 weeks. Linkage of RAS was identified using Primer-ID next-generation sequencing at a 15% cut-off. Results Of 177 patients, 169 (95.5%) were PI-naive. All 33 GT1b-infected patients achieved SVR12. In GT1a-infected patients, baseline NS5A RASs were prevalent (74.5%, 105/141) but NS3 RASs were uncommon. Baseline NS3 RASs had no impact on G/P efficacy and patients with baseline NS5A RASs showed a numerically but not statistically significantly lower SVR12 rate compared to those without NS5A RASs (89% vs. 97%). SVR12 was achieved in 34 of 35 (97%) patients without NS5A baseline substitution, and 53 of 57 (93%), 35 of 40 (88%), 5 of 8 (63%) with single, double-linked, and triple-linked NS5A substitutions, respectively. Among 13 patients with virologic failure, 4 acquired treatment-emergent NS3 RASs and 10 acquired NS5A RASs. Conclusion Baseline NS5A RASs were highly prevalent. The presence of an increasing number of linked NS5A RASs in GT1a showed a trend in decreasing SVR12 rates, although no specific NS5A RASs or their linkage pattern were associated with lower SVR12 rates. Lay summary Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C infection, but treatment failure occurs in some patients. Retreatment of patients who previously failed a regimen consisting of sofosbuvir and an NS5A inhibitor with a regimen of glecaprevir and pibrentasvir (G/P) is >90% effective. Herein, we analyzed samples from these patients and showed that retreatment efficacy with G/P is lower in patients with double- or triple-linked NS5A resistance mutations than in patients with single or no NS5A resistance mutations. Clinical trial number NCT03092375 .

ABBV-47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS-CoV-2. This first-in-human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID-19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double-blind, and placebo-controlled single ascending dose study of ABBV-47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non-hospitalized (confined) adults with mild to moderate COVID-19. Primary outcomes were grade 3 or higher study drug-related adverse events and infusion-related reactions. Secondary outcomes were pharmacokinetic parameters and concentration-time profiles to Day 29, immunogenicity (anti-drug antibodies), and antiviral activity (change in RT-PCR viral load) from baseline to Days 15 and 29. ABBV-47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV-47D11 were linear and showed dose-proportional increases in serum concentrations with ascending doses. The exploratory anti-SARS-CoV-2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV-47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter-individual variability and small sample size a statistical significance was not reached. There is potential for anti-SARS-CoV-2 activity with ABBV-47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit.

Background and Aims Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic HCV‐infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, open‐label study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of GLE and PIB in children ages 3 to < 12 years. Approach and Results Children with chronic HCV infection, genotype 1‐6, with or without compensated cirrhosis, were divided into three cohorts by age—cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)—and given weight‐based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were sustained virologic response at posttreatment week 12 (SVR12) and steady‐state exposure; secondary endpoints were rates of persistent viremia, relapse, and reinfection. Safety and laboratory abnormalities were assessed. Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 to < 30 kg), and 150 mg GLE + 60 mg PIB (12 to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by posttreatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two nonresponders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug‐related serious AEs occurred. Pharmacokinetic exposures were comparable to those of adults. Conclusions A pediatric formulation of GLE/PIB was highly efficacious and well tolerated in chronic HCV‐infected children 3 to < 12 years old.

Copyright infringement adversely affects the interest of copyright holders of images and videos which are uploaded to different websites and peer-to-peer image sharing systems. This paper addresses the problem of detecting copyright infringement so that copyright holders are given due credit for their work. There are several images and videos that are shared every day by millions of users with some amount of modification in images and videos originally uploaded by the copyright holders such as photographers, graphic designers, and video providers. Copyright violators, who are not the original creators of multimedia content modify them using image processing and frame modification techniques such as grayscale conversion, cropping, rotation, frame compression, and frame speed manipulation. Then, upload the tampered images and videos. To address this problem, we propose an IPFS-based (InterPlanetary File System-based) decentralized peer-to-peer image and video sharing platform built on blockchain technology. We use a perceptual hash (pHash) technique to detect copyright violations of multimedia. When multimedia is to be uploaded to the IPFS, the pHash of the same content is determined and checked against existing pHash values in the blockchain network. Similarity with existing pHash values would result in the multimedia being detected as tampered with. Blockchain technology offers the advantage of non-involvement of a third party and consequently the avoidance of a single point of failure.

