Projecting the economic burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study.

Background: The growing burden of chronic kidney disease (CKD) places substantial financial pressures on patients, healthcare systems, and society. An understanding of the costs attributed to CKD and kidney replacement therapy (KRT) is essential for evidence-based policy making. Inside CKD maps and projects the economic burden of CKD across 31 countries/regions from 2022 to 2027. Methods: A microsimulation model was developed that generated virtual populations using national demographics, relevant literature, and renal registries for the 31 countries/regions included. Patient-level country/region-specific cost data were extracted via a pragmatic local literature review and under advisement from local experts. Direct cost projections were generated for diagnosed CKD (by age, stage 3a-5), KRT (by modality), cardiovascular complications (heart failure, myocardial infarction, stroke), and comorbidities (hypertension, type 2 diabetes). Findings: For the 31 countries/regions, Inside CKD projected that annual direct costs (US$) of diagnosed CKD and KRT would increase by 9.3% between 2022 and 2027, from $372.0 billion to $406.7 billion. Annual KRT-associated costs were projected to increase by 10.0% from $169.6 billion to $186.6 billion between 2022 and 2027. By 2027, patients receiving KRT are projected to constitute 5.3% of the diagnosed CKD population but contribute 45.9% of the total costs. Interpretation: The economic burden of CKD is projected to increase from 2022 to 2027. KRT contributes disproportionately to this burden. Earlier diagnosis and proactive management could slow disease progression, potentially alleviating the substantial costs associated with later CKD stages. Data presented here can be used to inform healthcare resource allocation and shape future policy. Funding: AstraZeneca.

Corrigendum: Pilot report: objective quantification of trabecular meshwork pigmentation using densitometry and the NIDEK GS-1 gonioscope in glaucoma patients.

[This corrects the article DOI: 10.3389/fopht.2023.1322178.].

Flying microbes-survival in the extreme conditions of the stratosphere during a stratospheric balloon flight experiment.

Earth's stratosphere is characterized by hypobaric conditions, low temperatures, and high intensities of ultraviolet (UV) and cosmic radiation as well as low water and nutrient availability. While it is not considered a permanent habitat for microorganisms, they can be transported to the stratosphere by storms, volcanic action, or human activity. The impact of those extreme conditions on microorganisms and their survival were tested by sending a sample gondola to the stratosphere. The sample gondola was built to allow exposure of Bacillus subtilis endospores at different angles to the sun. It moreover had holders for three environmental samples to test the effect of stratospheric conditions on complex microbial communities. The gondola attached to a stratospheric balloon was launched near Kiruna, Sweden, ascended to ~25 km, and drifted eastward for ~200 km. Samples were exposed to pressures as low as 2 kPa and temperatures as low as -50°C as well as high UV radiation. Survival rates of B. subtilis were determined by comparing the numbers of colony-forming units (CFUs) for the different exposure angles. Survival was negatively correlated with exposure angle, indicating the significant impact of UV radiation. The effect of stratospheric conditions on environmental samples was assessed by comparing most probable numbers, microbial community composition, and substrate-use profiles to controls that had stayed on the ground. Cultivation was possible from all samples with survival rates of at least 1%, and differences in community composition were observed. Survival of environmental microorganisms might have been supported by the sample matrix, which provided protection from radiation and desiccation. IMPORTANCE: Earth's stratosphere is a hostile environment that has challenged microbial survival. We set out to test the effect of stratosphere exposure on survival of single species (Bacillus subtilis) and complex microbial communities from soils and sediment. B. subtilis survival was strongly impacted by sun exposure, i.e., ultraviolet (UV) radiation, with only 1% survival at full sun exposure. Complex microbial communities had high survival rates, and the soil or sediment matrix may have provided protection against radiation and desiccation, supporting the survival of environmental microorganisms.

Comparison of Ultrasound Attenuation Imaging Using a Linear versus a Conventional Convex Probe: A Volunteer Study.

