Search

During continuous venoveno haemofiltration (CVVH), extracorporeal drug clearance is dependant on blood flow, ultrafiltration rate, albumin binding, and the drug’s molecular weight and volume of distribution. Drug doses are adjusted assuming reduced drug clearance by the renal system and CVVH. High volume haemofiltration, pre-dilution and different filter membranes can greatly alter drug clearance. Consequently, assessing the adequacy of cephalosporin dosing during CVVH is complex; under- or overdosing may occur. We studied the pharmacokinetic properties of ceftriaxone during CVVH in vitro. Renaflow filters were used to model 6, 20 and 50 kg patients. Each circuit and reservoir was prepared with a known volume of Hartmann’s solution, human albumin solution 4.5% or blood. Pump speed and exchange rate were standardised for weight. Haemosol BO was used as the replacement fluid with 70% pre-dilution. Following paired sampling from the circuit and ultrafiltrate fluid, ceftriaxone was injected into the circuit. Paired samples were taken up to 720 minutes. Ceftraxione concentrations were determined using high performance liquid chromatography (HPLC). Maximum circuit concentrations (Cmax) at 2 minutes for albumin were 3.5, 2.65 and 4.85 mg/l, for blood were 4.5, 6.5 and 5.55 mg/l and for Hartmann’s were 1.65, 2.95 and 3.65 mg/l for 6kg, 20kg and 50kg models. The sieving coefficients (Sc) from blood (ratio of mean concentrations in the ultrafiltrate/circuits samples) were 0.31 and 0.51 with T1/2 (the half life) 62 and 20 minutes in the 6kg and the 20kg circuits, respectively. The data suggest in an in vitro model of ceftriaxone is rapidly cleared during CVVH. Albumin circuits had the lowest Sc and longest terminal T1/2, reflecting protein binding of the drug and suggest ceftriaxone clearance may be more rapid in hypoalbuminaemic patients. The Cmax was lower in the Hartmann circuits, possibly reflecting precipitation of the drug with calcium in this solution. [ABSTRACT FROM PUBLISHER]

Coccidioidomycosis is caused by Coccidioides species, a fungus endemic to the desert regions of the southwestern United States, and is of particular concern for African Americans. We performed a PubMed search of the English-language medical literature on coccidioidomycosis in African Americans and summarized the pertinent literature. Search terms were coccidioidomycosis, Coccidioides, race, ethnicity, African, black, and Negro. The proceedings of the national and international coccidioidomycosis symposia were searched. All relevant articles and their cited references were reviewed; those with epidemiological, immunologic, clinical, and therapeutic data pertaining to coccidioidomycosis in African Americans were included in the review. Numerous studies documented an increased predilection for severe coccidioidal infections, coccidioidomycosis-related hospitalizations, and extrapulmonary dissemination in persons of African descent; however, most of the published studies are variably problematic. The immunologic mechanism for this predilection is unclear. The clinical features and treatment recommendations are summarized. Medical practitioners need to be alert to the possibility of coccidioidomycosis in persons with recent travel to or residence in an area where the disease is endemic. [ABSTRACT FROM AUTHOR]

BACKGROUND: Amylin, a 37-amino-acid peptide hormone, is a potent inhibitor of gastric emptying. It is co-secreted by the pancreatic beta cells in response to enteral nutrient intake. Feed intolerance is common in preterm neonates and often presents as increased gastric residual volume (GRV). It is therefore hypothesised that serum amylin concentrations are raised in preterm neonates with poor gastric emptying, which may contribute to this observed feed intolerance. OBJECTIVE: To determine serum amylin concentrations in feed-intolerant preterm neonates. Patients and methods: Feed-intolerant (nTOL) preterm neonates (GRV >50% of a previous 4 h feed volume on two consecutive occasions) were matched for gestation, birth weight and postnatal age with feed-tolerant (TOL) neonates. Blood samples were analysed for amylin concentration. Seventy neonates were studied with median (interquartile range) gestation of 29 weeks (28-33) and birth weight of 1.3 kg (1.0-1.8). RESULTS: Serum amylin concentration and percentage GRV (median (interquartile range)) were significantly higher in the nTOL (47.9 pmol/l (21.4-79.8), 150% (100-350)) than the TOL (8.7 pmol/l (5.7-16), 5% (0-5)) group (p<0.001). In the nTOL group, a positive correlation was observed between serum amylin and GRV (r = 0.78, 95% CI 0.59 to 0.89, p<0.001), days to reach full enteral feeds (r = 0.40, 95% CI 0.08 to 0.68, p = 0.02), and days to discharge (r = 0.43, 95% CI 0.09 to 0.68, p = 0.01). CONCLUSIONS: Amylin may be responsible for delaying establishment of enteral nutrition in preterm neonates by virtue of its inhibitory effect on gastric emptying. Serum amylin concentrations in these neonates correlate with GRVs and time to reach full enteral feeds. [ABSTRACT FROM AUTHOR]

