126 research outputs found
Accuracy of contrast-enhanced CT and predictive factors for extracapsular spread in unknown primary head and neck squamous cell cancer
AIM: To determine the accuracy of contrast-enhanced computed tomography (CECT) for nodal extracapsular spread (ECS) and identify predictive radiological signs and clinicopathological features for ECS in unknown-primary head and neck squamous cell cancer (UPHNSCC). MATERIALS AND METHODS: The CECT imaging of patients who underwent primary neck dissection for UPHNSCC during 2011β2015 was analysed. The largest pathological-looking node at each radiologically involved level was evaluated in consensus by two head and neck radiologists. Parameters included longest diameter, margin sharpness, haziness in adjacent fat, necrosis, and loss of fat plane with adjacent structures. Independent assessment was also made regarding the presence/absence of ECS. Findings and clinicopathological parameters were correlated with histopathology. RESULTS: Thirty-one patients with 39 neck levels had metastatic nodal involvement determined on CECT. Confirmed ECS was found at 26 levels in 23 patients. Sensitivity of radiological assessment for ECS by nodal level was 81β85% (95% confidence interval [CI]=65β93%) and specificity 46β54% (95% CI=19β81%); kappa 0.87. On univariate analysis based on the largest involved node per patient, longest diameter being β₯30 mm (p=0.007), haziness in adjacent fat (p=0.023), increasing age (p=0.006), and more advanced pathological nodal status (p=0.027) were statistically significantly associated with ECS. Haziness and increasing age were independent predictors on multivariate analysis (odds ratio [OR]=26.4 and 1.24). CONCLUSION: Expert assessment of ECS on CECT had good sensitivity with excellent interobserver agreement. A longest nodal diameter of β₯30 mm, haziness in the surrounding fat on CECT, advanced pathological nodal status, and advancing patient age were significantly associated with ECS in UPHNSCC patients, findings not previously reported
A Randomized Trial Evaluating Prosaptideβ’ for HIV-Associated Sensory Neuropathies: Use of an Electronic Diary to Record Neuropathic Pain
Objectives: To examine the efficacy and safety of Prosaptideβ’ (PRO) for the treatment of painful HIV-associated sensory neuropathies (HIV-SN). Design: A randomized, double-blind, placebo-controlled, multicenter study in participants with sensory neuropathy. Pain modulating therapy was discontinued prior to baseline. Participants were stratified by sural sensory nerve action potential (SNAP) amplitude. Participants were trained to use an electronic diary (ED) to record pain. Setting: Peripheral neuropathies are common complications of HIV infection. The pathogenesis is unknown and currently treatments are restricted to symptomatic measures. We examined PRO against placebo (PBO) for treatment of painful HIV-SN and performed a post-hoc evaluation of an electronic diary (ED) to record HIV-associated neuropathic pain. Participants: Eligible participants included adults with neurologist-confirmed painful HIV-SN.Interventions 2, 4, 8, or 16 mg/d PRO or PBO administered via subcutaneous (SC) injection for six weeks. Neurotoxic antiretroviral drug usage was held constant.Outcome Measures Changes from baseline in the weekly average of evaluable daily random prompts measuring pain using the Gracely pain scale and adverse events. Results: 237 participants were randomized. The study was stopped after a planned futility analysis. There were no between-group differences in the frequency of adverse events or laboratory toxicities. The 6-week mean (sd) Gracely pain scale changes were β0.12 (0.23), β0.24 (0.35), β0.15 (0.32), β0.18 (0.34), and β0.18 (0.32) for the 2, 4, 8, 16 mg, and PBO arms respectively. A similar variability of pain changes recorded using the ED were noted compared to previous trials that used paper collection methods.Conclusions 6-week treatment with PRO was safe but not effective at reducing HIV-associated neuropathic pain. Use of an ED to record neuropathic pain is novel in HIV-SN, resulted in reasonable compliance in recording pain data, but did not decrease the variability of pain scores compared to historical paper collection methods. Trial Registration: Current Controlled Trials NCT0028637
Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy
BackgroundIn patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurrence within local nodal basins without improving overall survival or quality of life. However, the study was conducted prior to the current era of adjuvant systemic therapies and when CLND was the standard approach for microscopic nodal disease. As such, there is currently no data on the role of adjuvant RT in patients with melanoma who recur during or after adjuvant immunotherapy, including those that may or may not have undergone prior CLND. In this study, we aimed to answer this question.MethodsPatients with resected stage III melanoma who received adjuvant anti-programmed cell death protein-1 (PD-1) (Β±ipilimumab) immunotherapy with a subsequent locoregional (lymph node and/or in-transit metastases) recurrence were retrospectively identified. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was rate of subsequent locoregional recurrence; secondary outcomes were locoregional recurrence-free survival (lr-RFS2) and overall RFS (RFS2) to second recurrence.ResultsIn total, 71 patients were identified: 42 (59%) men, 30 (42%) BRAF V600E mutant, 43 (61%) stage IIIC at diagnosis. Median time to first recurrence was 7 months (1β44), 24 (34%) received adjuvant RT and 47 (66%) did not. Thirty-three patients (46%) developed a second recurrence at a median of 5 months (1β22). The rate of locoregional relapse at second recurrence was lower in those who received adjuvant RT (8%, 2/24) compared with those who did not (36%, 17/47, p=0.01). Adjuvant RT at first recurrence was associated with an improved lr-RFS2 (HR 0.16, p=0.015), with a trend towards an improved RFS2 (HR 0.54, p=0.072) and no effect on risk of distant recurrence or overall survival.ConclusionThis is the first study to investigate the role of adjuvant RT in patients with melanoma with locoregional disease recurrence during or after adjuvant anti-PD-1-based immunotherapy. Adjuvant RT was associated with improved lr-RFS2, but not risk of distant recurrence, demonstrating a likely benefit in locoregional disease control in the modern era. Further prospective studies are required to validate these results
Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)
\We present the sixth catalog of Kepler candidate planets based on nearly 4
years of high precision photometry. This catalog builds on the legacy of
previous catalogs released by the Kepler project and includes 1493 new Kepler
Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these
candidates have best fit radii <1.5 R_earth. This brings the total number of
KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many
of these new candidates at the low signal-to-noise limit may be false alarms
created by instrumental noise, and discuss our efforts to identify such
objects. We re-evaluate all previously published KOIs with orbital periods of
>50 days to provide a consistently vetted sample that can be used to improve
planet occurrence rate calculations. We discuss the performance of our planet
detection algorithms, and the consistency of our vetting products. The full
catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement
Serie
M(atrix) Theory: Matrix Quantum Mechanics as a Fundamental Theory
A self-contained review is given of the matrix model of M-theory. The
introductory part of the review is intended to be accessible to the general
reader. M-theory is an eleven-dimensional quantum theory of gravity which is
believed to underlie all superstring theories. This is the only candidate at
present for a theory of fundamental physics which reconciles gravity and
quantum field theory in a potentially realistic fashion. Evidence for the
existence of M-theory is still only circumstantial---no complete
background-independent formulation of the theory yet exists. Matrix theory was
first developed as a regularized theory of a supersymmetric quantum membrane.
