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Designing a voting system that ensures fairness, privacy, and security is a significant challenge. The lack of trust in election systems among large sections of society worldwide is a major concern for democracy. Flawed voting systems pose a threat to democracies, including governing bodies, co-operating societies, and student councils. Vote rigging, hacking of electronic voting machines (EVMs), election manipulation, and booth capturing are the key issues with the current electoral system. To address these issues, we propose using novel technologies such as blockchain and Merkel trees, which are wellknown for their security benefits. Our system builds on popular blockchain frameworks that provide blockchain as a service, while preserving participants' anonymity and enabling public scrutiny. Blockchain is a unique technology of our time that promises to enhance the resilience of digital voting platforms. It presents an opportunity to leverage the benefits of blockchain, such as cryptographic foundations and transparency, to achieve an efficient digital voting system.

Peritoneum is a serosal membrane lining the solid viscera and the hollow viscus of the abdomen and is made of a single layer of mesothelial cells. The most common primaries that spread to the peritoneum include gastrointestinal, ovarian, colorectal, and peritoneal metastases can be seen at some point during the disease course in 15 to 43%, 60 to 70% and 15 to 20% of patients, respectively. Other malignancies involving the peritoneum such as primary peritoneal carcinoma, peritoneal mesothelioma, peritoneal lymphomatosis, pseudomyxoma peritonei from low-grade appendiceal mucinous neoplasm, are far less common. The review strives to provide a framework for diagnosis and management of the disease.

Preoperative diagnosis of gallbladder cancer (GBC) remains a challenge. Unwarranted extensive surgery for benign disease and undertreatment for GBC pose challenges. We aimed to analyze the utility, diagnostic accuracy, and limitations of intraoperative frozen section (FS), for primary diagnosis of suspected gallbladder malignancy.Patients with suspected GBC underwent a cystic-plate cholecystectomy and FS for primary diagnosis. The procedure was considered adequate if FS suggested a benign pathology. A radical cholecystectomy was performed if FS favoured GBC, or in patients with high intra-operative suspicion of malignancy. All FS records were compared with final histopathology.FS guided the surgical strategy in 491 of 575 resections (85.4%). FS had a sensitivity of 88.3%, specificity of 99.6%, a positive predictive value of 99.4% and a negative predictive value of 92.7%. The diagnostic accuracy of FS was 95.1%. With routine use of intraoperative FS, only 10 out of 491 patients (2%) required a revised surgical strategy.For radiologically suspected GBC it is prudent to confirm the histological diagnosis by use of intraoperative FS before undertaking radical resections. This study emphasizes the safety and accuracy of FS as an adjunct for directing optimal surgical strategy in suspected GBC.

With firms increasingly relying on external knowledge resources for solving complex problems, the role of digital platforms, which make this external search efficient, has become significant. For such platforms, of which Kaggle is an example, a perennial challenge is to elicit high-quality solutions from their voluntary contributors. To this end, our work underscores the importance of platform-wide design decisions for the quality of solutions that the platform's users generate. We show that a social feature that offers reputational gain may lead to significant quality improvements. Therefore, we recommend that platforms should view such features more favorably and include them. In addition, our work also suggests that firms that are using digital platforms to engage with external knowledge sources should time their activities, keeping in mind platform-wide design changes given that such changes can directly impact the firm's surplus.

Cervical cancer is the fourth most common cancer in women globally and the second most common cancer in Indian women, more common in lower socioeconomic strata. Improvement in survival and decrease in morbidity reflect the earlier detection with screening and imaging, as well as multifactorial multimodality therapy integrating surgery, and concurrent chemoradiation therapy providing superior therapeutic benefits. Imaging plays a vital role in assessing the extent of disease and staging of cervical cancer. The appropriateness criteria of a modality are different from its availability based on infrastructure, medical facilities, and resource status. Although in an ideal situation, magnetic resonance imaging (MRI) would be of greatest value in locoregional assessment of extent of disease and fluorodeoxyglucose positron emission tomography-computed tomography for distant staging; often, an ultrasonography, chest radiograph, and bone scans are utilized, with contrast-enhanced computed tomography representing a fair superior diagnostic accuracy, and can be reported as per the RECIST 1.1 criteria. MRI is also of good utility in the assessment of residual disease, predicting response and detecting small volume recurrence. MRI offers the highest diagnostic accuracy in determining parametrial invasion and hence surgical planning; so also, MRI-guided radiation planning helps in more accurate graded radiation dose planning in radiation therapy. Stage and therapy-based surveillance imaging should be encouraged and recommended.

Background: The pandemic of COVID-19 infection has almost paralyzed the world since the first infection was reported in December 2019. We have seen 3 waves of infection in the country, out of which the second wave caused by the delta variant was the most severe. Along with the preventive measures of masking, maintaining social distance, and handwashing, the vaccines seemed to be the most logical next step. Many vaccines received emergency use approvals with hardly any efficacy and adverse effects data available with the process inducing a significant amount of anxiety among the public. This survey was aimed at understanding the attitude and perception of our hospital employees towards COVID-19 vaccination. Methods: This is a cross-sectional study conducted among health care workers (HCW) at CMC, Vellore between March 2021 to July 2021. The HCWs who are willing to participate in this study were recruited and collected the quantitative data on their attitude and perception towards COVID vaccine. In-depth interviews were conducted among those who did not take vaccine to understand the reasons for not taking vaccine. The data were analyzed using statistical package for the social sciences (SPSS). Results: The survey results were analyzed on 435 HCWs. 58.4 percent of the HCWs trust the institutional protocols as the trusted source of information about vaccine. Most of the HCWs agreed that vaccines are the only protective way, and they are safe and effective. Conclusions: Sensitization and awareness programs with transparency of vaccine development processes, safety and efficacy will help remove barriers.

