The Worth of the Humanities

What is the worth of humanities teaching and research? This collaborative report, based on meetings at McGill and Vanderbilt Universities, argues that humanities researchers and teachers help make an historical, public, meaningful world. It outlines the character of the relationship between the humanities on one side and artistic and political work on the other. It suggests several challenges facing the humanities and provides a short list of recommendations

Unimpeded Growth of Tumour in Hosts Pre-immunized with Tyrosyl- or Dinitrophenyl-coated Tumour Cells

Techniques are described for hapten attachment to the cell membranes of mouse tumour cells. Dinitrophenylation and tyrosylation could be achieved without substantial loss of viability as measured by dye exclusion. In addition hapten coated tumour cells were capable of initiating new tumour formation in syngeneic hosts. Pre-immunization of recipient mice with hapten coated tumour cells did not increase their resistance to tumour formation upon subsequent challenge with graded doses of untreated tumour cells

Doctor Faustus and the Literary System: A Supplementary Response to Paul Budra

Response to Paul Budra's essay "Doctor Faustus: Death of a Bibliophile.

Demonstrating a phytotechnological design-approach

In this master’s thesis the field of phytotechnology is investigated. Phytotechnology is a collection of largely unexploited methods and processes that aim to employ the abilities of plants to manage contaminants in our environments. In Sweden, as well as the rest of the world, contaminated stormwater is a significant problem with negative impacts on areas such as natural and built environments, human health and recreational opportunities. This work demonstrates a phytotechnological design-approach to planning spaces with the purpose of combining management of contaminated stormwater with the enhancement of ecological, social and economic aspects of the semi-urban environment. The purpose of this thesis is to illuminate phytotechnology‘s potential in this regard and show how landscape architects can use it as a means of planning and designing spaces that serve as integral parts of sustainable stormwater management systems. Furthermore, the opportunities and challenges that face this endeavour are studied and discussed. Phytotechnology is fundamentally based on the natural sciences – and plant science more specifically. My background in plant biotechnology at Umeå Plant Science Centre prior to my studies at the Swedish University of Agriculture allow this thesis to largely be devoted to this aspect. However, application of any plants and their associated infrastructure in the built environment falls within the purview of urban planning and landscape architecture. Therefore, this thesis incorporates many fields and should be viewed as an interdisciplinary effort. A literature review covering this broad area is presented. The review describes the processes of remediation; the opportunities and the challenges that face the further development of the field and how this relates to landscape architecture and its practitioners; and why phytotechnology is not a fully accepted practice despite the fact that it rests on firm scientific grounds. The application of phytotechnology has also been demonstrated in this thesis. A design-approach developed by the landscape architects Kate Kennen and Nial Kirkwood has been employed to the construction of a site program aimed at improving the remediation capacity and the ecological, economical and social values of an existing stormwater management pond in Upplands Väsby, Sweden. The site program reveals among other the opportunity to: remediate larger amounts of contaminants and additional contaminant types; increase the areas biodiversity and ecological resilience; allow for potential economic benefits and land-value increases; sustain nationally important cultural values such as open agricultural landscapes in close proximity to urban centres; and provide improved recreational and educational areas in green environments. The challenges that face phytotechnology are shown in the literary review and the site program. Among these challenges are: the unpredictable success that phytotechnological systems currently have, the physical limitations of plants to reach contaminants on certain sites and the efficiency of remediation. Furthermore, difficulties with planning, maintenance and acquiring the necessary expert professionals required to complete a phytotechnological project are revealed. This is also discussed in regards to how we can use phytotechnology as landscape architects and how we can contribute to furthering the field as a whole. One of the conclusions of this thesis is that in this era of increasingly negative anthropogenic impact on our environments – and in turn on ourselves - phytotechnology offers largely unexploited value to landscape architects, natural environments and society as a whole.I denna uppsats undersöks ämnet fytoteknologi. Fytoteknologi är en samling underutnyttjade metoder som syftar till att hantera föroreningar med hjälp av växter. I Sverige, såväl som i resten av världen, är förorenat dagvatten ett betydande problem som påverkar den byggda miljön såväl som naturmarken kring och i den. Dessa problem innefattar bland annat cancerogena och hormonrubbande effekter på människor och djur, ekonomiska påfrestningar på samhället och begränsande rekreativa möjligheter. Ett tillvägagångssätt för att tillämpa fytoteknologi vid planering av multifunktionella dagvattenhanteringssystem i semi-urbana miljöer visas på i denna uppsats. Syftet är att belysa fytoteknologis potential såväl som hur och om landskapsarkitekter kan använda sig av denna teknologi för att planera och gestalta grönytor som del av ett större dagvattenhanteringssytem. Även teknologins möjligheter och utmaningar har studerats och diskuteras. Fytoteknologi är i grunden baserat på naturvetenskap - och mer specifikt på växtbiologi. Min tidigare bakgrund inom växtbioteknik från Umeå Plant Science Centre tillåter denna uppsats att behandla de växtbiologiska aspekterna mer utförligt. Vilka växter som planteras i den byggda miljön ligger dock oftast på landskapsarkitektens bord. På grund av det ovanstående inkorporerar denna uppsats flera fält och kan ses som ett försök att arbeta mer interdisciplinärt. En litteratursammanställning av detta breda fält presenteras. Sammanställningen beskriver de biofysiska processerna bakom fytoteknologi; möjligheterna och utmaningarna som fältets fortsatta utveckling står inför; och varför fytoteknologi inte är en fullt accepterad metod för hantering av föroreningar trots att den vilar på goda vetenskapliga grunder. Även teknologins tillämpning i praktiken beskrivs. Landskapsarkitekterna Kate Kennen och Nial Kirkwood har utvecklat en metod för detta ändamål. Metoden har i detta arbete tillämpats på en dagvattendam i Upplands Väsby för vilken ett gestaltningsprogram har tagits fram. Programmet visar bland annat att det med hjälp av fytoteknologiska metoder finns en möjlighet att samtidigt: rena dagvattnet på fler typer samt större mängder av föroreningar; öka områdets biologiska mångfald och ekologiska resiliens; tillåta potentiella ekonomiska besparingar och markvärdesökningar; bibehålla nationellt viktiga kulturmiljöer i närheten av ett urbant centrum; och bistå med förbättrade rekreationsmöjligheter i gröna miljöer. De utmaningar och begränsningar som fytoteknologi står inför presenteras och visas exempel på både i litteratursammanställnigen såväl som i programmet för dagvattendammen i Upplands Väsby. Bland dessa utmaningar och begränsningar är: svårgaranterade resultat av specifika fytoteknologiska planteringar, växters biologiska begränsningar och effektiviteten av hanteringen av föroreningar. Vidare visas på utmaningar i planeringsskedet, förvaltningen och koordineringen av relevant expertkompetens. Ovanstående diskuteras med hänsyn till hur landskapsarkitekter kan nyttja fytoteknologi och hur de kan bidra till att föra fältet framåt. En av slutsatserna i denna uppsats är att i denna tid av ständigt ökande antropogen påverkan på våra miljöer – och därmed oss själva – erbjuder fytoteknologi outnyttjat värde för landskapsarkitekter, våra miljöer, dess invånare och för samhället i stort