Migraine is a common disorder in women. The 1-year prevalence of migraine is 18% in women compared with 6% in men. Migraine most commonly occurs during the reproductive years, affecting 27% of women 30 to 49 years of age. The predominance of this disorder and its social, functional, and economic consequences make migraine an important issue in women's health. The hormonal milieu has a substantial effect on migraine in women. An understanding of these hormonal influences in the various stages of life in females is essential to the management and prevention of migraines. This article reviews migraine prevention strategies with an emphasis on specific therapies for each stage of a woman's life. [ABSTRACT FROM AUTHOR]

Unintended pregnancy continues to be a serious public health issue in the United States. Of the 3 million unplanned pregnancies per year, 60% occur in women using some form of contraception. Educating and helping women choose a contraceptive agent that best suits their needs will improve compliance and contraceptive efficacy. A multitude of new contraceptive agents are now available. We review new hormonal contraceptive options and discuss newer oral agents, extended-cycle contraception, and innovative delivery methods. [ABSTRACT FROM AUTHOR]

The assessment and care of female adolescents by primary care physicians can be facilitated with increased knowledge about this stage of development, the health care risks faced by these patients, and the resources available to aid in their care. With a focus on preventive health maintenance, this concise review addresses these areas as well as how to build relationships with female adolescent patients, conduct age-appropriate interviews and tests, and maintain patient confidentiality. [ABSTRACT FROM AUTHOR]

Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases., (© 2024. The Author(s).)

The excitation of acoustic waves by a unidirectional transducer, integrated in a piezoelectric cylindrical tube or disk, can lead to a time-independent torque. This phenomenon, demonstrated earlier in experiments and analyzed with coupling-of mode theory, is explained in detail, starting on the level of lattice dynamics of a piezoelectric crystal. Expressions are derived for the stationary torque in the form of integrals over the volume or surface of the piezoelectric, involving the electric potential and displacement field associated with the acoustic waves generated by the transducer. Simulations have been carried out with the help of the finite element method for a tube made of PZT for two cases: A pre-defined potential on the surface of the tube and metal electrodes buried in the piezoelectric. The displacement field and electric potential of the high-frequency acoustic waves (between 200 and 300 kHz) were computed and used in the evaluation of the integrals. The attenuation due to various loss channels of the acoustic waves in the system has been analyzed in detail, as this plays a crucial role for the efficiency of torque generation. It is conjectured that time-reversal symmetry, present in the absence of attenuation, prohibits the generation of a static torque at least in the linear limit. A qualitative comparison is made between the simulations and earlier experiments. Discrepancies are attributed to lack of knowledge of the relevant material constants of the piezoelectric and to a simplified modeling of the electrode geometry in the cylindrical tube, which was necessary for reasons of numerical accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Non-neutralizing anti-idiotype antibodies against a therapeutic monoclonal antibody (mAb) play a crucial role in the creation of total pharmacokinetic (PK) assays and total target engagement (TE) assays during both pre-clinical and clinical development. The development of these anti-idiotype antibodies is challenging. In this study, we utilized a hybridoma platform to produce a variety of anti-idiotype antibodies against GSK2857914, a humanized IgG1 anti-BCMA monoclonal antibody. The candidate clones were evaluated using surface plasmon resonance (SPR) and bio-layer interferometry (BLI) for binding affinity, binding profiling, matrix interference, and antibody pairing determination. We discovered that three anti-idiotype antibodies did not prevent BCMA from binding to GSK2857914. All three candidates demonstrated high binding affinities. One of the three exhibited minimal matrix inference and could pair with the other two candidates. Additionally, one of the three clones was biotinylated as a capture reagent for the total PK assay, and another was labeled with ruthenium as a detection reagent for both the total PK assay and total TE assay. The assay results clearly show that these reagents are genuine non-neutralizing anti-idiotypic antibodies and are suitable for total PK and TE assay development. Based on this and similar studies, we conclude that the hybridoma platform has a high success rate for generating non-neutralizing anti-idiotype antibodies. Our methodology for developing and characterizing non-neutralizing anti-idiotype antibodies to therapeutic antibodies can be generally applied to any antibody-based drug candidate's total PK and total TE assay development., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Purpose: Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc receptor (FcRn)-mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS-modified equivalent, VIR-7831-WT, in cynomolgus monkeys., Methods: 89 Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on the respiratory tract, and a physiologically based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values., Results: SUV mean uptake in the pulmonary bronchi for 89 Zr-VIR-7831 was statistically higher than for 89 Zr-VIR-7831-WT at days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively) and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUV mean uptake ratio for both mAbs was 0.25 on day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31 and 0.55, respectively. Radiomics analysis showed VIR-7831 had mean-centralized PET SUV distribution in the lung and liver, indicating more uniform uptake than VIR-7831-WT., Conclusion: The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89 Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89 Zr label sheds light on the sites of antibody catabolism., (© 2022. The Author(s).)