Background The objective of this post-hoc analysis was to assess the efficacy and safety of upadacitinib in psoriatic arthritis (PsA) patients with axial involvement. Methods Post-hoc analysis of SELECT-PsA 1 and SELECT-PsA 2 in patients randomized to upadacitinib 15 mg (UPA15), placebo (switched to UPA15 at week 24), or adalimumab 40 mg (ADA; SELECT-PsA 1 only). Axial involvement was determined by investigator judgement (yes or no; based on the totality of available clinical information, such as duration and characteristics of back pain, age of onset, and previous lab investigations and imaging, if available) alone, or investigator judgement and patient-reported outcome (PRO)-based criteria (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4 and BASDAI Q2 ≥ 4). Efficacy outcomes that describe axial disease activity, including BASDAI endpoints, such as change from baseline in the overall BASDAI score or proportion of patients achieving BASDAI50 (≥ 50% improvement from baseline), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints, such as mean change from baseline in overall ASDAS or proportion of patients achieving ASDAS inactive disease or low disease activity, were evaluated at weeks 12, 24, and 56, with nominal P-values shown. Treatment-emergent adverse events (TEAEs) are summarized through week 56. Results 30.9% of patients in SELECT-PsA 1 and 35.7% in SELECT-PsA 2 had axial involvement by investigator judgement alone; 22.6% (SELECT-PsA 1) and 28.6% (SELECT-PsA 2) had axial involvement by investigator judgement and PRO-based criteria. Greater proportions of patients achieved BASDAI50 with UPA15 versus placebo using either criterion, and versus ADA using investigator judgement alone, at week 24 in SELECT-PsA 1 (investigator alone: UPA15, 59.0%, placebo, 26.9%, P P = 0.015; investigator and PRO-based: UPA15, 60.4%, placebo, 29.3%, P P = 0.074), with comparable findings in SELECT-PsA 2. Similar results were observed with UPA15 for additional BASDAI and ASDAS endpoints at weeks 12 and 24, with improvements maintained at week 56. Rates of TEAEs were generally similar across sub-groups irrespective of axial involvement status. Conclusions PsA patients with axial involvement determined by predefined criteria showed greater BASDAI and ASDAS responses with UPA15 versus placebo, and numerically similar/greater responses versus ADA. Safety results were generally comparable between patients with or without axial involvement. Trial registration ClinicalTrials.gov: SELECT-PsA 1, NCT03104400; SELECT-PsA 2, NCT0310437.

Background: Drakshasava is a general health tonic, carminative and blood purifier. It is used in the treatment of anemia, digestive & cardiac disorders. A review of the literature suggested that modern analytical methods are not reported for the phytochemical evaluation of drakshasava. Objective: To report phytochemical evaluation of Drakshasava Formulation by Spectroscopic & Chromatographic Methods. Materials and methods: Total phenolic, flavonoid, sugar and reducing sugar content in marketed drakshasava formulations were estimated by a UV-Vis spectrophotometer. The markers and extract of drakshasava formulations I & II were scanned by FTIR spectrophotometer individually to find the common bands of the vibrational spectra of markers and formulations. The markers and extract of drakshasava formulations I & II were subjected to HPLC analysis. Results: UV-Vis spectrophotometer analysis revealed that total phenolic, flavonoid, total sugar, & total reducing sugar of marketed drakshasava formulations were within the limit of ayurvedic pharmacopeia. The gradient mobile phase solvent A (HPLC grade water containing 0.85% w/v ortho phosphoric acid) and solvent B (acetonitrile) were optimized by considering the resolution, peak shape, and symmetry. Conclusion: The evaluation parameters reported in this article could be used as a standard reference for quality management of marketed drakshasava formulations.

The enhancement in electric power quality using a single-stage solar PV integrated Unified Power Quality Conditioner (UPQC) has been discussed in this paper. The UPQC is the combination of Distributed static compensator (DSTATCOM) and Dynamic Voltage Restorer (DVR) having the common DC voltage supply link. The DSTATCOM compensates for the load current associated problems like load power factor improvement, even and odd current harmonics elimination etc. Also, it performs the additional work of transferring power from the solar PV system to the load of the distribution system. The DVR compensates the voltage-associated power quality problems like source voltage sag, source voltage swell, and voltage distortion. Discussed UPQC with distributed generation system works on modified synchronously rotating reference frame theory. With the help of the discussed system, the two outcomes are achieved such as clean and renewable energy generation and power quality enhancement. The system is designed in MATLAB Simulink environment and then system performance is verified on Real-Time Digital Simulator (OPAL-RT OP4510) in Software in Loop Simulation (SIL) and Hardware in Loop Simulation (HIL) platforms.

Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis.The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373.Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs 35 [23%] of 157 patients; p0·0001; treatment difference 22%, 95% CI 12-32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment.Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis.AbbVie.

Background: Pyrimidines have been shown to possess numerous biological activities, such as antimicrobial, anticancer, anticonvulsant, antiviral, and anti-inflammatory. Objective: Encouraged by these data, the synthesis of 2-((1H-benzo[d]imidazol-2-yl)methylthio)-4- amino-6-phenylpyrimidine-5-carbonitrile (3a-g) was performed. Methods: 4-amino-2-mercapto-6-phenylpyrimidine-5-carbonitrile was dissolved in an aqueous sodium hydroxide solution, and to this clear solution, 2-chloromethyl-1H-benzimidazole in methanol was added, and the reaction mixture was stirred under reflux to get the desired product. The structures of the newly synthesized compounds were confirmed by their physical, chemical, and spectral data. The synthesized derivatives were screened for their in vitro antibacterial activity against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, by using ciprofloxacin as a reference standard. While, their antifungal activity was evaluated against Aspergillus niger and Candida albicans using fluconazole as a reference drug. The docking study was performed to check the interactions of target compounds (3a-g) with homo sapiens DHFR (PDB: 1S3V), bacterial (S. aureus) DHFR (PDB: 2W9T), and DHPS (PDB: 1AD4) protein. The dock score and binding interactions were recorded. Result: The antimicrobial activity study indicated compounds with chloro (3b), fluoro (3f), and bromo (3g) substituents to show good antibacterial as well as antifungal activity. The docking study revealed that the same compounds, i.e., 3b, 3f, and 3g, showed good dock score and comparable interactions compared to the reference ligand (trimethoprim/sulfadiazine), which confirmed their selectivity. Conclusion: It can be presumed that the synthesized compounds have the capability for further promotion as novel antimicrobial agents.

