Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a ...repurposed agent for treating COVID-19.
In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population).
Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred.
In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.
Abstract
Introduction: There is limited data on the impact of race on tumor location and TMPRSS2-ERG (ERG) gene fusion status in Prostate Cancer (PCa). African American men (AAM) often lack the ERG ...fusion and are likely to experience poor outcomes. Nonetheless, the extent to which ERG status, race, and tumor location impacts PCa outcomes remains unclear.
Methods: This multi-institutional study included a retrospective cohort of 495 AAM and 422 European American men (EAM) who received prostatectomy at Moffitt Cancer Center (MCC) and University of Pennsylvania Health system (UPHS). To assess the race-dependent variation in ERG protein expression and its association with tumor location and PCa pathology, ERG antibody staining on 4 micron sections of FFPE blocks were carried out on all samples. ERG expression was categorized as ERGpos and ERGneg by two pathologists. Additionally, the staining pattern of ERG was analyzed within ERGpos tumors. A review of anatomic location of the dominant tumor lesions was performed and analyzed using methods of categorical analysis and logistic regression. Alpha value of < 0.05 was considered as statistically significant.
Results: In all samples, analysis of ERG immunohistochemistry (IHC) yielded 39.7% ERGpos and 60.6% ERGneg. Variability in histopathologic expression of ERG was significant between races with AAM being more likely to lack TMPRSS2-ERG fusion (ERGneg) compared to EAM, (62% vs 38%, p < 0.001). Lack of ERG fusion was also associated with anatomically distinct tumor location with 72.1% of anteriorly located tumors having ERGneg staining, while only 27.9% were ERGpos, (p < 0.001). Among ERGpos patients, AAM (65.2%) showed significant heterogeneous expression of ERG compared to EAM (31.8%). Furthermore, ERGneg status was associated with higher pretreatment PSA. In a multivariate logistic regression model adjusted for tumor location and race, ERGneg tumors were more likely to have Gleason Score 4+3=7 (Grade Group 3) or higher compared with ERGpos tumors, Odds ratio 2.07, 95% CI 1.20 - 3.56, p = 0.008.
Conclusions: The absence of TMPRSS2-ERG fusion is associated with higher grade disease and is a strong predictor for anatomic tumor location within the prostate gland. The clinical implications of ERGneg tumors among AAM and its association with anteriorly located tumors can be vital in addressing disparities in PCa.
Citation Format: Kosj Yamoah, Shivanshu Awasthi, Priti Lal, Arash O. Naghavi, Shelly Mahajan, Jong Y. Park, Rob Rounbehler, Travis Gerke, Anders Berglund, Julio PowSang, Jasreman Dhillon, Timothy R. Rebbeck. Clinical implications of tmprss2-erg fusion and tumor location in prostate cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1568.
Purpose
The purpose of this study/paper is to integrate distributed generation optimally in power system using plant propagation algorithm. Distributed generation is a growing concept in the field of ...electricity generation. It mainly comprises small generation units installed at calculated points of a power system network. The challenge of optimal allocation and sizing of DG is of utmost importance.
Design/methodology/approach
Plant propagation algorithm and particle swarm optimisation techniques have been implemented where a weighting factor-based multi-objective function is minimised. The objective is to cut down real losses and to improve the voltage profile of the system.
Findings
The results obtained using plant propagation algorithm technique for IEEE 33-bus systems are compared to those attained using particle swarm optimisation technique. The paper deals with the optimisation of weighting factor-based objective function, which counterpoises the losses and improves the voltage profile of the system and, therefore, helps to deliver the best outcomes.
Originality/value
This paper fulfils an identified need to study the multi-objective optimisation techniques for integration of distributed generation in the concerned power system network. The paper proposes a novel plant-propagation-algorithm-based technique in appropriate allocation and sizing of distributed generation unit.
The demand of electricity is soaring rapidly. Distributed generation (DG) is one of the most suitable alternatives to fulfill this swelling demand of energy. DG is a small scale generation which is ...directly installed in the distribution network or at load centre. Optimal allocation of DG is a vital factor in improving the voltage profile of the system and in reduction of total power losses. In this article, a detailed study of three different methods for DG allocation and sizing has been discussed. The first method is based on Newton Raphson load flow based technique to deduce the optimal location of DG in two different IEEE bus systems in MATLAB software. The next methodology is based on particle swarm optimization (PSO) technique where a multi-objective function is being minimized. The objective function has been modified and PSO has been implemented to attain optimal size and location of DG unit. The third method considered is based on human opinion dynamics evolutionary multi-objective optimization technique which is used to obtain the best possible size and location of DG unit in IEEE 14 and IEEE 30 bus systems. The human opinion dynamics method shows superiority in minimizing the size and location muti-objective function, over the other methods considered herein.
The authors report data concerning the safety, effectiveness, and patterns of failure obtained in a Phase I/II study of stereotactic body radiotherapy (SBRT) for spinal metastatic tumors.
Sixty-three ...cancer patients underwent near-simultaneous computed tomography-guided SBRT. Spinal magnetic resonance imaging was conducted at baseline and at each follow-up visit. The National Cancer Institute Common Toxicity Criteria 2.0 assessments were used to evaluate toxicity.
The median tumor volume of 74 spinal metastatic lesions was 37.4 cm3 (range 1.6-358 cm3). No neuropathy or myelopathy was observed during a median follow-up period of 21.3 months (range 0.9-49.6 months). The actuarial 1-year tumor progression-free incidence was 84% for all tumors. Pattern-of-failure analysis showed two primary mechanisms of failure: 1) recurrence in the bone adjacent to the site of previous treatment, and 2) recurrence in the epidural space adjacent to the spinal cord. Grade 3 or 4 toxicities were limited to acute Grade 3 nausea, vomiting, and diarrhea (one case); Grade 3 dysphagia and trismus (one case); and Grade 3 noncardiac chest pain (one case). There was no subacute or late Grade 3 or 4 toxicity.
