The Riddle of Vagueness

This anthology includes fourteen of Crispin Wrights’s highly influential essays on the phenomenon of vagueness in natural language, collectively representing almost half a century of cutting-edge systematic research. Key issues addressed include whether or under what assumptions vague expressions’ apparent tolerance of marginal changes in things to which they apply indicates that they are governed by inconsistent semantic rules, the varieties of Sorites paradox and the roots of the plausibility of their respective major premises, what it is for something to be a borderline case of a vague expression, whether vagueness should be viewed as fundamentally a semantic or an epistemic phenomenon, whether there is ‘higher-order’ vagueness, and what should be the appropriate logic for vague statements. The essays reprinted here jointly document the development of a distinctively original treatment of the philosophy and logic of vagueness, broadly analogous to the intuitionistic philosophy and logic for pure mathematics. Richard Kimberly Heck contributes an extended introductory essay, providing both an insightful critical overview of the development of the distinctive elements of Wright’s thought about vagueness, and indeed an invaluable advanced introduction to the topic.

Surgical site infections in spine surgery focused literature review. Case report

Surgical site infections are a serious problem in spine surgery, they significantly extend the patient’s stay in the ward, are associated with very high costs of patient treatment, and also have a negative impact on the final clinical results and may modify the treatment plan. The article presents the current literature outline concerning the risk factors of perioperative infections in spine surgery and the procedure. A clinical case of a patient was described, where the infection led to misfortune of the original treatment plan and the possibility of obtaining only a partial clinical improvement in the patient.

Post-intervention Effects of Varying Treatment Arms on Glycemic Failure and Beta-Cell Function in the TODAY Study

<b>Objective</b>: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that glycemic failure rates were significantly lower in youth randomized to metformin plus rosiglitazone treatment compared to metformin alone or metformin plus intensive lifestyle intervention. At end of study, rosiglitazone was permanently discontinued, and routine diabetes care resumed. Herein, we report post-intervention glycemic failure rates in TODAY participants over an additional 36 months of follow-up for the three original treatment arms and describe insulin sensitivity and beta-cell function outcomes. <p><b>Research Design and Methods</b>: A total of 699 participants were randomized during TODAY, of whom 572 enrolled in the TODAY2 observational follow-up. Glycemic failure was defined as HbA1c ≥8% over a 6-month period or inability to wean from temporary insulin therapy within 3 months after acute metabolic decompensation during TODAY or a sustained HbA1c ≥8% over two consecutive visits during TODAY2. Oral glucose tolerance tests were conducted and insulin sensitivity, insulinogenic index, and oral disposition index (oDI) were calculated.</p> <p><b>Results</b>: During the 36 months of TODAY2, glycemic failure rates did not differ among participants by original treatment group assignment. Insulin sensitivity and beta-cell function deteriorated rapidly during the 36 months of TODAY2 routine diabetes care, but did not differ by treatment group assignment.</p> <p><b>Conclusions</b>: The added benefit of preventing glycemic failure by using rosiglitazone as a second agent in youth-onset type 2 diabetes did not persist after its discontinuation. More work is needed to address this rapid progression to avoid long-term diabetes complications.</p>

Post-intervention Effects of Varying Treatment Arms on Glycemic Failure and Beta-Cell Function in the TODAY Study

<b>Objective</b>: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that glycemic failure rates were significantly lower in youth randomized to metformin plus rosiglitazone treatment compared to metformin alone or metformin plus intensive lifestyle intervention. At end of study, rosiglitazone was permanently discontinued, and routine diabetes care resumed. Herein, we report post-intervention glycemic failure rates in TODAY participants over an additional 36 months of follow-up for the three original treatment arms and describe insulin sensitivity and beta-cell function outcomes. <p><b>Research Design and Methods</b>: A total of 699 participants were randomized during TODAY, of whom 572 enrolled in the TODAY2 observational follow-up. Glycemic failure was defined as HbA1c ≥8% over a 6-month period or inability to wean from temporary insulin therapy within 3 months after acute metabolic decompensation during TODAY or a sustained HbA1c ≥8% over two consecutive visits during TODAY2. Oral glucose tolerance tests were conducted and insulin sensitivity, insulinogenic index, and oral disposition index (oDI) were calculated.</p> <p><b>Results</b>: During the 36 months of TODAY2, glycemic failure rates did not differ among participants by original treatment group assignment. Insulin sensitivity and beta-cell function deteriorated rapidly during the 36 months of TODAY2 routine diabetes care, but did not differ by treatment group assignment.</p> <p><b>Conclusions</b>: The added benefit of preventing glycemic failure by using rosiglitazone as a second agent in youth-onset type 2 diabetes did not persist after its discontinuation. More work is needed to address this rapid progression to avoid long-term diabetes complications.</p>

Post-intervention Effects of Varying Treatment Arms on Glycemic Failure and Beta-Cell Function in the TODAY Study