The study aimed to investigate the feasibility of attenuation imaging (ATI) measurements using a linear probe on healthy volunteers and compare measurements with the conventional convex probe. Attenuation imaging measurements of the liver tissue were taken using ultrasound with a convex and a linear probe in 33 volunteers by two examining doctors, and the measurements were repeated 4-5 weeks later by one of them. The ATI values for the linear probe were in the range of the values for the convex probe for both examiners. Measurements did not change significantly for 32 out of 33 volunteers after 4-5 weeks when using the linear probe. The size of the region of interest (ROI) only impacted the ATI values for the convex probe; it did not affect the values taken with the linear probe. Healthy volunteers were measured, and their attenuation values were compared to those from a convex probe, commonly used in steatosis evaluation. When both probes were positioned in the same liver area, they showed good agreement in attenuation values, though depth significantly affected the measurements, with both probes providing different values at different depths. The study's results aligned with previous research using the same system. Operator A and B's results were compared, demonstrating similar ranges of values for both probes. The linear probe has been demonstrated to allow for superficial measurements and attain ATI values in line with that of the convex probe in the liver.

Modelling atopic dermatitis in healthy human skin for the characterization of topical compounds.

Suitable human models for the development and characterization of topical compounds for inflammatory skin diseases such as atopic dermatitis are not readily available to date. We describe here the development of a translational model involving healthy human skin mimicking major aspects of AD and its application for the characterization of topical Janus kinase inhibitors. Full thickness human abdominal skin obtained from plastic surgery stimulated in vitro with IL4 and IL13 shows molecular features of AD. This is evidenced by STAT6 phosphorylation assessed by immunohistochemistry and analysis of skin lysates. Broad transcriptome changes assessed by AmpliSeq followed by gene set variation analysis showed a consistent upregulation of gene signatures characterizing AD in this model. Topical application of experimental formulations of compounds targeting the JAK pathway to full thickness skin normalizes the molecular features of AD induced by IL4 and IL13 stimulation. The inhibitory effects of topical JAK inhibitors on molecular features of AD are supported by pharmacokinetic analysis. The model described here is suited for the characterization of topical compounds for AD and has the potential to be extended to other inflammatory skin diseases and pathophysiological pathways.

A Universal Cognitive Bias in Word Order: Evidence From Speakers Whose Language Goes Against It.

There is a long-standing debate in cognitive science surrounding the source of commonalities among languages of the world. Indeed, there are many potential explanations for such commonalities-accidents of history, common processes of language change, memory limitations, constraints on linguistic representations, and so on. Recent research has used psycholinguistic experiments to provide empirical evidence linking common linguistic patterns to specific features of human cognition, but these experiments tend to use English speakers, who in many cases have direct experience with the common patterns of interest. Here we highlight the importance of testing populations whose languages go against cross-linguistic trends. We investigate whether adult monolingual speakers of Kîîtharaka, which has an unusual way of ordering words, mirror the word-order preferences of English speakers. We find that they do, supporting the hypothesis that universal cognitive representations play a role in shaping word order.

Confounders of Ultrasound Attenuation Imaging in a Linear Probe Using the Canon Aplio i800 System: A Phantom Study.

There have been studies showing attenuation imaging (ATI) with ultrasound as an approach to diagnose liver diseases such as steatosis or cirrhosis. So far, this technique has only been used on a convex probe. The goal of the study was to investigate the feasibility of ATI measurements using the linear array on a canon Aplio i800 scanner on certified phantoms. Three certified liver tissue attenuation phantoms were measured in five different positions using a linear probe. The effects of positioning and depth were explored and compared. The values were compared to the certified expected value for each phantom as well as the different measurement values for each measurement position. The ATI measurements on phantoms showed significant effect for the different probe positions and region of interest (ROI) depths. Values taken in the center with the probe perpendicular to the phantom were closest to certified values. Median values at 2.5-4.5 cm depth for phantoms 1 and 2 and 0.5-2.5 cm for phantom 3 were comparable with certified values. Measurements taken at a depth greater than 6 cm in any position were the least representative of the certified values (p-value < 0.01) and had the widest range throughout the different sessions. ATI measurements can be performed with the linear probe in phantoms; however, careful consideration should be given to depth dependency, as it can significantly affect measurement values. Remaining measurements at various depths within the 0.5-6.0 cm range showed deviation from the certified values of approximately 25%.

Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.

Orofacial clefts of the lip and palate are widely recognized to result from complex gene-environment interactions, but inadequate understanding of environmental risk factors has stymied development of prevention strategies. We interrogated the role of DNA methylation, an environmentally malleable epigenetic mechanism, in orofacial development. Expression of the key DNA methyltransferase enzyme DNMT1 was detected throughout palate morphogenesis in the epithelium and underlying cranial neural crest cell (cNCC) mesenchyme, a highly proliferative multipotent stem cell population that forms orofacial connective tissue. Genetic and pharmacologic manipulations of DNMT activity were then applied to define the tissue- and timing-dependent requirement of DNA methylation in orofacial development. cNCC-specific Dnmt1 inactivation targeting initial palate outgrowth resulted in OFCs, while later targeting during palatal shelf elevation and elongation did not. Conditional Dnmt1 deletion reduced cNCC proliferation and subsequent differentiation trajectory, resulting in attenuated outgrowth of the palatal shelves and altered development of cNCC-derived skeletal elements. Finally, we found that the cellular mechanisms of cleft pathogenesis observed in vivo can be recapitulated by pharmacologically reducing DNA methylation in multipotent cNCCs cultured in vitro. These findings demonstrate that DNA methylation is a crucial epigenetic regulator of cNCC biology, define a critical period of development in which its disruption directly causes OFCs, and provide opportunities to identify environmental influences that contribute to OFC risk.

A Modular Turn-On Strategy to Profile E2-Specific Ubiquitination Events in Living Cells.

A cascade of three enzymes, E1-E2-E3, is responsible for transferring ubiquitin to target proteins, which controls many different aspects of cellular signaling. The role of the E2 has been largely overlooked, despite influencing substrate identity, chain multiplicity, and topology. Here we report a method-targeted charging of ubiquitin to E2 (tCUbE)-that can track a tagged ubiquitin through its entire enzymatic cascade in living mammalian cells. We use this approach to reveal new targets whose ubiquitination depends on UbcH5a E2 activity. We demonstrate that tCUbE can be broadly applied to multiple E2s and in different human cell lines. tCUbE is uniquely suited to examine E2-E3-substrate cascades of interest and/or piece together previously unidentified cascades, thereby illuminating entire branches of the UPS and providing critical insight that will be useful for identifying new therapeutic targets in the UPS.

Manuka oil based ECMT-154 versus vehicle control for the topical treatment of eczema: study protocol for a randomised controlled trial in community pharmacies in Aotearoa New Zealand.

BACKGROUND: Eczema is a chronic, relapsing skin condition commonly managed by emollients and topical corticosteroids. Prevalence of use and demand for effective botanical therapies for eczema is high worldwide, however, clinical evidence of benefit is limited for many currently available botanical treatment options. Robustly-designed and adequately powered randomised controlled trials (RCTs) are essential to determine evidence of clinical benefit. This protocol describes an RCT that aims to investigate whether a manuka oil based emollient cream, containing 2% ECMT-154, is a safe and effective topical treatment for moderate to severe eczema. METHODS: This multicentre, single-blind, parallel-group, randomised controlled trial aims to recruit 118 participants from community pharmacies in Aotearoa New Zealand. Participants will be randomised 1:1 to receive topical cream with 2% ECMT-154 or vehicle control, and will apply assigned treatment twice daily to affected areas for six weeks. The primary outcome is improvement in subjective symptoms, assessed by change in POEM score. Secondary outcomes include change in objective symptoms assessed by SCORAD (part B), PO-SCORAD, DLQI, and treatment acceptability assessed by TSQM II and NRS. DISCUSSION: Recruitment through community pharmacies commenced in January 2022 and follow up will be completed by mid-2023. This study aims to collect acceptability and efficacy data of manuka oil based ECMT-154 for the treatment of eczema. If efficacy is demonstrated, this topical may provide an option for a novel emollient treatment. The community-based design of the trial is anticipated to provide a generalisable result. ETHICS AND DISSEMINATION: Ethics approval was obtained from Central Health and Disability Ethics Committee (reference: 2021 EXP 11490). Findings of the study will be disseminated to study participants, published in peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001096842. Registered on August 18, 2021 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382412&isReview=true ). PROTOCOL VERSION: 2.1 (Dated 18/05/2022).

