Remembrance : Reverie

https://digitalcommons.library.umaine.edu/mmb-ps/1612/thumbnail.jp

Maximum tumor diameter is associated with event-free survival in PET-negative patients with stage I/IIA Hodgkin lymphoma.

Introduction: the high cure rates achieved in early-stage (ES) Hodgkin lymphoma (HL) are one of the great successes of hemato-oncology, but late treatment-related toxicity undermines long-term survival. Improving overall survival and quality of life further will require maintaining disease control while potentially de-escalating chemotherapy and/or omitting radiotherapy to reduce late toxicity. Accurate stratification of patients is required to facilitate individualized treatment approaches. Response assessment using 18F-fluorodeoxyglucose positron emission tomography (PET) is a powerful predictor of outcome in HL,1,2 and has been used in multiple studies, including the United Kingdom National Cancer Research Institute Randomised Phase III Trial to Determine the Role of FDG–PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease (UK NCRI RAPID) trial, to investigate whether patients achieving complete metabolic remission (CMR) can be treated with chemotherapy alone.3-5 These PET-adapted trials have demonstrated that omitting radiotherapy results in higher relapse rates, but without compromising overall survival.3-5 For the 75% of patients who achieved CMR in RAPID, neither baseline clinical risk stratification (favorable/unfavorable) nor PET (Deauville score 1/2) predicted disease relapse; additional biomarkers are needed.1 Tumor bulk has long been recognized as prognostic in HL,1,6 but there remains uncertainty about the significance and definition of bulk in the era of PET-adapted treatment.7 We performed a subsidiary analysis of RAPID to assess the prognostic value of baseline maximum tumor dimension (MTD) in patients achieving CMR. Methods: ee have previously reported the RAPID trial design, primary results, and outcomes according to pretreatment risk stratification and PET score.1,3 Patients were aged 16 to 75 years with untreated ES-HL and without B-symptoms or mediastinal bulk (mass > 1/3 internal mediastinal diameter at T5/6).6 Metabolic response after 3 cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) was centrally assessed using PET (N = 562). Patients with CMR (ie, Deauville score 1-2) were randomly assigned to receive involved field radiotherapy (IFRT; n = 208) or no further therapy (NFT; n = 211). PET-positive patients (score, 3-5; n = 143) received a fourth cycle of ABVD and IFRT. Baseline disease assessment was performed by computed tomography, and bidimensional target lesion measurements were reported by local radiologists in millimeters. The association of baseline MTD with HL-related event-free survival (EFS: progression or HL-related death) and progression-free survival (PFS) (progression or any-cause death) was assessed using Kaplan-Meier and Cox regression analyses. Non-HL deaths were either related to primary treatment toxicity or occurred in HL remission.1 United Kingdom ethical approval for the RAPID trial was via the UK Multicentre Research ethics committee. Results and discussion: baseline patient characteristics have been previously described.1 Median age was 34 years (range, 16-75 years); 184 (37.4%) of 492 patients had unfavorable risk by European Organisation for Research and Treatment of Cancer criteria, and 155 (32.3%) of 480 by German Hodgkin Study Groupcriteria. Median MTD for patients achieving CMR was 3.0 cm (interquartile range, 2.0-4.0 cm) and 3.0 cm (interquartile range, 1.8-4.5 cm) in the NFT and IFRT groups, respectively, whereas PET-positive patients had a median MTD of 3.9 cm (interquartile range, 2.8-5.1 cm). After a median follow-up of 61.6 m, 44 HL progression events occurred: 21 NFT, 9 IFRT and 14 PET-positive. No patient received salvage treatment without documented progression. Only 5 HL-related deaths occurred (1 IFRT, 4 PET-positive), and 12 non-HL deaths (4 NFT, 6 IFRT, 2 PET-positive).1 For patients with CMR (N = 419), there was a strong association between MTD and EFS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.02-1.39; P = .02), adjusting for treatment group, with an approximate 19% increase in HL risk per centimeter increase in MTD. The association was similar in both treatment groups (NFT HR, 1.20 [95% CI, 0.99-1.44; P = .06]; IFRT HR, 1.19 [95% CI, 0.92-1.55; P = .19]). The observed effect sizes did not markedly change after adjusting for baseline clinical risk factors, and similar results were observed for PFS (supplemental Table 1). In contrast, for PET-positive patients, there was no association between MTD and EFS (HR, 0.88; 95% CI, 0.70-1.11; P = .29) or PFS (HR, 0.87; 95% CI, 0.70-1.08; P = .21). In an exploratory analysis within the NFT group, MTD was dichotomized using increasing 1-cm intervals to investigate the relationship between MTD thresholds and EFS. The largest effect size was observed with an MTD threshold of ≥5 cm (Table 1). Similar results were observed for PFS; this threshold also performed best in time-dependent receiver operating characteristic curve analyses. It was not possible to assess MTD thresholds in the IFRT group with only 9 events. Among all randomized patients, 79 (18.9%) had MTD of ≥5 cm, the majority with mediastinal (n = 43), supraclavicular (n = 17), or cervical (n = 16) locations. Five-year EFS for patients with MTD of ≥5 cm randomly assigned to NFT and IFRT was 79.3% (n = 39; 95% CI, 66.6%-92.0%) and 94.9% (n = 40; 95% CI, 88.0%-100%), respectively (P = .03; Figure 1)