Background/Aims Ixekizumab (IXE) is a high-affinity, monoclonal antibody targeting IL-17A and is approved for the treatment of psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. We report long-term, end-of-study-program, safety outcomes in adult patients with PsO, PsA and axSpA who received at least one dose of IXE over 5 years (PsO) or 3 years (PsA and axSpA). Methods An integrated safety analysis consisting of data from 25 randomised clinical trials (RCTs; 17 PsO, 4 PsA, 4 axSpA) was used to examine long-term safety of IXE. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for all pooled studies by years of therapy and overall through March 2022, and reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at successive year intervals. Additional safety outcomes included selected safety topics of interest (among others). Results A total of 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, with a cumulative IXE exposure of 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA were included in this analysis. The IRs per 100 PY for any TEAE were as follows: patients with PsO=32.5; PsA=50.3; axSpA=38.0. The most commonly reported TEAEs were nasopharyngitis (PsO, IR = 8.8; PsA, IR = 9.0; axSpA IR = 8.4) and upper respiratory tract infection (PsO, IR = 6.2; PsA, IR = 8.3; axSpA IR = 5.8). Serious AEs were reported by 969 patients with PsO (IR = 5.4), 134 patients with PsA (IR = 6), and 101 patients with axSpA (IR = 4.8). Forty-five deaths were reported (PsO=36 [IR = 0.2]; PsA=6 [IR = 0.3]; axSpA=3 [IR = 0.1]). The IRs per 100 PY of discontinuation from the study drug due to AE were as follows: PsO, 2.9; PsA, 5.1; axSpA, 3.1. IRs of injection site reactions were: PsO, 5.9; PsA, 11.6; axSpA, 7.4. IRs of allergic reactions were: PsO, 5.6; PsA, 4.5; axSpA, 4.2. IRs of serious infections were low (PsO, IR = 1.3; PsA, IR = 1.2; axSpA, IR = 1.1). IRs of Candida were low across all indications (PsO, 1.9; PsA, 2.0; axSpA, 1.2), as were IRs of opportunistic infections (PsO, 1.8; PsA, 1.8; axSpA, 1.3). IRs were also low across all indications for depression, major adverse cerebro-cardiovascular events and malignancies (all IRs ≤1.6). Cases of inflammatory bowel disease (IBD) were uncommon (IRs ≤0.8 across indications). Conclusion In this updated analysis with 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA, IXE maintained a long-term safety profile up to 5 years, consistent with previous reports. Disclosure A. Deodhar: Grants/research support; A.D. received direct payments from Eli Lilly and Company as a scientific consultant/speaker, and payments (investigator) made to Oregon Medical Research Center. A. Blauvelt: Consultancies; A.B. received consulting fee from AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor. Member of speakers’ bureau; A.B. discloses direct payment for speaker bureaus from AbbVie, UCB. S. Schwartzman: Consultancies; S.S. is a consultant with AbbVie, Janssen, Lilly, Myriad, Novartis, Regeneron, Sanofi, UCB, Stelexis, Jubilant, and Teijin. Grants/research support; S.S. reports grants/contracts from Eli Lilly and Company, is a board member on the National Psoriasis Foundation Medical Board and part of the Scientific Advisory Board at Myriad. C. Salvarani: None. M. Feely: Shareholder/stock ownership; M.F. is an employee and shareholder at Eli Lilly and Company. Other; M.F. participated on a Data Safety Monitoring or Advisory Board at Eli Lilly and Company, is a Clinical Instructor in Dermatology at Mount Sinai and discloses previous employment with MC Medical Group, reimbursement of fees from Eli Lilly and Company and from Advisory Boards at the DREAM USA South Beach Symposium, is a current member of the AAD Investment Committee, Prevention Medical Review Board and ASDS Social Media Ambassador, and former member of the WDS Practice Advisory Committee, WDS Finance and Investment Committee, WDS Fundraising and Philanthropic Activities Committee, and former AAD Media Expert Team member and NPF Social Ambassador. A. Kronbergs: Shareholder/stock ownership; A.K. is an employee and shareholder at Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N.E. is an employee and shareholder at Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D.Z. is an employee and shareholder at Eli Lilly and Company. E. Mevel: Shareholder/stock ownership; E.M. is an employee and shareholder at Eli Lilly and Company. T. Holzkaemper: Shareholder/stock ownership; T.H. is an employee and shareholder at Eli Lilly and Company. E. Krishnan: Shareholder/stock ownership; E.K. is an employee and shareholder at Eli Lilly and Company. M. Lebwohl: Consultancies; M.L. also reports consulting fees from AnaptysBio, Arcutis, Inc., Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BioMX, Boehringer-Ingelheim, Brickell Biotech, Castle Biosciences,, Corevitas, Dermavant Sciences, Evommune, Inc., Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd., Meiji Seika Pharma, Mindera, National Society of Cutaneous Medicine, New York College of Podiatric Medicine, Pfizer, Seanergy, SUN Pharma, Verrica, and Vial. Grants/research support; M.L. reports grants/contracts from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc. P. Rahman: Consultancies; P.R. received consulting fees from AbbVie, Janssen, Novartis, Eli Lilly and Company and Pfizer. Grants/research support; P.R. discloses grants or contracts received from Janssen and Novartis. H. Marzo-Ortega: Consultancies; H.M-O. also discloses consulting fees from Abbvie, Eli Lilly and Company, Janssen, Moonlake, Novartis, Pfizer, and UCB. Honoraria; H.M-O. discloses payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Biogen, Eli-Lilly, Janssen, Novartis, Pfizer, and UCB. Grants/research support; H.M-O. discloses grants or contracts received from Janssen, Novartis and UCB. Other; H. M-O. additionally discloses support for attending meetings and/or travel from UCB, participation on a Data Safety Monitoring Board or Advisory Board at Pfizer, leadership or fiduciary role in other board, society (paid or unpaid) in the Executive Committee ASAS, the Medical Advisory Board of NASS and as Chair of the British Society for Spondyloarthritis. C. Bullock: Shareholder/stock ownership; C. Bullock is an employee and minor shareholder in Lilly.

