1,622 research outputs found
The China firm: American elites and the making of British Colonial society
No full textWhat roles did Americans play in the expanding global empires of the nineteenth century? Thomas M. Larkin examines the Hong Kong–based Augustine Heard & Company, the most prominent American trading firm in treaty-port China, to explore the ways American elites at once made and were made by British colonial society. Following the Heard brothers throughout their firm’s rise and decline, The China Firm reveals how nineteenth-century China’s American elite adapted to colonial culture, helped entrench social and racial hierarchies, and exploited the British imperial project for their own profit as they became increasingly invested in its political affairs and commercial networks.
Through the central narrative of Augustine Heard & Co., Larkin disentangles the ties that bound the United States to China and the British Empire in the nineteenth century. Drawing on a vast range of archival material from Hong Kong, China, Boston, and London, he weaves the local and the global together to trace how Americans gained acceptance into and contributed to the making of colonial societies and world-spanning empires. Uncovering the transimperial lives of these American traders and the complex ways extraimperial communities interacted with British colonialism, The China Firm makes a vital contribution to global histories of nineteenth-century Asia and provides an alternative narrative of British empire
Efficacy of the combination of ipilimumab and nivolumab following progression on pembrolizumab in advanced melanoma with poor risk features
No full textImmune-checkpoint inhibitors in melanoma and kidney cancer: from sequencing to rational selection
No full textImmune-checkpoint inhibitors (ICPIs), including antibodies against cytotoxic T-lymphocyte associated antigen 4 and programmed cell death protein 1, have been shown to induce durable complete responses in a proportion of patients in the first-line and refractory setting in advanced melanoma and renal cell carcinoma. In fact, there are several lines of both targeted agents and ICPI that are now feasible treatment options. However, survival in the metastatic setting continues to be poor and there remains a need for improved therapeutic approaches. In order to enhance patient selection for the most appropriate next line of therapy, better predictive biomarkers of responsiveness will need to be developed in tandem with technologies to identify mechanisms of ICPI resistance. Adaptive, biomarker-driven trials will drive this evolution. The combination of ICPI with specific chemotherapies, targeted therapies and other immuno-oncology (IO) drugs in order to circumvent ICPI resistance and enhance efficacy is discussed. Recent data support the role for both targeted therapies and ICPI in the adjuvant setting of melanoma and targeted therapies in the adjuvant setting for renal cell carcinoma, which may influence the consideration of treatment on subsequent relapse. Approaches to select the optimal treatment sequences for these patients will need to be refined
Renal cell carcinoma
No full textRenal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy
Data and analysis supporting: Quantifying aquatic plant commonness and cooccurrence across scales to support ecological understanding and management
No full textData and R code necessary to reproduce the results of the publication. This DRUM submission includes a Quarto document for reproducing the analyses, a PDF markdown document that was generated from the Quarto file, and 11 files (10 .rds, 1 .csv) with the underlying data.
Note that 11 of the species in the dataset are protected species in Minnesota, for which locality information is required to be anonymized. These have been renamed “protected_spp1”, “protected_spp2”, etc. in data files denoted with the suffix “_anon”. The actual species names are used in the manuscript where applicable. This introduces some subtle differences in outputs from this repository relative to the results shown in the manuscript.These data and R statistical code support the publication, "Quantifying aquatic plant commonness and cooccurrence across scales to support ecological understanding and management," in Journal of Ecology. We analyzed aquatic plant surveys from 1,658 lakes across Minnesota and Wisconsin, USA, collected over two decades (2000-2022) and encompassing nearly one million sampling points. These data were collected by agency staff, consultants, researchers, and others who performed the thousands of aquatic plant surveys that enabled this work. For 106 focal taxa, we quantified commonness as occupancy (at regional and local scales) and cooccurrence as diversity fields (the mean species richness of lakes or sampling locations where each focal species occurred). We used statistical models that incorporated environmental, spatial, and temporal covariates to correct for biased sampling and isolate community processes from other influential factors, and leveraged the temporal span of the data to investigate interannual variability in commonness and cooccurrence.Funder: Minnesota Aquatic Invasive Species Research Center (MAISRC)Funding for this project was provided by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Minnesota Aquatic Invasive Species Research Center (MAISRC) and the Legislative-Citizen Commission on Minnesota Resources (LCCMR).Minnesota Agricultural Experiment StationMidwest Glacial Lakes PartnershipLarkin, Daniel J; Verhoeven, Michael R; Walsh, Jake R; Johnson, James A. (2026). Data and analysis supporting: Quantifying aquatic plant commonness and cooccurrence across scales to support ecological understanding and management. Retrieved from the Data Repository for the University of Minnesota (DRUM), https://doi.org/10.13020/hkyt-sv23
Real-world Experience With Sunitinib Treatment in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to Risk Score.
