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"Kerr, David"
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China's many dreams : comparative perspectives on China's search for national rejuvenation
\"China's new leader Xi Jinping has announced that the China Dream of great rejuvenation of the Chinese nation is now closer than ever.This book discusses the meaning and progress of Chinese national rejuvenation from multiple perspectives - government, civil society, ethnic relations, economic development, philanthropy, science policy, cultural diplomacy, strategic philosophy and international relations. The authors discuss critically China's progress towards becoming a strong, prosperous and well-governed country. They evaluate the ideas, policies and institutions that have permitted China to reach the current era of national rejuvenation; but they also indicate the problems that China has still to overcome and the barriers it will face in completing the mission of 'great rejuvenation'.China's Many Dreams provides insightful perspectives on the challenges facing China's future, making it essential reading for scholars, researchers and policy-makers interested in China's growth and development\"-- Provided by publisher.
Book
Deep learning for prediction of colorectal cancer outcome: a discovery and validation study
Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning.
More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival.
828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72–5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07–4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion.
A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes.
The Research Council of Norway.
Journal Article
Novel therapeutic strategies: targeting epithelial–mesenchymal transition in colorectal cancer
Epithelial–mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance apical–basal cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer, EMT has an important role in tumour progression, metastasis, and drug resistance. There has been accumulating evidence from preclinical and early clinical studies that show that EMT markers might serve as outcome predictors and potential therapeutic targets in colorectal cancer. This Review describes the fundamentals of EMT, including biology, newly partial EMT, and associated changes. We also provide a comprehensive summary of therapeutic compounds capable of targeting EMT markers, including drugs in preclinical and clinical trials and those with repurpose potential. Lastly, we explore the obstacles of EMT bench-to-bedside drug development.
Journal Article
Walking with greatness : my caddie life on the tour with Fred, Fuzzy, Vijay, Tiger, and more
\"Maryland-raised Cayce Kerr began his caddying career at the storied Congressional Country Club in 1986 and within a year had managed to work his way onto the PGA Tour, rubbing shoulders with the biggest names in the world of golf. Armed with quick wit and deep golf knowledge, he quickly established himself in the top echelon of his profession and never looked back, partnering with more than two dozen major champions and even working 30 Masters tournaments in a row from 1987 until 2016. In Walking with Greatness, Kerr reveals what really goes on inside and outside the ropes at the highest levels of golf. With a cast of characters including Ernie Els, Fred Couples, Vijay Singh, Fuzzy Zoeller, and Tiger Woods, this true insider's memoir pulls no punches in portraying life on the PGA Tour. Spanning indelible triumphs, improbable mishaps, and no shortage of hijinks, Kerr's adventures and observations will leave golf fans illuminated, entertained, and often literally laughing out loud\"-- Provided by publisher.
BOOK
Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial
Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour.
For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151.
Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00–5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5–78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7–80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89–1·25, p=0·54). The most common grade 3–4 adverse events were hand–foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of 959 in the capecitabine and bevacizumab group) and diarrhoea (102 [11%] vs 104 [11%]), and, with the addition of bevacizumab, expected increases were recorded in all-grade hypertension (320 [33%] vs 75 [8%]), proteinuria (197 [21%] vs 49 [5%]), and wound healing problems (30 [3%] vs 17 [2%]). 571 serious adverse events were reported (221 with capecitabine alone and 350 with capecitabine and bevacizumab). Most of these were gastrointestinal (n=245) or cardiovascular (n=169). 23 deaths within 6 months of randomisation were classified as being related to treatment, eight in the capecitabine alone group and 15 in the capecitabine and bevacizumab group.
The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used.
Roche.
Journal Article
Play it loud : instruments of rock & roll
Play It Loud celebrates the musical instruments that gave rock and roll its signature sound-from Louis Jordan's alto saxophone and John Lennon's Rickenbacker to the drum set owned by Metallica's Lars Ulrich, Lady Gaga's keytar, and beyond. Seven engrossing essays by veteran music journalists and scholars discuss the technical developments that fostered rock's seductive riffs and driving rhythms, the thrilling innovations musicians have devised to achieve unique effects, and the visual impact their instruments have had. Abundant photographs depict rock's most iconic instruments-including Jerry Lee Lewis's baby grand piano, Chuck Berry's Gibson ES-350T guitar, Bootsy Collins's star-shaped bass, Keith Moon's drum set, and the white Stratocaster Jimi Hendrix played at Woodstock-as works of art in their own right. Produced in collaboration with the Rock & Roll Hall of Fame, this astounding book goes behind the music to offer a rare and in-depth look at the instruments that inspired the musicians and made possible the songs we know and love. Exhibition: The Metropolitan Museum of Art, New York, USA (01.04-15.09.2019); The Rock & Roll Hall of Fame, Cleveland, USA (20.11.2019-13.09.2020). -- Book jacket.
