Computer-aided design of two-dimensional electric-type hyperthermia applicators using the finite-difference time-domain method

Journal ArticleA hyperthermia applicator design tool consisting of a finite-difference time-domain (FDTD) technique in combination with a graphical display of electric fields and normalized linear temperature rise is described. This technique calculates, rather than assumes, antenna current distributions; it includes mutual interactions between the body and the applicator, and it calculates driving-point impedance and power delivered to the applicator. Results show that the fundamental limitation of 2-D electric-type applicators is overheating of the fat by normal components of the electric field, which exist because of near fields and capacitive coupling with the muscle. Two factors which contribute to the capacitance are the muscle conductivity and the small antenna size in air. Two examples of applicators designed to avoid fat overheating are described: a 27-MHz segmented dipole for heating large tumors to 7 cm depth, and a 100-MHz dipole for small tumors to 5 cm depth. The first uses a water bolus, and the second uses a water bolus with low-permittivity strips to reduce normal fields at the antenna ends. The results of this study describe fundamental limitations of electric field applicators, and illustrate the use of a powerful applicator design tool that allows rapid evaluation of a wide range of ideas for applicators which would require months and years to test experimentally

Permanent Neonatal Diabetes in a Patient with a KCNJ11/Q52R Mutation Accompanied by Intermittent Hypoglycemia and Liver Failure

The most common monogenic cause of neonatal diabetes is mutation in KCNJ11, which encodes a potassium channel in pancreatic beta cells. Some mutations in this gene, including Q52R, have been described in association with neurological deficits, but never with hepatic involvement. We report the second case of neonatal diabetes in a patient with a KCNJ11/Q52R mutation. This patient's clinical course did not include obvious neurological deficits despite the presence of prematurity, but did include transient hyperbilirubinemia, and recurrent hypoglycemia. The phenotypic spectrum of KCNJ11 mutations is variable and is likely influenced by additional genetic and environmental factors

Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate. Results: Twenty-five patients were enrolled. The median age was 49 years (range, 22–77 years) and 52% were male. Median PFS was 2.27 months [95% confidence interval (CI), 1.9–3.9], and the 4-month PFS rate was 21.1% (95% CI, 9.7–45.9), which was not an improvement over the hypothesized null 4-month PFS rate of 28.3% (P ¼ 0.79). Median overall survival was 9.0 months (95% CI, 5.7–17.7). A partial response occurred in 2 (8%) of the evaluable patients (95% CI, 1.0–26.0), one with PIK3CA E542K-mutant embryonal rhabdomyosarcoma and another with spindle cell sarcoma. The disease control rate was 14/25 (56%; 95% CI, 34.9–75.6). The most common adverse events were diarrhea (84%), nausea (64%), and fatigue (56%). Conclusions: The combination of pazopanib and trametinib was tolerable without indication of added activity of the combination in STS. Further study may be warranted in RAS/RAF aberrant sarcomas. ©2017 AACR

HHS/CDC Legal Response to SARS Outbreak

Before the severe acute respiratory syndrome (SARS) outbreak, the Centers for Disease Control and Prevention’s (CDC) legal authority to apprehend, detain, or conditionally release persons was limited to seven listed diseases, not including SARS, and could only be changed using a two-step process: 1) executive order of the President of the United States on recommendation by the Secretary, U.S. Department of Health and Human Services (HHS), and 2) amendment to CDC quarantine regulations (42 CFR Parts 70 and 71). In April 2003, in response to the SARS outbreak, the federal executive branch acted rapidly to add SARS to the list of quarantinable communicable diseases. At the same time, HHS amended the regulations to streamline the process of adding future emerging infectious diseases. Since the emergence of SARS, CDC has increased legal preparedness for future public health emergencies by establishing a multistate teleconference program for public health lawyers and a Web-based clearinghouse of legal documents

Type Ibc supernovae in disturbed galaxies: evidence for a top-heavy IMF

We compare the radial locations of 178 core-collapse supernovae to the R-band and H alpha light distributions of their host galaxies. When the galaxies are split into `disturbed' and `undisturbed' categories, a striking difference emerges. The disturbed galaxies have a central excess of core-collapse supernovae, and this excess is almost completely dominated by supernovae of types Ib, Ic and Ib/c, whereas type II supernovae dominate in all other environments. The difference cannot easily be explained by metallicity or extinction effects, and thus we propose that this is direct evidence for a stellar initial mass function that is strongly weighted towards high mass stars, specifically in the central regions of disturbed galaxies.Comment: 22 pages, 5 figures, accepted for publication in Ap