In this study, we explore leadership practices in a dual-language elementary school led by three leaders of color committed to the ideals of cultural responsiveness. We employ an organizational leadership lens informed by aspects of culturally responsive school leadership (CRSL) and teaching (CRT) to interpret interview and observational data collected during the implementation of an equity-oriented engineering program for English learner (EL) students. In the midst of attempting to implement this school-research partnership, pre-existing tensions between the school's leadership and instructional culture rose to the forefront, offering the opportunity to analyze the data with this particular intersectional lens (organizational leadership and CRSL). Thus, subsequent data analysis focused not on program implementation but rather the existing challenges present in the school. Insights from our data suggest that both school leaders and teachers faced considerable challenges that appeared to stem from disparate understandings of how to achieve equity for their EL students. Ultimately, these challenges prevented leaders' successful enactment of CRSL within the existing organizational infrastructure. We suggest that the lack of explicit processes of critical consciousness defined the school culture and that accountability practices limited leaders' ability to implement CRSL.

The laser ultrasound (LU) technique has been used to determine dispersion curves for surface acoustic waves (SAW) propagating in AlScN/Al 2 O 3 systems. Polar and non-polar Al 0.77 Sc 0.23 N thin films were prepared by magnetron sputter epitaxy on Al 2 O 3 substrates and coated with a metal layer. SAW dispersion curves have been measured for various propagation directions on the surface. This is easily achieved in LU measurements since no additional surface structures need to be fabricated, which would be required if elastic properties are determined with the help of SAW resonators. Variation of the propagation direction allows for efficient use of the system's anisotropy when extracting information on elastic properties. This helps to overcome the complexity caused by a large number of elastic constants in the film material. An analysis of the sensitivity of the SAW phase velocities (with respect to the elastic moduli and their dependence on SAW propagation direction) reveals that the non-polar AlScN films are particularly well suited for the extraction of elastic film properties. Good agreement is found between experiment and theoretical predictions, validating LU as a non-destructive and fast technique for the determination of elastic constants of piezoelectric thin films.

Antibody-drug conjugates (ADCs) represent a rapidly evolving area of drug development and hold significant promise. To date, nine ADCs have been approved by the US Food and Drug Administration (FDA). These conjugates combine the target specificity of monoclonal antibodies with the anticancer activity of small-molecule therapeutics (also referred to as payload). Due to the complex structure, three analytes, namely ADC conjugate, total antibody, and unconjugated payload, are typically quantified during drug development; however, the benefits of measuring all three analytes at later stages of clinical development are not clear. The cytotoxic payloads, upon release from the ADC, are considered to behave like small molecules. Given the relatively high potency and low systemic exposure of cytotoxic payloads, drug-drug interaction (DDI) considerations for ADCs might be different from traditional small molecule therapeutics. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) convened an ADC working group to create an IQ ADC database that includes 26 ADCs with six unique payloads. The analysis of the ADC data in the IQ database, as well as nine approved ADCs, supports the strategy of pharmacokinetic characterization of all three analytes in early-phase development and progressively minimizing the number of analytes to be measured in the late-phase studies. The systemic concentrations of unconjugated payload are usually too low to serve as a DDI perpetrator; however, the potential for unconjugated payloads as a victim still exists. A data-driven and risk-based decision tree was developed to guide the assessment of a circulating payload as a victim of DDI., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

Aim: Ruthenium-labeled antibodies are commonly used detection reagents in bioanalysis assays and must be characterized to ensure quality. The aim of this work was to develop a method to determine the concentration and incorporation ratio (the degree of labeling [DOL]) of ruthenium-labeled antibodies by UV/VIS spectroscopy. Materials & methods: Free SULFO-TAG compound was scanned using UV/VIS and showed an absorbance peak at 292 nm. In contrast, antibodies demonstrate UV absorbance at 280 nm. After experimentally determining the extinction coefficients at 280 and 292 nm of free ruthenium and antibody, we generated a formula based on the Beer-Lambert law that calculates both concentration and DOL of these ruthenium-labeled antibodies. Conclusion: The concentration and DOL values determined by our method were comparable to those determined from bicinchoninic acid and LC/MS for the same reagents. This method creates a faster and more accessible reagent characterization process that uses far less reagent than the more traditional alternatives.

