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Abstract Background We assessed the hemodynamic performance of various prostheses and the clinical outcomes after aortic valve replacement, in different age groups. Methods One-hundred-and-twenty patients with isolated aortic valve stenosis were included in this prospective randomized randomised trial and allocated in three age-groups to receive either pulmonary autograft (PA, n = 20) or mechanical prosthesis (MP, Edwards Mira n = 20) in group 1 (age < 55 years), either stentless bioprosthesis (CE Prima Plus n = 20) or MP (Edwards Mira n = 20) in group 2 (age 55-75 years) and either stentless (CE Prima Plus n = 20) or stented bioprosthesis (CE Perimount n = 20) in group 3 (age > 75). Clinical outcomes and hemodynamic performance were evaluated at discharge, six months and one year. Results In group 1, patients with PA had significantly lower mean gradients than the MP (2.6 vs. 10.9 mmHg, p = 0.0005) with comparable left ventricular mass regression (LVMR). Morbidity included 1 stroke in the PA population and 1 gastrointestinal bleeding in the MP subgroup. In group 2, mean gradients did not differ significantly between both populations (7.0 vs. 8.9 mmHg, p = 0.81). The rate of LVMR and EF were comparable at 12 months; each group with one mortality. Morbidity included 1 stroke and 1 gastrointestinal bleeding in the stentless and 3 bleeding complications in the MP group. In group 3, mean gradients did not differ significantly (7.8 vs 6.5 mmHg, p = 0.06). Postoperative EF and LVMR were comparable. There were 3 deaths in the stented group and no mortality in the stentless group. Morbidity included 1 endocarditis and 1 stroke in the stentless compared to 1 endocarditis, 1 stroke and one pulmonary embolism in the stented group. Conclusions Clinical outcomes justify valve replacement with either valve substitute in the respective age groups. The PA hemodynamically outperformed the MPs. Stentless valves however, did not demonstrate significantly superior hemodynamics or outcomes in comparison to stented bioprosthesis or MPs.

Abstract Background The mental gland pheromone of male Plethodon salamanders contains two main protein components: a 22 kDa protein named Plethodon Receptivity Factor (PRF) and a 7 kDa protein named Plethodon Modulating Factor (PMF), respectively. Each protein component individually has opposing effects on female courtship behavior, with PRF shortening and PMF lengthening courtship. In this study, we test the hypothesis that PRF or PMF individually activate vomeronasal neurons. The agmatine-uptake technique was used to visualize chemosensory neurons that were activated by each protein component individually. Results Vomeronasal neurons exposed to agmatine in saline did not demonstrate significant labeling. However, a population of vomeronasal neurons was labeled following exposure to either PRF or PMF. When expressed as a percent of control level labeled cells, PRF labeled more neurons than did PMF. These percentages for PRF and PMF, added together, parallel the percentage of labeled vomeronasal neurons when females are exposed to the whole pheromone. Conclusion This study suggests that two specific populations of female vomeronasal neurons are responsible for responding to each of the two components of the male pheromone mixture. These two neural populations, therefore, could express different receptors which, in turn, transmit different information to the brain, thus accounting for the different female behavior elicited by each pheromone component.

Background: Bovine lactoferrin is increasingly being used as an ingredient in infant formula manufacture to enhance nutritional efficacy through the provision of growth, immunoprotective, and antimicrobial factors to the neonate., Objective: To evaluate method reproducibility of AOAC First Action Official Method 2021.07 for compliance with the performance requirements described in Standard Method Performance Requirement (SMPR®) 2020.005., Methods: Eight laboratories participated in the analysis of blind-duplicate samples of seven nutritional products. Samples were diluted in buffer, and an optical biosensor immunoassay was used in a direct-assay format to quantitate bovine lactoferrin by its interaction with an immobilized anti-lactoferrin antibody. Quantitation was accomplished by the external standard technique with interpolation from a four-parameter calibration regression., Results: After outliers were removed, precision as reproducibility was found to be within limits set in SMPR 2020.005 (≤ 9%) for six out of seven samples and all had acceptable Horwitz Ratio (HorRatR) values ranging from 1.0 to 2.1. Additionally, comparison with an alternative independent Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) First Action method (heparin cleanup LC-UV), showed negligible difference between results., Conclusion: The method described is suitable for the quantification of intact, undenatured bovine lactoferrin in powdered infant formulas. The SPIFAN Expert Review Panel evaluated the method and accompanying validation data from this multi-laboratory testing (MLT) study in July 2023 and recommended Official Method 2021.07 for adoption as a Final Action Official MethodSM., Highlights: A multi-laboratory validation study of an automated optical biosensor immunoassay for the determination of intact, undenatured bovine lactoferrin is described., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rationale: Twenty-one Community Rehabilitation Companies were set up following the division of the National Probation Services during 'Transforming Rehabilitation' in England and Wales, under a 2013 Ministry of Justice initiative. Reunification commenced in 2018. A study completed prior to these changes suggested that probation officers had had little training in recognising attention-deficit hyperactivity