Toxicity and Cosmesis Outcomes for Single Fraction Intra-Operative Electron Radiotherapy (IOERT) for Breast Cancer

Background: Adjuvant radiation therapy is proven to reduce local recurrence in patients with early stage breast cancer. To reduce toxicity, improve geographic accuracy, and reduce treatment time, IOERT can be utilized as an alternative to external beam radiation therapy. The study’s objective was to determine the short term toxicity and cosmesis profile of single fraction IOERT given as definitive treatment in a community setting. Materials and Methods: From Mar 2012 to Jul 2014, 84 patients (3 bilateral), ages 45-91 y.o. with stage 0-II were treated with IOERT (Mobetron, IntraOp Medical, Sunnyvale, CA). A single 21 Gy fraction was administered to the tumor bed after resection. IOERT was delivered using 4.5 – 6 cm applicators with electron energies from 6-12 MeV. At 2w, 6mo and 12mo, toxicity was assessed according to CTCAE Version 4.0 (range 0-4) and cosmesis based on a scale derived for national trials. Results: The median pathologic tumor size was 13 mm (4 tumors \u3e 25mm) with 34 tumors being IDC, 4 ILC, 20 DCIS, and 29 mixed histologies. After the initial resection with IOERT, 85 breasts had a negative margin. Two required re-excision due to positive margins. 65 SLN biopsies were completed, 61 were negative, 4 positive (1 completion ALND). Median follow up was 57.1 weeks. Toxicity (Grade at 2 weeks, 6 months, and 12 months in %): 0: 49, 69, 62 1: 44, 29, 35 2: 7, 2, 3 Cosmesis(Appearance at 2 weeks, 6 months, 12 months in %): Excellent: 71, 86, 79 Good: 28, 14, 21 Fair: 1, 0, 0 *No patients had a toxicity of 3 or 4; or a cosmesis of poor. Conclusion: Single fraction IOERT was well tolerated by all patients with no grade 3+ toxicity up to 12 months. At one year, 97% of patients had 0-1 grade toxicity and 100% of patients had excellent or good cosmesis. This treatment, consistent with current reports, meets critical criteria for incorporation into practice and reduces treatment by 3-6 weeks

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16,

Genetic Analysis for Grain Yield and Its Attributing Characters in Rice (Oryza sativa L.) under Irrigated Conditions of Prayagraj, Uttar Pradesh

The present investigation was carried out to assess the genetic variability parameters, correlation and path analysis in 23 rice genotypes for 13 quantitative traits viz Days to 50% flowering, Days to Maturity, Plant height (cm), Flag Leaf Length (cm), Flag Leaf Width (cm), Number of total tillers, Number of Productive Tillers, Panicle Length (cm), Biomass (g), Harvest Index (%), Number of Grains per Panicle, Test Weight (1000 grain weight), Grain Yield per Plant per Plant (g). in Kharif 2021 season at field experimentation centre, Department of Genetics and Plant Breeding, Naini Agricultural Institute, Sam Higginbottom University of Agriculture Technology and Sciences, Uttar Pradesh in Randomized Block Design in three replications. Analysis of variance indicated high significant differences among the genotypes for all the traits. Genotypes SHIATS DHAN-6, KSRV-12, SHIATS DHAN-2, KSRV-140 depicted highest Grain Yield per Plant. All the characters had expressed high estimates of heritability. There is no evidence for characters expressing moderate and low heritability from the present investigation. The studies on GCV and PCV indicated that the presence of high amount of variation and role of the environment on the expression of these traits. The correlation among the yield and yield attributing characters revealed that Grain Yield per Plant per plant was positively and significantly associated at both genotypic and phenotypic levels. In Phenotypic and Genotypic path analysis a detailed analysis of diagonal values showed positive direct effect Grain Yield

Estimation of Genetic Variability, Correlaton for Yield and Yield Compoments in Rice (Oryza sativa L.)

The present study consists of 23 rice genotypes including one check variety that were evaluated at Field Experimentation Centre of the Department of Genetics and Plant Breeding, Naini Agricultural Institute, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj (Allahabad), U.P. to study genetic variability, correlation and path coefficient for 13 quantitative characters. The experiment was conducted by using Randomized Block Design with three replications during Kharif -2021. Observation recorded to study the genetic variability parameters, correlation coefficient and path coefficient for yield and its attributing traits. On the basis of mean performance BPT-3291 was found to be superior in grain yield per hill followed by, SIGNET-5455, KSR-140 and RNR-15048 showed higher yield over the check (NDR359). High to moderate estimates of GCV and PCV were recorded for number of spikelets per panicle followed by number of tillers per hill, harvest index, biological yield, grain yield per hill, flag leaf width, test weight and number of panicles per hill. Grain yield indicated significant positive correlation with plant height followed by tillers per hill, panicles per hill, biological yield and harvest index in terms of phenotypic correlation coefficient whereas in terms of genotypic coefficient it showed positive and significant correlation. Path coefficient analysis showed positive significant direct effects on Biological Yield, Harvest Index and Number of Spikelets per Panicle at genotypic level whereas it showed positive and significant direct effect for days to fifty percent flowering, plant height, flag leaf width, number of panicles, test weight, biological yield, and harvest index at phenotypic level. Thus, these traits are identified as the efficient and potential for indirect selection for the improvement of rice productivity in the present experimental materials