Provenance provides information about how data came to be in its present state. Recently, many critical applications are working with data provenance and provenance security. However, the main challenges in provenance-based applications are storage representation, provenance security, and centralized approach. In this paper, the authors propose a secure trading framework which is based on the techniques of blockchain that includes various features like decentralization, immutability, and integrity in order to solve the trust crisis in centralized provenance-based system. To overcome the storage representation of data provenance, they propose JavaScript object notation (JSON) structure. To improve the provenance security, they propose the access control language (ACL) rule. To implement the JSON structure and ACL rules, permissioned blockchain based tool “Hyperledger Composer” has been used. They demonstrate that their framework minimizes the execution time when the number of transaction increases in terms of storage representation of data provenance and security.

The Internet of Medical Things (IoMT) is the next frontier in the digital revolution and it leverages IoT in the healthcare domain. The underlying technology has changed the current healthcare system by collecting real-time data of patients and providing a patient motioning system. But IoMT also presents a big challenge for data storage management, security, and privacy due to cloud-based storage. Today, this large volume of IoMT generated medical data is stored in the centralized storage system. However, centralization of patient sensitive information leads to a single point of failure, privacy, and security concern. To address these issues, we propose a smart contracts enabled consortium blockchain network. We integrated interplanetary file systems (IPFS) cluster node where smart contracts are deployed at the initial stage for authentication of patient’s and medical devices, the same cluster layer is also proposed as a distributed data storage layer for device-generated data after authentication and these data are securely transmitted over the consortium blockchain. The IPFS cluster node ensures the security and authentication of the devices and it also provides secure storage management in IoMT enabled healthcare system. The consortium network enables the privacy of data owing to hash-based storage in a block of IoMT enabled healthcare network.

Results of National Gas Hydrate Program-02 (NGHP-02) expedition have confirmed the resource potential of sand-hosted gas hydrate accumulations in the deep offshore of Krishna-Godavari Basin (KG Basin). NGHP-02 has identified two types of gas hydrate accumulations: one is thick, layer-type units developed in sand-rich facies at depths of a few 100 m below sea floor (mbsf), and the other, fracture type unit of variable thickness at shallow depths. Fracture-type and Layer-type gas hydrates were observed in Areas B, C, and E in the KG Basin as defined under NGHP-02. The importance of each type of gas hydrate occurrence as discovered during NGHP-02 has led to the need for microbial profiling. Different classes of microbes, anaerobic fermentative microbes (AFM), methanotrophs and sulphate reducing bacteria (SRB) were studied to understand the microbial system for biogenic gas generation in sedimentary sequences encountered in eight core holes (4 in Area B, 3 in Area C and 1 in Area E) as established during NGHP-02. This study reveals the availability of highest concentration of methane generating microbes that are closely associated with high total organic carbon (TOC) content in the identified gas hydrate bearing sedimentary units cored in each borehole. The presence of microbial consortia for methane generation through both processes, of reduction of CO2 and fermentation of formate/acetate has been confirmed. Stratigraphic correlation between drill sites have also been generated to better understand the spatial relationship of various microbial processes. An observation from the study, is that the entire late Miocene age sediments has potential to generate biogenic gas in Holes NGHP-02-05B, −17B, −22B and −23B. Late to early Pleistocene age sediments are showing methane generating activity in Holes NGHP-02-01C, −08B and −09B, while early Pleistocene to late Pliocene age sediments contains methane generating microbes in Holes NGHP-02-05B, −17B, −19B, −22B and −23B. The existence of methane generating biogenic microbial system in Areas B, C and E of KG Basin has been confirmed.