Background/Aims In PREVENT (NCT02696031), secukinumab decreased sacroiliac joints (SIJ) bone marrow oedema (BMO) in patients with non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks. We report radiographic progression and inflammation (BMO) assessed by X-ray and magnetic resonance imaging (MRI) of SIJ and spine over 2 years in PREVENT. Methods Patients (N = 555) were randomised (1:1:1) to secukinumab 150 mg, with loading dose (LD) or without (NL), or placebo. Switching to open-label secukinumab or standard of care (SoC) was permitted after Week (W) 20. By W52, all patients received open-label secukinumab or SoC. SIJ and spinal radiographs were collected at baseline and W104 and SIJ and spinal MR scans at baseline, W16, W52 and W104. Spinal radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and SIJ radiographs using modified New York criteria (mNYC). SIJ and spinal BMO was assessed using Berlin Active Inflammatory Lesions Scoring and Berlin MRI scoring, respectively. Average scores of two blinded central readers were used. W104 reading data are presented as observed. Results Radiographs showed most patients (88% secukinumab, 86% placebo) had no SIJ progression (defined as change ≤ smallest detectable change [SDC, 0.46] in total mNYC score) by W104; no patient had an increase ≥2. At W104, screening radiographs of eligible patients were re-evaluated alongside post-baseline images; ∼25% of screening radiographs (68/277 secukinumab; 34/139 placebo) were re-evaluated as mNYC-positive by > 1 reader. Of these, 11/68 patients in the secukinumab (16.2%) and 5/34 in the placebo (14.7%) groups were evaluated as mNYC-negative at W104. Most patients who were mNYC-negative at screening remained mNYC-negative through W104 (202 secukinumab [96.7%]; 102 placebo [97.1%]). Almost all patients (98%) treated with secukinumab 150 mg (pooled LD and NL) showed no structural progression (change in total mSASSS ≤ SDC, [80% agreement level] of 0.76 over 2 years. At baseline, 62 patients (43 secukinumab, 19 placebo) presented with ≥1 syndesmophyte (≥1 vertebral unit scored by ≥ 1 reader). Of those 16 (9 secukinumab [20.9%]; 7 placebo [36.8%]) developed ≥1 new syndesmophyte by W104. Whilst of 354 patients (237 secukinumab, 117 placebo) without syndesmophytes at baseline, only 8 (4 secukinumab [1.7%]; 4 placebo [3.4%]) developed ≥1 new syndesmophyte by W104. Secukinumab reduced SIJ BMO score at W16 (-1.2) and W52 (-1.5) with sustained reduction through W104 (-1.7) in the overall population; greater reduction was observed in patients with baseline score >2 (W16, -4.0; W52, -4.7; W104, -5.4). Baseline spinal inflammation on MRI was low (mean Berlin score: 0.82, secukinumab; 1.07, placebo) with no meaningful change up to W104 (0.56, secukinumab). Conclusion Most patients showed no radiographic progression through 2 years. There was some discrepancy between SIJ eligibility and efficacy reads. Secukinumab reduced SIJ inflammation (BMO) on MRI in patients with active nr-axSpA. Disclosure H. Marzo-Ortega: Consultancies; H.M.O. has received consultancy fees from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB. Member of speakers’ bureau; H.M.O. has received speakers bureau fees from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB. Grants/research support; H.M.O. has received grant/research support from Janssen, Novartis and UCB. J. Braun: Consultancies; J.B. has received consultancy fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. Member of speakers’ bureau; J.B. has received speakers bureau fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. Grants/research support; J.B. has received grant/research support from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. R. Blanco: Member of speakers’ bureau; R.B. has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Pfizer, Roche and UCB. Grants/research support; R.B. has received grant/research support from AbbVie, MSD and Roche. L.S. Gensler: Consultancies; L.S.G. has received consultancy fees from AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer and UCB. Grants/research support; L.S.G. has received grant/research support from Janssen, Novartis and UCB. F. van den Bosch: Consultancies; F.v.d.B. has received consultancy fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. Member of speakers’ bureau; F.v.d.B. has received speakers bureau fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. Grants/research support; F.v.d.B. has received grant/research support from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. S. Hall: Member of speakers’ bureau; S.H. has received speakers bureau fees from Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB; consultancy fees from Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. Grants/research support; S.H. has received and grant/research support from AbbVie, Janssen, Merck and UCB. H. Kameda: Consultancies; H.K. has received consultancy fees from AbbVie, Eli Lilly, Gilead Sciences, Janssen, Novartis, Pfizer, Sanofi, Taisho and UCB. Member of speakers’ bureau; H.K. has received speakers bureau fees from AbbVie, Asahi-Kasei, AstraZeneca, Boehringer Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis and Pfizer. Grants/research support; H.K. has received grant/research support from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Eisai, Mitsubishi Tanabe and Taisho. D. Poddubnyy: Consultancies; D.P. has received consultancy fees from AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis and UCB. Member of speakers’ bureau; D.P. has received speakers bureau fees from AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer and UCB. Grants/research support; D.P. has received grant/research support from AbbVie, Eli Lilly, MSD, Novartis and Pfizer. M.G.H. van de Sande: Consultancies; M.G.H.v.d.S. has received consultancy fees from AbbVie, Eli Lilly, Novartis and UCB. Member of speakers’ bureau; M.G.H.v.d.S. has received speakers bureau fees from Novartis and UCB. Grants/research support; M.G.H.v.d.S. has received grant/research support from Eli Lilly, Janssen, Novartis and UCB. D. van der Heidje: Other; D.v.d.H. has worked as a paid instructor for AbbVie, Bayer, BMS, Cyxone, Eisai, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Novartis, Pfizer and UCB; and as a Director of Imaging Rheumatology at BV. T. Zhuang: Shareholder/stock ownership; T.Z. is a shareholder of Novartis. Other; T.Z. is an employee of Novartis. A. Stefanska: Shareholder/stock ownership; A.S. is a shareholder of Novartis. Other; A.S. is an employee of Novartis. A. Readie: Shareholder/stock ownership; A.R. is a shareholder of Novartis. Other; A.R. is an employee of Novartis. H. Richards: Shareholder/stock ownership; H.R. is a shareholder of Novartis. Other; H.R. is an employee of Novartis. A. Deodhar: Consultancies; A.D. has received consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. Member of speakers’ bureau; A. D. has received speakers bureau fees from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; A.D. has received grant/research support from AbbVie, Eli Lilly, GSK, Novartis, Pfizer and UCB.

