Diplomacy of fear Smith, Denis
Diplomacy of fear,
1988, 19881215, 1988
eBook
The wartime alliance of the Soviet Union with Britain, the United States, Canada, and their allies very quickly unravelled after the war; in its place rose up the East-West enmity that remains today. ...Denis Smith here tells the story of how mutual conflict and misunderstanding led to the disintegration of the alliance with the Soviet Union, and of how Canada chose its place as a secondary member of the emerging American alliance. Smith draws on Canadian, British, and American historical archives of the years from the German invasion of Russia to the establishment of NATO. He emphasizes the unusual efforts that were made to bring the United States into a permanent international role, the West's tendency to see Russian post-war actions according to the model of Nazi Germany, and the extent to which fear and panic governed Western policy as it forze into the patterns of the cold War in 1947 and 1948. A clear picture emerges of the relationship between the work of officials in Canada's Department of External Affairs and the policies adopted by the Canadian government. Smith's clam reassessment of post-war history sheds considerable light on the roots of East-West relations in the later 1980s, and should assist current efforts to see these relations with renewed realism and good sense.
This special issue of the Journal of Contingencies and Crisis Management aims to consider the early lessons and implications of the coronavirus disease 2019 (COVID-19) pandemic for both the theory ...and practice of crisis management. The COVID-19 pandemic is essential because it represents the first major global health crisis of the 21st Century, and it also highlights the ‘messy’ nature of those management and policy problems which have the potential to escalate into a crisis and which can highlight the inadequate nature of management responses (Ackoff, 1981; Turner, 1994). Before outlining the aspects of these problems covered in this special issue, we need to highlight some of the challenges associated with the pandemic and its implications for the relationships between the processes of resilience and crisis management.Challenges associated with crisis management and organizational resilience (along with the linked concept of business continuity management BCM) were brought to the centre stage of organizational awareness during the COVID-19 pandemic. Inevitably, an extreme event on the global scale of COVID-19 generates a range of impacts across the organizational and societal landscape. There has been considerable discussion about how some organizations were resilient in the face of the task demands associated with the pandemic. In contrast, others could not respond effectively (see, e.g., Dayson et al., 2021). COVID-19 can be considered an extreme event—a low probability, high consequence event that generated a sense of crisis for many organizations. The move to lockdown and the constraints around supply chains moved many organizations into what could be seen as a crisis state in which they were close to the point of failure, and the pandemic was seen to generate a ‘perfect storm’ of challenges for many organizations to contend with (Hyndman, 2020; Slagle et al., 2021). At the same time, other organizations benefitted from the increased demand to provide protective equipment, develop vaccines and support the means of mobile working. The landscape of costs and benefits associated with the crisis was uneven, and this is particularly apparent in terms of the public health response and the emergence of what has been described as vaccine nationalism (Bollyky & Bown, 2020; Hassoun, 2021; Katz et al., 2021).The pandemic illustrated the fragile nature of many public health systems in dealing with the shock of an emergent virus and the assumptions that underpinned contingency planning for such events (Gostin, 2022; Parmet, 2022). One of these early assumptions was the need for herd immunity to deal with the transmission of the virus, a concept that has been subject to criticism within the public health community (Ashton, 2022). More recently, politicians have spoken of the need to live with the virus, and, in the United Kingdom, most of the COVID restrictions have been (or are due to be) lifted by the various devolved governments (Vaughan, 2022).
The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials.
We conducted a multinational, ...randomized, double-blind, placebo-controlled phase 3 trial of sunitinib in patients with advanced, well-differentiated pancreatic neuroendocrine tumors. All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline. A total of 171 patients were randomly assigned (in a 1:1 ratio) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo. The primary end point was progression-free survival; secondary end points included the objective response rate, overall survival, and safety.
The study was discontinued early, after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib. Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval CI, 0.26 to 0.66; P<0.001). A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied. The objective response rate was 9.3% in the sunitinib group versus 0% in the placebo group. At the data cutoff point, 9 deaths were reported in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (hazard ratio for death, 0.41; 95% CI, 0.19 to 0.89; P=0.02). The most frequent adverse events in the sunitinib group were diarrhea, nausea, vomiting, asthenia, and fatigue.
Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00428597.).
This document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org).
All French medical ...societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019.
The management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET.
These guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.
Enhancing community resilience has increasingly involved national and regional governments adopting a multi-stakeholder approach because of the potential interagency benefits. This has led to ...questions about how best to involve stakeholder groups in translating community resilience policies into practice. This exploratory study contributes to this discussion by addressing two key areas that are fundamental in the concerted effort to build community resilience to natural hazards: (1) stakeholder understanding of community resilience as a concept; and (2) the difficulties associated with the processes of risk assessment and preparedness that stakeholders face locally in building community resilience. Data were collected through semistructured interviews with 25 practitioners and experts within Scotland’s resilience community, and were analyzed through an inductive approach to thematic analysis. These data show how the interpretation of community resilience differs across stakeholder groups. Analysis of the data reveals challenges around the nature of the risk assessment and its role in shaping risk perception and communication. Significant complications occur in communicating about low probability-high consequence events, perceived territoriality, competing risk prioritizations, and the challenges of managing hazards within a context of limited resources. The implications of these issues for policy and practice are also discussed.