disorder (ADHD) and may have been underestimating its prevalence among their clientele. Given the substantial changes in probation staffing and organisation since 2018, a new study seems warranted., Aims: The aim of the study was to understand experiences of people under a community sentence who reported having ADHD and of probation staff working with them., Methods: Using a qualitative research design, one-to-one semi-structured interviews were conducted with client facing probation staff recruited from one Community Rehabilitation Company. Service users undertaking a community sentence who had been diagnosed with or self-identified as having ADHD were then identified and recruited by these staff; those who consented were also interviewed. Transcripts were analysed using a thematic analytic approach., Results: Thirteen probation staff and six male offenders under community sentences, agreed to participate and completed interviews. The overarching themes emerging from the two groups were similar, both reflecting on descriptions of ADHD; treatment of ADHD; experiences of having or working with ADHD in the wider community and in the criminal justice system specifically and visions of future support needs tied to the order. In addition, probation officers specifically raised the matter of payment by results. Both service users and probation staff identified gaps in knowledge, experience and services, but areas of good practice were also identified., Conclusion: The findings highlight the continuing under-acknowledgement of tailored clinical support for people serving a community sentence who have ADHD together with a lack of support and training about ADHD for probation staff. Return to the national organisation of probation services and recognition of need for a range of relevant skills offers a great opportunity for re-evaluating supervision and management of offenders under community sentences who have ADHD. These findings provide the basis for a template for developing knowledge and support provision for probation staff to recognise ADHD, or its likelihood, and their capacity to follow through with appropriately informed personalised supervision plans and access to specialist service advice and support., (© 2024 John Wiley & Sons Ltd.)

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'IX: people and places-diverse populations and locations of care', authors address the following themes: 'LGBTQIA+health in family medicine', 'A family medicine approach to substance use disorders', 'Shameless medicine for people experiencing homelessness', '''Difficult" encounters-finding the person behind the patient', 'Attending to patients with medically unexplained symptoms', 'Making house calls and home visits', 'Family physicians in the procedure room', 'Robust rural family medicine' and 'Full-spectrum family medicine'. May readers appreciate the breadth of family medicine in these essays., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Peripheral artery disease is known to affect males and females in different proportions. Disparate surgical outcomes have been quantified after endovascular aortic aneurysm repair, arteriovenous fistula creation, and treatment of critical limb ischemia. The aim of this study is to objectively quantify the sex differences in outcomes in patients undergoing open surgical intervention for aortoiliac occlusive disease., Methods: Patients were identified in the aortoiliac occlusive disease Vascular Quality Initiative database who underwent aorto-bifemoral bypass or aortic thromboendarterectomy as determined by Current Procedural Terminology codes between 2012 and 2019. Patients with a minimum of 1-year follow-up were included. Risk differences (RDs) by sex were calculated using a binomial regression model in 30-day and 1-year incidence of mortality and limb salvage. Additionally, incidence of surgical complications including prolonged length of stay (>10 days), reoperation, and change in renal function (>0.5 mg/dl rise from baseline), were recorded. Inverse probability weighting was used to standardize demographic and medical history characteristics. Multivariate logistic regression models were employed to conduct analyses of the before mentioned clinical outcomes, controlling for known confounders., Results: Of 16,218 eligible patients from the VQI data during the study period, 6538 (40.3%) were female. The mean age, body mass index, and race were not statistically different between sexes. Although there was no statistically significant difference detected in mortality between males and females at 30 days postoperatively, females had an increased crude 1-year mortality with an RD of 0.014 (95% confidence interval, 0.01-0.02; P value < .001. Males had a higher rate of a postoperative change in renal function with an RD of -0.02 (95% confidence interval, -0.03 to -0.01; P < .001)., Conclusions: Although there was no sex-based mortality difference at 30 days, there was a statistically significant increase in mortality in females after open aortoiliac intervention at 1 year based on our weighted model. Male patients are statistically significantly more likely to have a decline in renal function after their procedures when compared with females. Postoperative complications including prolonged hospital stay, reoperation, and wound disruption were similar among the sexes, as was limb preservation rates at 1 year. Further studies should focus on elucidating the underlying factors contributing to sex-based differences in clinical outcomes following aortoiliac interventions., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Taurine is recognized as an essential growth factor and as being critical in the maintenance of functional tissue regulation., Objective: To evaluate the analytical performance of a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for compliance with AOAC Standard