Grouping of PFAS for human health risk assessment: Findings from an independent panel of experts.

An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.

Fast Ion Transport in the Three-Dimensional Reversed-Field Pinch.

We report on the first comprehensive experimental and numerical study of fast ion transport in the helical reversed-field pinch (RFP). Classical orbit effects dominate the macroscopic confinement properties. The strongest effect arises from growth in the dominant fast ion guiding-center island, but substantial influence from remnant subdominant tearing modes also plays a critical role. At the formation of the helical RFP, neutron flux measurements indicate a drastic loss of fast ions at sufficient subdominant mode amplitudes. Simulations corroborate these measurements and suggest that subdominant tearing modes strongly limit fast ion behavior. Previous work details a sharp thermal transport barrier and suggests the helical RFP as an Ohmically heated fusion reactor candidate; the enhanced transport of fast ions reported here identifies a key challenge for this scheme, but a workable scenario is conceivable with low subdominant tearing mode amplitudes.

Direct Measurement of a Toroidally Directed Zonal Flow in a Toroidal Plasma.

Zonal flow appears in toroidal, magnetically confined plasmas as part of the self-regulated interaction of turbulence and transport processes. For toroidal plasmas having a strong toroidal magnetic field, the zonal flow is predominately poloidally directed. This Letter reports the first observation of a zonal flow that is toroidally directed. The measurements are made just inside the last closed flux surface of reversed field pinch plasmas that have a dominant poloidal magnetic field. A limit cycle oscillation between the strength of the zonal flow and the amplitude of plasma potential fluctuations is observed, which provides evidence for the self-regulation characteristic of drift-wave-type plasma turbulence. The measurements help advance understanding and gyrokinetic modeling of toroidal plasmas in the pursuit of fusion energy.

Observation of Electron Bernstein Wave Heating in a Reversed Field Pinch.

The first observation of rf heating in a reversed field pinch (RFP) using the electron Bernstein wave (EBW) is demonstrated on the Madison Symmetric Torus. Propagation across and heating in a stochastic magnetic field is observed. Novel techniques are required to measure the suprathermal electron tail generated by EBW heating in the presence of intense Ohmic heating. rf-heated electrons directly probe the edge transport properties in the RFP; measured loss rates imply a large noncollisional radial diffusivity.

Fast-particle-driven Alfvénic modes in a reversed field pinch.

Alfvénic modes are observed due to neutral beam injection for the first time in a reversed field pinch plasma. Modeling of the beam deposition and slowing down shows that the velocity and radial localization are high. This allows instability drive from inverse Landau damping of a bump-on-tail in the parallel distribution function or from free energy in the fast ion density gradient. Mode switching from a lower frequency toroidal mode number n=5 mode that scales with beam injection velocity to a higher frequency n=4 mode with Alfvénic scaling is observed.

Experimental evidence for a reduction in electron thermal diffusion due to trapped particles.

New high time resolution measurements of the electron thermal diffusion χ(e) throughout the sawtooth cycle of the Madison Symmetric Torus reversed-field pinch have been made by utilizing the enhanced capabilities of the upgraded multipoint, multipulse Thomson scattering system. These measurements are compared to the χ(e) due to magnetic diffusion predicted by using information from a new high spectral resolution zero-ß nonlinear resistive magnetohydrodynamic simulation performed, for the first time, at the Lundquist number of high current Madison Symmetric Torus plasmas (S≈4×10(6)). Agreement between the measured and predicted values is found only if the reduction in thermal diffusion due to trapped particles is taken into account.

A single receptor binds both insulin-like growth factor II and mannose-6-phosphate.

Amino acid sequences deduced from rat complementary DNA clones encoding the insulin-like growth factor II (IGF-II) receptor closely resemble those of the bovine cation-independent mannose-6-phosphate receptor (Man-6-P receptorCI), suggesting they are identical structures. It is also shown that IGF-II receptors are adsorbed by immobilized pentamannosyl-6-phosphate and are specifically eluted with Man-6-P. Furthermore, Man-6-P specifically increases by about two times the apparent affinity of the purified rat placental receptor for 125I-labeled IGF-II. These results indicate that the type II IGF receptor contains cooperative, high-affinity binding sites for both IGF-II and Man-6-P-containing proteins.

Measuring dynamic fast ion spatial profiles with fusion protons in the Madison Symmetric Torus.