Preventing liver disease with policy measures to tackle alcohol consumption and obesity: The HEPAHEALTH II study.

BACKGROUND & AIMS: Chronic liver disease (CLD) causes 1.8% of all deaths in Europe, many of them from liver cancer. We estimated the impact of several policy interventions in France, the Netherlands, and Romania. METHODS: We used a validated microsimulation model to assess seven different policy scenarios in 2022-2030: a minimum unit price (MUP) of alcohol of €0.70 or €1, a volumetric alcohol tax, a sugar-sweetened beverage (SSB) tax, food marketing restrictions, plus two different combinations of these policies compared against current policies (the 'inaction' scenario). RESULTS: All policies reduced the burden of CLD and liver cancer. The largest impact was observed for a MUP of €1, which by 2030 would reduce the cumulative incidence of CLD by between 7.1% to 7.3% in France, the Netherlands, and Romania compared with inaction. For liver cancer, the corresponding reductions in cumulative incidence were between 4.8% to 5.8%. Implementing a package containing a MUP of €0.70, a volumetric alcohol tax, and an SSB tax would reduce the cumulative incidence of CLD by between 4.29% to 4.71% and of liver cancer by between 3.47% to 3.95% in France, the Netherlands, and Romania. The total predicted reduction in healthcare costs by 2030 was greatest with the €1 MUP scenario, with a reduction for liver cancer costs of €8.18M and €612.49M in the Netherlands and France, respectively. CONCLUSIONS: Policy measures tackling primary risk factors for CLD and liver cancer, such as the implementation of a MUP of €1 and/or a MUP of €0.70 plus SSB tax could markedly reduce the number of Europeans with CLD or liver cancer. IMPACT AND IMPLICATIONS: Policymakers must be aware that alcohol and obesity are the two leading risk factors for chronic liver disease and liver cancer in Europe and both are expected to increase in the future if no policy interventions are made. This study assessed the potential of different public health policy measures to mitigate the impact of alcohol consumption and obesity on the general population in three European countries: France, the Netherlands, and Romania. The findings support introducing a €1 minimum unit price for alcohol to reduce the burden of chronic liver disease. In addition, the study shows the importance of targeting multiple drivers of alcohol consumption and obesogenic products simultaneously via a harmonized fiscal policy framework, to complement efforts being made within health systems. These findings should encourage policymakers to introduce such policy measures across Europe to reduce the burden of liver disease. The modeling methods used in this study can assist in structuring similar modeling in other regions to expand on this study's findings.

Understanding the needs of women undergoing breast ultrasound: Are male radiologists still needed?