Method Performance Requirements (SMPR®) for taurine analysis described in SMPR 2014.013., Method: Following protein precipitation with Carrez solutions, taurine is extracted and separated by HILIC with detection by triple quadrupole MS using multiple reaction monitoring (MRM). Stable isotope labeled (SIL) taurine internal standard is used for quantification to correct for losses in extraction and variations in ionization in the ion source., Results: The method was shown to meet the requirements specified in the SMPR with a linear range of 0.27-2700 mg/hg RTF (ready-to-feed), a limit of detection of 0.14 mg/hg RTF, acceptable recovery of 97.2-100.1%, and acceptable repeatability of 1.6-6.4% relative standard deviation. Additionally, the method was found to have no statistically significant bias compared with reference values for National Institute of Standards and Technology (NIST) 1849a certified reference material (CRM) (P-value = 0.95) and 1869 CRM (P-value = 0.31), and with results from AOAC 997.05 (P-value = 0.10)., Conclusions: A recent review of the method and validation data by the Stakeholder Program on Infant Formula and Adult Nutritionals (SPIFAN) Expert Review Panel (ERP) found that this method met all the criteria for analysis of taurine specified in SMPR 2014.013 and voted to adopt this method as First Action AOAC Official MethodSM2022.03., Highlights: A method for the analysis of taurine in infant formulas and adult nutritionals by HILIC-MS/MS is described. A single-laboratory validation (SLV) study demonstrated the applicability of the method to meet requirements of SMPR 2014.013. In December 2022, the SPIFAN ERP voted to adopt this method as First Action AOAC Official Method 2022.03., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Aflatoxin M1 (AFM1) is found in the milk of cows exposed to feed spoiled by Aspergillus fungi species. These fungi may produce the secondary metabolite aflatoxin B1, which is converted in the cow liver by hydroxylation to AFM1 and is then expressed in milk. AFM1 is regulated in milk and other dairy products because it can cause serious health issues, such as liver and kidney cancers, in humans and is an immunosuppressant., Objective: To optimize the chromatographic protocol and to extend the matrix scope to include a wider range of dairy products: whey powder, whey protein concentrate, whey protein isolate, liquid milk, skim milk powder, whole milk powder, adult nutritional products, and yogurt., Methods: AFM1 is extracted using 1% acetic acid in acetonitrile incorporating ionic salts. The AFM1 in the resulting extract is concentrated using an automated RIDA®CREST IMMUNOPREP® online cartridge coupled to quantification by HPLC-fluorescence., Results: The method was shown to be accurate, with acceptable recovery (81.2-97.1%) from spiked samples. Acceptable precision was confirmed, with a relative standard deviation (RSD) for repeatability of 6.6-11.2% and an RSD for intermediate precision of 7.5-16.7%. Method LOD and robustness experiments further demonstrated the suitability of this method for routine compliance testing. Analysis of an international proficiency trial sample generated results that were comparable with the value assigned from alternative independent methods., Conclusion: A method with improved chromatography for high-throughput, routine testing of AFM1 in an extended range of dairy products is described. The method was subjected to single-laboratory validation and was found to be accurate, precise, and fit for purpose., Highlights: Single-laboratory validation of an automated online immunoaffinity cleanup fluorescence HPLC method for AFM1 in whey proteins, milk powders, nutritional products, liquid milk, and yogurt. Allows for high-throughput analysis of AFM1 with enhanced chromatographic performance. Method applicable to the analysis of AFM1 in an extended range of milk and milk-based products., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Taurine is recognized as an essential growth factor and as being critical in the maintenance of functional tissue regulation., Objective: A rapid compliance method for the analysis of taurine that is applicable to infant formula and milk-based nutritional products is described., Method: Following protein precipitation with Carrez solutions, taurine in the sample extract is separated by hydrophilic interaction liquid chromatography (HILIC) with detection by triple quadrupole mass spectrometry using multiple reaction monitoring (MRM). Stable isotope-labeled taurine internal standard is used for quantification to correct for losses in extraction and variations in ionization in the ion source., Results: The method was shown to be accurate, with acceptable recovery of 99.6% (range = 91.1-106.5%). Results for National Institute of Standards and Technology (NIST)-certified reference materials showed no statistical bias for NIST 1849a (P = 0.96) and NIST 1869 (P = 0.88) when compared with reference values. No bias was found when results were compared with those of an international reference method, AOAC Official MethodSM997.05 (P = 0.18). Repeatability was estimated to be 3.1% RSDr (range: 2.4-4.0%, HorRat: 0.3), and intermediate precision was estimated to be 4.9% RSDiR (range: 2.2-7.7%)., Conclusions: Successful single-laboratory validation demonstrates that this rapid method is suitable for use in high-throughput laboratories as part of routine product compliance release testing of taurine in nutritional products., Highlights: A method for the analysis of taurine in infant formula and adult nutritionals by hydrophilic interaction liquid chromatography-mass spectrometry (LC-MS) is described. The method is suitable for use in high-throughput laboratories for routine product compliance testing of taurine. A single-laboratory validation study demonstrated the method to be accurate, precise, and fit for