Development and Validation of a Simple Method for the Detection of Fascaplysin in Plasma

Fascaplysin is a cytotoxic natural product isolated from a variety of Indo-Pacific marine organisms, primarily Fascaplysinopsis sponges and Didemnum tunicates. Positive xenograft studies involving this alkaloid structural class have indicated that fascaplysin may serve as an important lead compound for preclinical development. This study was undertaken as a prelude to a full pharmacokinetics and therapeutic assessment of fascaplysin. We describe here a simple plasma preparation and a rapid HPLC method for the detection of fascaplysin in mice. The method was validated by parameters including good linear correlation, a limit of quantification of 107.1 μg/ mL, and a good precision with a coefficient of variation of 0.92% for 10 μg/mL. This method provides excellent sensitivity and visualization of fascaplysin as a single peak allowing for rapid analysis of plasma samples involving absorption, distribution, and metabolism studies. A preliminary pharmacokinetics study in C57Bl/6 mice using 20.6 mg/kg fascaplysin yielded a biphasic curve with T½α=16.7 min, T½β=11.7 h, and C0 of 17.1 μg/mL

Tree Species Diversity Increases with Conspecific Negative Density Dependence Across an Elevation Gradient

Elevational and latitudinal gradients in species diversity may be mediated by biotic interactions that cause density-dependent effects of conspecifics on survival or growth to differ from effects of heterospecifics (i.e. conspecific density dependence), but limited evidence exists to support this. We tested the hypothesis that conspecific density dependence varies with elevation using over 40 years of data on tree survival and growth from 23 old-growth temperate forest stands across a 1,000-m elevation gradient. We found that conspecific-density-dependent effects on survival of small-to-intermediate-sized focal trees were negative in lower elevation, higher diversity forest stands typically characterised by warmer temperatures and greater relative humidity. Conspecific-density-dependent effects on survival were less negative in higher elevation stands and ridges than in lower elevation stands and valley bottoms for small-to-intermediate-sized trees, but were neutral for larger trees across elevations. Conspecific-density-dependent effects on growth were negative across all tree size classes and elevations. These findings reveal fundamental differences in biotic interactions that may contribute to relationships between species diversity, elevation and climate

A report on the study of land-sourced pollutants and their impacts on water quality in and adjacent to the Great Barrier Reef: an assessment to guide the development of management plans to halt any decline in the water quality of river catchments draining to the Reef, as a result of land-based pollution, and to achieve the long-term goal of reversing any trend in declining water quality

Includes 'Summary statement of the Reef Science Panel regarding water quality in and adjacent to the Great Barrier Reef

Airborne lidar detection and characterization of internal waves in a shallow fjord

A dual-polarization lidar and photography are used to sense internal waves in West Sound, Orcas Island, Washington, from a small aircraft. The airborne lidar detected a thin plankton layer at the bottom of the upper layer of the water, and this signal provides the depth of the upper layer, amplitude of the internal waves, and the propagation speed. The lidar is most effective when the polarization filter on the receiver is orthogonal to the transmitted light, but this does not depend significantly on whether the transmitted light is linearly or circularly polarized. The depolarization is greater with circular polarization, and our results are consistent with a single parameter Mueller scattering matrix. Photographs of the surface manifestation of the internal waves clearly show the propagation direction and width of the phase fronts of the internal waves, even though the contrast is low (2%). Combined with the lidar profile, the total energy of the internal wave packet was estimated to be 9 MJ

Wandering as a sociomaterial practice : extending the theorization of GPS tracking in cognitive impairment

Electronic tracking through global positioning systems (GPSs) is used to monitor people with cognitive impairment who “wander” outside the home. This ethnographic study explored how GPS-monitored wandering was experienced by individuals, lay carers, and professional staff. Seven in-depth case studies revealed that wandering was often an enjoyable and worthwhile activity and helped deal with uncertainty and threats to identity. In what were typically very complex care contexts, GPS devices were useful to the extent that they aligned with a wider sociomaterial care network that included lay carers, call centers, and health and social care professionals. In this context, “safe” wandering was a collaborative accomplishment that depended on the technology’s materiality, affordances, and aesthetic properties; a distributed knowledge of the individual and the places they wandered through, and a collective and dynamic interpretation of risk. Implications for design and delivery of GPS devices and services for cognitive impairment are discussed