INTRODUCTION: A trend towards less male radiologists specializing in breast ultrasound was observed. A common notion in the field of breast radiology is, that female patients feel more comfortable being treated by female radiologists. The aim of the study was to understand and report the needs of women undergoing breast ultrasound with regards to the sex of the radiologist performing the investigation. METHODS: Informed consent was obtained from all patients prior to inclusion in a prospective bi-center quality study. At center 1 (72 patients), the women were examined exclusively by female radiologists, at center 2 (100 patients) only by male radiologists. After the examination the patients were asked about their experiences and their wishes for the future. RESULTS: Overall, women made no distinction between female and male radiologists; 25% of them wanted a female radiologist and 1.2% wanted a male radiologist. The majority (74%) stated that it made no difference whether a female or male radiologist performed the examination. The majority of women in group 2, who were investigated exclusively by male radiologists, stated that they had no preferences with regard to the sex of the radiologist (93%); 5% of the women wished to be investigated solely by a female radiologist and 2% exclusively by a male radiologist. DISCUSSION: The majority of women undergoing breast ultrasound are unconcerned about the radiologist's sex. It would appear that women examined by male radiologists are less selective about the sex of the examining radiologist. TRIAL REGISTRATION: Written informed consent was obtained from all patients. All patient data were anonymized. The physicians had no access to any further personal data. National regulations did not require dedicated ethics approval with anonymized lists or retrospective questionnaires.

Pharmacokinetic analysis of acute and dietary exposure to piperonyl butoxide in the mouse.

Piperonyl butoxide (PBO) is a popular insecticide synergist present in thousands of commercial, agricultural, and household products. PBO inhibits cytochrome P450 activity, impairing the ability of insects to detoxify insecticides. PBO was recently discovered to also inhibit Sonic hedgehog signaling, a pathway required for embryonic development, and rodent studies have demonstrated the potential for in utero PBO exposure to cause structural malformations of the brain, face, and limbs, or more subtle neurodevelopmental abnormalities. The current understanding of the pharmacokinetics of PBO in mice is limited, particularly with respect to dosing paradigms associated with developmental toxicity. To establish a pharmacokinetic (PK) model for oral exposure, PBO was administered to female C57BL/6J mice acutely by oral gavage (22-1800 mg/kg) or via diet (0.09 % PBO in chow). Serum and adipose samples were collected, and PBO concentrations were determined by HPLC-MS/MS. The serum concentrations of PBO were best fit by a linear one-compartment model. PBO concentrations in visceral adipose tissue greatly exceeded those in serum. PBO concentrations in both serum and adipose tissue decreased quickly after cessation of dietary exposure. The elimination half-life of PBO in the mouse after gavage dosing was 6.5 h (90 % CI 4.7-9.5 h), and systemic oral clearance was 83.3 ± 20.5 mL/h. The bioavailability of PBO in chow was 41 % that of PBO delivered in olive oil by gavage. Establishment of this PK model provides a foundation for relating PBO concentrations that cause developmental toxicity in the rodent models to Sonic hedgehog signaling pathway inhibition.

From entertainment to extortion: Tunisian children's online experiences.

BACKGROUND: Information and communication technologies (ICTs) have become a fundamental part of children's lives and development. However, children need to acquire the skills and knowledge to manage the risks that technology presents. OBJECTIVES: This child-centric research on children's online experiences aims to understand the benefits Tunisian children derive from the internet, the risks and harms to which they are exposed, and how aware and resilient Tunisian children are to these online risks and harms. PARTICIPANTS AND SETTING: 113 children, aged 13-17, participated in focus groups in five governorates across Tunisia. METHODS: Qualitative data was collected from 16 focus group discussions then data was analyzed using inductive and deductive thematic coding. RESULTS: The internet offers Tunisian children educational, social, entertainment, and mental health benefits, in addition to personal development and commercial opportunities. Hacking and the use of fake Facebook profiles were highlighted as facilitators of online bullying, sexual harassment, and extortion, all of which disproportionately affected girls. Children demonstrated personal responsibility for their online activity but recognized that children and parents should have greater awareness about the risks the internet poses. CONCLUSIONS: The young people included in the study reported that they enjoy numerous benefits from internet access and demonstrate some resilience to online risks and harms. However, there is a need for societal and institutional change, through a combination of awareness raising, targeted support for children and parents, and improving the capacity of key actors to prevent online violence while ensuring an effective response and victim support.

External validation of a multivariable prediction model for identification of pneumonia and other serious bacterial infections in febrile immunocompromised children.