Background: Given varied forms of stressors in the backdrop of the COVID 19 pandemic, adolescents are particularly vulnerable to specific mental health challenges. It pertinent to explore how adolescents differ from adults regarding the comprehensive mental health facets amid the 'new normal, i.e., the duration between the first and second wave of COVID-19 in a developing country like India. The present study aimed to compare the comprehensive mental health facets of adolescents with the adults. Also, it aimed to explore the association of mental health facets with age, perceived stress, coping and impact of pandemic. Methods: The study followed a cross-sectional design with 1,027 participants [456 adolescents; 347 young and 224 middle age-adults] recruited from schools and colleges. The Comprehensive DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure, Perceived Stress Scale and Brief COPE Scale were used for assessment. The difference between groups was analyzed using the Chi-Square Test of Independence and correlational analysis was done using Spearman Rank Correlation. Multiple regression analyses were performed for the mental health facets along with bootstrapping method. Results: 33.77% of adolescents, 25.65% of young adults, and 17.41% of middle-aged adults reported that their symptoms started during the pandemic. Compared to adults, the adolescents reported higher depression, anxiety, suicidal ideations, anger, and somatic complaints. Significantly higher adolescent females (39.9%) were found to have sleep disturbances compared to their male counterparts (25.5%). Therefore, it can be observed Adolescents are more clinically vulnerable in most domains. The correlational analysis showed that most mental health domains, except substance use showed moderate-to-low correlations with ‘Impact of COVID’. Perceived stress, impact of COVID, self-distraction, self-blaming were significant independent positive predictors for all the mental health domains except substance use. ‘Age’ was negatively associated with depression anxiety, repetitive thoughts, personality changes, suicidal ideations and memory, and positively associated with ‘substance use’ at low levels. Maladaptive coping was moderately positively correlated with all the mental health domains. Conclusion: It can be observed Adolescents are more clinically vulnerable in most domains. This study provides a comprehensive analysis for assessment and clinical decision-making to combat the mental health problems arising and exacerbating due to the COVID-19 pandemic. The findings will help in planning and implementing an appropriate interventional program, and making policy decisions related to the vulnerable group of adolescents.

Today healthcare industries are maintaining COVID-19 patients' information electronically which includes patients' diagnostic reports, patients' private information, and doctor prescriptions. However, the COVID-19, patient sensitive information is currently stored in centralized or third-party storage model. One of the key challenge of centralized storage model is the preserving privacy of patient information and transparency in the system. The privacy risk include illegitimate access to sensitive information of patient such as identification details access and misutilization of patient information and their clinical records. To overcome this challenge, we proposed a distributed on-chain and off-chain storage model using consortium blockchain and interplanetary file systems (IPFS). The proposed framework though maintaining patient privacy makes it easier for legitimate entities like healthcare providers (e.g., physicians and clinical staffs) to access clinical data of COVID-19 patients'.

David Bernstein,1 Rakesh Tripathi,2 Daniel E Cohen2 1Zucker School of Medicine, Hofstra University, Hempstead, New York, NY, USA; 2AbbVie Inc., North Chicago, IL, USA Background: This international, phase 2, open-label, multicenter study (ClinicalTrials.gov Identifier: NCT01609933) was conducted to evaluate the safety and efficacy of an enhanced regimen consisting of the direct-acting antivirals (DAAs) ombitasvir, paritaprevir, and ritonavir administered for 24 weeks, combined with pegylated interferon-α2a plus ribavirin (pegIFN-α2a/RBV) for 48 weeks, in patients with chronic hepatitis C virus (HCV) genotype 1 infection who had experienced virologic failure with a prior DAA regimen. This study was undertaken at a time when options were limited for the retreatment of patients who had failed prior DAA therapy. Methods and results: Thirty-two patients were enrolled; the majority were male (78%) and White (94%), and the median age was 54.5 years. Twelve weeks after the last dose of study drug, sustained virologic response was achieved in 81.3% of patients. Five patients prematurely discontinued the study drugs and one patient relapsed. Safety and tolerability were similar to prior studies of pegIFN-α2a/RBV alone.Conclusion: Given the availability of highly efficacious DAA regimens that are both IFN- and RBV-free, this regimen is no longer relevant in today’s HCV treatment landscape. Keywords: direct-acting antiviral, retreatment, virologic failure