Analysis of the data obtained in the present study supports the safety and effectiveness of SBRT in cases of spinal metastatic cancer. The authors consider it prudent to routinely treat the pedicles and posterior elements using a wide bone margin posterior to the diseased vertebrae because of the possible direct extension into these structures. For patients without a history of radiotherapy, more liberal spinal cord dose constraints than those used in this study could be applied to help reduce failures in the epidural space.
The demand of electricity is soaring rapidly. Distributed genera-tion (DG) is one of the most suitable alternatives to fulfill this swellingdemand of energy. DG is a small scale generation which is ...directly in-stalled in the distribution network or at load centre. Optimal allocationof DG is a vital factor in improving the voltage profile of the system andin reduction of total power losses. In this article, a detailed study of threedifferent methods for DG allocation and sizing has been discussed. Thefirst method is based on Newton Raphson load flow based technique todeduce the optimal location of DG in two different IEEE bus systems inMATLAB software. The next methodology is based on particle swarmoptimization (PSO) technique where a multi-objective function is beingminimized. The objective function has been modified and PSO has beenimplemented to attain optimal size and location of DG unit. The thirdmethod considered is based on human opinion dynamics evolution-ary multi-objective optimization technique which is used to obtain thebest possible size and location of DG unit in IEEE 14 and IEEE 30 bussystems. The human opinion dynamics method shows superiority inminimizing the size and location muti-objective function, over the othermethods considered herein.
Soybean genome encodes a family of four inositol 1,3,4 trisphosphate 5/6 kinases which belong to the ATP-GRASP group of proteins. Inositol 1,3,4 trisphosphate kinase-2 (
GmItpk2
), catalyzing the ...ATP-dependent phosphorylation of Inositol 1,3,4 trisphosphate (IP3) to Inositol 1,3,4,5 tetra phosphate or Inositol 1,3,4,6 tetra phosphate, is a key enzyme diverting the flux of inositol phosphate pool towards phytate biosynthesis. Although considerable research on characterizing genes involved in phytate biosynthesis is accomplished at genomic and transcript level, characterization of the proteins is yet to be explored. In the present study, we report the isolation and expression of single copy
Itpk
2 (948 bp) from
Glycine max cv
Pusa-16 predicted to encode 315 amino acid protein with an isoelectric point of 5.9. Sequence analysis revealed that
Gm
ITPK2 shared highest similarity (80%) with
Phaseolus vulgaris.
The predicted 3D model confirmed 12 α helices and 14 β barrel sheets with ATP-binding site close to β sheet present towards the C-terminus of the protein molecule. Spatio-temporal transcript profiling signified
GmItpk2
to be seed specific, with higher transcript levels in the early stage of seed development. The present study using various molecular and bio-computational tools could, therefore, help in improving our understanding of this key enzyme and prove to be a potential target towards generating low phytate trait in nutritionally rich crop like soybean.
Purpose
Pilocytic astrocytoma (PA) is a common pediatric glioma that is generally characterized by indolent growth. However, there are reports of PA disseminating throughout the central nervous ...system. Given the rarity of dissemination, the appropriate treatment for these patients is poorly defined. In this case series, we describe the clinical characteristics and treatment outcomes of six children treated for disseminated PA at our institution and review the current published literature.
Methods
Six cases of disseminated PA treated at the University of Texas MD Anderson Cancer Center were identified. Demographics, disease characteristics, and follow-up data were compiled. Fifty-three reported cases were identified in the published literature.
Results
Our cohort’s mean age at presentation was 7 years, and the mean time to identification of disseminated disease was 12 months after initial diagnosis. Two patients underwent chemotherapy, and all underwent proton beam radiation therapy to all or part of the craniospinal axis. With a median follow-up of 24 months after radiation therapy, five of six patients were alive, four with stable disease and one with progressive disease.
Conclusions
Treatment of disseminated PA is frequently multi-modal, including surgical resection, chemotherapy, and radiation therapy. On the basis of early clinical data, extended-field radiation therapy is a viable option for treating disseminated PA.
The utilization of distributed generation (DG) is growing day by day and it has become an indispensable part of power generation across the world. Because of its cost effectiveness and eco-friendly ...nature, it has improved the reliability of the network system. Due to the augmentation of DG penetration, the nature of distribution network is remodeled from a passive network to an active network. The integration of DG unit is profitable if it is optimally placed. Various models of DG are developed for its optimal deployment. In this paper, Particle Swarm Optimization (PSO) technique is proposed for optimal deployment and size of DG source.
The demand of electricity is soaring rapidly. Distributed generation (DG) is one of the most suitable alternatives to fulfill this swelling demand of energy. DG is a small scale generation which is ...directly installed in the distribution network or at load centre. Optimal allocation of DG is a vital factor in improving the voltage profile of the system and in reduction of total power losses. DG size ranges from a few kilowatts (kW) to 10 Megawatts (MW). This paper suggests a load flow based methodology to deduce the optimal location of DG in three different IEEE bus systems in MATLAB software. A load flow study based on Newton Raphson method is executed on modified IEEE 5 bus, IEEE 14 bus and IEEE 30 bus systems. A single DG source of 2 MW delivering only real power is used in this paper. With the integration of this DG unit at an optimum location, there is a considerable reduction in active power losses and reactive power losses of the system and also the voltage profile is improved significantly.
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