Neutral beam injected fast ions play a dominant role in both the field reversed configuration (FRC) at TAE Technologies and the Madison Symmetric Torus (MST) reversed field pinch (RFP), making fast ion diagnosis a major pillar of both research programs. And as strongly self-organized plasmas, the FRC and RFP similarly exhibit dynamic relaxation events which can redistribute fast ions. Recently, a collaboration between TAE Technologies and the University of Wisconsin was conducted to develop a method for measuring a fast changing fast ion spatial profile with a fusion proton detector and to investigate commonalities between the two plasmas. The steerable detector was designed and built at TAE and installed on MST. The fusion proton emission profile resulting from injection of a 25 kV deuterium neutral beam is measured with better than 5 cm spatial resolution and 100 µs temporal resolution over the course of several 10s of shots. The fast ion density profile, forward modeled by tracing the orbits of the 3 MeV protons through a reconstructed magnetic equilibrium, is observed to flatten during global magnetic tearing mode activity, dropping by 30% in the core and increasing by a similar amount at the edge. The equilibrium profile is observed to be consistent with measurements made with a collimated neutron detector.

Detection of both T-cell and Ia-like antigens on cells from patients with acute myelomonocytic leukemia and chronic myelogenous leukemia in blast crisis.

Appropriately absorbed antisera to the lymphoblastoid cell lines HSB and SB detect a human T-lymphocyte-associated antigen (TLAA) and the human Ia-like antigens, respectively. Cells from some patients with acute myelomonocytic leukemia (AMML) and chronic myelogenous leukemia in blast crisis expressed both TLAA and Ia antigens when tested in a complement-dependent microcytotoxicity assay (greater than 90% lysis with both antisera). When patients were in remission, expression of TLAA and Ia antigens returned to normal values. Quantitative absorption of anti-TLAA serum with increasing numbers of AMML cells showed that these cells could remove reactivity of the serum for both HSB and human thymocytes. Similarly, absorption of anti-Ia serum with AMML cells removed all serological reactivity when this serum was tested on chronic lymphocytic leukemia cells or normal B-cells. These serological findings were confirmed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis studies using radiolabeled antigens. Cells from an AMML patient were labeled with 125I using lactoperoxidase; both the TLAA and Ia antigens were precipitated from the resulting solubilized membrane preparation. Leukemic cells from one AMML patient and one patient with chronic myelogenous leukemia in blast crisis were studied for Ia and TLAA antigens with a double fluorescence technique. Over 80% of the cells showed dual fluorescence.

Analysis techniques for diagnosing runaway ion distributions in the reversed field pinch.

An advanced neutral particle analyzer (ANPA) on the Madison Symmetric Torus measures deuterium ions of energy ranges 8-45 keV with an energy resolution of 2-4 keV and time resolution of 10 µs. Three different experimental configurations measure distinct portions of the naturally occurring fast ion distributions: fast ions moving parallel, anti-parallel, or perpendicular to the plasma current. On a radial-facing port, fast ions moving perpendicular to the current have the necessary pitch to be measured by the ANPA. With the diagnostic positioned on a tangent line through the plasma core, a chord integration over fast ion density, background neutral density, and local appropriate pitch defines the measured sample. The plasma current can be reversed to measure anti-parallel fast ions in the same configuration. Comparisons of energy distributions for the three configurations show an anisotropic fast ion distribution favoring high pitch ions.

X-ray analysis of electron Bernstein wave heating in MST.

A pulse height analyzing x-ray tomography system has been developed to detect x-rays from electron Bernstein wave heated electrons in the Madison symmetric torus reversed field pinch (RFP). Cadmium zinc telluride detectors are arranged in a parallel beam array with two orthogonal multi-chord detectors that may be used for tomography. In addition a repositionable 16 channel fan beam camera with a 55° field of view is used to augment data collected with the Hard X-ray array. The chord integrated signals identify target emission from RF heated electrons striking a limiter located 12° toroidally away from the RF injection port. This provides information on heated electron spectrum, transport, and diffusion. RF induced x-ray emission from absorption on harmonic electron cyclotron resonances in low current (<250 kA) RFP discharges has been observed.

A collimated neutron detector for RFP plasmas in MST.