Background/Aims Patients with PsA and axial involvement have higher disease activity and greater reductions in quality of life; however, there are no accepted criteria for identifying axial involvement in PsA. The objective of this post-hoc analysis is to assess the efficacy of upadacitinib (UPA), a Janus kinase inhibitor, on axial symptoms in patients with active PsA and axial involvement defined by investigator assessment and PRO-based criteria from two phase 3 SELECT trials. Methods Patients with active PsA (≥3 swollen joints and ≥3 tender joints) and prior inadequate response or intolerance to ≥ 1 non-biologic (SELECT-PsA 1) or ≥ 1 biologic (SELECT-PsA 2) DMARD were randomly assigned to once daily oral UPA 15 mg or 30 mg, placebo (PBO), or every other week subcutaneous adalimumab (ADA) 40 mg (SELECT-PsA 1 only). At baseline, axial involvement in PsA was determined by investigator assessment based on the totality of clinical information, such as duration and character of back pain, age of onset, and previous imaging. In addition to investigator assessment, PRO-based criteria for axial involvement (BASDAI ≥4 and BASDAI Question 2 ≥4 at baseline) were applied for this analysis to identify patients with active disease. Efficacy in the sub-group of patients defined using both investigator assessment and PRO-based criteria was evaluated at week 24 for UPA 15 mg vs PBO and ADA (SELECT-PsA 1 only). Data were analyzed using mixed-effect model repeated measures (MMRM) or non-responder imputation (NRI), with nominal P-values shown. Results Based on investigator assessment alone, 31.3% (n = 534/1704) of patients in SELECT-PsA 1 and 34.2% (n = 219/641) in SELECT-PsA 2 were defined as having axial involvement. When both investigator assessment and PRO-based criteria were applied, 23.1% (n = 393/1704) of patients in SELECT-PsA 1, or 73.6% (n = 393/534) of those defined using investigator assessment alone, and 27.5% (n = 176/641) in SELECT-PsA 2, or 80.4% (n = 176/219) using investigator assessment alone, met the combined criteria for axial involvement. In both studies, UPA 15 mg showed significantly greater clinical responses vs PBO at week 24 across all endpoints assessed. In SELECT-PsA 1, UPA showed numerically greater responses than ADA at week 24 across all BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints. The proportion of patients achieving ASDAS clinically important improvement (CII) at week 24 was significantly greater with UPA vs ADA based on nominal P-value. Conclusion Patients with active PsA and axial involvement defined by both investigator assessment and PRO-based criteria demonstrated statistically greater clinical responses related to their axial involvement with UPA 15 mg compared to PBO, and consistently numerically higher responses compared to ADA, at week 24 in the SELECT-PsA trials. Findings from this post-hoc analysis are consistent with previous data based on investigator assessment alone. Disclosure X. Baraliakos: Consultancies; X.B has acted as a consultant for AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB. Member of speakers’ bureau; X.B is a member of speaker bureau for AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB. Grants/research support; X.B has received grant/research AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB. R. Ranza: Consultancies; R.R has Acted as a consultant for AbbVie, Janssen, Novartis, and Pfizer. Member of speakers’ bureau; R.R is a member of speaker bureaus for AbbVie, Janssen, Novartis, and Pfizer. A. Ostor: Consultancies; A.O has acted as a consultant for AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche. Member of speakers’ bureau; A.O is a member of speaker bureaus for AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche. F. Ciccia: Consultancies; F.C. has acted as a consultant for AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB. Member of speakers’ bureau; F.C is a member of speaker bureaus for AbbVie, Bristol-Myers Squibb, Celgene, Novartis, Pfizer, and UCB. Grants/research support; F.C has received grant/research support from AbbVie, Celgene, Pfizer, Roche, and UCB. L.C. Coates: Honoraria; L.C has has received honoraria from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Medac, Novartis, Pfizer, and UCB. Grants/research support; L.C has received grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer. S. Rednic: Consultancies; S.R is a consultant for AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, and Pfizer. Grants/research support; S.R has received grant/research support from AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and UCB. J. Walsh: Consultancies; J.W has received consultancy fees from AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB. Grants/research support; J.W has Grants from AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB. T. Gao: Shareholder/stock ownership; T.O is an employee of AbbVie and may hold options and stocks. A. Lertratanakul: Shareholder/stock ownership; A.P is an employee of AbbVie and may hold options and stocks. I. Song: Shareholder/stock ownership; I.S is an employee of AbbVie and may hold options and stocks. F. Fabiana Ganz: Shareholder/stock ownership; F.G is an employee of AbbVie and may hold options and stocks. K. Douglas: Shareholder/stock ownership; K.D is an employee of AbbVie and may hold options and stocks. A. Deodhar: Consultancies; A.D has received consultation fees from AbbVie, Amgen, Aurinia, BMS, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB. Honoraria; A.D has received honoraria's from AbbVie, Amgen, Aurinia, BMS, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB. Grants/research support; A.D has received grant/research support from AbbVie, GSK, Lilly, Novartis, Pfizer and UCB.

