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"Mark, M."
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Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial
Approximately 25% of all patients with non-small-cell lung cancer present with resectable stage IB–IIIA disease, and although perioperative chemotherapy is the standard of care, this treatment strategy provides only modest survival benefits. On the basis of the activity of immune checkpoint inhibitors in metastatic non-small-cell lung cancer, we designed a trial to test the activity of the PD-L1 inhibitor, atezolizumab, with carboplatin and nab-paclitaxel given as neoadjuvant treatment before surgical resection.
This open-label, multicentre, single-arm, phase 2 trial was done at three hospitals in the USA. Eligible patients were aged 18 years or older and had resectable American Joint Committee on Cancer-defined stage IB–IIIA non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0–1, and a history of smoking exposure. Patients received neoadjuvant treatment with intravenous atezolizumab (1200 mg) on day 1, nab-paclitaxel (100 mg/m2) on days 1, 8, and 15, and carboplatin (area under the curve 5; 5 mg/mL per min) on day 1, of each 21-day cycle. Patients without disease progression after two cycles proceeded to receive two further cycles, which were then followed by surgical resection. The primary endpoint was major pathological response, defined as the presence of 10% or less residual viable tumour at the time of surgery. All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT02716038, and is ongoing but no longer recruiting participants.
Between May 26, 2016, and March 1, 2019, we assessed 39 patients for eligibility, of whom 30 patients were enrolled. 23 (77%) of these patients had stage IIIA disease. 29 (97%) patients were taken into the operating theatre, and 26 (87%) underwent successful R0 resection. At the data cutoff (Aug 7, 2019), the median follow-up period was 12·9 months (IQR 6·2–22·9). 17 (57%; 95% CI 37–75) of 30 patients had a major pathological response. The most common treatment-related grade 3–4 adverse events were neutropenia (15 [50%] of 30 patients), increased alanine aminotransferase concentrations (two [7%] patients), increased aspartate aminotransferase concentration (two [7%] patients), and thrombocytopenia (two [7%] patients). Serious treatment-related adverse events included one (3%) patient with grade 3 febrile neutropenia, one (3%) patient with grade 4 hyperglycaemia, and one (3%) patient with grade 2 bronchopulmonary haemorrhage. There were no treatment-related deaths.
Atezolizumab plus carboplatin and nab-paclitaxel could be a potential neoadjuvant regimen for resectable non-small-cell lung cancer, with a high proportion of patients achieving a major pathological response, and manageable treatment-related toxic effects, which did not compromise surgical resection.
Genentech and Celgene.
Journal Article
The smell of battle, the taste of siege : a sensory history of the Civil War
\"Historical accounts of major events have almost always relied upon what those who were there witnessed. Nowhere is this truer than in the nerve-shattering chaos of warfare, where sight seems to confer objective truth and acts as the basis of reconstruction. In The Smell of Battle, The Taste of Siege, historian Mark M. Smith considers how all five senses, including sight sound, smell, taste, and touch, shaped the experience of the Civil War and thus its memory, exploring its full sensory impact on everyone from the soldiers on the field to the civilians waiting at home. From the eardrum-shattering barrage of shells announcing the outbreak of war at Fort Sumter; to the stench produced by the corpses lying in the mid-summer sun at Gettysburg; to the siege of Vicksburg, once a center of Southern culinary aesthetics and starved into submission, Smith recreates how Civil War was lived. Relying on first-hand accounts, Smith focuses on sense, one for each event, offering a wholly new perspective. At Bull Run, the similarities between the colors of the Union and Confederate uniforms created concern over what later would be called 'friendly fire' and helped decide the outcome of the first major battle. He evokes what it might have felt like to be in the HL Hunley submarine, in which eight men worked in darkness in a space 48 inches high, 42 inches wide. Often argued to be the first 'total war,' the Civil War overwhelmed the senses because of its unprecedented nature and scope, rendering sight less reliable and engaging the nonvisual senses. Sherman's March was little less than a full-blown assault on Southern sense and sensibility, leaving nothing untouched. The Smell of Battle, The Taste of Siege offers readers a way to experience of the Civil War with fresh eyes\"--Provided by publisher.