The neutron emissivity profile in the Madison Symmetric Torus is being reconstructed through the use of a collimated neutron detector. A scintillator-photomultiplier tube (PMT) system is employed to detect the fusion neutrons with the plasma viewing volume defined by a 55 cm deep, 5 cm diameter aperture. Effective detection of neutrons from the viewing volume is achieved through neutron moderation using 1300 lbs of high density polyethylene shielding, which modeling predicts attenuates the penetrating flux by a factor of 104 or more. A broad spectrum of gamma radiation is also present due to the unconfined fusion proton bombardment of the thick aluminum vacuum vessel. A 15 cm cylindrical liquid scintillator of 3.8 cm diameter is used to further increase directional sensitivity. A fast (5 ns rise time) preamplifier and digitization at 500 MHz prevent pulse pile-up even at high count rates (∼104/s). The entire neutron camera system is situated on an adjustable inclining base which provides the differing plasma viewing volumes necessary for reconstruction of the neutron emissivity profile. This profile, directly related to the fast-ion population, allows for an investigation of the critical fast-ion pressure gradient required to destabilize a neutral beam driven Alfvénic mode which has been shown to transport fast ions.

Development towards a fast ion loss detector for the reversed field pinch.

A fast ion loss detector has been constructed and implemented on the Madison Symmetric Torus (MST) to investigate energetic ion losses and transport due to energetic particle and MHD instabilities. The detector discriminates particle orbits solely on pitch and consists of two thin-foil, particle collecting plates that are symmetric with respect to the device aperture. One plate collects fast ion signal, while the second aids in the minimization of background and noise effects. Initial measurements are reported along with suggestions for the next design phase of the detector.

Long-term follow-up of living kidney donors: quality of life after donation.

The University of Minnesota has been a strong advocate of living donor kidney transplants. The benefits for living donor recipients have been well documented. The relative low risk of physical complications during donation has also been well documented. Less well understood is the psychosocial risk to donors. Most published reports have indicated an improved sense of well-being and a boost in self-esteem for living kidney donors. However, there have been some reports of depression and disrupted family relationships after donation, even suicide after a recipient's death. To determine the quality of life of our donors, we sent a questionnaire to 979 who had donated a kidney between August 1, 1984, and December 31, 1996. Of the 60% who responded, the vast majority had an excellent quality of life. As a group, they scored higher than the national norm on the SF-36, a standardized quality of life health questionnaire. However, 4% were dissatisfied and regretted the decision to donate. Further, 4% found the experience extremely stressful and 8% very stressful. We used multivariate analysis to identify risk factors for this poor psychosocial outcome and found that relatives other than first degree (odds ratio=3.5, P=0.06) and donors whose recipient died within 1 year of transplant (odds ratio=3.3, P=0.014) were more likely to say they would not donate again if it were possible. Further, donors who had perioperative complications (odds ratio=3.5, P=0.007) and female donors (odds ratio=1.8, P=0.1) were more likely to find the overall experience more stressful. Overall, the results of this study are overwhelmingly positive and have encouraged us to continue living donor kidney transplants.

Enhanced calmodulin binding concurrent with increased kinase-dependent phosphorylation of cytoskeletal proteins following a single subcutaneous injection of diisopropyl phosphorofluoridate in hens.

Diisopropyl phosphorofluoridate (DFP) produces Type I organophosphorus compound-induced delayed neurotoxicity (OPIDN) in adult female chickens. We have proposed that calcium/calmodulin protein kinase II (CaM kinase II) plays a role in the development of OPIDN by increasing the phosphorylation of cytoskeletal proteins. We investigated in vivo the effects of treatment of DFP on CaM kinase II-dependent phosphorylation. In isolated brain supernatants from DFP-treated hens, calmodulin binding increased concurrent with increases in CaM kinase II-dependent autophosphorylation and phosphorylation of cytoskeleton proteins. There were no changes in the relative amounts of the enzyme based on immunobinding studies of antibodies to the CaM kinase II. In the absence of any exogenously added substrate. CaM kinase II and microtubule associated protein-2 (MAP-2) exhibited substantially increased phosphorylation, 833 and 275%, respectively, over brain supernatants from untreated hens. Moreover, isolated brain supernatants from treated hens with exogenously added cytoskeletal proteins and myelin basic protein (MBP) exhibited significant increases in phosphorylation over control, 233, 332 and 60%, for MAP-2, tubulin, and MBP, respectively. 125I-Calmodulin binding studies revealed a 136% increase in calmodulin binding to CaM kinase II in treated hens when compared to control groups. The data suggest that in vivo DFP treatment increases the percentage of unphosphorylated, active CaM kinase II resulting in increased calmodulin binding and subsequent enhanced phosphorylation of cytoskeletal proteins that leads to their aggregation and the production of axonal degeneration.

Effects of a protective foam on scrubbing and gloving.