Introduction and aim: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an open-label multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. Materials and methods: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA

Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse with 17 confirmed and 4 provisional subtypes. In this report, HCV GT4-infected patient samples from Phase 2/3 clinical studies were analysed to characterize global demographics and genetic diversity of GT4 infection among patients treated with ombitasvir (OBV, NS5A inhibitor) plus paritaprevir/r (NS3/4A inhibitor codosed with ritonavir). Among 17 subtypes isolated from GT4-infected patients in the PEARL-I and AGATE-I studies, subtype prevalence by country of enrolment and country of origin suggested that subtypes 4a and 4d were likely circulating in Europe, while heterogeneous GT4 subtypes and a portion of GT4a detected in European and North American countries were likely due to immigration of HCV-infected patients from Africa. The distributions of birth cohort and race were also significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. In addition, phylogenetic analyses of NS5A sequences revealed clustering within subtype 4a which segregated by the patient-reported country of origin and the presence of the L30R/S polymorphism. HCV NS5A sequences derived from GT4a-infected patients who originated from Europe and the United States clustered separately from sequences derived from patients who originated from Egypt, suggesting that genetically distinct strains of subtype 4a may be circulating globally. Finally, NS5A baseline polymorphisms were frequently detected at amino acid positions of interest for the inhibitor-class and OBV retained activity against 37 of 39 NS5A GT4 clinical isolates, with no impact on treatment outcome in the PEARL-I and AGATE-I studies.

A teknofibra material walker which protects heat sensitive parts mounted in close proximity to high temperatures with balanced detector provides a smart solution for the elderly who are unable to walk without an assistive device. The walker provides a balance detection system which continuously calculates the dynamic state of walking of the elderly person with respect to the walker system and assist the elderly by generating an alarm if the system tends to become unstable. The sensor mounted at different places in the walker system continuously monitors the position of the elderly person through proximity and alert the user when he tries to cross the base of support area of the walker so that one can come back or slow down the walking speed and protect himself from falling. The walker with a compact design with three wheel foldable systems and sitting capability extended support for sitting is provided in the base of walker structure so as to male system stable. The three wheeled, foldable, made of light weighted and heat resisting material with sitting arrangements makes the overall structure very useful for elderly.

Treatment of HCV genotype (GT) 2-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) without ribavirin for 12 weeks in the phase 2 study M12-536, and with ribavirin for 16 weeks in phase 3 study GIFT II resulted in SVR rates of 72.2% to 91.5%. Overall, 11 out of 125 patients with GT2a and 37 out of 79 patients with GT2b infection experienced virologic failure. The prevalence of baseline polymorphisms in NS3 and NS5A and their the impact on treatment outcome, as well as the development of viral resistance in GT2-infected patients experiencing virologic failure were evaluated by HCV NS3 and NS5A population and clonal sequence analyses. Baseline polymorphisms in NS3 that confer resistance to paritaprevir were rare in both GT2a- and GT2b-infected patients, while baseline polymorphisms in NS5A that confer resistance to ombitasvir were detected in 11.2% and 14.1% of the GT2a- and GT2b-infected patients, respectively. There was no significant impact of baseline polymorphisms on treatment outcome in Japanese patients. The most common treatment-emergent substitutions at the time of virologic failure occurred at amino acid positions 168 in NS3 and 28 in NS5A in both GT2a- and GT2b-infected patients. Although there was a higher rate of virologic failure in patients with GT2b infection, the resistance analyses presented in this report support the conclusion that testing for baseline resistance-associated polymorphisms is not warranted for HCV GT2-infected patients treated with a regimen of ombitasvir/paritaprevir/ritonavir + ribavirin for 16 weeks.