Background/Aims Ixekizumab (IXE) has demonstrated efficacy at week (wk) 16 which was maintained through 2 years (yrs) and was associated with a consistent safety profile in patients (pts) with r- and nr-axSpA, who are bDMARD-naïve and TNFi-experienced. We aimed to report safety and efficacy from the COAST programme at 3 yrs: 1 yr of the originating studies (COAST-V/W/X) and 2 yrs of COAST-Y. Methods COAST-Y (NCT03129100) is the phase 3, long-term extension study of the 3 originating studies COAST-V/W/X. Pts continued with the dose received at the end of the originating trial at week (wk) 52, either with 80 mg IXE every 4 wks (Q4W) or every 2 wks (Q2W). Pts assigned to adalimumab (ADA) or placebo (PBO) were re-randomised to IXE Q4W or Q2W at wk 16 in COAST-V and -W. Pts who received PBO for 52 wks in COAST-X were switched to IXE Q4W to continue in COAST-Y. Starting at wk 116 (wk 64 of COAST-Y), pts receiving IXE Q4W could have their dose escalated to Q2W based on investigator's opinion. This analysis focused on pts receiving ≥1 dose of IXE Q4W, observed data while on IXE Q2W dose escalation are excluded. Continuous data are summarised as observed. Safety data while on IXE were analysed for pts who received ≥1 dose of IXE; observed data while on PBO or ADA are excluded. Results A total of 932 pts received ≥1 dose of IXE, 414 received ≥1 dose of IXE Q4W, and 562/932 (60%) pts completed 3 yrs of follow-up (PBO→IXE Q4W, 63/119 (53%); ADA→IXE Q4W, 29/44 (66%); and IXE Q4W→IXE Q4W, 114/251(45%)). Through 3 yrs, the most frequently reported treatment-emergent adverse events were infections [incidence rate (IR) 25.7/100 patient years (PY)] and injection site reactions [IR 7.4/100 PY], the majority of which were mild/moderate in severity. Serious adverse events were reported at an IR of 4.8/100 PY, of which osteoarthritis was the most frequent at 0.4/100 PY. A total of 3 deaths were reported among all pts who received ≥1 dose of IXE [IR 0.1/100 PY]. For all patients, baseline disease activity (Ankylosing Spondylitis Disease Activity Score; ASDAS) was high. A similar improvement in disease activity through 3 yrs was confirmed across additional efficacy endpoints. Conclusion This analysis in COAST-Y demonstrated that the safety profile is consistent with the established safety profile, with no new safety signals observed. Patients on IXE Q4W had sustained improvement through 3 years. Disclosure A. Deodhar: Consultancies; A. Deodhar has served as a speaker and/or consultant for: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos NV, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB Pharma. D. Poddubnyy: Shareholder/stock ownership; D. Poddubnyy has served as a speaker and/or consultant for: AbbVie, BIOCAD, Bristol Myers Squibb, Eli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Samsung Bioepis, and UCB Pharma. Grants/research support; D.P. has received grant and/or research support from: AbbVie, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, and Pfizer. P. Rahman: Consultancies; P. Rahman has served as a speaker for: Abbott, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, and Pfizer. Grants/research support; P.R. has received grant and/or research support from: Janssen and Novartis. R. Bolce: Shareholder/stock ownership; R. Bolce is an employee and shareholder of: Eli Lilly and Company. S. Liu Leage: Shareholder/stock ownership; S. Liu-Leage is an employee and shareholder of: Eli Lilly and Company. A. Kronbergs: Shareholder/stock ownership; A. Kronbergs is an employee and shareholder of: Eli Lilly and Company. C. Johnson: Shareholder/stock ownership; C. Johnson is an employee and shareholder of: Eli Lilly and Company. A. Leung: Corporate appointments; A. Leung is an employee of: Syneos Health; and a contractor for: Eli Lilly and Company. D. van der Heijde: Consultancies; D. van der Heijde has served as a consultant for: AbbVie, Bayer Pharmaceuticals, Bristol Myers Squibb, Cyxone, Eisai, Eli Lilly and Company, Galapagos NV, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB Pharma. Other; D. van der Heijde is the director of: Imaging Rheumatology BV. A. Kiprianos (Non-author Presenter): Shareholder/stock ownership; A. Kiprianos is an employee and shareholder in Lilly.

Air Preheater (APH) is a regenerative heat exchanger employed in thermal power plants to save fuel by improving their thermal efficiency. Monitoring the health of APH vis-a-vis its fouling is critical because fouling often results in forced outages of the power plant, incurring huge revenue losses. APH fouling is a complex thermo-chemical phenomenon governed by flue gas composition, operating temperatures, fuel type and ambient conditions. Absence of sensors within the APH make it difficult to estimate the level of fouling and its progression even for an experienced operator. Attempts to estimate APH fouling in real-time via modeling are scarce. Here we present a physics-informed neural network (PINN) that tracks the health of an APH by real-time estimation of fouling conditions within the APH as a function of real-time sensor measurements. To account for multi-fluid operation in a multi-sector design of APH, the domain is decomposed into several sub-domains. PINN is applied to each sub-domain and the overall solution is ensured by applying continuity conditions at the sub-domain interfaces. The model predicts the interior temperatures and fouling zones within the APH using external sensor measurements such as air temperature and gas composition. The model predictions are consistent with physics and yet computationally efficient in run-time. The model does not need sensor data but can be improved further by accommodating available sensor data. The real-time predictions by the model improve operator’s visibility in fouling. The predictions can be used further for estimating the remaining useful cycle life of the APH, thereby avoiding forced outages. The model can easily be integrated with the digital twin of an APH for its predictive maintenance.