Menopause in human females and subsequent ovarian hormone deficiency, particularly concerning 17β-estradiol (E2), increase the risk for metabolic dysfunctions associated with obesity, diabetes type 2, cardiovascular diseases, and dementia. Several studies indicate that these disorders are also strongly associated with compositional changes in the intestinal microbiota; however, how E2 deficiency and hormone therapy affect the gut microbial community is not well understood. Using a rat model, we aimed to evaluate how ovariectomy (OVX) and subsequent E2 administration drive changes in metabolic health and the gut microbial community, as well as potential associations with learning and memory. Findings indicated that OVX-induced ovarian hormone deficiency and E2 treatment had significant impacts on several health-affecting parameters, including (a) the abundance of some intestinal bacterial taxa (e.g., Bifidobacteriaceae and Porphyromonadaceae ), (b) the abundance of microbial short-chain fatty acids (SCFAs) (e.g., isobutyrate), (c) weight/BMI, and (d) high-demand spatial working memory following surgical menopause. Furthermore, exploratory correlations among intestinal bacteria abundance, cognition, and BMI underscored the putative influence of surgical menopause and E2 administration on gut-brain interactions. Collectively, this study showed that surgical menopause is associated with physiological and behavioral changes, and that E2-linked compositional changes in the intestinal microbiota might contribute to some of its related negative health consequences. Overall, this study provides novel insights into interactions among endocrine and gastrointestinal systems in the post-menopausal life stage that collectively alter the risk for the development and progression of cardiovascular, metabolic, and dementia-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zeibich, Koebele, Bernaud, Ilhan, Dirks, Northup-Smith, Neeley, Maldonado, Nirmalkar, Files, Mayer, Bimonte-Nelson and Krajmalnik-Brown.)

Aim: Investigations have shown that for the antibody-drug conjugate (ADC) belantamab mafodotin, concentrations of the cysteine-conjugated metabolite, Cys-mcMMAF, were overestimated in the presence of the ADC during sample processing when utilizing a historical SPE method. Results: A new assay was developed utilizing an acidic protein precipitation to remove the ADC early in the extraction process, thus eliminating the risk of overestimating Cys-mcMMAF in the presence of belantamab mafodotin. In vitro experiments demonstrated a linear relationship between the concentration of belantamab mafodotin and the release of Cys-mcMMAF. Extensive stability assessments were performed to cover storage of study samples. Conclusion: This work emphasized the critical importance of understanding the performance of a bioanalytical method for free toxic payload in the presence of the ADC.

Background: High-quality critical reagents are essential to the successful support of biotherapeutic drug development regardless of the analytical platform used for support. The lack of such a reagent, early in the development lifecycle of a biotherapeutic can have detrimental impact on resource and translation of data across development phases. Results: Here, a pharmacokinetic assay case study is shared that illustrates what can occur when there is a lack of a reproducible and sustainable critical reagent early in the development lifecycle of a biotherapeutic. Various assay formats and critical reagents, as well as reagents generation programs, were initiated to find a reagent and assay format which was fit for purpose. Conclusions: Identification of appropriate critical reagents early in the development lifecycle of a biotherapeutic as advantageous.

In numerical calculations, guided acoustic waves, localized in two spatial dimensions, have been shown to exist and their properties have been investigated in three different geometries, (i) a half-space consisting of two elastic media with a planar interface inclined to the common surface, (ii) a wedge made of two elastic media with a planar interface, and (iii) the free edge of an elastic layer between two quarter-spaces or two wedge-shaped pieces of a material with elastic properties and density differing from those of the intermediate layer. For the special case of Poisson media forming systems (i) and (ii), the existence ranges of these 1D guided waves in parameter space have been determined and found to strongly depend on the inclination angle between surface and interface in case (i) and the wedge angle in case (ii). In a system of type (ii) made of two materials with strong acoustic mismatch and in systems of type (iii), leaky waves have been found with a high degree of spatial localization of the associated displacements, although the two materials constituting these structures are isotropic. Both the fully guided and the leaky waves analyzed in this work could find applications in non-destructive evaluation of composite structures and should be accounted for in geophysical prospecting, for example. A critical comparison is presented of the two computational approaches employed, namely a semi-analytical finite element scheme and a method based on an expansion of the displacement field in a double series of special functions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nipple-sparing mastectomy continues to grow in popularity as oncologic indications for preserving the nipple areolar complex have become less stringent and more patients with genetic predispositions to breast cancer seek aesthetically superior prophylactic mastectomy reconstructions. Nonetheless, nipple malposition remains a common and disturbing complication. This article proposes several anatomic variations that predispose to nipple malposition and a strategy to avoid it through a reliable, easily reproducible method of preoperative marking and intraoperative stabilization.

Nonlinearity can give rise to intermodulation distortions in surface acoustic wave (SAW) devices operating at high input power levels. To understand such undesired effects, a finite element method (FEM) simulation model in combination with a perturbation theory is applied to find out the role of different materials and higher order nonlinear tensor data for the nonlinearities in such acoustic devices. At high power, the SAW devices containing metal, piezoelectric substrate, and temperature compensating (TC) layers are subject to complicated geometrical, material, and other nonlinearities. In this paper, third-order nonlinearities in TC-SAW devices are investigated. The materials used are LiNbO 3 -rot128YX as the substrate and copper electrodes covered with a SiO 2 film as the TC layer. An effective nonlinearity constant for a given system is determined by comparison of nonlinear P-matrix simulations to third-order intermodulation measurements of test filters in a first step. By employing these constants from different systems, i.e., different metallization ratios, in nonlinear periodic P-matrix simulations, a direct comparison to nonlinear periodic FEM-simulations yields scaling factors for the materials used. Thus, the contribution of the different materials to the nonlinear behavior of TC-SAW devices is obtained and the role of metal electrodes, substrate, and TC film are discussed in detail.