Book
Mainstream partial nitritation–anammox in municipal wastewater treatment: status, bottlenecks, and further studies
Driven by energy neutral/positive of wastewater treatment plants, significant efforts have been made on the research and development of mainstream partial nitritation and anaerobic ammonium oxidation (anammox) (PN/A) (deammonification) process since the early 2010s. To date, feasibility of mainstream PN/A process has been demonstrated and proven by experimental results at various scales although with the low loading rates and elevated nitrogen concentration in the effluent at low temperatures (15–10 °C). This review paper provides an overview of the current state of research and development of mainstream PN/A process and critically analyzes the bottlenecks for its full-scale application. The paper discusses the following: (i) the current status of research and development of mainstream PN/A process; (ii) the interactions among aerobic ammonium-oxidizing bacteria, aerobic nitrite-oxidizing bacteria, anammox bacteria, and heterotrophic bacteria; (iii) the suppression of aerobic nitrite-oxidizing bacteria; (iv) process and bioreactors; and (v) suggested further studies including efficient and robust carbon concentrating pretreatment, deepening of understanding competition between autotrophic nitrogen-converting organisms, intensification of biofilm anammox activity, reactor design, and final polishing.
Journal Article
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer
Patients with non–small-cell lung cancer were randomly assigned to three cycles of chemotherapy with or without nivolumab, an anti–PD-1 antibody. Event-free survival was longer with nivolumab than without it (31.6 months vs. 20.8 months), and the percentage of patients with a pathological complete response was 24.0% and 2.2%, respectively.
Journal Article
Intelligence : from secrets to policy
\"Mark M. Lowenthal's trusted guide is the go-to resource for understanding how the intelligence community's history, structure, procedures, and functions affect policy decisions. In this Eighth Edition, the author addresses cyber security and cyber intelligence throughout, expands the coverage of collection, comprehensively updates the chapters on nation state issues and transnational issues, and looks at foreign intelligence services, both large and small\"-- Provided by publisher.
Book
Fundamental rate-loss tradeoff for optical quantum key distribution
Since 1984, various optical quantum key distribution (QKD) protocols have been proposed and examined. In all of them, the rate of secret key generation decays exponentially with distance. A natural and fundamental question is then whether there are yet-to-be discovered optical QKD protocols (without quantum repeaters) that could circumvent this rate-distance tradeoff. This paper provides a major step towards answering this question. Here we show that the secret key agreement capacity of a lossy and noisy optical channel assisted by unlimited two-way public classical communication is limited by an upper bound that is solely a function of the channel loss, regardless of how much optical power the protocol may use. Our result has major implications for understanding the secret key agreement capacity of optical channels—a long-standing open problem in optical quantum information theory—and strongly suggests a real need for quantum repeaters to perform QKD at high rates over long distances.
An open question in quantum key distribution (QKD) is whether there exist protocols avoiding the exponential decay of the secret key generation rate with distance. Takeoka
et al.
show a fundamental tradeoff between the secret-key generation rate and the channel loss for optical repeater-less QKD protocols.
Journal Article
Quantifying the magic of quantum channels
To achieve universal quantum computation via general fault-tolerant schemes, stabilizer operations must be supplemented with other non-stabilizer quantum resources. Motivated by this necessity, we develop a resource theory for magic quantum channels to characterize and quantify the quantum 'magic' or non-stabilizerness of noisy quantum circuits. For qudit quantum computing with odd dimension d, it is known that quantum states with non-negative Wigner function can be efficiently simulated classically. First, inspired by this observation, we introduce a resource theory based on completely positive-Wigner-preserving quantum operations as free operations, and we show that they can be efficiently simulated via a classical algorithm. Second, we introduce two efficiently computable magic measures for quantum channels, called the mana and thauma of a quantum channel. As applications, we show that these measures not only provide fundamental limits on the distillable magic of quantum channels, but they also lead to lower bounds for the task of synthesizing non-Clifford gates. Third, we propose a classical algorithm for simulating noisy quantum circuits, whose sample complexity can be quantified by the mana of a quantum channel. We further show that this algorithm can outperform another approach for simulating noisy quantum circuits, based on channel robustness. Finally, we explore the threshold of non-stabilizerness for basic quantum circuits under depolarizing noise.
Journal Article