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Contrast-induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)-acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double-blind, placebo-controlled, three-period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso-osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three-arm randomized, double-blind, placebo-controlled parallel-group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno-protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Migrant and seasonal farmworking (MSFW) women patients experience substantially more intimate partner violence (IPV) than the general population, but few health-care providers screen patients for IPV. While researchers have examined screening practices in health-care settings, none have exclusively focused on MSFW women., Objective: The aim of this phenomenological study was to explore the experiences of health-care providers who have screened for and/or addressed IPV with MSFW women patients., Design: Researchers utilized descriptive phenomenology to capture the lived experiences of these health-care providers. Data were analysed using Colaizzi's seven-stage framework., Setting and Participants: Interviews were conducted with nine female participants - all of whom: (i) were clinically active health-care providers within the MSFW community, (ii) were bilingual in English and Spanish or had access to a translator, (iii) had treated MSFW patients who had experienced IPV and (iv) were at least 18 years of age., Results: Participants' experiences were reflected in four emergent themes: (i) provider-centered factors, (ii) patient-centered factors, (iii) clinic-centered factors and (iv) community-centered factors. Participants described barriers to establish routine IPV assessment, decrease patient ambivalence and increase on-site support and community resources., Discussion and Conclusions: This study aimed to generate a greater understanding of the experiences of health-care providers with screening for and addressing IPV with MSFW patients. Implications and recommendations for research, clinical practice and policy are provided., (© 2015 The Authors. Health Expectations Published by John Wiley & Sons Ltd.)

Molecular dynamics and other molecular simulation methods rely on a potential energy function, based only on the relative coordinates of the atomic nuclei. Such a function, called a force field, approximately represents the electronic structure interactions of a condensed matter system. Developing such approximate functions and fitting their parameters remains an arduous, time-consuming process, relying on expert physical intuition. To address this problem, a functional programming methodology was developed that may enable automated discovery of entirely new force-field functional forms, while simultaneously fitting parameter values. The method uses a combination of genetic programming, Metropolis Monte Carlo importance sampling and parallel tempering, to efficiently search a large space of candidate functional forms and parameters. The methodology was tested using a nontrivial problem with a well-defined globally optimal solution: a small set of atomic configurations was generated and the energy of each configuration was calculated using the Lennard-Jones pair potential. Starting with a population of random functions, our fully automated, massively parallel implementation of the method reproducibly discovered the original Lennard-Jones pair potential by searching for several hours on 100 processors, sampling only a minuscule portion of the total search space. This result indicates that, with further improvement, the method may be suitable for unsupervised development of more accurate force fields with completely new functional forms., (Copyright (c) 2007 Wiley Periodicals, Inc.)

This study investigated the similarity of Icelandic and English versions of the Basic Personality Inventory (BPI), a 240-item measure of psychopathology. Eighty-nine native Icelandic graduate students studying in North America completed both language versions of the BPI in a counterbalanced order with a retest interval of approximately one month. The results of this bilingual retest study confirmed the adequacy of the Icelandic translation. Specifically, scale means, test-retest coefficients, and reliability coefficients demonstrated that the BPI performed highly similarly in both language versions. These findings provide additional support for the adequacy and applicability of the Icelandic translation of the BPI.

The validity of a four-subtest short form (SF4) of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) was evaluated in a sample of incarcerated Caucasian and Native youth 16 to 18 years of age. A test-retest methodology was used in which 21 subjects received SF4 first and 26 subjects received the full WAIS-R first. Results showed that SF4 has validity as an estimate of Full Scale IQ, but with accuracy limitations. In addition to the IQ overestimates and misclassification rates that have been found in other short form research, this study showed that a large overestimate of about 11 points occurred on average when SF4 followed the standard administration.

The stability of Wechsler Adult Intelligence Scale-Revised IQs was investigated for 52 students 16 years of age. Half of the subjects were retested after a 3-month interval; half after an 18-month interval. Stability coefficients were uniformly high for both retest intervals. Gains in Verbal, Performance, and Full Scale IQ over 3 months were similar to practice effects reported for adult subjects. However, IQs for males retested after 18 months increased beyond the practice effect. Females retested after 18 months showed the same result only on Verbal IQ. The findings remind clinicians of the important distinction between relative and absolute stability, especially for 16-year-old students tested with the WAIS-R.

The evaluation of two- and four-subtest short forms of the WAIS-R has proceeded with little empirical attention to the effects of shortened administration time upon test performance. Routinely, the full WAIS-R has been administered and short form estimates extracted from the complete set of test results. Time and motivational/attentional factors can be evaluated by the administration of short form subtests first, followed by the remaining subtests in standard order or, alternatively, by the test-retest paradigm with short and complete WAIS-R versions. Limitations of these methodologies and existing empirical results are discussed.