NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring \u3e1 year after whole-breast irradiation, \u3c3 \u3ecm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 \u3e1 to ≤2 cm, and 1 \u3e2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare

Johnson Space Center's Risk and Reliability Analysis Group 2008 Annual Report

The Johnson Space Center (JSC) Safety & Mission Assurance (S&MA) Directorate s Risk and Reliability Analysis Group provides both mathematical and engineering analysis expertise in the areas of Probabilistic Risk Assessment (PRA), Reliability and Maintainability (R&M) analysis, and data collection and analysis. The fundamental goal of this group is to provide National Aeronautics and Space Administration (NASA) decisionmakers with the necessary information to make informed decisions when evaluating personnel, flight hardware, and public safety concerns associated with current operating systems as well as with any future systems. The Analysis Group includes a staff of statistical and reliability experts with valuable backgrounds in the statistical, reliability, and engineering fields. This group includes JSC S&MA Analysis Branch personnel as well as S&MA support services contractors, such as Science Applications International Corporation (SAIC) and SoHaR. The Analysis Group s experience base includes nuclear power (both commercial and navy), manufacturing, Department of Defense, chemical, and shipping industries, as well as significant aerospace experience specifically in the Shuttle, International Space Station (ISS), and Constellation Programs. The Analysis Group partners with project and program offices, other NASA centers, NASA contractors, and universities to provide additional resources or information to the group when performing various analysis tasks. The JSC S&MA Analysis Group is recognized as a leader in risk and reliability analysis within the NASA community. Therefore, the Analysis Group is in high demand to help the Space Shuttle Program (SSP) continue to fly safely, assist in designing the next generation spacecraft for the Constellation Program (CxP), and promote advanced analytical techniques. The Analysis Section s tasks include teaching classes and instituting personnel qualification processes to enhance the professional abilities of our analysts as well as performing major probabilistic assessments used to support flight rationale and help establish program requirements. During 2008, the Analysis Group performed more than 70 assessments. Although all these assessments were important, some were instrumental in the decisionmaking processes for the Shuttle and Constellation Programs. Two of the more significant tasks were the Space Transportation System (STS)-122 Low Level Cutoff PRA for the SSP and the Orion Pad Abort One (PA-1) PRA for the CxP. These two activities, along with the numerous other tasks the Analysis Group performed in 2008, are summarized in this report. This report also highlights several ongoing and upcoming efforts to provide crucial statistical and probabilistic assessments, such as the Extravehicular Activity (EVA) PRA for the Hubble Space Telescope service mission and the first fully integrated PRAs for the CxP's Lunar Sortie and ISS missions

The purpose of mess in action research: building rigour though a messy turn

Mess and rigour might appear to be strange bedfellows. This paper argues that the purpose of mess is to facilitate a turn towards new constructions of knowing that lead to transformation in practice (an action turn). Engaging in action research - research that can disturb both individual and communally held notions of knowledge for practice - will be messy. Investigations into the 'messy area', the interface between the known and the nearly known, between knowledge in use and tacit knowledge as yet to be useful, reveal the 'messy area' as a vital element for seeing, disrupting, analysing, learning, knowing and changing. It is the place where long-held views shaped by professional knowledge, practical judgement, experience and intuition are seen through other lenses. It is here that reframing takes place and new knowing, which has both theoretical and practical significance, arises: a 'messy turn' takes place

Diagnosing ventilator-associated pneumonia (VAP) in UK NHS ICUs:the perceived value and role of a novel optical technology

BACKGROUND: Diagnosing ventilator-associated pneumonia (VAP) in an intensive care unit (ICU) is a complex process. Our aim was to collect, evaluate and represent the information relating to current clinical practice for the diagnosis of VAP in UK NHS ICUs, and to explore the potential value and role of a novel diagnostic for VAP, which uses optical molecular alveoscopy to visualise the alveolar space. METHODS: Qualitative study performing semi-structured interviews with clinical experts. Interviews were recorded, transcribed, and thematically analysed. A flow diagram of the VAP patient pathway was elicited and validated with the expert interviewees. Fourteen clinicians were interviewed from a range of UK NHS hospitals: 12 ICU consultants, 1 professor of respiratory medicine and 1 professor of critical care. RESULTS: Five themes were identified, relating to [1] current practice for the diagnosis of VAP, [2] current clinical need in VAP diagnostics, [3] the potential value and role of the technology, [4] the barriers to adoption and [5] the evidence requirements for the technology, to help facilitate a successful adoption. These themes indicated that diagnosis of VAP is extremely difficult, as is the decision to stop antibiotic treatment. The analysis revealed that there is a clinical need for a diagnostic that provides an accurate and timely diagnosis of the causative pathogen, without the long delays associated with return of culture results, and which is not dangerous to the patient. It was determined that the technology would satisfy important aspects of this clinical need for diagnosing VAP (and pneumonia, more generally), but would require further evidence on safety and efficacy in the patient population to facilitate adoption. CONCLUSIONS: Care pathway analysis performed in this study was deemed accurate and representative of current practice for diagnosing VAP in a UK ICU as determined by relevant clinical experts, and explored the value and role of a novel diagnostic, which uses optical technology, and could streamline the diagnostic pathway for VAP and other pneumonias. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41512-022-00117-x