Background: Gender bias has been identified as one of the drivers of gender disparity in academic medicine. Bias may be reinforced by gender subordinating language or differential use of formality in forms of address. Professional titles may influence the perceived expertise and authority of the referenced individual. The objective of this study is to examine how professional titles were used in the same and mixed-gender speaker introductions at Internal Medicine Grand Rounds (IMGR)., Methods: A retrospective observational study of video-archived speaker introductions at consecutive IMGR was conducted at two different locations (Arizona, Minnesota) of an academic medical center. Introducers and speakers at IMGR were physician and scientist peers holding MD, PhD, or MD/PhD degrees. The primary outcome was whether or not a speaker's professional title was used during the first form of address during speaker introductions at IMGR. As secondary outcomes, we evaluated whether or not the speakers professional title was used in any form of address during the introduction., Results: Three hundred twenty-one forms of address were analyzed. Female introducers were more likely to use professional titles when introducing any speaker during the first form of address compared with male introducers (96.2% [102/106] vs. 65.6% [141/215]; p < 0.001). Female dyads utilized formal titles during the first form of address 97.8% (45/46) compared with male dyads who utilized a formal title 72.4% (110/152) of the time (p = 0.007). In mixed-gender dyads, where the introducer was female and speaker male, formal titles were used 95.0% (57/60) of the time. Male introducers of female speakers utilized professional titles 49.2% (31/63) of the time (p < 0.001)., Conclusion: In this study, women introduced by men at IMGR were less likely to be addressed by professional title than were men introduced by men. Differential formality in speaker introductions may amplify isolation, marginalization, and professional discomfiture expressed by women faculty in academic medicine.

Background: Sustainable school buildings hold much promise to reducing operating costs, improve occupant well-being and, ultimately, teacher and student performance. However, there is a scarcity of evidence on the effects of sustainable school buildings on health and performance indicators. We sought to create a framework for a multidisciplinary research agenda that links school facilities, health, and educational outcomes., Methods: We conducted a nonsystematic review of peer review publications, government documents, organizational documents, and school climate measurement instruments., Results: We found that studies on the impact of physical environmental factors (air, lighting, and thermal comfort) on health and occupant performance are largely independent of research on the social climate. The current literature precludes the formation of understanding the causal relation among school facilities, social climate, occupant health, and occupant performance., Conclusions: Given the average age of current school facilities in the United States, construction of new school facilities or retrofits of older facilities will be a major infrastructure investment for many municipalities over the next several decades. Multidisciplinary research that seeks to understand the impact of sustainable design on the health and performance of occupants will need to include both an environmental science and social science perspective to inform best practices and quantification of benefits that go beyond general measures of costs savings from energy efficiencies., (© 2017, American School Health Association.)

In this clinical update, we selected recent publications relevant to common neurological concerns in women, with specific attention to stroke, cognition, and headache. We have chosen to highlight articles on sex differences in stroke and stroke treatment, the effect of hormone therapy on stroke risk and on cognition, and symptoms of the migraine postdrome.