Descriptive Complexity of Deterministic Polylogarithmic Time and Space

We propose logical characterizations of problems solvable in deterministic polylogarithmic time (PolylogTime) and polylogarithmic space (PolylogSpace). We introduce a novel two-sorted logic that separates the elements of the input domain from the bit positions needed to address these elements. We prove that the inflationary and partial fixed point vartiants of this logic capture PolylogTime and PolylogSpace, respectively. In the course of proving that our logic indeed captures PolylogTime on finite ordered structures, we introduce a variant of random-access Turing machines that can access the relations and functions of a structure directly. We investigate whether an explicit predicate for the ordering of the domain is needed in our PolylogTime logic. Finally, we present the open problem of finding an exact characterization of order-invariant queries in PolylogTime.Comment: Submitted to the Journal of Computer and System Science

Creative professional users musical relevance criteria

Although known item searching for music can be dealt with by searching metadata using existing text search techniques, human subjectivity and variability within the music itself make it very difficult to search for unknown items. This paper examines these problems within the context of text retrieval and music information retrieval. The focus is on ascertaining a relationship between music relevance criteria and those relating to relevance judgements in text retrieval. A data-rich collection of relevance judgements by creative professionals searching for unknown musical items to accompany moving images using real world queries is analysed. The participants in our observations are found to take a socio-cognitive approach and use a range of content and context based criteria. These criteria correlate strongly with those arising from previous text retrieval studies despite the many differences between music and text in their actual content

Credimus

We believe that economic design and computational complexity---while already important to each other---should become even more important to each other with each passing year. But for that to happen, experts in on the one hand such areas as social choice, economics, and political science and on the other hand computational complexity will have to better understand each other's worldviews. This article, written by two complexity theorists who also work in computational social choice theory, focuses on one direction of that process by presenting a brief overview of how most computational complexity theorists view the world. Although our immediate motivation is to make the lens through which complexity theorists see the world be better understood by those in the social sciences, we also feel that even within computer science it is very important for nontheoreticians to understand how theoreticians think, just as it is equally important within computer science for theoreticians to understand how nontheoreticians think

Randomisation and Derandomisation in Descriptive Complexity Theory

We study probabilistic complexity classes and questions of derandomisation from a logical point of view. For each logic L we introduce a new logic BPL, bounded error probabilistic L, which is defined from L in a similar way as the complexity class BPP, bounded error probabilistic polynomial time, is defined from PTIME. Our main focus lies on questions of derandomisation, and we prove that there is a query which is definable in BPFO, the probabilistic version of first-order logic, but not in Cinf, finite variable infinitary logic with counting. This implies that many of the standard logics of finite model theory, like transitive closure logic and fixed-point logic, both with and without counting, cannot be derandomised. Similarly, we present a query on ordered structures which is definable in BPFO but not in monadic second-order logic, and a query on additive structures which is definable in BPFO but not in FO. The latter of these queries shows that certain uniform variants of AC0 (bounded-depth polynomial sized circuits) cannot be derandomised. These results are in contrast to the general belief that most standard complexity classes can be derandomised. Finally, we note that BPIFP+C, the probabilistic version of fixed-point logic with counting, captures the complexity class BPP, even on unordered structures

Associations between neighbourhood characteristics and depression: a twin study.

BACKGROUND: Depression is an important contributor to the global burden of disease. Besides several known individual-level factors that contribute to depression, there is a growing recognition that neighbourhood environment can also profoundly affect mental health. This study assessed associations between three neighbourhood constructs-socioeconomic deprivation, residential instability and income inequality-and depression among adult twin pairs. The twin design is used to examine the association between neighbourhood constructs and depression, controlling for selection factors (ie, genetic and shared environmental factors) that have confounded purported associations. METHODS: We used multilevel random-intercept Poisson regression among 3738 same-sex twin pairs from a community-based twin registry to examine the association between neighbourhood constructs and depression. The within-pair association controls for confounding by genetic and environmental factors shared between twins within a pair, and is the main parameter of interest. Models were adjusted for individual-level income, education and marital status, and further by neighbourhood-level population density. RESULTS: When twins were analysed as individuals (phenotypic model), all neighbourhood constructs were significantly associated with depression. However, only neighbourhood socioeconomic deprivation showed a significant within-pair association with depression. A 10-unit within-pair difference in neighbourhood socioeconomic deprivation was associated with 6% greater depressive symptoms (1.06, 95% CI 1.01 to 1.11); the association did not substantially change in adjusted models. CONCLUSION: This study provides new evidence linking neighbourhood socioeconomic deprivation with greater depression. Future studies should employ longitudinal designs to better test social causation versus social selection