purpose., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The traditionally reported outcomes for patients with ischemic wounds have centered on amputation-free survival. However, that discounts the importance of other patient-centered outcomes such as the wound healing time (WHT) and wound-free period (WFP). We evaluated the long-term wound outcomes of patients treated for chronic limb-threatening ischemia at our institution., Methods: From 2014 to 2017, we identified all patients with chronic limb-threatening ischemia and ischemic wounds using symptomatic and hemodynamic criteria. The primary data included the wound size, wound location, WIfI (wound, ischemia, foot infection) grade, WHT, WFP, minor and major amputation, and death. Wounds were not considered healed if the patient had required a major amputation or had died before wound healing. The WHT was calculated as the interval in days between the diagnosis and determination of a healed wound. The WFP was calculated as the interval in days between a healed wound and wound recurrence, major amputation, death, or the end of the study period. A comparison of the wound healing parameters stratified by revascularization status was performed using the Student t test. A generalized linear model adjusted for age, sex, initial wound size, and WIfI grade was used to evaluate the risk of wound healing with and without revascularization., Results: A total of 256 patients had presented with 372 wounds. Of the 256 patients, 48% had undergone revascularization. During the study period, 97 minor amputations and 100 major amputations had been required, and 132 patients had died. The average wound size was 13.9 ± 52.0 cm 2 ; however, for the 155 wounds that had healed, the average size was only 4.0 ± 9.6 cm 2  (P = .002). No differences were found in the wound size when stratified by revascularization status (P = .727). Adjusted for the initial wound size, the risk of wound healing was not different when stratified by revascularization (risk ratio, 1.22; 95% confidence interval, 0.80-1.87; P = .354). For those whose wounds had healed, the average WHT and WFP were 173 ± 169 days and 775 ± 317 days, respectively. The WHT was not faster for the revascularized group (155 days vs 188 days; P = .221). When stratified by revascularization status, the rate of wound recurrence was 4.6 vs 8.9 wounds per 100 person-years for the revascularized and nonrevascularized groups, respectively (P = .125)., Conclusions: In our study, we found that, except for patients who presented with severe ischemia, revascularization was not associated with improved rates of wound healing. Among the wounds that healed, regardless of the initial ischemia grade, revascularization was not associated with a faster WHT or longer WFPs., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Bovine lactoferrin is increasingly being used as an ingredient in infant formula manufacture to enhance nutritional efficacy through the provision of immunoprotective, growth, and antimicrobial factors to the neonate., Objective: To evaluate the analytical performance of an optical biosensor immunoassay for compliance with the method performance requirements described in SMPR 2020.005., Method: Following dilution of the sample in buffer, an automated, label-free, real-time optical biosensor immunoassay was used in a direct assay format to quantitate bovine lactoferrin by its interaction with an immobilized anti-lactoferrin antibody. Quantitation was accomplished by the external standard technique with interpolation from a 4-parameter calibration regression., Results: The analytical range (0-200 mg/hg), method detection limit (0.8 mg/hg), recovery (96.1-109.2%), and repeatability (1.0-5.3%) complied with the requirements given in the lactoferrin SMPR. The method was shown to be specific for native, intact lactoferrin; thermally denatured lactoferrin generated no measurable binding response., Conclusion: The method described is suitable for the quantification of intact, undenatured lactoferrin in milk products, infant formulas (bovine milk protein-based, soy protein-based, and amino acid-based), and adult nutritionals and has been demonstrated to meet the performance requirements defined in SMPR 2020.005., Highlights: A single-laboratory validation (SLV) of an automated biosensor immunoassay for the determination of intact, undenatured lactoferrin is described., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Tennessee Dace, Chrosomus tennesseensis (Starnes and Jenkins 1988), is a small minnow (Cypriniformes: Leuciscidae) found in the upper Tennessee River watershed and Graves Creek, in the Mobile River watershed. Chrosomus tennesseensis occurs sporadically throughout its range and has been listed as vulnerable by the IUCN (NatureServe). Until recently, C. tennesseensis had been known only to occur in the upper Tennessee River watershed, however, it has been discovered in headwaters of the Black Warrior River of the Mobile River watershed. We sequenced the mitochondrial genome of C. tennesseensis collected in the Mobile River watershed to better understand the colonization of the Mobile River watershed and the interspecific relationships of Chrosomus . Furthermore, the availability of the mitochondrial genome will assist in designing specific environmental DNA (eDNA) primers that will allow for less intrusive sampling of threatened and endangered Chrosomus species., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Direct measurement of the bioavailable α-tocopherol content presents a significant analytical challenge and requires chiral separation of the α-tocopherol stereoisomers., Objective: The objective of the study was to validate an analytical method for the analysis of α-tocopherol stereoisomers in infant formulas and dairy products., Method: Samples were saponified at elevated temperature and lipophilic components