In this paper we propose an algorithm for load balancing in distributed data centers based on game theory. We model the load balancing problem as a non-cooperative game among the front-end proxy servers. We model the operating cost associated with a data center as a weighted linear combination of the energy cost and the latency cost. We propose a non-cooperative load balancing game with the objective of minimizing the operating cost and obtain the structure of Nash equilibrium. Based on this structure, a distributed load balancing algorithm is designed. We compare the performance of the proposed algorithm with the existing approaches. Numerical results demonstrate that the solution achieved by the proposed algorithm approximates the global optimal solution in terms of the cost and it also ensures fairness among the users.

With the advancement in sensor technology and the proliferation of low-cost electronic circuits, Internet of Things (IoT) is emerging as a promising technology for realization of smart cities. However, challenges such as security, privacy, trust, scalability, verifiability, and centralization prevent faster adaptations of IoT-driven smart cities. Thus, in this paper, a Trustworthy Privacy-Preserving Secured Framework (TP2SF) for smart cities is presented. This framework includes three modules namely: a trustworthiness module, a two-level privacy module, and an intrusion detection module. In trustworthiness module, address-based blockchain reputation system is designed. In the two-level privacy module, a blockchain based enhanced Proof of Work (ePoW) technique is simultaneously applied with Principal Component analysis (PCA) to transform data into a new reduced shape for preventing inference and poisoning attacks. In the intrusion detection module, an optimized gradient tree boosting system (XGBoost) is deployed. Finally, due to inherited strengths and weaknesses of Fog–Cloud architecture, we present a blockchain-IPFS integrated Fog–Cloud infrastructure namely, CloudBlock and FogBlock to deploy proposed TP2SF framework in smart city. The TP2SF framework is evaluated using two realistic IoT-based datasets, namely ToN-IoT and BoT-IoT. The findings indicate the superiority of TP2SF framework over other state-of-the-art techniques in both nonblockchain and blockchain systems.

The recent epidemic of Zika virus (ZIKV) has created a major global health concern. Here, the crystal structure of the full-length ZIKV NS5 protein at 3.05 Å resolution is presented to facilitate the structure-based design of antiviral agents against ZIKV., The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5′-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

This work focuses on the possibility of optimum utilization of Industrial by-product by replacing the natural sand with Pond Ash and Slag in the concrete. This work also aims in the prediction of 28 days strength using early age measurement of resistivity and compressive strength. Mechanical properties of modified concrete have been obtained and compared with that of the standard mix of concrete. Uniaxial electrical resistivity measurement has been performed on the samples. These observations have been compared with results given by previous researchers. Using these comparison performances based quality control, diffusion of chloride and corrosion of rebar in concrete has been assessed. Further, statistical model has been generated for the prediction of 28 days compressive strength by Response Surface Method (RSM) using early age measurement of resistivity and compressive strength as dependent variables. The results obtained indicate that, for slag model the ultimate strength is not much affected rather resistivity has been significantly improved; consequently it has better quality, reduced corrosion and lower diffusion coefficient. In order to compare the results obtained from the RSM model and experimental method, an error analysis had been performed. The errors are approximately 3.63% for the prediction of 28 days strength.

Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) are potent and pangenotypic hepatitis C virus (HCV) direct-acting antivirals. This report describes the baseline polymorphisms and treatment-emergent substitutions in NS3 or NS5A detected in samples from HCV genotype 1-infected patients receiving 3-day monotherapy of glecaprevir or pibrentasvir, respectively. None of the NS3 polymorphisms detected in the 47 baseline samples collected prior to glecaprevir monotherapy conferred reduced susceptibility to glecaprevir. The NS3 A156T substitution, which conferred resistance to glecaprevir but had low replication efficiency, emerged in one genotype 1a-infected patient among the 35 patients with available post-baseline sequence data. Baseline NS5A polymorphisms were detected in 12 of 40 patients prior to pibrentasvir monotherapy, most polymorphisms were single-position NS5A amino acid substitutions that did not confer resistance to pibrentasvir. Among the 19 patients with available post-baseline NS5A sequence data, 3 had treatment-emergent NS5A substitutions during pibrentasvir monotherapy. All treatment-emergent NS5A substitutions were linked multiple-position, almost exclusively double-position, substitutions that conferred resistance to pibrentasvir. Replicons engineered with these double-position substitutions had low replication efficiency. In conclusion, resistance-conferring substitutions emerged in a small number of genotype 1-infected patients during glecaprevir or pibrentasvir monotherapy, unlike other NS5A inhibitors, pibrentasvir did not select single-position NS5A substitutions during monotherapy.

Over 2,200 patients infected with hepatitis C virus (HCV) genotypes (GT) 1 to 6, with or without cirrhosis, who were treatment naive or experienced to interferon, ribavirin, and/or sofosbuvir were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight registrational phase 2 and 3 clinical studies. High rates of sustained virologic response at 12 weeks postdosing (SVR12) were achieved with a

Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising 40% of their preexisting viral population, the 24-week SVR (SVR 24 ) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients.

Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography.

The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively. In vitro , the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log 10 was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. NCT01074008.)

Glecaprevir (formerly ABT-493) is a novel hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) with pangenotypic activity. It inhibited the enzymatic activity of purified NS3/4A proteases from HCV genotypes 1 to 6 in vitro (half-maximal [50%] inhibitory concentration = 3.5 to 11.3 nM) and the replication of stable HCV subgenomic replicons containing proteases from genotypes 1 to 6 (50% effective concentration [EC 50 ] = 0.21 to 4.6 nM). Glecaprevir had a median EC 50 of 0.30 nM (range, 0.05 to 3.8 nM) for HCV replicons containing proteases from 40 samples from patients infected with HCV genotypes 1 to 5. Importantly, glecaprevir was active against the protease from genotype 3, the most-difficult-to-treat HCV genotype, in both enzymatic and replicon assays demonstrating comparable activity against the other HCV genotypes. In drug-resistant colony selection studies, glecaprevir generally selected substitutions at NS3 amino acid position A156 in replicons containing proteases from genotypes 1a, 1b, 2a, 2b, 3a, and 4a and substitutions at position D/Q168 in replicons containing proteases from genotypes 3a, 5a, and 6a. Although the substitutions A156T and A156V in NS3 of genotype 1 reduced susceptibility to glecaprevir, replicons with these substitutions demonstrated a low replication efficiency in vitro . Glecaprevir is active against HCV with most of the common NS3 amino acid substitutions that are associated with reduced susceptibility to other currently approved HCV PIs, including those at positions 155 and 168. Combination of glecaprevir with HCV inhibitors with other mechanisms of action resulted in additive or synergistic antiviral activity. In summary, glecaprevir is a next-generation HCV PI with potent pangenotypic activity and a high barrier to the development of resistance.