Systems for local best management practices : in literature and in practice

Genom sammanställningen av litteratur och utvärdering av dagvattenstrategin för ett befintligt exploateringsprojekt i Sala, Sverige bidrar denna uppsats till att tydliggöra behovet av lokalt omhändertagande av dagvatten (LOD) för att tackla växande utmaningar associerade med urbanisering och klimatförändringar. Aktuell litteratur på sex dagvattenhanteringssystem som kan med varierande lämplighet användas på två vägsträckor i exploateringsprojektet sammanställs. Sammanställningen kontrasteras med en kvalitativ utvärdering av dagvattenstrategin på exploateringsprojektet (bestående av en samling rapporter, utredningar och planer) och demonstrerar därigenom främst två saker: (1) hur forskningen manifesteras i praktiken och (2) längs med vilka parametrar som utvecklingen av dagvattenstrategin på exploateringsprojektet i Sala potentiellt kan ske. Slutsatser dras om att dagvattenstrategin till stor del följer den aktuella litteraturen men att detaljeringsgraden som är nödvändig för att uppnå strategins huvudsakliga mål är bristande. Med litteraturöversikten över systemen för LOD identifieras bland annat vilka hanteringssystem som bäst lämpar sig för rening av dagvattnet från fosfor och att den i rapporterna föreslagna lösningen med skelettjordar kan kompletteras med användningen av biokol som substrat.Through a review of current literature and the assessment of a development project’s strategy for best management practice (BMP) in Sala, Sweden this thesis illuminates the need for local BMPs in contributing to the mitigation of issues arising from urbanization and climate change. The current literature on six systems for local BMPs that are applicable in the development project in Sala are reviewed. They are consequently contrasted with the qualitative assessment of the strategy for stormwater management (consisting of reports, investigations and site plans) which serve to demonstrate two fundamental points: (1) how current literature on BMPs manifests itself in practice and (2) along which parameters the continued development of the strategy for stormwater management likely should follow. Conclusions are drawn that the strategy in large part follows current literature but that its level of detail is insufficient in achieving its goals. With the review of BMPs as a basis, the best system for removal of phosphor is identified as well as recommending the supplement of biochar in structural soils

Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors

Purpose: In the Phase II GEOMETRY mono-1 study, the potent and selective mesenchymal-epithelial transition (MET) inhibitor capmatinib exhibited considerable efficacy in MET exon 14 skipping (METex14)–mutated metastatic non–small cell lung cancer at a dose of 400 mg BID. The current recommended dose is 400 mg BID in tablet formulation, with or without food. This article reports the pharmacokinetic (PK) profile, safety, and tolerability of capmatinib 300 and 400 mg BID given with food in MET-dysregulated advanced solid tumors. Methods: This multicenter, open-label, Phase I study enrolled adult patients with MET-dysregulated advanced solid tumors. In the dose escalation phase, capmatinib tablets were orally administered at a dose of 300 mg BID with food; if tolerated, the dose escalation cohort of 400 mg BID was to be opened to enrollment. In the expansion phase, patients were to be enrolled at the higher of the tolerated doses. Tablets were taken within 30 minutes of an unrestricted meal type, except on cycle 1 day 1 (C1D1) and cycle 1 day 7 (C1D7), when they were given with a high-fat meal. The primary objectives were to determine the higher of the tolerated study doses and assess PK variables, with a secondary objective of safety. Findings: Overall, 35 patients (300 mg BID, n = 8; 400 mg BID, n = 27) with MET-dysregulated advanced solid tumors were enrolled; all patients had received prior antineoplastic therapy, and the most common primary site was lung (45.7%). Among PK-evaluable patients, the median T for capmatinib after administration with a high-fat meal (on C1D1/C1D7) was 4.0 to 5.6 hours across doses. At steady state (C1D7), capmatinib accumulation was low across dose levels (geometric mean of accumulation ratios, 1.29–1.69), with an increase in exposure (AUC and C ) from 300 to 400 mg BID. There were no occurrences of dose-limiting toxicity. All patients experienced at least 1 adverse event, and treatment-related adverse events occurred in 28 patients (80%; 300 mg BID, n = 6; 400 mg BID, n = 22), the most frequent of which were fatigue (37.1%) and nausea (34.3%). Implications: Capmatinib tablet formulation at a dose of up to 400 mg BID with food is well tolerated in patients with MET-dysregulated advanced solid tumors, with safety observations consistent with the existing profile under fasted conditions. These findings support the capmatinib dosing recommendation of 400 mg BID with or without food. ClinicalTrials.gov identifier: NCT02925104

Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial

IMPORTANCE Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. OBJECTIVE To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized (1: 1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m(2)) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries. INTERVENTION Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year. MAIN OUTCOMES AND MEASURES The primary objectivewas DFS; secondary objectives included distant disease-free survival, overall survival, cardiac DFS, and safety. RESULTS In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease-free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m(2) had inferior and those treated with 100 mg/m(2) had similar DFS as patients in the 1-year group. CONCLUSIONS AND RELEVANCE Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Peer reviewe

Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal.

To the editor: the optimal management of cancer patients is increasingly dependent on individualized treatments guided by tumor sequencing data. As comprehensive genomic tests become routine in many disease settings and academic centers promote omics-guided clinical trial recruitment, accurate and scalable data interpretation represents a major challenge. The meticulous task of matching tumor alterations with approved or experimental therapies relies heavily on the expertise of each center