Mechanical Properties of Dissimilar A356/SAPH440 Lap Joints by the Friction Stir Spot Welding and Self-Piercing Riveting

Aluminum alloy A356-T6 and automotive steel sheet SAPH440 were joined using friction stir spot welding and self-piercing riveting. The maximum tensile shear strength values in weld joints were approximately 3.5 kN at a rotation speed of 500 rpm and plunge depth of 1.0 mm. It was confirmed that the intermetallic compound layer of weld joints below 9.23 m did not exceed the permissible thickness 10 m of Al–Fe joints. The self-piercing riveting joints exhibited maximum tensile- shear strength of 7.9 kN, which was higher than that of the weld joints. However, during the riveting process, cracking appeared in the joint on the aluminum side, which was caused by lack of ductility of cast aluminum. In addition, it was observed that the cracks on the aluminum side were getting larger, as the radius of the lower mold increased.Алюминиевый сплав А356-Т6 и автомобильную листовую сталь SAPH440 соединяли с помощью точечной ротационной сварки трением и самопробивной клепки. Максимальный предел прочности на сдвиг при растяжении для сварных соединений составлял примерно 3,5 кН при скорости вращения 500 об/мин и глубине проникновения 1,0 мм. Доказано, что слой интерметаллидов сварных соединений толщиной менее 9,23 мкм не превышал допустимый уровень в 10 мкм для соединений Al–Fe. Клепаные соединения имели предел прочности 7,9 кН в отличие от сварных соединений. Однако при клепке на алюминии появлялись трещины ввиду низкой пластичности литого материала, при этом трещины подрастали по мере увеличения радиуса нижней формы

Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics

In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source, limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin, flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable light-emitting diodes (LEDs), with the ability to operate at wavelengths ranging from UV to blue, green-yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications.114419Ysciescopu

INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG)

BACKGROUND: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progression free survival compared to placebo (INTEGRATE, phase 2). Regorafenib 80 mg daily in combination with nivolumab 3 mg/kg showed promising objective response rates (REGONIVO). METHODS/DESIGN: INTEGRATE II (INTEGRATE IIa and IIb) platform comprises two international phase III randomised controlled trials (RCT) with 2:1 randomisation in favor of experimental intervention. INTEGRATE IIa (double-blind) compares regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle to placebo. INTEGRATE IIb (open label) compares REGONIVO, regorafenib 90 mg days 1 to 21 in combination with intravenous nivolumab 240 mg days 1 and 15 each 28-day cycle with investigator's choice of chemotherapy (control). Treatment continues until disease progression or intolerable adverse events as per protocol. Eligible participants include adults with AGOC who have failed two or more lines of treatment. Stratification is by location of tumour (INTEGRATE IIa only), geographic region, prior VEGF inhibitor and prior immunotherapy use (INTEGRATE IIb only). Primary endpoint is overall survival. Secondary endpoints are progression free survival, objective response rate, quality of life, and safety. Tertiary/correlative objectives include biomarker and pharmacokinetic evaluation. DISCUSSION: INTEGRATE II provides a platform to evaluate the clinical utility of regorafenib alone, as well as regorafenib in combination with nivolumab in treatment of participants with refractory AGOC. TRIAL REGISTRATION: INTEGRATE IIa prospectively registered 1 April 2016 Australia New Zealand Clinical Trial Registry: ACTRN12616000420448 (ClinicalTrials.gov NCT02773524). INTEGRATE IIb prospectively registered 10 May 2021 ClinicalTrials.gov: NCT04879368.Lyn Ley Lam, Nick Pavlakis, Kohei Shitara, Katrin M. Sjoquist, Andrew J. Martin, Sonia Yip, Yoon, Koo Kang, Yung, Jue Bang, Li, Tzong Chen, Markus Moehler, Tanios Bekaii, Saab, Thierry Alcindor, Christopher J. O, Callaghan, Niall C. Tebbutt, Wendy Hague, Howard Chan, Sun Young Rha, Keun, Wook Lee, Val Gebski, Anthony Jaworski, John Zalcberg, Timothy Price, John Simes, and David Goldstei

Coevolutionary systems and PageRank

Coevolutionary systems have been used successfully in various problem domains involving situations of strategic decision-making. Central to these systems is a mechanism whereby finite populations of agents compete for reproduction and adapt in response to their interaction outcomes. In competitive settings, agents choose which solutions to implement and outcomes from their behavioral interactions express preferences between the solutions. Recently, we have introduced a framework that provides both qualitative and quantitative characterizations of competitive coevolutionary systems. Its two main features are: (1) A directed graph (digraph) representation that fully captures the underlying structure arising from pairwise preferences over solutions. (2) Coevolutionary processes are modeled as random walks on the digraph. However, one needs to obtain prior, qualitative knowledge of the underlying structures of these coevolutionary digraphs to perform quantitative characterizations on coevolutionary systems and interpret the results. Here, we study a deep connection between coevolutionary systems and PageRank to address this issue. We develop a principled approach to measure and rank the performance (importance) of solutions (vertices) in a given coevolutionary digraph. In PageRank formalism, B transfers part of its authority to A if A dominates B (there is an arc from B to A in the digraph). In this manner, PageRank authority indicates the importance of a vertex. PageRank authorities with suitable normalization have a natural interpretation of long-term visitation probabilities over the digraph by the coevolutionary random walk. We derive closed-form expressions to calculate PageRank authorities for any coevolutionary digraph. We can precisely quantify changes to the authorities due to modifications in restart probability for any coevolutionary system. Our empirical studies demonstrate how PageRank authorities characterize coevolutionary digraphs with different underlying structures

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362