Genetic Improvement @ ICSE 2020

Following Prof. Mark Harman of Facebook's keynote and formal presentations (which are recorded in the proceedings) there was a wide ranging discussion at the eighth international Genetic Improvement workshop, GI-2020 @ ICSE (held as part of the 42nd ACM/IEEE International Conference on Software Engineering on Friday 3rd July 2020). Topics included industry take up, human factors, explainabiloity (explainability, justifyability, exploitability) and GI benchmarks. We also contrast various recent online approaches (e.g. SBST 2020) to holding virtual computer science conferences and workshops via the WWW on the Internet without face-2-face interaction. Finally we speculate on how the Coronavirus Covid-19 Pandemic will affect research next year and into the future

A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3–4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3–4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916

Depths and Thermal Habitat Used by Large versus Small Northern Pike in Three Minnesota Lakes

We monitored depths and temperatures used by large (>71‐cm) versus small Northern Pike Esox lucius in three north‐central Minnesota lakes with either acoustic telemetry or archival tags. Individual Northern Pike demonstrated flexibility in depths used within a season and between years. The fish had some tolerance for low levels of dissolved oxygen (<3 mg/L), but depth selection was generally constrained by low dissolved oxygen in summer and winter. The fish more fully exploited all available depths during winter and thermal turnover periods. During July and August, large Northern Pike tended to follow the thermocline into cooler water as upper water layers warmed. Selection ratios indicated that large Northern Pike preferred water temperatures of 16–21°C during August when temperatures up to 28°C were available. In two lakes providing dense overhead cover from water lilies in shallow water, small Northern Pike used warmer, shallower water compared with large fish during summer. In a third lake providing no such cover, small fish were more often in deeper, cooler water. For small Northern Pike, temperature seemed to be a secondary habitat consideration behind the presence of shallow vegetated cover. This study provided detailed temperature selection information that will be useful when considering temperature as an ecological resource for different sizes of Northern Pike.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141595/1/tafs1629.pd

Carbonyl‐ β ‐Cyclodextrin as a Novel Binder for Sulfur Composite Cathodes in Rechargeable Lithium Batteries

As one of the essential components in electrodes, the binder affects the performance of a rechargeable battery. By modifying β ‐cyclodextrin ( β ‐CD), an appropriate binder for sulfur composite cathodes is identified. Through a partial oxidation reaction in H 2 O 2 solution, β ‐CD is successfully modified to carbonyl‐ β ‐cyclodextrin (C‐ β ‐CD), which exhibits a water solubility ca. 100 times that of β ‐CD at room temperature. C‐ β ‐CD possesses the typical properties of an aqueous binder: strong bonding strength, high solubility in water, moderate viscosity, and wide electrochemical windows. Sulfur composite cathodes with C‐ β ‐CD as the binder demonstrate a high reversible capacity of 694.2 mA h g (composite) −1 and 1542.7 mA h g (sulfur) −1 , with a sulfur utilization approaching 92.2%. The discharge capacity remains at 1456 mA h g (sulfur) −1 after 50 cycles, which is much higher than that of the cathode with unmodified β ‐CD as binder. Combined with its low cost and environmental benignity, C‐ β ‐CD is a promising binder for sulfur cathodes in rechargeable lithium batteries with high electrochemical performance. The sulfur utilization and cycling stability of composite cathodes in rechargeable lithium batteries are enhanced by carbonyl‐ β ‐cyclodextrin (C‐ β ‐CD) as the binder in sulfur composite cathodes. This is made possible by the fact that C‐ β ‐CD is highly soluble in water, ca. 100 times more soluble than β ‐CD at room temperature, and because it exhibits strong bonding strength.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96706/1/adfm_201201847_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96706/2/1194_ftp.pd