OBJECTIVE: To externally validate and update the Feverkids tool clinical prediction model for differentiating bacterial pneumonia and other serious bacterial infections (SBIs) from non-SBI causes of fever in immunocompromised children. DESIGN: International, multicentre, prospective observational study embedded in PErsonalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union (PERFORM). SETTING: Fifteen teaching hospitals in nine European countries. PARTICIPANTS: Febrile immunocompromised children aged 0-18 years. METHODS: The Feverkids clinical prediction model predicted the probability of bacterial pneumonia, other SBI or no SBI. Model discrimination, calibration and diagnostic performance at different risk thresholds were assessed. The model was then re-fitted and updated. RESULTS: Of 558 episodes, 21 had bacterial pneumonia, 104 other SBI and 433 no SBI. Discrimination was 0.83 (95% CI 0.71 to 0.90) for bacterial pneumonia, with moderate calibration and 0.67 (0.61 to 0.72) for other SBIs, with poor calibration. After model re-fitting, discrimination improved to 0.88 (0.79 to 0.96) and 0.71 (0.65 to 0.76) and calibration improved. Predicted risk <1% ruled out bacterial pneumonia with sensitivity 0.95 (0.86 to 1.00) and negative likelihood ratio (LR) 0.09 (0.00 to 0.32). Predicted risk >10% ruled in bacterial pneumonia with specificity 0.91 (0.88 to 0.94) and positive LR 6.51 (3.71 to 10.3). Predicted risk <10% ruled out other SBIs with sensitivity 0.92 (0.87 to 0.97) and negative LR 0.32 (0.13 to 0.57). Predicted risk >30% ruled in other SBIs with specificity 0.89 (0.86 to 0.92) and positive LR 2.86 (1.91 to 4.25). CONCLUSION: Discrimination and calibration were good for bacterial pneumonia but poorer for other SBIs. The rule-out thresholds have the potential to reduce unnecessary investigations and antibiotics in this high-risk group.

Characterization of Chiral Nanostructured Surfaces Made via Colloidal Lithography.

Optically anisotropic materials were produced via colloidal lithography and characterized using scanning electronic microscopy (SEM), confocal microscopy, and polarimetry. A compact hexagonal array mask composed of silica sub-micron particles was fabricated via the Langmuir-Blodgett self-assembly technique. Subsequently, the mask pattern was transferred onto monocrystalline silicon and commercial glass substrates using ion beam etching in a vacuum. Varying the azimuthal angle while etching at oblique incidence carved screw-like shaped pillars into the substrates, resulting in heterochiral structures depending on the azimuthal angle direction. To enhance the material's optical properties through plasmon resonance, gold films were deposited onto the pillars. Polarimetric measurements were realized at normal and oblique incidences, showing that the etching directions have a clear influence on the value of the linear birefringence and linear dichroism. The polarimetric properties, especially the chiroptical responses, increased with the increase in the angle of incidence.

Increased In Vivo Exposure of N-(4-Hydroxyphenyl) Retinamide (4-HPR) to Achieve Plasma Concentrations Effective against Dengue Virus.

N-(4-hydroxyphenyl) retinamide (4-HPR, or fenretinide) has promising in vitro and in vivo antiviral activity against a range of flaviviruses and an established safety record, but there are challenges to its clinical use. This study evaluated the in vivo exposure profile of a 4-HPR dosage regime previously shown to be effective in a mouse model of severe dengue virus (DENV) infection, comparing it to an existing formulation for human clinical use for other indications and developed/characterised self-emulsifying lipid-based formulations of 4-HPR to enhance 4-HPR in vivo exposure. Pharmacokinetic (PK) analysis comprising single-dose oral and IV plasma concentration-time profiles was performed in mice; equilibrium solubility testing of 4-HPR in a range of lipids, surfactants and cosolvents was used to inform formulation approaches, with lead formulation candidates digested in vitro to analyse solubilisation/precipitation prior to in vivo testing. PK analysis suggested that effective plasma concentrations could be achieved with the clinical formulation, while novel lipid-based formulations achieved > 3-fold improvement. Additionally, 4-HPR exposure was found to be limited by both solubility and first-pass intestinal elimination but could be improved through inhibition of cytochrome P450 (CYP) metabolism. Simulated exposure profiles suggest that a b.i.d dosage regime is likely to maintain 4-HPR above the minimum effective plasma concentration for anti-DENV activity using the clinical formulation, with new formulations/CYP inhibition viable options to increase exposure in the future.

