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Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 0 ( P P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. Objective: To present the voting results from APCCC 2021. Design, setting, and participants: The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. Results and limitations: The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making. © 2022 The Author(s)

The authors regret that Axel Heidenreich was added to the author list in error. The author list is now corrected as above, however the affiliations of remaining authors have been retained. The authors would like to apologise for any inconvenience caused. © 2022 The Author(s)

The effects of alpha (α) particles on the transport of helium ash driven by collisionless trapped electron mode (CTEM) turbulence are analytically studied using quasi-linear theory in tokamak deuterium (D) and tritium (T) plasmas. Under the parameters used in this work, the transport of helium ash is mainly determined by the diffusion due to very weak convection. It is found that the ratio between helium ash diffusivity and effective electron thermal conductivity (D He/χ eff) driven by CTEM turbulence, which is a proper normalized parameter for quantifying the efficiency of helium ash removal, is smaller than unity. This indicates the less efficient removal of helium ash through CTEM turbulence as compared with ion temperature gradient (ITG) turbulence in [Angioni et al 2009 Nucl. Fusion 49 055013]. However, the efficiency of helium ash removal is increased 55% by the presence of 3% α particles with their density gradient being equivalent to that of electrons, and this enhancement can be further strengthened by steeper profile of α particles. This is mainly because the enhancement of helium ash diffusivity by α particles is stronger than that of the effective electron thermal conductivity. Moreover, the higher fraction of T ions, higher temperature ratio between electrons and thermal ions as well as flatter electron density profile, the stronger enhancement of D He/χ eff, and α particles further strengthen the favorable effects of these parameters on the removal of helium ash.

Aims Although there is emerging evidence to suggest equivalent oncological outcomes using a watch and wait approach compared with primary total mesorectal excision surgery, there is a paucity of evidence about the safety and efficacy of this approach in routine clinical practice. Here we report the long-term outcomes and quality of life from patients managed with watch and wait following a clinical complete response (cCR) to neoadjuvant therapy. Materials and methods Patients with adenocarcinoma of the rectum with cCR following neoadjuvant therapy managed using watch and wait were retrospectively identified. Demographic data, performance status, pretreatment staging information, oncological and surgical outcomes were obtained from routinely collected clinical data. Quality of life was measured by trained clinicians during telephone interviews. Results Over a 7-year period, 506 patients were treated for rectal cancer, 276 had neoadjuvant therapy and 72 had a cCR (26.1%). Sixty-three were managed with watch and wait. Thirteen patients had mucosal regrowth. There was no significant difference in the incidence of metastatic disease between the surgical and watch and wait cohorts (P = 0.38). The 13 patients with mucosal regrowth underwent salvage surgery. Eleven of the patients who underwent surgical resection had R0 resections. There was also a statistically and clinically significant improvement in the Functional Assessment of Cancer Therapy – Colorectal (FACT-C) trial outcome index (P = 0.022). Conclusion This study shows that watch and wait is safe and effective outside of tertiary referral centres. It suggests that an opportunistic cCR is durable and when mucosal regrowth occurs it can be salvaged. Finally, we have shown that quality of life is probably improved if a watch and wait approach is adopted.

At the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, 10 important areas of controversy in advanced prostate cancer management were identified and discussed, and experts voted on 123 predefined consensus questions. The full report of the results is summarised here. © 2020 The Authors Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. Objective: To present the results from the APCCC 2019. Design, setting, and participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. Results and limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making. © 2020 The Authors

In this work, plasma is produced by irradiating a Ti target with 10 ns pulsed Nd:YAG (λ = 1064 nm) laser. The laser fluence at the target was varied in the range of 2–20.3 J/cm2. The ion signal from freely expanding Ti plasma in vacuum was characterized with the help of ion collector and time-of-flight electrostatic energy analyzer. The ion charge state was found to increase with the laser fluence and maximum available ion charge in this fluence range is Ti4+. A correlation between the intensities of various ion charge states was observed, which indicates that higher charge states are most probably produced through stepwise ionization mechanism. It is also observed that charge state distribution of plasma can be controlled by variation of the laser fluence. In addition, energy distribution of ion charge states Tin+ (n = 1–4) is measured by varying back plate voltage of the electrostatic energy analyzer for a fixed laser fluence of 20.3 J/cm2. Ions energy distributions were in the range of 0.36–3.0 keV and the most probable ion energy was found to increase linearly with ion charge state. The estimated equivalent potential at the laser fluence of 20.3 J/cm2 is about 310 V. These results are in good agreement with the predictions of electrostatic model of ion acceleration in laser plasma.

We examine the feasibility of a drift-induced instability of Dirac fermions in monolayer graphene in a weak periodic potential, taking into account of a steady current. In this work, we treat magnetic field induced Landau quantization including the effects of drift induced current (an in-plane dc electric field), and analyze both the inter-and the intra-Landau band aspects of the magnetoplasmon spectrum. We employ the framework of self-consistent-field approximation to determine the plasmon spectrum. The existence of the drift induced instability regions in the intra-Landau band magnetoplasmon spectrum as a function of inverse magnetic field is shown and discussed. The unstable intra-Landau band plasmon excitation could be a potential source of THz radiation with electronic device applications.