Cell-free (cf)DNA-based testing has undergone increasingly wide adoption, including assays for the detection of circulating tumor DNA. Due to nucleosome protection, cfDNA has a distinctive fragment size of 160 to 180 bp. However, cfDNA can be contaminated with high molecular weight genomic DNA from blood cells released in plasma during sample collection. Such contamination can lead to decreased sensitivity or inconsistent results in cfDNA next-generation sequencing assays. This article describes a technical advancement in which a quantitative PCR method is used for high molecular weight contamination assessment and input mass adjustment, and has been demonstrated to improve consistency of performance in a circulating tumor DNA next-generation sequencing workflow.

ObjectivesIxekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A (IL-17A), has shown significant efficacy in the treatment of psoriatic arthritis (PsA) and sustained long-term clinical response without unexpected new safety outcome for an IL-17A inhibitor. Here, we report the updated safety profile of ixekizumab up to 3 years in patients with PsA.MethodsThis is an integrated safety analysis from four clinical trials in patients with PsA who received at least one dose of ixekizumab. Treatment-emergent adverse events (TEAEs) and selected adverse events (AEs) exposure-adjusted incidence rates (EAIRs) per 100 patient-years up to 3 years of exposure are reported.ResultsA total of 1401 patients with a cumulative ixekizumab exposure of 2247.7 patient-years were included in this analysis. The EAIR of patients with ≥1 TEAE was 50.3 per 100 patient-years and most TEAEs were mild to moderate in severity. Serious AEs were reported by 134 patients (EAIR=6.0). The most reported TEAEs were nasopharyngitis (EAIR=9.0) and upper respiratory tract infection (EAIR=8.3). Infections in general and injection site reactions were the most common TEAEs; the incidence rates of serious cases were low (EAIR ≤1.2). The EAIRs of malignancies (EAIR=0.7), inflammatory bowel disease (EAIR=0.1) including ulcerative colitis and Crohn’s disease, depression (EAIR=1.6), and major adverse cerebro-cardiovascular events (EAIR=0.5) were low. As assessed, based on year of exposure, incidence rates were decreasing or constant over time.ConclusionsIn this analysis, the overall safety profile and tolerability of ixekizumab are consistent with the known safety profile in patients with PsA. No new or unexpected safety events were detected.Trial registration numberNCT01695239,NCT02349295,NCT02584855,NCT03151551.

Diagnosis and management of axial spondyloarthritis (axSpA) has vastly improved over the past two decades. With advances in the discernment of immunopathogenesis of this disease, new therapies have become available, which are associated with substantial improvement in symptoms, signs and quality of life. The four broad categories of approved treatment options are physical therapy and exercise (which have been known to be beneficial for millennia), NSAIDs (since the 1950s), TNF inhibitors (first FDA approval in 2003) and IL-17 inhibitors (first FDA approval in 2016). In addition, there have been a host of new developments in the axSpA field, including new treatment guidelines, the FDA approval of three biologic DMARDs to treat non-radiographic axSpA, the FDA and EMA approval of Janus kinase (JAK) inhibitors for ankylosing spondylitis, new data on the effect of biologic DMARDs on structural progression in ankylosing spondylitis, strategy trials on tapering or stopping TNF inhibitors in patients in remission, trials of treat-to-target strategy in axSpA, and several new molecules in phase III studies. This Review explores the developments in the management of axSpA.

Objective To evaluate response rates at week 16 with ixekizumab in patients with radiographic axial SpA (r-axSpA) and elevated or normal/low baseline inflammation measured by serum CRP or spinal MRI using data from two randomized, double-blind, placebo (PBO)-controlled phase III trials. Methods Biologic-naïve (COAST-V) or TNF inhibitor-experienced (COAST-W) adults with active r-axSpA received 80 mg ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) or PBO or active reference [40 mg adalimumab every 2 weeks (ADAQ2W) in COAST-V. At week 16, patients receiving ixekizumab continued as assigned and patients receiving PBO or ADA were rerandomized 1:1 to IXEQ2W or IXEQ4W through week 52. Assessment of SpondyloArthritis international Society 40% (ASAS40) response rates were examined by baseline CRP (≤5 or >5 mg/l) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine inflammation score ( Results In the COAST-V/W integrated dataset (N = 567), significantly more patients treated with ixekizumab achieved ASAS40 response at week 16 by CRP ≤5 mg/l (27% IXEQ4W, P 5 mg/l (39% IXEQ4W, P Conclusion Ixekizumab demonstrated efficacy in the treatment of AS/r-axSpA in patients with and without elevated CRP or evidence of spinal inflammation on MRI. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov): NCT02696785, NCT02696798

Introduction: The concept of total pain encompasses a person’s physical, psychological, social, spiritual, and practical struggles. Effective pain and symptom management are the core elements of palliative care which aims at reducing suffering and improving quality of life (QOL) throughout the course of illness and need to be addressed with multidisciplinary coordinated approach in a timely manner. It may be challenging for palliative care providers to address all these distressing issues during short out-patient consultations. Hence, Respite Palliative Care Unit (RPCU) is an appropriate place to provide holistic patient care. Case Description: A 59-year-old widow, from Muslim community, was following up with Palliative Medicine out-patient department for management of progressively increasing chest pain with frequent exacerbations. She remained unsatisfied with the pain management and reported moderate to severe intensity of pain despite maximal pain management using multimodal approaches. We planned to systematically explore and address the issues leading to uncontrolled pain and distress. The patient was admitted to RPCU for holistic pain management and continuity of care. We explored and addressed the complex psycho-socio-spiritual aspects contributing to the total pain experience to achieve better symptom control and improve her overall well-being. Conclusion: This case report emphasizes the role of RPCU in effective and holistic management of psychosocial, spiritual issues, difficult communication, and advanced care planning. This model of palliative care can be a valuable addition to various health-care set-ups in the developing countries for improvement of patient care.