were extracted into an organic solvent, with subsequent chromatographic separation of the α-tocopherol stereoisomers achieved by HPLC with a chiral column and fluorescence detection., Results: The method was shown to be accurate, with spike recoveries of 91.9-108.8% for RRR-α-tocopherol and 90.1-104.7% for α-tocopherol, with no statistical bias against NIST 1849a certified reference material (P-value = 0.54) and an HPLC-UV analytical method (P-value = 0.48). Acceptable precision was confirmed, with repeatabilities estimated at 3.5% RSDr (HorRat = 0.6) for RRR-α-tocopherol and 4.6% RSDr (HorRat = 0.4) for α-tocopherol., Conclusions: A straightforward chiral chromatographic method for the analysis of stereoisomeric forms of α-tocopherol is described. In a single analytical run, the method can quantify: (i) the total α-tocopherol content; (ii) the nutritionally important RRR-α-tocopherol and/or 2 R, 4'-ambo, 8'-ambo-α-tocopherol contents; (iii) the amount of all-rac-α-tocopherol, all-rac-α-tocopheryl acetate, or all-rac-α-tocopheryl succinate fortified into the product., Highlights: An accurate and precise chiral chromatographic method for the analysis of isomeric forms of α-tocopherol is described. The method is able to distinguish between natural and synthetic tocopherol sources. The method is accurate and precise and is suitable either for routine product compliance testing during product manufacture or as a possible reference method., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Aflatoxins are secondary metabolites produced by a number of species of Aspergillus fungi. Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 and is found in the milk of cows fed with feed spoilt by Aspergillus species. AFM1 is carcinogenic, especially in the liver and kidneys, and mutagenic, and is also an immunosuppressant in humans., Objective: A high-throughput method for the quantitative analysis of AFM1 that is applicable to liquid milk, cheese, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), and whey powder (WP) was developed and validated., Method: AFM1 in cheese, milk, and protein products is extracted using 1% acetic acid in acetonitrile with citrate salts. The AFM1 in the resulting extract is concentrated using RIDA®CREST/IMMUNOPREP® ONLINE cartridges followed by quantification by HPLC‒fluorescence., Results: The method was shown to be accurate for WP, WPC, WPI, MPC, liquid milk, and cheese, with acceptable recovery (81-112%) from spiked samples. Acceptable precision for WP, WPC, WPI, MPC, liquid milk, and cheese was confirmed, with repeatabilities of 4-12% RSD and intermediate precisions of 5-13% RSD. Method detection limit and ruggedness experiments further demonstrated the suitability of this method for routine compliance testing. An international proficiency scheme (FAPAS) cheese sample showed that this method gave results that were comparable with those from other methods., Conclusions: A method for high-throughput, routine testing of AFM1 is described. The method was subjected to single-laboratory validation and was found to be accurate, precise, and fit-for-purpose., Highlights: An automated online immunoaffinity cleanup HPLC‒fluorescence method for milk proteins, cheese, and milk was developed and single-laboratory validated. It allows for high-throughput analysis of AFM1 and can be used for the analysis of AFM1 in whey protein products., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The clinical relevance of echocardiographic measurements of right heart size and function in dogs with pulmonary hypertension (PH) is unknown., Objective: To determine if echocardiographic measurements of right heart size and right ventricular (RV) function are associated with survival times in dogs with PH., Animals: Eighty-two client-owned dogs., Methods: Retrospective study where data from medical records and baseline echocardiographic examinations were collected and measured in a standardized manner. Owners or primary veterinarians were contacted for outcome data., Results: Enlargement of the right atrium (88%), RV (69%), and pulmonary artery (72%) was common. One-third of the cases had reduced RV function quantified by two-dimensional echocardiography-derived tricuspid annular plane systolic excursion (TAPSE). Decreased TAPSE was significantly (P = .008) more common in dogs with PH not secondary to left heart disease (LHD; 43%) compared to dogs with PH secondary to LHD (14%) but median survival times (182, 95% confidence interval [CI] = 39-309 versus 298, 95% CI = 85-314 days, respectively) were not significantly different (P = .78). Right atrial area (hazard ratio [HR] = 2.72, 95% CI = 1.58-4.70), TAPSE < 3.23 mm/kg 0.284 (HR = 2.19, 95% CI = 1.28-3.74), and right heart failure (HR = 2.05, 95% CI = 1.18-3.57) were independently associated with shorter survival time (P ≤ .04)., Conclusions and Clinical Importance: Right atrial area, RV function (TAPSE < 3.23 mm/kg 0.284 ), and right heart failure offer clinically relevant prognostic information in dogs with PH. Results support the quantitative assessment of right heart size and function in dogs with PH., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Thiamine and pantothenic acid play a critical role in numerous metabolic reactions and are typically supplemented in infant and adult nutritional formulas as thiamine chloride hydrochloride and calcium pantothenate salts., Objective: A rapid compliance method for the analysis of thiamine and pantothenic acid applicable to infant formula and milk-based nutritional products is described., Method: Proteins are removed by centrifugal ultrafiltration, followed by analysis by reversed-phase liquid chromatography‒tandem mass spectrometry (LC-MS/MS), with quantitation accomplished by internal standard technique., Results: The method was shown to be accurate, with acceptable recovery (thiamine, 99.3-101.1%; pantothenic