Glecaprevir and pibrentasvir are hepatitis C virus (HCV) pangenotypic inhibitors targeting NS3/4A protease and NS5A, respectively. This once-daily, fixed-dose combination regimen demonstrated high sustained virologic response 12 weeks postdosing (SVR 12 ) rates in CERTAIN-1 and CERTAIN-2 studies in Japanese HCV-infected patients, with a low virologic failure rate (1.2%). There were no virologic failures among direct-acting antiviral (DAA)-treatment-naive genotype 1a (GT1a) ( n = 4)-, GT1b ( n = 128)-, and GT2 ( n = 97)-infected noncirrhotic patients treated for 8 weeks or among GT1b ( n = 38)- or GT2 ( n = 20)-infected patients with compensated cirrhosis treated for 12 weeks. Two of 33 DAA-experienced and 2 of 12 GT3-infected patients treated for 12 weeks experienced virologic failure. Pooled resistance analysis, grouped by HCV subtype, treatment duration, prior treatment experience, and cirrhosis status, was conducted. Among DAA-naive GT1b-infected patients, the baseline prevalence of NS3-D168E was 1.2%, that of NS5A-L31M was 3.6%, and that of NS5A-Y93H was 17.6%. Baseline polymorphisms in NS3 or NS5A were less prevalent in GT2, with the exception of the common L/M31 polymorphism in NS5A. Among DAA-experienced GT1b-infected patients (30/32 daclatasvir plus asunaprevir-experienced patients), the baseline prevalence of NS3-D168E/T/V was 48.4%, that of NS5A-L31F/I/M/V was 81.3%, that of the NS5A P32deletion was 6.3%, and that of NS5A-Y93H was 59.4%. Common baseline polymorphisms in NS3 and/or NS5A had no impact on treatment outcomes in GT1- and GT2-infected patients; the impact on GT3-infected patients could not be assessed due to the enrollment of patients infected with diverse subtypes and the limited number of patients. The glecaprevir-pibrentasvir combination regimen allows a simplified treatment option without the need for HCV subtyping or baseline resistance testing for DAA-naive GT1- or GT2-infected patients. (The CERTAIN-1 and CERTAIN-2 studies have been registered at ClinicalTrials.gov under identifiers NCT02707952 and NCT02723084, respectively.)

Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC 50 ) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC 50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC 50 , only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC 50 , very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors.

The extraction of roads from digital images is essential for automatic mapping, effective urban planning and updating of GIS databases. The very high spatial resolution images (VHR) taken by space and space probes are the main source of an accurate extraction of the route. The extraction of road networks in remote urban areas of images plays an important role in many urban applications (eg. Road traffic, geometric correction of remote sensing images in cities, updating geographical information, etc.). Because of the complex geometry of buildings and the geometry of sensor detection, it is generally difficult to distinguish the road from its background. In this research work the image segmentation techniques used for image remote sensing are discussed and evaluated. It has been found that there is no perfect method for image segmentation because the result of image segmentation depends on many factors, i.e. Pixel color, consistency, intensity, image similarity, image content and problem area. In this research work, a hybrid method is proposed for the extraction of paths from high resolution images based on the segmentation of the mean and HFT segmentation. The proposed method includes: noise suppression using the Lucy-Richardson algorithm, then a further improvement of the contrast between the initial segmentation of road and non-road pixels using the segmentation means k and finally HFT based segmentation. Simulation will be conducted on remote sensing images in urban, suburban and rural areas to demonstrate the proposed method and compare it with other similar approaches. The results show the validity and superior performance of the proposed extraction method.

Information extraction is a very challenging task because remote sensing images are very complicated and can be influenced by many factors. The information we can derive from a remote sensing image mostly depends on the image segmentation results. Image segmentation is an important processing step in most image, video and computer vision applications. Extensive research has been done in creating many different approaches and algorithms for image segmentation. Labeling different parts of the image has been a challenging aspect of image processing. Segmentation is considered as one of the main steps in image processing. It divides a digital image into multiple regions in order to analyze them. It is also used to distinguish different objects in the image. Several image segmentation techniques have been developed by the researchers in order to make images smooth and easy to evaluate. Various algorithms for automating the segmentation process have been proposed, tested and evaluated to find the most ideal algorithm to be used for different types of images. In this paper a review of basic image segmentation techniques of satellite images is presented.