Bilingual phonological contrast perception: The influence of Quanzhou Southern Min on Mandarin non-sibilant fricative discrimination.

This study explores the discrimination of Mandarin non-sibilant fricatives by bilingual speakers (N = 40) of Quanzhou Southern Min (L1) and Mandarin (L2) in different phonological contexts, including rounded vowels and the glide [w]. The results of the ABX discrimination task indicate significant contextual effects of the following sound, in line with predictions based on the Perceptual Assimilation model (PAM) [Best (1995). J. Phon. 20(3), 305-330]. Additionally, the observed result could not be fully explained by the acoustic distance between stimuli, and discrimination ability was better for speakers with more exposure to and use of Mandarin.

Influence of Measurement Depth and Acquisition Parameters on Shear Wave Speed and Shear Wave Dispersion in Certified Phantoms Using a Canon Aplio Clinical Ultrasound Scanner.

OBJECTIVE: The aim of the work described here was to investigate the relative contribution of confounding factors on liver shear wave speed (SWS) and shear wave dispersion slope (SWDS) measurements in three certified phantoms using a Canon Aplio clinical ultrasound scanner. METHODS: A Canon Aplio i800 i-series ultrasound system (Canon Medical Systems Corporation, Otawara, Tochigi, Japan) with i8CX1 convex array (center frequency = 4 MHz) was used to examine dependencies caused by the depth, width and height of the acquisition box (AQB), the depth and size of the region of interest (ROI), the AQB angle and the pressure of the ultrasound probe on the surface of the phantom. RESULTS: Results revealed that depth is the most significant confounder in both SWS and SWDS measurements. AQB angle, height and width and ROI size exhibited minimal confounding effects on measurements. For SWS, the most consistent measurement depth is when the top of the AQB is placed between 2 and 4 cm, and the ROI is located between 3 and 7 cm deep. For SWDS, results indicate that measurement values significantly decrease with depth from the surface of the phantom until approximately 7 cm deep, and consequently no stable area of AQB placement or ROI depth exists. CONCLUSION: In contrast to SWS, the same ideal acquisition depth range cannot necessarily be applied to SWDS measurements because of a significant depth dependency.

A New Interpretation of Relative Importance on an Analysis of Per and Polyfluorinated Alkyl Substances (PFAS) Exposures on Bone Mineral Density.

BACKGROUND: The relative contribution of environmental contaminants is an important, and frequently unanswered, question in human or ecological risk assessments. This interpretation of relative importance allows determination of the overall effect of a set of variables relative to other variables on an adverse health outcome. There are no underlying assumptions of independence of variables. The tool developed and used here is specifically designed for studying the effects of mixtures of chemicals on a particular function of the human body. METHODS: We apply the approach to estimate the contributions of total exposure to six PFAS (perfluorodecanoic acid, perfluorohexane sulfonic acid, 2-(N-methyl-PFOSA) acetate, perfluorononanoic acid, perfluoroundecanoic acid and perfluoroundecanoic acid) to loss of bone mineral density relative to other factors related to risk of osteoporosis and bone fracture, using data from subjects who participated in the US National Health Examination and Nutrition Surveys (NHANES) of 2013-2014. RESULTS: PFAS exposures contribute to bone mineral density changes relative to the following variables: age, weight, height, vitamin D2 and D3, gender, race, sex hormone binding globulin, testosterone, and estradiol. CONCLUSION: We note significant alterations to bone mineral density among more highly exposed adults and significant differences in effects between men and women.