More recently, the theory appeared in a different guise as the discrete
light-cone quantization of M-theory in flat space. These two approaches to
matrix theory are described in detail and compared. It is shown that matrix
theory is a well-defined quantum theory which reduces to a supersymmetric
theory of gravity at low energies. Although the fundamental degrees of freedom
of matrix theory are essentially pointlike, it is shown that higher-dimensional
fluctuating objects (branes) arise through the nonabelian structure of the
matrix degrees of freedom. The problem of formulating matrix theory in a
general space-time background is discussed, and the connections between matrix
theory and other related models are reviewed.Comment: 56 pages, 3 figures, LaTeX, revtex style; v2: references adde
A Tabletop X-Ray Tomography Instrument for Nanometer-Scale Imaging: Integration of a Scanning Electron Microscope with a Transition-Edge Sensor Spectrometer
X-ray nanotomography is a powerful tool for the characterization of nanoscale
materials and structures, but is difficult to implement due to competing
requirements on X-ray flux and spot size. Due to this constraint,
state-of-the-art nanotomography is predominantly performed at large synchrotron
facilities. Compact X-ray nanotomography tools operated in standard analysis
laboratories exist, but are limited by X-ray optics and destructive sample
preparation techniques. We present a laboratory-scale nanotomography instrument
that achieves nanoscale spatial resolution while changing the limitations of
conventional tomography tools. The instrument combines the electron beam of a
scanning electron microscope (SEM) with the precise, broadband X-ray detection
of a superconducting transition-edge sensor (TES) microcalorimeter. The
electron beam generates a highly focused X-ray spot in a metal target, while
the TES spectrometer isolates target photons with high signal-to-noise. This
combination of a focused X-ray spot, energy-resolved X-ray detection, and
unique system geometry enable nanoscale, element-specific X-ray imaging in a
compact footprint. The proof-of-concept for this approach to X-ray
nanotomography is demonstrated by imaging 160 nm features in three dimensions
in a Cu-SiO2 integrated circuit, and a path towards finer resolution and
enhanced imaging capabilities is discussed.Comment: The following article has been submitted to Physical Review Applie
A tabletop x-ray tomography instrument for nanometer-scale imaging: demonstration of the 1,000-element transition-edge sensor subarray
We report on the 1,000-element transition-edge sensor (TES) x-ray
spectrometer implementation of the TOMographic Circuit Analysis Tool (TOMCAT).
TOMCAT combines a high spatial resolution scanning electron microscope (SEM)
with a highly efficient and pixelated TES spectrometer to reconstruct
three-dimensional maps of nanoscale integrated circuits (ICs). A 240-pixel
prototype spectrometer was recently used to reconstruct ICs at the 130 nm
technology node, but to increase imaging speed to more practical levels, the
detector efficiency needs to be improved. For this reason, we are building a
spectrometer that will eventually contain 3,000 TES microcalorimeters read out
with microwave superconducting quantum interference device (SQUID)
multiplexing, and we currently have commissioned a 1,000 TES subarray. This
still represents a significant improvement from the 240-pixel system and allows
us to begin characterizing the full spectrometer performance. Of the 992
maximimum available readout channels, we have yielded 818 devices, representing
the largest number of TES x-ray microcalorimeters simultaneously read out to
date. These microcalorimeters have been optimized for pulse speed rather than
purely energy resolution, and we measure a FWHM energy resolution of 14 eV at
the 8.0 keV Cu K line.Comment: 5 pages, 4 figures, submitted to IEEE Transactions on Applied
Superconductivit
Lower Miocene Stratigraphy along the Panama Canal and Its Bearing on the Central American Peninsula
Before the formation of the Central American Isthmus, there was a Central American Peninsula. Here we show that southern Central America existed as a peninsula as early as 19 Ma, based on new lithostratigraphic, biostratigraphic and strontium chemostratigraphic analyses of the formations exposed along the Gaillard Cut of the Panama Canal. Land mammals found in the Miocene Cucaracha Formation have similar body sizes to conspecific taxa in North America, indicating that there existed a terrestrial connection with North America that allowed gene flow between populations during this time. How long did this peninsula last? The answer hinges on the outcome of a stratigraphic dispute: To wit, is the terrestrial Cucaracha Formation older or younger than the marine La Boca Formation? Previous stratigraphic studies of the Panama Canal Basin have suggested that the Cucaracha Formation lies stratigraphically between the shallow-marine Culebra Formation and the shallow-to-upper-bathyal La Boca Formation, the latter containing the Emperador Limestone. If the La Boca