Objectives: Bioidentical hormone therapy (BHT) is available in the United States in formulations that have been approved by the Food and Drug Administration (FDA) but also in formulations that have not been so approved. The aim of this study was to evaluate the knowledge, beliefs, and prescribing practices of BHT among healthcare providers., Study Design: A cross-sectional self-selected responder survey was conducted of health care providers attending primary care Continuing Medical Education (CME) conferences in the United States from May 2012 to April 2013. The questionnaire consisted of 26 items assessing knowledge, beliefs, and current practice around BHT., Results: A total of 366 survey responses were analyzed. Though 69.8% of respondents accurately identified the definition of BHT, only 45.3% were aware that BHT is available in FDA-approved products and 34.2% of respondents incorrectly identified that BHT is available only in custom-compounded formulations. Of those who had prescribed CC-BHT, less than half agreed with the statement "I am comfortable prescribing BHT" (45.4%)., Conclusions: Our study showed that many practitioners are unaware that bioidentical hormones are available in FDA-approved products. Knowledge gaps identified by this survey highlight the need for and importance of education to further dispel misinformation surrounding the topic., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The existence of acoustic waves with displacements localized at the tip of an isotropic elastic wedge was rigorously proven by Kamotskii, Zavorokhin and Nazarov. This proof, which is based on a variational approach, is extended to rectangular anisotropic wedges. For two high-symmetry configurations of rectangular edges in elastic media with tetragonal symmetry, a criterion is derived that allows identifying the boundary between the regions of existence for wedge modes of even and odd symmetry in regions of parameter space, where even- and odd-symmetry modes do not exist simultaneously. Furthermore, rectangular edges with non-equivalent surfaces are analyzed, and it is shown that at rectangular edges of cubic elastic media with one (110) surface and one (001) surface, a tip-localized guided wave always exists, apart from special cases that are characterized., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Laser pulses focused near the tip of an elastic wedge generate acoustic waves guided at its apex. The shapes of the acoustic wedge wave pulses depend on the energy and the profile of the exciting laser pulse and on the anisotropy of the elastic medium the wedge is made of. Expressions for the acoustic pulse shapes have been derived in terms of the modal displacement fields of wedge waves for laser excitation in the thermo-elastic regime and for excitation via a pressure pulse exerted on the surface. The physical quantity considered is the local inclination of a surface of the wedge, which is measured optically by laser-probe-beam deflection. Experimental results on pulse shapes in the thermo-elastic regime are presented and confirmed by numerical calculations. They pertain to an isotropic sharp-angle wedge with two wedge-wave branches and to a non-reciprocity phenomenon at rectangular silicon edges., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To understand the pregnancy, childbirth, and parental leave plans and experiences of trainees in multiple graduate medical education (GME) programs at a single institution., Method: In 2013, the authors developed and deployed a voluntary, Internet-based survey of trainees in 269 residency and fellowship programs across the three sites of the Mayo School of Graduate Medical Education. The survey assessed pregnancy-related issues, including use of relevant institutional policies, changes in work due to pregnancy, and activities during pregnancy and parental leave. The authors analyzed the responses to make comparisons across groups., Results: Forty-two percent (644/1,516) of trainees responded. Less than half (264; 41%) had children, and 46 (7%) were currently pregnant (themselves or their partners). Among parents, 24 (of 73; 33%) women and 28 (of 81; 35%) men planned to have another child during their current training program, and 13 (18%) women and 14 (17%) men planned to do so during their next training program. Among nonparents, 40 (of 135; 30%) women and 36 (of 111; 32%) men planned pregnancies during their current training program, and 25 (19%) women and 14 (13%) men planned pregnancies during their next training program. Of respondents eligible for parental leave, 81 (of 83; 98%) women and 89 (of 101; 88%) men had used it., Conclusions: Approximately 40% of respondents planned to have children during their GME training; most will require family leave and institutional support. GME programs should pursue policies and practices to minimize the effects of these leaves on their workforce.

Objectives The Centers for Disease Control and Prevention recommends a reproductive life plan (RLP) to promote individual responsibility for preconception health. The objectives of this study were to determine existing awareness of RLPs in a cohort of reproductive-age adults and to evaluate their knowledge level and beliefs about reproductive life planning. Methods We performed a cross-sectional survey study of adults ages 18-40 years old seeking care at the student health center of a large public university. Participation was voluntary. Survey responses were analyzed by age and gender. Results A total of 559 surveys were collected and analyzed. Only 24 % of participants had heard of an RLP although a majority (62.9 %) agreed that it is important to develop an RLP. Most respondents (85.4 %) preferred to receive information about reproductive life planning from a primary care provider or obstetrician-gynecologist, while only 4.2 % of patients surveyed reported ever being actually asked about an RLP by their healthcare provider. Among those who agreed that an RLP was important, knowledge of specific aspects of an RLP was lacking. Conclusions In our cohort of reproductive-age adults, general health literacy regarding RLPs was poor. Most of the young adults who responded to our survey did not know what an RLP was and even fewer had ever discussed one with their health provider.

We would like to introduce a new section in the Journal of Women's Health, the Clinical Update. Important studies are continually published in both this Journal and other medical publications. However, it is difficult for busy providers to stay current with the changing literature. The Clinical Update is designed to serve as a review of recently published, high-impact, and potentially practice-changing journal articles, digested for our readers. The Clinical Update will be published on a quarterly basis. Each edition of the update will focus on a specific women's health topic, with planned topics to include menopause, sexual dysfunction, breast health, contraception, osteoporosis, and cardiovascular disease.

We have investigated the acoustic properties of silicon dioxide thin films. Therefore, we determined the phase velocity dispersion of LiNbO3 substrate covered with SiO2 deposited by a plasma enhanced chemical vapor deposition and a physical vapor deposition (PVD) process using differential delay lines and laser ultrasonic method. The density p and the elastic constants (c11 and c44) can be extracted by fitting corresponding finite element simulations to the phase velocities within an accuracy of at least +4%. Additionally, we propose two methods to improve the accuracy of the phase velocity determination by dealing with film thickness variation of the PVD process.

