Image-guided fluorescence tomography in head & neck surgical models

Clinical indications for fluorescence-guided surgery continue to expand, and are being spurred by the rapid development of new agents that improve biological targeting.1 There is a corresponding need to develop imaging systems that quantify fluorescence - not only at the tissue surface, but at depth. We have recently described an image-guided fluorescence tomography system that leverages geometric data from intraoperative cone-beam CT and surgical navigation,2 and builds on finite-element method software (NIRFAST) for diffuse optical tomography (DOT).3 DOT systems have most commonly been used for sub-surface inclusions buried within tissue (e.g., breast and neurological tumors). Here, we focus on inclusion models relevant to tumors infiltrating from the mucosal surface (an “iceberg” model), as is most often the case in head and neck cancer, where over 85% of tumors are squamous cell carcinoma.4 This work presents results from simulations, tissue-simulating anatomical phantoms, and animal studies involving infiltrative tumor models. The objective is to characterize system performance across a range of inclusion diameters, depths, and optical properties. For example, Fig. 1 shows a fluorescence reconstruction of a simulated tonsil tumor in an oral cavity phantom. Future clinical studies are necessary to assess in vivo performance and intraoperative workflow. Please click Additional Files below to see the full abstract

Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?

Thermal performance curves (TPCs), which quantify how an ectotherm\u27s body temperature (Tb ) affects its performance or fitness, are often used in an attempt to predict organismal responses to climate change. Here, we examine the key - but often biologically unreasonable - assumptions underlying this approach; for example, that physiology and thermal regimes are invariant over ontogeny, space and time, and also that TPCs are independent of previously experienced Tb. We show how a critical consideration of these assumptions can lead to biologically useful hypotheses and experimental designs. For example, rather than assuming that TPCs are fixed during ontogeny, one can measure TPCs for each major life stage and incorporate these into stage-specific ecological models to reveal the life stage most likely to be vulnerable to climate change. Our overall goal is to explicitly examine the assumptions underlying the integration of TPCs with Tb , to develop a framework within which empiricists can place their work within these limitations, and to facilitate the application of thermal physiology to understanding the biological implications of climate change

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Review: A Publication of LMDA, the Literary Managers and Dramaturgs of the Americas, volume 17, issue 1

Contents include: Editor\u27s Page: A Note from New LMDA President, Brian Quirt; Think Dramaturgically, Act Locally! A Conference Overview; I Was Mugged at My First LMDA Conference; First-Timer Fragments; Conference Photos; Introducing the Lessing (and Joe and Michael); A Message Faxed from Romania; Acceptance Speech, Michael Lupu; Producing The Belle\u27s Stratagem; Dramaturging Justice: The Exonerated Project at the Alley Theatre; Past President Liz Engeleman: Some Appreciations; The Toronto Mini-Conference (reprinted from the LMDA Canada newsletter); Gateway to the Americas, The LMDA Delegation, A Report from Mexico; Imag[in]ing Poverty: Creative Critical Dramaturgy for Suzan-Lori Parks\u27s In the Blood; Hester, La Negrita in Iowa City, Staging Spells and Homelessness in Suzan-Lori Parks\u27s In the Blood; The Future of Theatre is...(a creative contest); Seventh Annual Call for LMDA Residency Proposals. Issue editors: D.J. Hopkins, Madeleine Oldham, Carlenne Lacostahttps://soundideas.pugetsound.edu/lmdareview/1034/thumbnail.jp

Atypical tracheobronchial vascular compression

Vascular compression of the tracheobronchial tree frequently presents early in infancy with significant airway compromise. For this reason, the pediatric otolaryngologist is often consulted early in the assessment of these patients. Three unusual cases of tracheobronchial vascular compression are presented. The diagnosis and management of children with tracheobronchial vascular compression is discussed, stressing the importance of synchronous airway anomalies and associated congenital cardiac anomalies. Although surgical intervention may be corrective in most cases of vascular compression, persistent tracheomalacia may necessitate tracheotomy for a prolonged period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29058/1/0000091.pd

Spatial and Sex-Specific Variation in Growth of Albacore Tuna (Thunnus alalunga) across the South Pacific Ocean

Spatial variation in growth is a common feature of demersal fish populations which often exist as discrete adult sub-populations linked by a pelagic larval stage. However, it remains unclear whether variation in growth occurs at similar spatial scales for populations of highly migratory pelagic species, such as tuna. We examined spatial variation in growth of albacore Thunnus alalunga across 90° of longitude in the South Pacific Ocean from the east coast of Australia to the Pitcairn Islands. Using length-at-age data from a validated ageing method we found evidence for significant variation in length-at-age and growth parameters (L∞ and k) between sexes and across longitudes. Growth trajectories were similar between sexes up until four years of age, after which the length-at-age for males was, on average, greater than that for females. Males reached an average maximum size more than 8 cm larger than females. Length-at-age and growth parameters were consistently greater at more easterly longitudes than at westerly longitudes for both females and males. Our results provide strong evidence that finer spatial structure exists within the South Pacific albacore stock and raises the question of whether the scale of their “highly migratory” nature should be re-assessed. Future stock assessment models for South Pacific albacore should consider sex-specific growth curves and spatial variation in growth within the stock