A time-resolving Langmuir probe was used to investigate the expansion of tungsten plasma produced by the pulsed Nd-YAG laser (wavelength = 1064 nm, pulse duration = 10 ns). Current–voltage (IV) plots at various times after the laser shot hit the target were obtained from probe electron and ion currents. Langmuir probe theory was used to determine the temporal variation of the plasma potential, electron temperature and electron density. These plasma parameters sharply rise to a maximum value and then slowly decrease during the plume expansion. For the laser irradiance of 10.88 × 108 W/cm2, maximum values of plasma potential, electron temperature and electron density were about 24 V, 15.8 eV and 2.24 × 1016 cm−3 respectively. The measurements performed with time-of-flight electrostatic energy analyzer confirmed the presence of highly charged tungsten ions in the plasma and charge state of ions found to increase with the laser irradiance.

Key thermal hydraulic parameters of the 3 MW TRIGA Mark-II research reactor operating under steady-state conditions were investigated using the thermal hydraulic codes NCTRIGA, PARET and COOLOD-N2. Results of the neutronic analysis performed by 3-D Monte Carlo code MCNP4C were used in NCTRIGA and coupled output of neutronic analysis carried out by using 3-D diffusion code CITATION and 3-D Monte Carlo code MCNP4B2 were used in the PARET to study the steady-state thermal hydraulic behavior of the reactor. To benchmark the NCTRIGA, PARET and COOLOD-N2 models, data were obtained from different measurements executed by thermocouples in the instrumented fuel elements (C1 and D2) and the hottest fuel element (C4) during the steady-state operation both under forced and natural convection mode and compared with the calculation found to be quite consistent. The mass flow rates needed for input to PARET and COOLOD-N2 were taken from final safety analysis report (FSAR) for a downward forced coolant flow equivalent to 3500 gpm. For natural convection cooling of reactor, mass flow rate was generated using NCTRIGA code. The testing of the NCTRIGA, PARET and COOLOD-N2 model calculations through benchmarking the available TRIGA experimental and operational data showed that NCTRIGA, PARET and COOLOD-N2 codes can successfully be used to analyze the thermal hydraulic behavior of the reactor for the steady-state operation under both natural and forced convection mode of coolant flow to predict the safety margins. The result obtained in this investigation can be used for upgrading the current core configuration of the TRIGA reactor.

Ischemic stroke is a leading cause of death and disability worldwide. Much of the long-term disability occurs in patients with Emergent Large Vessel Occlusion (ELVO). In fact, in these patients, occlusion of a major intracerebral artery results in a large area of brain injury often resulting in

Electron beam evaporated Sn-doped In2O3 films have been prepared from the starting material with composition of (1 − x) In2O3 − -x SnO2, where x = 0.0, 0.010, 0.025, 0.050, 0.090, and 0.120. X-ray photoelectron spectroscopy, Rutherford backscattering spectrometry, and X-ray diffraction analysis were carried out on the films. Luminous transmittance and electrical resistivity of the films, show weak dependence on x. The composition of the film ([Sn][In] atomic ratio) was found to differ from that of the starting material. In fact, the atomic ratio was higher in the film than in the starting material by a factor which increases with x (ranging from 1.0 to 2.6). There is a relatively broad resistivity minimum in the layer atomic ratio range SnIn = 0.06 − -0.09. These results compare well with those reported in the literature for Sn-doped In2O3 films, prepared by pyrolitic (spray) method.

The efficacy of curcumin and capsaicin in causing regression of pre-established cholesterol gallstones (CGS) was investigated in male mice. After confirming the formation of CGS in 100% of the animals, they were fed a diet containing 0.5% curcumin or 5 mg% capsaicin for 5 or 10 weeks. Five weeks feeding of curcumin or capsaicin diet caused a regression of CGS in 45 and 64% of the animals respectively. Ten weeks feeding of these spice principles caused regression of CGS in 80% of the animals. The biliary cholesterol decreased and phospholipids and bile acids increased with increase in the duration of spice principle feeding. Feeding of a control diet to the animals bearing CGS neither caused regression of CGS nor influenced the biliary lipids significantly.

The efficacy of curcumin and capsaicin in reducing the incidence of cholesterol gallstones (CGS), induced experimentally by feeding a lithogenic diet, was examined in weanling mice and hamsters. After feeding the lithogenic diet for the optimal duration of 10 weeks for mice and 6 weeks for hamsters, CGS were found in 100% of mice and hamsters. Feeding a diet containing 0.5% curcumin or capsaicin 5 mg/100 g for 6 weeks to hamsters reduced the incidence of CGS to 44 or 22%, respectively, compared with the lithogenic group (100%). Biliary cholesterol concentrations and cholesterol:phospholipid ratios (C:PL) were markedly reduced by curcumin and capsaicin feeding. Further cholesterol saturation indices (CSI) of the curcumin and capsaicin groups were 0.54 and 0.35, respectively, compared with 1.56 for the lithogenic group. A dose-response study in which mice were fed on a lithogenic diet supplemented with capsaicin 1.5, 5 or 15 mg/100 g showed that a 5-mg containing diet was more effective than the other 2 in reducing CGS incidence, biliary, serum and liver cholesterol, C:PL ratio, and CSI of bile. Hence, curcumin and capsaicin appear to be potent antilithogenic agents.

The authors propose a frequency-domain technique for the design of multivariable control systems by matching the frequency responses of the compensated closed-loop system and a 'desired' closed-loop system. It is a generalization of the single-input single-output technique. The unknown controller parameters are determined by minimizing a weighted mean-square error between the frequency responses of the compensated closed-loop system and the desired closed-loop system, which leads to solving linear algebraic equations involving the controller parameters. The technique is illustrated by a numerical example. >