AVIATOR, a phase 2 clinical trial, evaluated ritonavir-boosted paritaprevir (a protease inhibitor), ombitasvir (an NS5A inhibitor), and dasabuvir (a nonnucleoside polymerase inhibitor) (the three-drug [3D] regimen) with or without ribavirin (RBV) for 8, 12, or 24 weeks in 406 HCV genotype 1 (GT1)-infected patients. The rate of sustained virologic response 24 weeks after treatment ranged from 88% to 100% across the arms of the 3D regimen with or without RBV; 20 GT1a-infected patients and 1 GT1b-infected patient experienced virologic failure (5.2%). Baseline resistance-conferring variants in NS3 were rare. M28V in GT1a and Y93H in GT1b were the most prevalent preexisting variants in NS5A, and C316N in GT1b and S556G in both GT1a and GT1b were the most prevalent variants in NS5B. Interestingly, all the GT1a sequences encoding M28V in NS5A were from the United States, while GT1b sequences encoding C316N and S556G in NS5B were predominant in the European Union. Variants preexisting at baseline had no significant impact on treatment outcome. The most prevalent treatment-emergent resistance-associated variants (RAVs) in GT1a were R155K and D168V in NS3, M28T and Q30R in NS5A, and S556G in NS5B. The single GT1b-infected patient experiencing virologic failure had no RAVs in any target. A paritaprevir-ritonavir dose of 150/100 mg was more efficacious in suppressing R155K in NS3 than a 100/100-mg dose. In patients who failed after receiving 12 or more weeks of treatment, RAVs were selected in all 3 targets, while most patients who relapsed after 8 weeks of treatment did so without any detectable RAVs. Results from this study guided the selection of the optimal treatment regimen, treatment duration, and paritaprevir dose for further development of the 3D regimen. (This study has been registered at ClinicalTrials.gov under registration number NCT01464827.)

1Post doctoral research fellow, Johns Hopkins Hospital, Baltimore, MD. 2Superintendent in-Chief, Additional Director, Faizabad, India. 3ART Officer, District Hospital, Pratapgarh, India. Backorund: Tuberculosis (TB) remains a worldwide health problem. In 2013, an estimated 9 million people developed TB, most of which in South East Asian Region. Of these, 13 percent were HIV positives. India alone accounts for 24 percent of total TB cases making it the world's TB capital. HIV increases persons susceptibility to TB and in resource-strained country like India, TB could be one of the earliest manifestations in people with HIV. Study Geography, Design and Methods: A predesigned and pretested questionnaire was used to collect data in at ART clinic Pratapgarh, UP. Blood samples were tested for HIV infection using ELISA or Western Blot. All positive patients were transferred to RNTCP to be screened for pulmonary TB by using standard technique. Results

A 23-day-old male baby with a history of perinatal hypoxia presented with refusal of feeds and abdominal distension. The child had a right-sided cystic upper abdominal mass and features of neonatal septicemia. Abdominal ultrasound (US) and contrast-enhanced CT scan showed bilateral adrenal abscesses. Laparotomy with drainage of the abscesses successfully treated the condition. The literature on the subject is reviewed.

The paper focuses on an evaluation of particle filter based facial feature tracker. Particle filter is a successful tool in the non-linear and the non-Gaussian estimation problems. We developed a particle filter based facial points tracker with a simple observation model based on sum-of-squared differences (SSD) between the intensities. Multistate face component model is used to estimate the occluded feature points. The important distances are calculated from tracked points. Two kinds of classification schemes are considered, the hidden Markov model (HMM) as sequence based recognizer and support vector machine (SVM) as frame based recognizer. A comparative study is shown in the classification of five basic expressions, i.e., anger, sadness, happiness, surprise and disgust. The tests are conducted on Cohn-Kanade and MMI face expression databases.

Bilateral eventration of the diaphragm associated with malrotation of gut and unilateral renal agenesis is a very rare entity. The authors treated a seven mth old male child who presented to them with respiratory distress and gastrointestinal problem. The child was anemic and was in type II respiratory failure. His X-ray chest showed bilateral eventration of diaphragm and ultrasonography abdomen was consistent with left renal agenesis which was confirmed by radionuclide scan. Bilateral plication of the diaphragm done with correction of malrotation which was diagnosed peroperatively. The association of these three anomalies are rare and to be kept in mind whenever treating a patient with bilateral eventration of the diaphragm.