Point-of-Care Ultrasound Use in Nephrology: A Survey of Nephrology Program Directors, Fellows, and Fellowship Graduates.

Rationale & Objective: Adoption of point-of-care ultrasound (POCUS) into nephrology practice has been relatively slow. We surveyed US nephrology program directors, their fellows, and graduates from a single training program regarding current/planned POCUS training, clinical use, and barriers to training and use. Study Design: Anonymous, online survey. Setting & Participants: All US nephrology program directors (n=151), their fellows (academic year 2021-2022), and 89/90 graduates (1980-2021) of the Walter Reed Nephrology Program. Analytical Approach: Descriptive. Results: 46% (69/151) of program directors and 33% (118/361) of their fellows responded. Response rate was 62% (55/89) for Walter Reed graduates. 51% of program directors offered POCUS training, most commonly bedside training in non-POCUS oriented rotations (71%), didactic lectures (68%), and simulation (43%). 46% of fellows reported receiving POCUS training, but of these, many reported not being sufficiently trained/not confident in kidney (56%), bladder (50%), and inferior vena cava assessment (46%). Common barriers to training reported by program directors were not enough trained faculty (78%), themselves not being sufficiently trained (55%), and equipment expense (51%). 64% of program directors and 55% of fellows reported <10% of faculty were able to perform POCUS. 64% of fellows reported having too little POCUS training. 72% of program directors and 77% of graduates felt POCUS should be incorporated into the fellowship curriculum. 59% of fellows and 61% of graduates desired hands-on POCUS training rather than didactic lectures or simulation. Limitations: Loss of respondents as program directors and fellows progressed through the survey. Conclusions: Nephrology program directors, fellows, and graduates surveyed want POCUS training incorporated into the fellowship curriculum. No group felt sufficiently trained to confidently perform POCUS, and the major barrier to training was lack of sufficiently trained faculty. This highlights the need to "train the trainers" before POCUS can be fully integrated into fellowship training and regularly used in nephrology practice.

Galactic cosmic ray effects on iron and nickel isotopes in iron meteorites.

We present model calculations for cosmogenic production rates in order to quantify the potential effects of spallation and neutron capture reactions on Fe and Ni isotopes in iron meteorites. We aim to determine whether the magnitude of any cosmogenic effects on the isotopic ratios of Fe and/or Ni may hinder the search for nucleosynthetic variations in these elements or in the application of the 60Fe-60Ni chronometer. The model shows that neutron capture reactions are the dominant source of shifts in Fe and Ni isotopic ratios and that spallation reactions are mostly negligible. The effects on 60Ni are sensitive to the Co/Ni ratio in the metal. The total galactic cosmic ray (GCR) effects on 60Ni and 64Ni can be minimized through the choice of normalizing isotopes (61Ni/58Ni versus 62Ni/58Ni). In nearly all cases, the GCR effects (neutron capture and/or spallation) on Fe and Ni isotopic ratios are smaller than the current analytical resolution of the isotopic measurements. The model predictions are compared to the Fe and Ni isotopic compositions measured in a suite of six group IAB irons with a range of cosmic ray exposure histories. The experimental data are in good agreement with the model results. The minimal effects of GCRs on Fe and Ni isotopes should not hamper the search for nucleosynthetic variations in these two elements or the application of the 60Fe-60Ni chronometer in iron meteorites or chondrites.

Excess 180W in IIAB iron meteorites: Identification of cosmogenic, radiogenic, and nucleosynthetic components.

The origin of 180W excesses in iron meteorites has been a recently debated topic. Here, a suite of IIAB iron meteorites was studied in order to accurately determine the contribution from galactic cosmic rays (GCR) and from potential decay of 184Os to measured excesses in the minor isotope 180W. In addition to W isotopes, trace element concentrations (Re, Os, Ir, Pt, W) were determined on the same samples, as well as their cosmic ray exposure ages, using 36Cl-36Ar systematics. These data were used in combination with an improved model of GCR effects on W isotopes to correct effects resulting from neutron capture and spallation reactions. After these corrections, the residual 180W excesses correlate with Os/W ratios and indicate a clear contribution from 184Os decay. A newly derived decay constant is equivalent to a half-life for 184Os of (3.38 ± 2.13) × 1013 a. Furthermore, when the data are plotted on an Os-W isochron diagram, the intercept (ε 180Wi = 0.63 ± 0.35) reveals that the IIAB parent body was characterized by a small initial nucleosynthetic excess in 180W upon which radiogenic and GCR effects were superimposed. This is the first cogent evidence for p-process variability in W isotopes in early Solar System material.

Chronic Kidney Disease: Detection and Evaluation.

Chronic kidney disease affects 47 million people in the United States and is associated with significant health care costs, morbidity, and mortality. Because this disease can silently progress to advanced stages, early detection is critical for initiating timely interventions. Multiple guidelines recommend at least annual screening with serum creatinine, urine albumin/creatinine ratio, and urinalysis for patients with risk factors, particularly diabetes mellitus, hypertension, and a history of cardiovascular disease. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for chronic kidney disease in the general population, and the American College of Physicians recommends against screening asymptomatic adults without risk factors. Persistently elevated serum creatinine and albuminuria are diagnostic and prognostic hallmarks of chronic kidney disease. Lower levels of albuminuria are associated with adverse renal and cardiovascular outcomes. Serum cystatin C is a novel biomarker that is most useful when a false-positive decreased estimated glomerular filtration rate calculated from serum creatinine is suspected. New guidelines incorporate albuminuria into the classification framework for chronic kidney disease and elaborate on identification of the disease, the frequency of follow-up, and recommendations for nephrology referral. Nephrology consultation is indicated for patients with an estimated glomerular filtration rate less than 30 mL per minute per 1.73 m2, persistent urine albumin/creatinine ratio greater than 300 mg per g or urine protein/creatinine ratio greater than 500 mg per g, or if there is evidence of a rapid loss of kidney function. A multidisciplinary approach between primary care physicians, nephrologists, and other subspecialists for implementing early interventions, providing education, and planning for advanced renal disease is key for effective management.