No full textBACKGROUND: ADONIS is an ongoing observational study in 9 European countries, designed to evaluate treatment patterns/outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib and/or second-line axitinib post sunitinib. We present an evaluation of sunitinib efficacy by risk group, in the real-world setting examined in ADONIS. PATIENTS AND METHODS: Patients were enrolled at the start of first-line sunitinib treatment or second-line axitinib post sunitinib treatment. Evaluation of sunitinib efficacy was assessed by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center risk criteria. RESULTS: For all patients in this analysis (N = 467), the median progression-free survival was 23.8 months (95% confidence interval [CI], 16.5-28.5 months), 11.8 months (95% CI, 8.1-17.4 months), and 4.6 months (95% CI, 2.5-7.7 months) for IMDC favorable-, intermediate-, and poor-risk groups, respectively. The median overall survival was 97.1 months (95% CI, 46.3 months-not evaluable [NE]), 33.5 months (95% CI, 20.5-46.6 months), and 10.0 months (95% CI, 4.5-19.8 months) for the respective risk groups. Data on individual risk factors were available for a subgroup of patients, allowing analysis by intermediate risk by 1 versus 2 risk factors. When including this subgroup (n = 120), the median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 months (95% CI, 16.3 months-NE), 20.5 months (15.5 months-NE), and 15.1 months (4.1 months-NE), respectively. CONCLUSIONS: For patients overall and by risk-group stratification, survival estimates were aligned with previously published data. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration of outcome data from different sources is needed to confirm these observations
Systematic literature review for the association of biomarkers with efficacy of anti-PD-1 inhibitors in advanced melanoma.
No full textAim: Summarize the literature assessing biomarkers in predicting efficacy of anti-PD-1 therapy for patients with high-risk unresectable or metastatic melanoma. Materials & methods: Relevant studies were identified via a systematic literature review. Results: About 334 unique biomarkers or biomarker combinations were identified from 121 citations. Neutrophil-to-lymphocyte ratio was the most frequently studied biomarker, followed by C-reactive protein. Fifty-nine biomarkers were significantly associated with overall survival (OS), 51 with progression-free survival (PFS) and 44 with response. Twenty biomarkers were associated with both OS and PFS; two were associated with OS, PFS and response (MHC-II and tumor mutational burden). Conclusion: Numerous biomarkers could potentially predict the efficacy of anti-PD-1-based therapy for melanoma patients. However, confirmatory studies are needed as well as determination of implications for clinical decision-making
"Tell me what is 'better'!" How medical students experience feedback, through the lens of self-regulatory learning.
No full textINTRODUCTION: While feedback aims to support learning, students frequently struggle to use it. In studying feedback responses there is a gap in explaining them in relation to learning theory. This study explores how feedback experiences influence medical students' self-regulation of learning. METHODS: Final-year medical students across three campuses (Ireland, Bahrain and Malaysia) were invited to share experiences of feedback in individual semi-structured interviews. The data were thematically analysed and explored through the lens of self-regulatory learning theory (SRL). RESULTS: Feedback interacts with learners' knowledge and beliefs about themselves and about learning. They use feedback to change both their cognitive and behavioural learning strategies, but how they choose which feedback to implement is complex. They struggle to generate learning strategies and expect teachers to make sense of the "how" in addition to the "what"" in planning future learning. Even when not actioned, learners spend time with feedback and it influences future learning. CONCLUSION: By exploring our findings through the lens of self-regulation learning, we advance conceptual understanding of feedback responses. Learners' ability to generate "next steps" may be overestimated. When feedback causes negative emotions, energy is diverted from learning to processing distress. Perceived non-implementation of feedback should not be confused with ignoring it; feedback that is not actioned often impacts learning
Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib
No full textThe BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials
Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma.
No full textBACKGROUND: No biomarkers have been established to predict treatment efficacy in renal cell carcinoma (RCC). In an exploratory retrospective analysis of a Phase 2 study, we constructed composite biomarker scores (CBSs) to predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic RCC randomised to receive lenvatinib-plus-everolimus. METHODS: Of 40 biomarkers tested, the 5 most strongly associated with PFS (HGF, MIG, IL-18BP, IL-18, ANG-2) or OS (TIMP-1, M-CSF, IL-18BP, ANG-2, VEGF) were used to make a 5-factor PFS-CBS or OS-CBS, respectively. A 2-factor CBS was generated with biomarkers common to PFS-CBS and OS-CBS. Patients were divided into groups accordingly (5-factor-CBS high: 3-5, CBS-low: 0-2; 2-factor-CBS high: 1-2, CBS-low: 0). RESULTS: PFS/OS with lenvatinib-plus-everolimus were significantly longer in the 5-factor CBS-high group versus the CBS-low group (P = 0.0022/P < 0.0001, respectively). In the CBS-high group, PFS/OS were significantly longer with lenvatinib-plus-everolimus versus everolimus (P < 0.001/P = 0.0079, respectively); PFS was also significantly longer with lenvatinib-plus-everolimus versus lenvatinib (P = 0.0046). The 5-factor-CBS had a predictive role in PFS and OS after multivariate analysis. Similar trends were observed with the 2-factor-CBS for PFS (i.e., lenvatinib-plus-everolimus versus everolimus). CONCLUSIONS: The 5-factor CBS may identify patients with metastatic RCC who would benefit from lenvatinib-plus-everolimus versus everolimus; additional validation is required. CLINICAL TRIAL REGISTRATION: The clinical trial registration number is NCT01136733
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