Objectives: The goal of this study was to use a status epilepticus steady-state chemical model in rats using the convulsant, 3-mercaptopropionic acid (3-MPA), and to compare the changes in striatal neurotransmission on a slow (5min) and fast (60s) timescale. In vivo microdialysis was combined with electrophysiological methods in order to provide a complete evaluation of the dynamics of the results obtained., Objective: To compare the effects of a steady-state chemical model pof status epilepticus on striatal amino-acid and amine neurotransmitters contents, as measured via in vivo microdialysis combined with electrophysiological methods. Measurements were performed on samples collected every 60s and every 5min. "Fast" (60s) and "slow" (5min) sampling timescales were selected, to gain more insight into the dynamics of GABA synthesis inhibition and of its effects on other neurotransmitters and on cortical electrical activity., Methods: 3-MPA was administered in the form of an intra-venous load (60mg/kg) followed by a constant infusion (50mg/kg/min) for min. Microdialysis samples were collected from the striatum at intervals of 5min and 60s and analyzed for biogenic amine and amino acid neurotransmitters. ECoG activity was monitored via screws placed over the cortex., Results: In the 5min samples, glutamate (Glu) increased and γ-aminobutyric acid (GABA) decreased monotonically while changes in dopamine (DA) concentration were bimodal. In the sixty second samples, Glu changes were bimodal, a feature that was not apparent with the 5min samples. ECoG activity was indicative of status epilepticus., Conclusions: This study describes the combination of in vivo microdialysis with electrophysiology to monitor the effect of 3-MPA on neurotransmission in the brain. This led to a better understanding of the chemical changes in the striatum due to the applied 3-MPA chemical model of status epilepticus., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The study aims to compare methods of determining headache directionality (imploding, exploding, and/or ocular headaches) in women with migraine, investigate the concordance between physician assignment and patient self-assignment of pain directionality, and evaluate whether patients assigned their headaches to the same direction when queried using different methods. Directionality of migraine headache pain (imploding, exploding, or ocular) may reflect differences in the underlying pathogenesis of individual migraine attacks among and within individuals. Emerging evidence suggests that directionality of pain in migraine sufferers may predict response to onabotulinumtoxin A. The best method of determining headache directionality in migraine sufferers has not been systematically explored., Methods: We conducted a prospective cross-sectional survey study of 198 female patients with migraine presenting to a Women's Health Clinic. Patients determined the directionality (imploding, exploding, and/or ocular) of their own migraine pain by choosing among 3 pictures graphically representing directionality and also by responding to a written question regarding directionality. Clinicians then classified directionality of migraine pain using structured interviews. Concordance between clinician assignment of directionality and patient self-assignment was determined with Kappa coefficients., Results: Subjects were females between the ages of 18 and 77 years (mean 48 years). According to patient selection of representative pictures, 62 (31.6%) had imploding headaches with or without ocular pain, 36 (18.4%) had exploding headaches with or without ocular pain, 78 (39.8%) had ocular pain only, and 20 (10.2%) had imploding and exploding headaches with or without ocular pain. Two subjects did not respond. According to patient responses to a written question, 80 (41.0%) had imploding headaches with or without ocular pain, 53 (27.2%) had exploding headaches with or without ocular pain, 46 (23.6%) had ocular pain only, and 16 (8.2%) had imploding and exploding headaches with or without ocular pain. Three subjects did not respond. For physician assignment, 69 (34.9%) subjects had imploding headaches with or without ocular pain, 89 (45%) had exploding headaches with or without ocular pain, 14 (7.1%) had ocular pain only, and 26 (13.1%) had imploding and exploding headaches with or without ocular pain. The concordance (Kappa coefficient) between physician assignment of headache directionality with patient response to the written question was 0.33 (weak agreement), between physician assignment and patient assignment via selection of representative pictures was 0.35 (weak agreement), and between patient assignment via written question and via selection of representative pictures was 0.35 (weak agreement)., Conclusions: The assignment of headache directionality varied substantially depending upon the method of determination. The concordance between clinician assignment, patient-self assignment via answering a written question, and patient self-assignment via choosing a representative picture was weak. Improved methods of determining pain directionality are needed., (© 2014 American Headache Society.)

Background: Mentoring plays an important role in career success of academic medical faculty. New mentoring models such as peer mentoring have emerged., Aim: To evaluate the long-term impact of a facilitated peer mentoring program on academic achievements., Method: Women faculty at the instructor or assistant professor rank were recruited to voluntarily participate in a facilitated peer mentoring program. Recruitment occurred over 3.8 years between 2005 and 2009. A 26-item questionnaire to assess academic skill, career satisfaction, and self-efficacy was administered before program participation and again with seven additional questions in 2011. Curriculum vitae were reviewed retrospectively to tally peer-reviewed publications, other academic activities, and promotions., Results: Participants had long-term improvement in their perceived mastery of academic skills. Peer-reviewed publications, book chapters, abstracts, posters, and other academic activities increased when activities before the program were compared to those in the five years after program enrollment. At follow-up, participants reported positive perceptions of the program and 44% continued to work with their original peer mentor groups., Conclusions: Involvement in the facilitated peer mentoring program was associated with increased skills and academic activities for most participants. Future studies are needed to assess its applicability and success among various demographic groups in academic medicine.