High precision measurements of non-mass-dependent effects in nickel isotopes in meteoritic metal via multicollector ICPMS.

We measured the Ni isotopic composition of metal from a variety of meteorite groups to search for variations in the 60Ni abundance from the decay of the short-lived nuclide 60Fe (t(1/2) = 1.49 My) and for possible nucleosynthetic effects in the other stable isotopes of Ni. We developed a high-yield Ni separation procedure based on a combination of anion and cation exchange chromatography. Nickel isotopes were measured on a single-focusing, multicollector, inductively coupled mass spectrometer (MC-ICPMS). The external precision on the mass-bias-corrected 60Ni/58Ni ratio (+/-0.15 epsilon; 2sigma) is comparable to similar studies using double-focusing MC-ICPMS. We report the first high-precision data for 64Ni, the least abundant Ni isotope, obtained via MC-ICPMS. The external precision on the mass-bias-corrected 64Ni/58Ni ratio (+/-1.5 epsilon; 2sigma) is better than previous studies using thermal ionization mass spectrometry. No resolvable excesses relative to a terrestrial standard in the mass-bias-corrected 60Ni/58Ni ratio were detected in any meteoritic metal samples. However, resolvable deficits in this ratio were measured in the metal from several unequilibrated chondrites, implying a 60Fe/56Fe ratio of approximately 1 x 10(-6) at the time of Fe/Ni fractionation in chondritic metal. A 60Fe/56Fe ratio of (4.6 +/- 3.3) x 10(-7) is inferred at the time of Fe/Ni fractionation on the parent bodies of magmatic iron meteorites and pallasites. No clearly resolvable non-mass-dependent anomalies were detected in the other stable isotopes of Ni in the samples investigated here, indicating that the Ni isotopic composition in the early solar system was homogeneous (at least at the level of precision reported here) at the time of meteoritic metal formation.

A T-cell-dependent humoral immune response is preserved during the administration of the nerve agent pre-treatment pyridostigmine bromide in a murine model.

Immune regulation, either via the autonomic nervous system or by a proposed "non-neuronal" cholinergic system, suggests that the immune system may be susceptible to perturbation by compounds affecting cholinergic function. Here, the current UK and US nerve agent pre-treatment, pyridostigmine bromide (PB) and the related anti-acetylcholinesterase (AChE) compounds physostigmine (PHY) and BW284c51 were tested for their ability to affect mouse splenocyte function in vitro. In addition, PB, at a dose equivalent to that received during pre-treatment for nerve agent poisoning, was tested for its effect on a T-cell-dependent humoral response to antigen in vivo in the mouse. None of the anti-AChEs tested affected concanavalin A (Con A)-, anti-CD3- or lipopolysaccharide LPS-driven splenocyte proliferation, in vitro, at concentrations expected to give effective nerve agent pre-treatment. However, higher concentrations (>100 microM) particularly of PHY caused some inhibition of the proliferative responses. In vivo, PB or saline was administered via 28-day mini-osmotic pumps to give a 25-40% inhibition of whole blood AChE in the PB-treated animals. During PB or saline administration, primary and secondary doses (i.p.) of sheep red blood cells (SRBC) were given and the humoral response determined by monitoring anti-SRBC IgM and IgG levels. Splenocytes isolated from the experimental animals were also examined for their proliferative and cytokine responses to stimulation. No remarkable effects of PB were seen during the period of AChE inhibition on the humoral immune response. However, a modest elevation in IL-2 and IFN(gamma) in Con A-stimulated lymphocytes was seen in PB-treated animals following pump removal. Overall these data suggest that, in vivo, the SRBC stimulated T-cell-dependent immune response is unaffected by the administration of PB at pre-treatment doses.

An in vitro investigation of the effects of the nerve agent pretreatment pyridostigmine bromide on human peripheral blood T-cell function.

The current pretreatment against nerve agent poisoning deployed by the UK and US armed forces is the acetylcholinesterase (EC 3.1.1.7) inhibitor pyridostigmine bromide (PB). At higher doses, PB is also used to treat the autoimmune disease myasthenia gravis. In both cases, the therapeutic effect is mediated by inhibition of acetylcholinesterase (AChE) at cholinergic synapses. However, the location of AChE is not restricted to these sites. AChE, acetylcholine (ACh) receptors and choline acetyltransferase have been reported to be expressed by T cells, suggesting that cholinergic signalling may exert some modulatory influence on T-cell function and consequently on the immune system. The aim of this study was to investigate the role of the T-cell cholinergic system in the immunological activation process and to examine whether inhibitors of AChE such as PB affect immune function. To investigate this, human peripheral blood mononuclear cells (PBMC) were stimulated using either mitogen, cross-linking of the T-cell receptor and co-receptors with antibodies (anti-CD3/CD28) or by antigen presentation in the presence of various AChE inhibitors and ACh receptor agonists or antagonist. Several indices were used to assess T-cell activation, including the secretion of IL-2, cell proliferation and expression of CD69. Treatment with PB had no significant effect on the immunological assays selected. Physostigmine (PHY), a carbamate compound similar to PB, consistently showed inhibition of T-cell activation, but only at concentrations in excess of those required to inhibit AChE. No evidence was found to support previously published findings showing muscarinic enhancement of cell proliferation or IL-2 secretion.