Book
A clinical decision support system optimising adjuvant chemotherapy for colorectal cancers by integrating deep learning and pathological staging markers: a development and validation study
The DoMore-v1-CRC marker was recently developed using deep learning and conventional haematoxylin and eosin-stained tissue sections, and was observed to outperform established molecular and morphological markers of patient outcome after primary colorectal cancer resection. The aim of the present study was to develop a clinical decision support system based on DoMore-v1-CRC and pathological staging markers to facilitate individualised selection of adjuvant treatment.
We estimated cancer-specific survival in subgroups formed by pathological tumour stage (pT<4 or pT4), pathological nodal stage (pN0, pN1, or pN2), number of lymph nodes sampled (≤12 or >12) if not pN2, and DoMore-v1-CRC classification (good, uncertain, or poor prognosis) in 997 patients with stage II or III colorectal cancer considered to have no residual tumour (R0) from two community-based cohorts in Norway and the UK, and used these data to define three risk groups. An external cohort of 1075 patients with stage II or III R0 colorectal cancer from the QUASAR 2 trial was used for validation; these patients were treated with single-agent capecitabine. The proposed risk stratification system was evaluated using Cox regression analysis. We similarly evaluated a risk stratification system intended to reflect current guidelines and clinical practice. The primary outcome was cancer-specific survival.
The new risk stratification system provided a hazard ratio of 10·71 (95% CI 6·39–17·93; p<0·0001) for high-risk versus low-risk patients and 3·06 (1·73–5·42; p=0·0001) for intermediate versus low risk in the primary analysis of the validation cohort. Estimated 3-year cancer-specific survival was 97·2% (95% CI 95·1–98·4; n=445 [41%]) for the low-risk group, 94·8% (91·7–96·7; n=339 [32%]) for the intermediate-risk group, and 77·6% (72·1–82·1; n=291 [27%]) for the high-risk group. The guideline-based risk grouping was observed to be less prognostic and informative (the low-risk group comprised only 142 [13%] of the 1075 patients).
Integrating DoMore-v1-CRC and pathological staging markers provided a clinical decision support system that risk stratifies more accurately than its constituent elements, and identifies substantially more patients with stage II and III colorectal cancer with similarly good prognosis as the low-risk group in current guidelines. Avoiding adjuvant chemotherapy in these patients might be safe, and could reduce morbidity, mortality, and treatment costs.
The Research Council of Norway.
Journal Article
The World War I book
Combining authoritative, exciting text and bold images, The World War I Book explores the historical background of the war, its causes, all of the key events across the major theatres of conflict, and its aftermath. Using the original, graphic-led approach of the series, entries profile more than 90 of the key events during and surrounding the conflict -- from the growing tensions between Europe's major powers to the assassination of Archduke Franz Ferdinand, the German invasion of Belgium, the endless slaughter in the trenches, the American entry into the war, the Russian Revolution, the Armistice, and the creation of the League of Nations.
BOOK
Designing deep learning studies in cancer diagnostics
The number of publications on deep learning for cancer diagnostics is rapidly increasing, and systems are frequently claimed to perform comparable with or better than clinicians. However, few systems have yet demonstrated real-world medical utility. In this Perspective, we discuss reasons for the moderate progress and describe remedies designed to facilitate transition to the clinic. Recent, presumably influential, deep learning studies in cancer diagnostics, of which the vast majority used images as input to the system, are evaluated to reveal the status of the field. By manipulating real data, we then exemplify that much and varied training data facilitate the generalizability of neural networks and thus the ability to use them clinically. To reduce the risk of biased performance estimation of deep learning systems, we advocate evaluation in external cohorts and strongly advise that the planned analyses, including a predefined primary analysis, are described in a protocol preferentially stored in an online repository. Recommended protocol items should be established for the field, and we present our suggestions.The number of publications on deep learning for cancer diagnostics is rapidly increasing, but clinical translation is slow. This Perspective advocates performance estimation in external cohorts and strongly advises that a primary analysis is predefined in a standardized protocol preferentially stored in an online repository.
Journal Article