Purpose: Over the past 30 years, the number and type of academic faculty tracks have increased, and researchers have found differences in promotion rates between track types. The authors studied the gender distribution of medical school faculty on the traditional tenure track (TTT) and clinician-educator track (CET) types., Method: The authors analyzed gender and academic track type distribution data from the March 31, 2011, snapshot of the Association of American Medical Colleges' Faculty Roster. Their final analysis included data from the 123 medical schools offering the TTT type and the 106 offering the CET type, which excluded any schools with 10 or fewer faculty on each track type., Results: The original dataset included 134 medical schools representing 138,508 full-time faculty members, 50,376 (36%) of whom were women. Of the 134 medical schools, 128 reported at least one of four track types: TTT, CET, research track, and other. Of the 83 medical schools offering the CET type, 64 (77%) had a higher proportion of female than male faculty on that track type. Of the 102 medical schools offering the TTT type, only 20 (20%) had a higher proportion of female than male faculty on that track type., Conclusions: Medical schools offering the CET type reported higher proportions of female faculty on that track type. Given that faculty on the CET type lag behind their TTT colleagues in academic promotion, these findings may contribute to continued challenges in gaining academic and leadership parity for women in academic medicine.

The characteristic features and applications of linear and nonlinear guided elastic waves propagating along surfaces (2D) and wedges (1D) are discussed. Laser-based excitation, detection, or contact-free analysis of these guided waves with pump-probe methods are reviewed. Determination of material parameters by broadband surface acoustic waves (SAWs) and other applications in nondestructive evaluation (NDE) are considered. The realization of nonlinear SAWs in the form of solitary waves and as shock waves, used for the determination of the fracture strength, is described. The unique properties of dispersion-free wedge waves (WWs) propagating along homogeneous wedges and of dispersive wedge waves observed in the presence of wedge modifications such as tip truncation or coatings are outlined. Theoretical and experimental results on nonlinear wedge waves in isotropic and anisotropic solids are presented., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In vivo effects of microperfusion of a GABA synthesis inhibitor (3-MPA) into the striatum and hippocampus on amino acid concentrations and electrical neuronal activity were investigated. Paradoxical elevations in GABA in the striatum (5-fold in anesthetized and 50-fold in awake rats) and hippocampus (2-fold in anesthetized and 15-fold in awake rats) were documented under steady-state concentrations of 3-MPA along with expected increases in glutamate (a 15-fold increase and a 250-fold increase in the striatum of anesthetized and awake rats, respectively; a 7-fold increase and a 25-fold increase in the hippocampus of anesthetized and awake rats, respectively). There was no clear epileptiform or seizure activity. Explanations for the paradoxical increase in GABA are offered, and emphasis is placed on the dependency of disinhibition on the model in which its effects are studied as well as on the prevailing level of activation of the probed network., (© 2013. Published by Elsevier Inc. All rights reserved.)

Fecal incontinence (FI) is a devastating disorder that is more prevalent than previously realized. FI is the involuntary loss of stool. Many factors contribute to the pathophysiology of FI, including advanced age, bowel irregularity, parity, and obesity. A detailed history and focused rectal examination are important to making the diagnosis and determining contributing causes. Although multiple diagnostic studies are available to assess the cause of FI, specific guidelines that delineate when testing should be done do not exist. Clinicians must weigh the risk, benefit, and burden of testing against the need for empiric treatment. All types of FI are initially managed in the same way, which includes lifestyle modification to reduce bowel derangements, improved access to toileting, and initiation of a bulking regimen to improve stool consistency. If initial conservative management fails, pharmaco-logic agents, biofeedback, or surgery may be indicated.

Plasmids have long been recognized as an important driver of DNA exchange and genetic innovation in prokaryotes. The success of plasmids has been attributed to their independent replication from the host's chromosome and their frequent self-transfer. It is thought that plasmids accumulate, rearrange and distribute nonessential genes, which may provide an advantage for host proliferation under selective conditions. In order to test this hypothesis independently of biases from culture selection, we study the plasmid metagenome from microbial communities in two activated sludge systems, one of which receives mostly household and the other chemical industry wastewater. We find that plasmids from activated sludge microbial communities carry among the largest proportion of unknown gene pools so far detected in metagenomic DNA, confirming their presumed role of DNA innovators. At a system level both plasmid metagenomes were dominated by functions associated with replication and transposition, and contained a wide variety of antibiotic and heavy metal resistances. Plasmid families were very different in the two metagenomes and grouped in deep-branching new families compared with known plasmid replicons. A number of abundant plasmid replicons could be completely assembled directly from the metagenome, providing insight in plasmid composition without culturing bias. Functionally, the two metagenomes strongly differed in several ways, including a greater abundance of genes for carbohydrate metabolism in the industrial and of general defense factors in the household activated sludge plasmid metagenome. This suggests that plasmids not only contribute to the adaptation of single individual prokaryotic species, but of the prokaryotic community as a whole under local selective conditions.