Spiraling of conductors in a helical winding of a transformer may lead to a catastrophic failure under the action of torsional short-circuit electromagnetic forces. Torsional forces are produced by ...the interaction of the axial component of the short-circuit current and the radial component of the leakage magnetic flux density. In this paper, 3-D magnetostatic analysis has been performed to determine the leakage magnetic-field distribution in a 130-MVA power transformer. Torsional electromagnetic forces are calculated from the analysis to determine circumferential displacements of conductors of its low-voltage helical winding. Furthermore, mechanical stress components are computed and a factor of safety is defined, which gives an indication as to whether the winding conductors are in the elastic or plastic zone. The numerical results thus obtained by the finite-element method are verified using the first principles from mechanics. The effect of looseness in the inner support structure on the von-Mises equivalent stress and, hence, on the factor of safety has been studied.
Systemic Therapies for Hepatocellular Carcinoma in India Jahagirdar, Vinay; Rama, Kaanthi; Habeeb, Mohammed F. ...
Journal of clinical and experimental hepatology,
November-December 2024, 2024-11-00, 20241101, Letnik:
14, Številka:
6
Journal Article
Recenzirano
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in India. This review explores the epidemiological trends and the landscape of systemic therapy for HCC in the Indian ...context, acknowledging the recent shift in etiology from viral hepatitis to lifestyle-associated factors.
A comprehensive review of the literature was conducted, including data from the Global Cancer Observatory and the Indian Council of Medical Research, along with a critical analysis of various clinical trials. The article investigates systemic therapies in-depth, discussing their mechanisms, efficacy, and adaptation to Indian healthcare framework.
Progression-free survival with a hazard ratio of ≤0.6 compared to sorafenib, overall survival of ∼16–19 months, and objective response rate of 20–30% are the defining thresholds for systemic therapy clinical trials. Systemic therapy for advanced HCC in India primarily involves the use of tyrosine kinase inhibitors such as sorafenib, lenvatinib, regorafenib, and cabozantinib, with sorafenib being the most commonly used drug for a long time. Monoclonal antibodies such as ramucirumab and bevacizumab and immune-checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, are expanding treatment horizons. Lenvatinib has emerged as a cost-effective alternative, and the combination of atezolizumab and bevacizumab has demonstrated superior outcomes in terms of overall survival and progression-free survival. Despite these advances, late-stage diagnosis and limited healthcare accessibility pose significant challenges, often relegating patients to palliative care.
Addressing HCC in India demands an integrative approach that not only encompasses advancements in systemic therapy but also targets early detection and comprehensive care models. Future strategies should focus on enhancing awareness, screening for high-risk populations, and overcoming infrastructural disparities. Ensuring the judicious use of systemic therapies within the constraints of the Indian healthcare economy is crucial. Ultimately, a nuanced understanding of systemic therapeutic options and their optimal utilization will be pivotal in elevating the standard of HCC care in India.
Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: ...“bleeding risk-treatment paradox” (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients’ bleeding risk (ie, exhibit a RTP) have higher bleeding rates.
We examined 28,005 PCIs from the National Cardiovascular Data Registry CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention, bivalirudin, and vascular closure devices. Patients’ predicted bleeding risk was based on National Cardiovascular Data Registry CathPCI bleeding model and categorized as low (<2.0%), moderate (2.0%-6.4%), or high (≥6.5%) risk tertiles. BAS use was considered risk-concordant if: at least 1 BAS was used for moderate risk; 2 BAS were used for high risk and bivalirudin or vascular closure devices were not used for low risk. Absence of risk-concordant BAS use was defined as RTP. We analyzed inter-hospital and inter-physician variation in RTP, and the association of RTP with post-PCI bleeding.
Amongst 28,005 patients undergoing PCI by 103 physicians at 7 hospitals, RTP was observed in 12,035 (43%) patients. RTP was independently associated with a higher likelihood of bleeding even after adjusting for predicted bleeding risk, mortality risk and potential sources of variation (OR 1.66, 95% CI 1.44-1.92, P < .001). A higher prevalence of RTP strongly and independently correlated with worse bleeding rates, both at the physician-level (Wilk's Lambda 0.9502, F-value 17.21, P < .0001) and the hospital-level (Wilk's Lambda 0.9899, F-value 35.68, P < .0001). All the results were similar in a subset of PCIs conducted since 2015 – a period more reflective of the contemporary practice.
Bleeding RTP is a strong, independent predictor of bleeding. It exists at the level of physicians and hospitals: those with a higher rate of RTP had worse bleeding rates. These findings not only underscore the importance of recognizing bleeding risk upfront and using BAS in a risk-aligned manner, but also inform and motivate national efforts to reduce PCI-related bleeding.