Formation is younger than the Cucaracha Formation, as many think, then the peninsula was short-lived (1β2 m.y.), having been submerged in part by the transgression represented by the overlying La Boca Formation. On the other hand, our data support the view that the La Boca Formation is older than the Cucaracha Formation. Strontium dating shows that the La Boca Formation is older (23.07 to 20.62 Ma) than both the Culebra (19.83β19.12 Ma) and Cucaracha (Hemingfordian to Barstovian North American Land Mammal Ages; 19β14 Ma) formations. The Emperador Limestone is also older (21.24β20.99 Ma) than the Culebra and Cucaracha formations. What has been called the βLa Boca Formationβ (with the Emperador Limestone), is re-interpreted here as being the lower part of the Culebra Formation. Our new data sets demonstrate that the main axis of the volcanic arc in southern Central America more than likely existed as a peninsula connected to northern Central America and North America for much of the Miocene, which has profound implications for our understanding of the tectonic, climatic, oceanographic and biogeographic history related to the formation of the Isthmus of Panama
A new measure for multi-professional medical team communication: design and methodology for multilingual measurement development
BackgroundAs implementation science in global health continues to evolve, there is a need for valid and reliable measures that consider diverse linguistic and cultural contexts. A standardized, reproducible process for multilingual measure development may improve accessibility and validity by participants in global health settings. To address this need, we propose a rigorous methodology for multilingual measurement development. We use the example of a novel measure of multi-professional team communication quality, a determinant of implementation efforts.MethodsThe development and translation of this novel bilingual measure is comprised of seven steps. In this paper, we describe a measure developed in English and Spanish, however, this approach is not language specific. Participants are engaged throughout the process: first, an interprofessional panel of experts and second, through cognitive interviewing for measure refinement. The steps of measure development included: (1) literature review to identify previous measures of team communication; (2) development of an initial measure by the expert panel; (3) cognitive interviewing in a phased approach with the first language (English); (4): formal, forward-backward translation process with attention to colloquialisms and regional differences in languages; (5) cognitive interviewing repeated in the second language (Spanish); (6) language synthesis to refine both instruments and unify feedback; and (7) final review of the refined measure by the expert panel.ResultsA draft measure to assess quality of multi-professional team communication was developed in Spanish and English, consisting of 52 questions in 7 domains. This measure is now ready for psychometric testing.ConclusionsThis seven-step, rigorous process of multilingual measure development can be used in a variety of linguistic and resource settings. This method ensures development of valid and reliable tools to collect data from a wide range of participants, including those who have historically been excluded due to language barriers. Use of this method will increase both rigor and accessibility of measurement in implementation science and advance equity in research and practice
Cooperative Adaptation to Establishment of a Synthetic Bacterial Mutualism
To understand how two organisms that have not previously been in contact can establish mutualism, it is first necessary to examine temporal changes in their phenotypes during the establishment of mutualism. Instead of tracing back the history of known, well-established, natural mutualisms, we experimentally simulated the development of mutualism using two genetically-engineered auxotrophic strains of Escherichia coli, which mimic two organisms that have never met before but later establish mutualism. In the development of this synthetic mutualism, one strain, approximately 10 hours after meeting the partner strain, started oversupplying a metabolite essential for the partner's growth, eventually leading to the successive growth of both strains. This cooperative phenotype adaptively appeared only after encountering the partner strain but before the growth of the strain itself. By transcriptome analysis, we found that the cooperative phenotype of the strain was not accompanied by the local activation of the biosynthesis and transport of the oversupplied metabolite but rather by the global activation of anabolic metabolism. This study demonstrates that an organism has the potential to adapt its phenotype after the first encounter with another organism to establish mutualism before its extinction. As diverse organisms inevitably encounter each other in nature, this potential would play an important role in the establishment of a nascent mutualism in nature
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