We report a series of 3 Adult-onset Still's disease (AOSD)-like presentations in previously healthy females following vaccination with the ChAdOx1 nCoV-19 vaccine, and also compare them with similar cases reported in literature through a PubMed database search. Our first patient had a high spiking bi-quotidian type of fever with myalgia, sore throat, and arthritis with onset 10-day post-vaccination, with laboratory features of hyper inflammation responding to only naproxen. She was off treatment after 2 months. The second patient, with onset 3-week post-vaccination, had a more severe illness, requiring high dose immunosuppression. In our third case, the onset of illness was slightly delayed i.e., 3-month post-vaccination, but she had the most severe disease with macrophage activation syndrome at presentation requiring immunosuppression and biologicals. The underlying mechanism may be linked to the activation of Toll-like receptors (TLR)-TLR-7 and TLR-9-leading to a robust immune response. These 3 cases highlight the immunogenicity of COVID-19 vaccines, with the possibility of occurrence of new-onset systemic hyper-inflammation illness which can happen a few days following the vaccination, sometimes even delayed to months, and can range in severity from mild to even life-threatening. More cases need to be studied to understand the profile and prognosis of these syndromes in the long run.

Purpose The COVID pandemic has greatly impacted cancer care, with survivorship care being accorded low priority. We aimed to assess the impact of the COVID pandemic on survivorship services at our centre, as well as on survivors of childhood cancer (CCS). Methods We analyzed the trends in survivorship care at our centre from March 2020 to June 2021 compared to previous years. We also conducted an online survey of adolescent and young adult (AYA-CCS) following up at the After Completion of Treatment Clinic, Mumbai, to assess the impact of the COVID pandemic and ensuing restrictions on our cohort of survivors. Sibling responses were used as comparator (CTRI/2020/11/029029). Results There was a decrease in in-person follow-ups and increase in remote follow-ups over the first few months of the pandemic. While in-person visits steadily increased after October 2020 and reached pre-pandemic numbers, distant follow-ups continue to be higher than pre-pandemic. Evaluable responses from the survey of 88 AYA-CCS and 25 siblings revealed new-onset health concerns in 29.5% of AYA-CCS, missed follow-up visit in 52% and varying degrees of mental health issues in 12.5%. While most survivors were able to cope with the stresses of the pandemic, 20% of siblings reported being unable to cope. Conclusions Survivorship services continue to be affected well into the pandemic, with increased use of distant follow-ups. While AYA-CCS experienced significant physical, mental health issues and psychosocial concerns as a result of the COVID pandemic, they coped better than siblings during this stressful time, possibly due to multiple, holistic support systems including family, peer support groups and healthcare team. Supplementary Information The online version contains supplementary material available at 10.1007/s00520-021-06788-4.

New hydrogels from alkyl thiolactosides and thiocellobiosides are easy and inexpensive to fabricate. These materials have excellent properties, including good mechanical strength and are thixotropic with rapid self-healing after strain is applied.

Garcinia indica is polygamodaceous tree. Being woody plant chromosome count is often limited by their small and huge chromosome number. In any plant obtaining well spread and less distorted chromosome preparations by conventional squash spread method is intricate due to presence of cell wall. Present study described in detailed method of enzyme digestion mediated protoplast dropping for preparing metaphasechromosomes from plant leaf tissues. Pretreatment of samples with 2 mM 8- hydroxyquinoline solution was seen to be best to accumulate maximum (Mitotic index: 71.4%) number of metaphases. The best chromosomal morphology and spreading were obtained after methanol: Glacial acetic acid (3:1) fixative treatment with clear cytoplasmic background. Among the various concentrations of cellulase / pectinase used in the study, maximum number of protoplast were released after 3 hours treatment with 5 % cellulase / pectinase mixture. Chromosomes staining with giemsa stain for 10 min was observed to be sufficient to stained the chromosomes more intensely with cleared morphological details. The methodology described here offers a reliable method for chromosome preparation and is suitable for routine karyotype analysis of large sample sizes.

Pseudanabaena limnetica, the cyanophycean microalga, like other members of Cyanophycea, is an excellent source of pigments such as phycocyanin, proteins, carotenoids and polysaccharides. These strains also form a large proportion of algal biomass. The P.limnetica strain can grow in the extreme environmental conditions and it grows well in SW-BG 11 medium under laboratory conditions. In the present investigation, this cyanobacteria strain was isolated from the salt pans of Mulund Mumbai areas and it was cultivated in the lab under controlled conditions of light and temperature with optimum parameters of nitrate and carbonate concentrations. The culture was cultivated in the 60L photo bioreactor systems with the (65,000-85,000 lux) at 45?C in the SW-BG11 medium. The optimization experiments were carried out at the indoor and outdoor conditions. The nitrate and carbonate concentrations were optimized for obtaining maximum amount of algal biomass along with the blue-green phycocyanin pigment. The phycocyanin pigment was lyophilized for its further incorporation into the food and cosmetics products. The spectroscopic calculations of phycocyanin, allophycocyanin and phycoerythrin was done at 620, 650 and 562 nm using the Bennett and Bogorad equation. From the results obtained, it was concluded that 0.1gms/L and 1.5gms/L of the carbonate and nitrate concentrations, respectively, were the ideal concentrations for the further experiments for the cost effective production of P. limnetica in the SW-BG 11 medium. The outdoor conditions were found to be favorable for obtaining the maximum biomass and phycocyanin pigment production which would - make it more cost effective, commercially.