acid, 99.2-108.6%). A certified reference material (NIST 1849a), showed no statistical bias (α = 0.05) for thiamine (P = 0.64); although a statistically significant bias (P < 0.01) for pantothenic acid was found, the nominal bias was only 4.7% (mean = 7.1 mg/hg; certified value = 6.8 mg/hg). A comparison of results by LC-MS/MS and current methods showed negligible bias (mean bias: thiamine, 0.01 mg/hg; pantothenic acid, 0.17 mg/hg) and no statistical significance (α = 0.05; thiamine, P = 0.399; pantothenic acid, P = 0.058). Acceptable precision was demonstrated with a repeatability of 7.2% repeatability relative standard deviation (RSDr) (HorRat: 0.6) and an intermediate precision of 7.0% RSD for thiamine, and a repeatability of 5.7% RSDr (HorRat: 0.5) and an intermediate precision of 6.1% RSD for pantothenic acid., Conclusions: This rapid method is intended for use in high-throughput laboratories as part of routine product compliance release testing of thiamine and pantothenic acid in manufactured infant and milk-based nutritional products., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Sorbic acid (E, E-2, 4-hexadienoic acid) is added as a preservative to cheese because of its fungistatic and antimicrobial activity., Objective: A facile method for the analysis of sorbic acid that is applicable to sliced processed cheese and grated cheese products., Method: A cheese sample and dry-ice mixture was blended and sorbic acid was extracted with methanol and analyzed by HPLC-ultraviolet with external standardization. A large sample size was used to overcome sample inhomogeneity due to imprecise sorbic acid addition techniques during production and sorbic acid migration through the fat over time., Results: The method was shown to be accurate for both processed cheese and grated Cheddar cheese, with acceptable spike recovery (93.7, 103.7%, respectively), and no bias (α = 0.05) against an international reference method (p = 0.59, p = 0.13, respectively) was found. Acceptable precision was confirmed for both processed cheese slices and grated Cheddar cheese, with repeatability of 5.3% and 4.3% relative standard deviation, respectively, and intermediate precision Horwitz ratio values of 1.3 and 1.7 for processed cheese slices and grated Cheddar cheese, respectively. Method detection limit and ruggedness experiments further demonstrated the suitability of this method for routine compliance testing., Conclusions: A method for high-throughput, routine testing of sorbic acid is described. The method was subjected to single-laboratory validation and was found to be accurate, precise, and fit-for-purpose., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The present study was undertaken to investigate whether Latina and African American women with arthritis-related knee pain and primary care providers who treat them believe their treatment decisions would benefit from having more information about the impact of treatment on their quality of life, medical care costs, and work productivity., Methods: We conducted 4 focus groups of Latina and African American women over age 45 years who had knee pain. We also conducted 2 focus groups with primary care providers who treated Latina and African American women for knee pain. The participants were recruited from the community. They were asked their opinions about a decision tool that presented information on a range of treatment options and their impacts on quality of life, medical care costs, and work productivity. They were asked whether providing this information would help them make better treatment decisions. We analyzed the focus group transcripts using ATLAS.ti., Results: We found that minority women and primary care providers endorsed the use of a decision-making tool that provided information of the impact of treatment on quality of life, medical care costs, and work productivity. Providers felt that patients would benefit from having the additional information but were concerned about its complexity and some patients' ability to comprehend the information., Conclusion: Latina and African American women could make more informed treatment decisions for their knee pain using a decision-making tool that provides them with significant information about how various treatment options may impact their quality of life, medical care costs, and workforce productivity., (© 2019, American College of Rheumatology.)

We use numerical simulations to study the possible spatiotemporal effects of brine release from five desalination plants, located along the Israeli Mediterranean coastline. It is commonly believed that salinity anomalies, associated with brine discharge from desalination plants, causes effects which are confined to an area of several hundreds of meters from the discharge outfall. We show that discharging brine using diffusers produces small but robust salinity anomalies that propagate tens of kilometers as density currents (DCs). In contrast, premixing the brine with power plant cooling water compensates the negative buoyancy and prevents their generation. The propagating DCs can impact coastal water dynamics by increasing the velocities and transports in alongshore and downslope directions. The spreading and trajectories of the DCs was strongly influenced by seasonal stratification. In winter, due to a mixed water column, the DCs were relatively focused and propagate downslope. While in the summer they are confined to a narrow band along the coastline. Our model results highlight the possibility that brine discharge might have a large scale, non-negligible effect on shelf circulation than previously considered. Further studies are needed to assess the environmental, dynamical and ecological effects of desalination brine propagation, especially in the far field., 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 © 2020 Elsevier Ltd. All rights reserved.)