Abstract
Several thousand core-collapse supernovae (CCSNe) of different flavors have been discovered so far. However, identifying their progenitors has remained an outstanding open question in ...astrophysics. Studies of SN host galaxies have proven to be powerful in providing constraints on the progenitor populations. In this paper, we present all CCSNe detected between 2009 and 2017 by the Palomar Transient Factory. This sample includes 888 SNe of 12 distinct classes out to redshift
z
≈ 1. We present the photometric properties of their host galaxies from the far-ultraviolet to the mid-infrared and model the host-galaxy spectral energy distributions to derive physical properties. The galaxy mass function of Type Ic, Ib, IIb, II, and IIn SNe ranges from 10
5
to 10
11.5
M
⊙
, probing the entire mass range of star-forming galaxies down to the least-massive star-forming galaxies known. Moreover, the galaxy mass distributions are consistent with models of star-formation-weighted mass functions. Regular CCSNe are hence direct tracers of star formation. Small but notable differences exist between some of the SN classes. Type Ib/c SNe prefer galaxies with slightly higher masses (i.e., higher metallicities) and star formation rates than Type IIb and II SNe. These differences are less pronounced than previously thought. H-poor superluminous supernovae (SLSNe) and SNe Ic-BL are scarce in galaxies above 10
10
M
⊙
. Their progenitors require environments with metallicities of < 0.4 and < 1 solar, respectively. In addition, the hosts of H-poor SLSNe are dominated by a younger stellar population than all other classes of CCSNe. Our findings corroborate the notion that low metallicity and young age play an important role in the formation of SLSN progenitors.
Acute coronary syndrome (ACS) admissions are common and costly. The association between comprehensive ACS care pathways, outcomes, and costs are lacking. From 434,172 low-risk, uncomplicated ACS ...patients eligible for early discharge (STEMI 35%, UA/NSTEMI 65%) from the Premier database, we identified ACS care pathways, by stratifying low-risk, uncomplicated STEMI and UA/NSTEMI patients by access site for PCI (trans-radial intervention TRI vs transfemoral intervention TFI) and by length of stay (LOS). Associations with costs and outcomes (death, bleeding, acute kidney injury, and myocardial infarction at 1-year) were tested using hierarchical, mixed-effects regression, and projections of cost savings with change in care pathways were obtained using modeling. In low-risk uncomplicated STEMI patients, compared with TFI and LOS ≥3 days, a strategy of TRI with LOS <3 days and TFI with LOS <3 days were associated with cost savings of $6,206 and $4,802, respectively. Corresponding cost savings for UA/NSTEMI patients were $7,475 and $6,169, respectively. These care-pathways did not show an excess risk of adverse outcomes. We estimated that >$300 million could be saved if prevalence of the TRI with LOS <3 days and TFI with LOS <3 days strategies are modestly increased to 20% and 70%, respectively. In conclusion, we demonstrate the potential opportunity of cost savings by repositioning ACS care pathways in low-risk and uncomplicated ACS patients, toward transradial access and a shorter LOS without an increased risk of adverse outcomes.
Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific ...(BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .
Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular ...factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of
the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of
into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that
is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between
transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle.
Study Type – Therapy (individual cohort)
Level of Evidence 2b
What's known on the subject? and What does the study add?
It has been documented that currently used anti‐muscarinics can cause adverse ...effects on the CNS.
This study adds knowledge that the OAB population has more CNS disorders that make them vulnerable to the potential CNS effects of OAB anti‐muscarinics.
OBJECTIVE
•
To determine the proportion of patients with overactive bladder (OAB) potentially at risk for adverse events by assessing their pre‐existing central nervous system (CNS), cardiovascular (CV) and other co‐morbidities.
PATIENTS AND METHODS
•
The GE Centricity Electronic Medical Record database was utilized to identify patients with a diagnosis of OAB using International Classification of Diseases, Ninth Revision (ICD‐9) codes or a prescription between 1 January 1996 and 30 March 2007 for an OAB anti‐muscarinic agent.
•
Matched non‐OAB patients were assigned the same index date as the corresponding OAB patient. Based on the presence of ≥ one pharmacy claim for an OAB anti‐muscarinic agent, the OAB cohort was stratified as treated or untreated. A random sample of age‐ and gender‐matched patients formed a non‐OAB control cohort.
•
An additional and separate analysis focusing on all co‐morbidities was performed examining non‐OAB patients who were matched to OAB patients on 1:1 propensity score matching, based on age, body mass index (BMI) and gender at baseline.
•
Charlson Comorbidity Index (CCI), using ICD‐9 codes, and the Chronic Disease Score (CDS), using prescribed drugs, were calculated.
RESULTS
•
When compared with non‐OAB patients (N= 77 272; 83.2% women; median age 64 years), OAB patients (N= 41 440; 83.6% women; median age 65 years) had more overall CNS co‐morbidities (45.4 vs 29.0%; P < 0.001).
•
In addition, OAB patients had a higher use of medications with anti‐muscarinic effects (39.6 vs 25.4%; P < 0.001). OAB patients were also more likely to have CV co‐morbidities (57.6 vs 44.6%; P < 0.001).
•
CNS co‐morbidities were slightly more common in untreated (n= 8 106) than in treated (n= 33 334) OAB patients (47.2 vs 45.0%; P < 0.001). CV co‐morbidities were higher in treated OAB patients (58.8 vs 53.7%; P < 0.001).
•
In the additional separate analysis, which focused on all co‐morbidities, patients with OAB had higher mean CCI and CDS scores than patients without OAB (CCI: 1.17 vs 1.11 P < 0.001; CDS: 2.95 vs 1.74 P < 0.001).
•
After controlling for other covariates, the linear regressions (n= 22 544) showed that OAB patients had higher CCI and CDS than patients without OAB.
CONCLUSIONS
•
Among OAB patients, CNS, CV and all co‐morbidities were more prevalent than in non‐OAB patients.
•
Prior exposure to CNS medications was more prevalent in OAB patients who received anti‐muscarinic treatment than in those who did not.
•
Co‐morbidities and concomitant medications affecting the CNS and the CV system should be taken into account when making the decision on the most appropriate OAB treatment option for each individual patient.
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