<b>Objective</b>: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that glycemic failure rates were significantly lower in youth randomized to metformin plus rosiglitazone treatment compared to metformin alone or metformin plus intensive lifestyle intervention. At end of study, rosiglitazone was permanently discontinued, and routine diabetes care resumed. Herein, we report post-intervention glycemic failure rates in TODAY participants over an additional 36 months of follow-up for the three original treatment arms and describe insulin sensitivity and beta-cell function outcomes. <p><b>Research Design and Methods</b>: A total of 699 participants were randomized during TODAY, of whom 572 enrolled in the TODAY2 observational follow-up. Glycemic failure was defined as HbA1c ≥8% over a 6-month period or inability to wean from temporary insulin therapy within 3 months after acute metabolic decompensation during TODAY or a sustained HbA1c ≥8% over two consecutive visits during TODAY2. Oral glucose tolerance tests were conducted and insulin sensitivity, insulinogenic index, and oral disposition index (oDI) were calculated.</p> <p><b>Results</b>: During the 36 months of TODAY2, glycemic failure rates did not differ among participants by original treatment group assignment. Insulin sensitivity and beta-cell function deteriorated rapidly during the 36 months of TODAY2 routine diabetes care, but did not differ by treatment group assignment.</p> <p><b>Conclusions</b>: The added benefit of preventing glycemic failure by using rosiglitazone as a second agent in youth-onset type 2 diabetes did not persist after its discontinuation. More work is needed to address this rapid progression to avoid long-term diabetes complications.</p>

The rescue intervention strategy for asthma patients under severe air pollution: a protocol for a single-centre prospective randomized controlled trial

Background Asthma is a common chronic airway inflammatory disease. Exacerbations of asthma not only accelerate the progression of the disease but also increase the incidence of hospitalization and death. Studies have shown that air pollution is a high-risk factor for asthma exacerbations. However, few treatment strategies have been recommended to reduce the risk of severe air pollution-related asthma exacerbations. Methods/design This is a single-centre, prospective, randomized and standard treatment parallel control clinical trial. Seventy-two asthma patients in the nonexacerbation stage according to GINA guidelines 2017 will be recruited and randomized into the rescue intervention strategy (RIS) group and control group. Original treatments for the participants will include no use of inhaled medicine, the use of short-acting β-agonists (SABA) on demand or the use of budesonide/formoterol (160 μg/4.5 μg/dose, 1–2 dose/time, b.i.d.). The rescue intervention strategy for the RIS group will be budesonide/formoterol plus the original treatment until the severe pollution ends (air quality index, AQI < 200). The control group will maintain the original treatment. The follow-up observation period will last 1 year. The primary outcome is the frequency of asthma exacerbations per year. Secondary outcomes include the mean number of unplanned outpatient visits, emergency visits, hospitalizations, medical costs and mortality caused by asthma exacerbations per patient per year. Discussion The results of this trial will provide a novel strategy to guide clinical practice in decreasing the risk of asthma exacerbations under severe air pollution. Trial registration ChiCTR ChiCTR1900026757. Registered on 20 October 2019—retrospectively registered

‘Ali al-Ghumuqi (Kayaev) as the Historian of Caucasus’ Muslim Peoples

The paper is an attempt at writing of the new conceptual biography of a renowned Muslim reformist leader in late tsarist and early Soviet Caucasus. After ‘Ali al- Ghumuqi more known under the name of Kayaev (1878–1943) from the Dagestani village of Ghumuq fell the victim of the Stalinist political repressions and then was gradually rehabilitated, historians often presented him a leftist journalist and politician close to the Bolsheviks, sometimes also a bibliophile who collected one of the largest private libraries of Muslim Oriental manuscripts and documents. Seriously revising this not very correct image the authors of this article investigate rather his academic research activities that allow rethinking Kayaev as a Muslim historian revisionist. The focus is made on his Oriental source studies that traced the future development of the famous Dagestani school of academic Oriental studies in the twentieth century, as well as on Kayaev’s original treatment of Muslim historiography he considered through the lenses of Muslim peoples’ development as principal historical actors.

Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials

Background We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS. Methods Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAFV600-mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Prognostic subgroups identified by RPA were then applied to pooled treatment cohorts. The primary endpoint was ppOS, defined as time from first PD to death from any cause. Results RPA identified baseline lactate dehydrogenase (LDH), baseline disease stage, Eastern Cooperative Oncology Group performance status at PD, and ppRx as significant prognostic factors for ppOS. Median ppOS was longest in patients with normal baseline LDH, stage M1c disease at baseline, and ppRx with immunotherapy or targeted therapy (12.2 months; 95% CI 10.3–16.1) and shortest in those with elevated baseline LDH > 2 × upper limit of normal (2.3 months; 95% CI 1.8–2.7). Original treatment assignment did not impact ppOS. Across treatment cohorts, patients treated with immunotherapy or targeted therapy after PD had better ppOS than those given other treatments. Conclusion A combination of factors at baseline (LDH, disease stage) and PD (performance status, ppRx) impact ppOS outcomes. ppRx with immunotherapy or targeted therapy is an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov: NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM).

Anxiety, time, and agency

This article scrutinizes two concepts central to the ontological security framework, agency and anxiety. Its point of departure is the view that conceptions of agency are expressed in the attempt to become ontologically secure, which requires a more careful look at how humans try to satisfy the need for a ‘stable sense of Self’ by putting in place ‘anxiety controlling mechanisms’. This, in turn, raises the question what these mechanisms are supposed to control, which shifts attention to the concept of ‘anxiety’. Going back to Kierkegaard's original treatment and Heidegger's existential phenomenology, the article reviews the emergence of anxiety as a core feature of the human condition and highlights what it calls the ‘anxiety paradox’: the tendency of reflexive humans facing the freedom of being in time to attach themselves to constructs that provide a sense of temporal continuity, or certainty. The article argues that the existing ontological security literature is trapped in this paradox and therefore cannot account for radical forms of agency.