Background: For nutritional purposes, the measurement of vitamin D3 (defined as the sum of vitamin D3 and previtamin D3) is required to obtain an accurate and reliable estimate of its content in foods. An often neglected aspect in the development of methods for the analysis of vitamin D3 is accounting for any potential analytical bias in the results associated with differential thermal isomerization between previtamin D and vitamin D., Conclusions: For LC-UV methods using a vitamin D2 internal standard, cold saponification, or direct lipid extraction techniques should be avoided, unless chromatographic separation of vitamin D2, vitamin D3, and their previtamin forms is achieved so that UV absorbance corrections can be made. For both LC-UV and LC-MS methods using calciferol internal standards, the simplest solution to avoid analytical bias due to the presence of previtamin D is to utilize heating conditions (typically during saponification) such that previtamin D and vitamin D in the sample and the internal standard reach an equivalent equilibrium state prior to instrumental analysis. Only under such circumstances is the integration of previtamin D unnecessary to obtain accurate results for vitamin D3., Highlights: A detailed discussion of the quantitation of vitamin D3 in food with concise recommendations for avoiding measurement bias as a consequence of differential thermal isomerization., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fluoreno[2,1-a]fluorene, a molecule comprising fused ortho-quinodimethane units in a 1,5-napthoquinodimethane core, has been prepared and investigated with spectroscopy (UV-Vis-NIR, 1 H-NMR and Raman), SQUID magnetometry, spectroelectrochemistry and quantum chemistry. While para-quinodimethanes with a 2,6-substitution pattern exist as closed-shell species and meta-quinodimethanes with 2,7-substitution favour a ground electronic state with very large diradical character, our 1,5-substituted ortho-naphthoquinodimethane-based system exhibits an intermediate degree of diradical character.

Background: Biotin and folate are B-group vitamins that play a critical role in numerous metabolic reactions, and they are supplemented to infant and adult nutritional formulas as free biotin and folic acid., Objective: We describe a rapid method for the analysis of biotin and folic acid that is applicable to liquid milk, milk powders, infant formula, and milk-based nutritional products., Methods: Samples are autoclaved, centrifuged, filtered, and analyzed by HPLC-MS/MS, with quantitation accomplished by the internal standard technique., Results: The method was shown to be accurate, with acceptable spike recovery (biotin: 96.5-108.2%; folic acid: 92.6-104.4%), and no bias (α = 0.05) against either a certified reference material (biotin: P = 0.70; folic acid: P = 0.23) or established analytical method (biotin: P = 0.10; folic acid: P = 0.48) was found. Acceptable precision was confirmed with repeatability relative standard deviation (RSDr) and Horwitz ratio (HorRat) values (biotin: RSDr = 0.5-5.6%, HorRatr = 0.1-0.6; folic acid: RSDr = 2.0-3.1%, HorRatr = 0.3-0.5). Method detection limit and ruggedness experiments further demonstrated the suitability of this method for routine compliance testing., Conclusions: This rapid method is intended for use in high-throughput laboratories as part of the routine product compliance release testing of biotin and folic acid in the manufacturing of infant formulas and adult nutritional products.

The [2,1-a]- and [1,2-a]-isomers of fluorenofluorenedione have been synthesized via intramolecular Friedel-Crafts acylations. DFT calculations indicate that the [1,2-a]-isomer adopts a twisted, helical C 2 -symmetric structure and that its protonated form is the thermodynamic product of the Friedel-Crafts acylation in hot sulfuric acid. Absorption spectroscopy and cyclic voltammetry measurements provide experimental estimations of frontier molecular orbital energy levels, which are reported and discussed.

Background: Disparities in the presentation of knee osteoarthritis (OA) and in the utilization of treatment across sex, racial, and ethnic groups in the United States are well documented., Objectives: We used a Markov model to calculate lifetime costs of knee OA treatment. We then used the model results to compute costs of disparities in treatment by race, ethnicity, sex, and socioeconomic status., Research Design: We used the literature to construct a Markov Model of knee OA and publicly available data to create the model parameters and patient populations of interest. An expert panel of physicians, who treated a large number of patients with knee OA, constructed treatment pathways. Direct costs were based on the literature and indirect costs were derived from the Medical Expenditure Panel Survey., Results: We found that failing to obtain effective treatment increased costs and limited benefits for all groups. Delaying treatment imposed a greater cost across all groups and decreased benefits. Lost income because of lower labor market productivity comprised a substantial proportion of the lifetime costs of knee OA. Population simulations demonstrated that as the diversity of the US population increases, the societal costs of racial and ethnic disparities in treatment utilization for knee OA will increase., Conclusions: Our results show that disparities in treatment of knee OA are costly. All stakeholders involved in treatment decisions for knee OA patients should consider costs associated with delaying and forgoing treatment, especially for disadvantaged populations. Such decisions may lead to higher costs and worse health outcomes.

