Using Low-Dose Radiation to Potentiate the Effect of Induction Chemotherapy in Head and Neck Cancer: Results of a Prospective Phase 2 Trial

Purpose: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN). Experimental Design: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m2) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site complete response rate; secondary included overall survival, progression-free survival (PFS), disease-specific survival, and toxicity. Results: A total of 24 evaluable patients were enrolled. Primary sites included oropharynx (62.5%), larynx (20.8%), oral cavity (8.3%), and hypopharynx (8.3%). Grade 3/4 toxicities included neutropenia (20%), leukopenia (32%), dehydration/hypotension (8%), anemia (4%), infection (4%), pulmonary/allergic rhinitis (4%), and diarrhea (4%). Primary site response rate was 23/24 (95.8%): 15/24 (62.5%) complete response, 8/24 (33.3%) partial response, and 1/24 (4.2%) stable disease. With median follow-up of 7.75 years, 9-year rates for overall survival were 49.4% (95% confidence interval [CI], 30.5-79.9), PFS was 72.2% (CI, 55.3-94.3), and disease-specific survival was 65.4% (44.3-96.4). Conclusion: Chemopotentiating LDFRT combined with paclitaxel and carboplatin is effective in SCCHN and provided an excellent median overall survival of 107.2 months, with median PFS not yet reached in this locally advanced SCCHN cohort. This compares favorably to prior investigations and caused fewer grade 3 and 4 toxicities than more intensive, 3-drug induction regimens. This trial demonstrates the innovative use of LDFRT as a potentiator of chemotherapy

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Microstructural asymmetry of the corticospinal tracts predicts right-left differences in circle drawing skill in right-handed adolescents

Most humans show a strong preference to use their right hand, but strong preference for the right hand does not necessarily imply a strong right–left asymmetry in manual proficiency (i.e., dexterity). Here we tested the hypothesis that intra-individual asymmetry of manual proficiency would be reflected in microstructural differences between the right and left corticospinal tract (CST) in a cohort of 52 right-handed typically-developing adolescents (11–16 years). Participants were asked to fluently draw superimposed circles with their right dominant and left non-dominant hand. Temporal regularity of circle drawing movements was assessed for each hand using a digitizing tablet. Although all participants were right-handed, there was substantial inter-individual variation regarding the relative right-hand advantage for fluent circle drawing. All subjects underwent whole-brain diffusion tensor imaging at 3 Tesla. The right and left CST were defined as regions-of-interest and mean fractional anisotropy (FA) and diffusivity values were calculated for right and left CST. On average, mean FA values were higher in the left CST relative to right CST. The degree of right–left FA asymmetry showed a linear relationship with right–left asymmetry in fluent circle drawing after correction for age and gender. The higher the mean FA values were in the left dominant CST relative to the right non-dominant CST, the stronger was the relative right-hand advantage for regular circle drawing. These findings show that right–left differences in manual proficiency are highly variable in right-handed adolescents and that this variation is associated with a right-left microstructural asymmetry of the CST

New and improved demonstrations, each illustrating a single scientific paper

Thesis (Ed.M.)--Boston Universit

Simple nonlinear models suggest variable star universality

Dramatically improved data from observatories like the CoRoT and Kepler spacecraft have recently facilitated nonlinear time series analysis and phenomenological modeling of variable stars, including the search for strange (aka fractal) or chaotic dynamics. We recently argued [Lindner et al., Phys. Rev. Lett. 114 (2015) 054101] that the Kepler data includes "golden" stars, whose luminosities vary quasiperiodically with two frequencies nearly in the golden ratio, and whose secondary frequencies exhibit power-law scaling with exponent near -1.5, suggesting strange nonchaotic dynamics and singular spectra. Here we use a series of phenomenological models to make plausible the connection between golden stars and fractal spectra. We thereby suggest that at least some features of variable star dynamics reflect universal nonlinear phenomena common to even simple systems.Comment: 9 pages, 9 figures, accepted for publication in Physica

Disrupted seasonal biology impacts health, food security and ecosystems

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

PurposeWe compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity.Methods and MaterialsWe reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity.ResultsAt 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742; nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction.ConclusionsSurvival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function

Improving oceanic overflow representation in climate models : the Gravity Current Entrainment Climate Process Team

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 90 (2009): 657-670, doi:10.1175/2008BAMS2667.1.Oceanic overflows are bottom-trapped density currents originating in semienclosed basins, such as the Nordic seas, or on continental shelves, such as the Antarctic shelf. Overflows are the source of most of the abyssal waters, and therefore play an important role in the large-scale ocean circulation, forming a component of the sinking branch of the thermohaline circulation. As they descend the continental slope, overflows mix vigorously with the surrounding oceanic waters, changing their density and transport significantly. These mixing processes occur on spatial scales well below the resolution of ocean climate models, with the result that deep waters and deep western boundary currents are simulated poorly. The Gravity Current Entrainment Climate Process Team was established by the U.S. Climate Variability and Prediction (CLIVAR) Program to accelerate the development and implementation of improved representations of overflows within large-scale climate models, bringing together climate model developers with those conducting observational, numerical, and laboratory process studies of overflows. Here, the organization of the Climate Process Team is described, and a few of the successes and lessons learned during this collaboration are highlighted, with some emphasis on the well-observed Mediterranean overflow. The Climate Process Team has developed several different overflow parameterizations, which are examined in a hierarchy of ocean models, from comparatively well-resolved regional models to the largest-scale global climate models.The Gravity Current Entrainment Climate Process Team was funded by NSF grants OCE-0336850 and OCE-0611572 and NOAA as a contribution to U.S.CLIVAR