The concept of the undercommons offers a lens for complicating the discourse of conviviality in education. In this paper, the authors draw on learning experiences opened through black feminisms, ...decoloniality and anti-coloniality, and new materialisms in an experimental graduate course. Presenting stories drawn from a shared educational space, they theorise fugitive convivial praxis and elucidate insurgent opportunities for intellectual study that nurture decolonial undercurrents of the university apparatus. Such engagements allowed for radical vulnerability in coming together through processes of ethical care, place-making, and counter-expressive thinking especially when coded formations of diversity insist on colonial logics and modes of operation in higher education. With curiosities and questions emerging in the undercommons, the authors also consider remote learning during the coronavirus pandemic toward future possibilities.
Digital storytelling as part of study creates an opening for reworking ideas. It marks an instance of recognition to access alternative ways of knowing, thinking, and doing. Guided by radical black ...studies and decolonizing methodologies, the authors draw on insights from digital storytelling to extend current understandings of educational research, theory, and practice. The connections across five digital stories are highlighted through a retrospective analysis of educational journeys to and beyond doctoral study. The digital stories are presented in a series of plateaus to (1) challenge the constraints of academic writing and (2) signal methodological openings in collective restorying. To that end, the authors unravel processes of becoming, trouble the pedagogical encounters in their work, and push for otherwise possibilities to make room for the not-yet.
Efficacy of treatments for VIPoma: A GTE multicentric series Brugel, Mathias; Walter, Thomas; Goichot, Bernard ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
December 2021, 2021-12-00, 20211201, 2021-12, Letnik:
21, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning ...symptoms and tumor burden have been poorly described in VIPoma.
Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma.
We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received.
Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025).
Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.
The phase 3 KEYNOTE‐177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite‐instability‐high ...(MSI‐H)/mismatch‐repair‐deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression‐free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE‐177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval CI 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio HR 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment‐related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune‐mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first‐line pembrolizumab as a standard of care for patients from Asia with MSI‐H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.
We report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis of the phase 3 KEYNOTE‐177 study which evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite‐instability‐high(MSI‐H)/mismatch‐repair‐deficient (dMMR) metastatic colorectal cancer (mCRC). Median PFS was not reached (NR) with pembrolizumab versus 10.4 months with chemotherapy (hazard ratio HR 0.56, 95% confidence interval CI 0.26–1.20), median OS was NR versus 30.0 months (HR 0.65, 95% CI 0.27–1.55), ORR was 50% versus 46%, and grade 3/4 treatment‐related adverse events were reported by two patients (9%) versus 20 (80%). These data support first‐line pembrolizumab as a standard of care for patients from Asia with MSI‐H/dMMR mCRC.
Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) regimen has become a new standard for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the ...anus (SCCA) after demonstrating improved efficacy (12-month PFS of 47%) in the Epitopes-HPV02 trial. Antibodies targeting the checkpoint inhibitor (CKI) programmed cell death protein-1 (PD1) have demonstrated the efficacy as monotherapies in second-line treatment of SCCA. The aim of this study is to evaluate the combination of atezolizumab and mDCF as first-line chemotherapy in a non-comparative multicentre randomized phase II study of advanced SCCA patients.
Patients with chemo-naive advanced histologically proven SCCA, metastatic or unresectable locally advanced recurrence, and Eastern Cooperative Oncology Group-performance status (ECOG-PS) < 2 will be eligible. The primary endpoint is a 12-month PFS rate. Using one-arm non-parametric survival with unilateral alpha type I error of 5% and a statistical power of 80%, the upper critical value for the 12-month PFS rate is 47% to reject H0. Assuming 5% lost to follow-up, 99 patients will be randomized on a 2:1 basis, 66 to the experimental arm (arm A, mDCF plus atezolizumab) and 33 to the standard arm (arm B, mDCF). In both arms, 8 cycles of mDCF will be administered. In arm A, patients receive mDCF with a fixed dose of atezolizumab (800 mg every 2 weeks) and are followed up to 1 year. Secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and an extensive biomarker programme and its correlation with the treatment efficacy.
Although the Epitopes-HPV02 trial has changed long-lasting prognosis of patients with SCCA in advanced stage disease, more than 50% of patients will progress at 12 months. The purpose of the SCARCE trial to establish the addition of atezolizumab to mDCF as a new standard in this rare disease. Associated biomarker studies and the control arm could contribute to better understanding of the potential synergic and tumour resistance mechanisms in SCCA.
NCT03519295.
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