OBJECTIVE: To test the effects of a skin protectant on surgical scrub and glove integrity. DESIGN: Forty-nine healthy adult volunteers were assigned (12 subjects per group) to apply a protective foam (DermaMed; Benchmark Enterprises, Salt Lake City, Utah) in conjunction with surgical scrub in one of the following formulations: 70% isopropyl alcohol, a liquid detergent base containing 4% chlorhexidine gluconate, a liquid detergent base containing 7.5% povidone-iodine, or a nonantimicrobial liquid soap (control). According to a standard protocol, subjects performed a surgical scrub on 3 days (every other day). Foam was applied after surgical scrub on day 1 and before surgical scrub on day 3. No foam was applied on day 2. Subjects were gloved for 2 hours after surgical scrub. SETTING: Laboratory setting. RESULTS: On all test days, there were significant differences in bacterial reduction by products (chlorhexidine gluconate or alcohol > povidone-iodine > control). When controlling for baseline counts and products used, there were no significant differences in colony-forming unit counts on hands with or without foam immediately after scrubbing or at 2 hours after scrub on gloved or ungloved hands, nor were there differences in glove leakage rates when foam was on hands. CONCLUSIONS: Such protectants can be used without detrimental effects to scrub effectiveness or glove integrity.

Marfan's syndrome.

Although Marfan's syndrome is not a frequent occurrence in critical care, serious cardiovascular problems can exist, requiring intensive care. This article has identified the manifestations in those coping with Marfan's syndrome. Critical care nurses need to be aware of the clinical presentation and pathophysiology of the problem to understand the treatment and assist in patient education.

Design of a retarding potential grid system for a neutral particle analyzer.

The ion energy distribution in a magnetically confined plasma can be inferred from charge exchange neutral particles. On the Madison Symmetric Torus (MST), deuterium neutrals are measured by the Florida A&M University compact neutral particle analyzer (CNPA) and the advanced neutral particle analyzer (ANPA). The CNPA energy range covers the bulk deuterium ions to the beginning of the fast ion tail (0.34-5.2 keV) with high-energy resolution (25 channels) while the ANPA covers the vast majority of the fast ion tail distribution (∼10-45 keV) with low energy resolution (10 channels). Though the ANPA has provided insight into fast ion energization in MST plasma, more can be gained by increasing the energy resolution in that energy range. To utilize the energy resolution of the CNPA, fast ions can be retarded by an electric potential well, enabling their detection by the diagnostic. The ion energy distribution can be measured with arbitrary resolution by combining data from many similar MST discharges with different energy ranges on the CNPA, providing further insight into ion energization and fast ion dynamics on MST.

Time-resolved ion energy distribution measurements using an advanced neutral particle analyzer on the MST reversed-field pinch.

An advanced neutral particle analyzer (ANPA) capable of simultaneously measuring hydrogen and deuterium ions of energies up to 45 keV has recently been developed for use on the Madison Symmetric Torus. The charge-to-mass separation allows for separate analysis of bulk deuterium ions and hydrogen ions injected with a 1 MW, 25 keV neutral beam. Orientation of the ANPA allows sampling of different regions of ion velocity space; a radial viewport favors collection of ions with high v(perpendicular)∕|v| while a recently installed tangential viewport favors ions with high v(||)∕|v|, such as those from the core-localized fast ion population created by the neutral beam. Signals are observed in the ANPA's highest energy channels during periodic magnetic reconnection events, which are drivers of anisotropic, non-Maxwellian ion energization in the reversed-field pinch. ANPA signal strength is dependent on the background neutral density, which also increases during magnetic reconnection events, so careful analysis must be performed to identify the true change in the ion distribution. A Monte Carlo neutral particle tracing code (NENE) is used to reconstruct neutral density profiles based on D(α) line emission, which is measured using a 16-chord filtered photodiode array.

Calibration of an advanced neutral particle analyzer for the Madison Symmetric Torus reversed-field pinch.

A new E∥B neutral particle analyzer, which has recently been installed on Madison Symmetric Torus (MST) reversed-field pinch (RFP), has now been calibrated, allowing the measurement of the fast ion density and energy distribution. This diagnostic, dubbed the advanced neutral particle analyzer (ANPA), can simultaneously produce time resolved measurements of the efflux of both hydrogen and deuterium ions from the plasma over a 35 keV energy range with an energy resolution of 2-4 keV and a time resolution of 10 µs. These capabilities are needed to measure both majority ion heating that occurs during magnetic reconnection events in MST and the behavior of the fast ions from the 1 MW hydrogen neutral beam injector on MST. Calibration of the ANPA was performed using a custom ion source that resides in the flight tube between the MST and the ANPA. In this work, the ANPA will be described, the calibration procedure and results will be discussed, and initial measurements of the time evolution of 25 keV neutral beam injection-born fast ions will be presented.