The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in many disease states, including tumor cells, either by growth factor receptor tyrosine kinases or by the genetic mutation and amplification of key pathway components. A variety of PI3K isoforms play differential roles in cancers. As such, the development of PI3K inhibitors from novel compound classes should lead to differential pharmacological and pharmacokinetic profiles and allow exploration in various indications, combinations, and dosing regimens. A screening effort aimed at the identification of PI3Kγ inhibitors for the treatment of inflammatory diseases led to the discovery of the novel 2,3-dihydroimidazo[1,2-c]quinazoline class of PI3K inhibitors. A subsequent lead optimization program targeting cancer therapy focused on inhibition of PI3Kα and PI3Kβ. Herein, initial structure-activity relationship findings for this class and the optimization that led to the identification of copanlisib (BAY 80-6946) as a clinical candidate for the treatment of solid and hematological tumors are described., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The factors that contribute to musculoskeletal healthcare disparities may influence the results of studies regarding the long-term outcome of orthopaedic implants. Patient decisions regarding their healthcare and their subsequent outcomes are influenced by health literacy. Providing patients with the information that they need to consent to treatment must be provided in a culturally competent manner. The influence of the physician or healthcare provider on the treatment choice varies depending on the type of decision-making process: patient-based, physician-based, or shared decision making. Respecting the patient's autonomy while acknowledging the knowledge and experience of the physician, we advocate for shared decision making. This may require modification of existing regulations regarding informed consent. Furthermore, federal and state directives have been put into place to address healthcare disparities, especially with respect to culturally competent care and access to proper healthcare.

Real-world applications will inevitably entail divergence between samples on which chemometric classifiers are trained and the unknowns requiring classification. This has long been recognized, but there is a shortage of empirical studies on which classifiers perform best in 'external validation' (EV), where the unknown samples are subject to sources of variation relative to the population used to train the classifier. Survey of 286 classification studies in analytical chemistry found only 6.6% that stated elements of variance between training and test samples. Instead, most tested classifiers using hold-outs or resampling (usually cross-validation) from the same population used in training. The present study evaluated a wide range of classifiers on NMR and mass spectra of plant and food materials, from four projects with different data properties (e.g., different numbers and prevalence of classes) and classification objectives. Use of cross-validation was found to be optimistic relative to EV on samples of different provenance to the training set (e.g., different genotypes, different growth conditions, different seasons of crop harvest). For classifier evaluations across the diverse tasks, we used ranks-based non-parametric comparisons, and permutation-based significance tests. Although latent variable methods (e.g., PLSDA) were used in 64% of the surveyed papers, they were among the less successful classifiers in EV, and orthogonal signal correction was counterproductive. Instead, the best EV performances were obtained with machine learning schemes that coped with the high dimensionality (914-1898 features). Random forests confirmed their resilience to high dimensionality, as best overall performers on the full data, despite being used in only 4.5% of the surveyed papers. Most other machine learning classifiers were improved by a feature selection filter (ReliefF), but still did not out-perform random forests., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The potential of analytical chemistry to predict sensory qualities of food materials is a major current theme. Standard practice is cross-validation (CV), where a set of chemical and associated sensory data is partitioned so chemometric models can be developed on training subsets, and validated on held-out subsets. CV demonstrates prediction, but is an unlikely scenario for industrial operations, where concomitant data acquisition for model development and test materials would be unwieldy. We evaluated cocoa materials of diverse provenance, and analyzed on different dates to those used in model development. Liquor extracts were analyzed by flow-injection electrospray-mass spectrometry (FIE-MS), a novel method for sensory quality prediction. FIE-MS enabled prediction of sensory qualities described by trained human panelists. Optimal models came from the Weka data-mining algorithm SimpleLinearRegression, which learns a model for the attribute giving minimal training error, which was (-)-epicatechin. This flavonoid likewise dominated partial least-squares (PLS)-regression models. Refinements of PLS (orthogonal-PLS or orthogonal signal correction) gave poorer generalization to different test sets, as did support vector machines, whose hyperparameters could not be optimized in training to avoid overfitting. In conclusion, if chemometric overfitting is avoided, chemical analysis can predict sensory qualities of food materials under operationally realistic conditions.

Objective: To assess characteristics of active motor units (MUs) during volitional vastus medialis (VM) activation in adults with symptomatic knee osteoarthritis (OA) across the spectrum of radiographic severity and age-comparable healthy control volunteers., Methods: We evaluated 39 participants (age 65+/-3 years) in whom weight-bearing knee X-rays were assigned a Kellgren & Lawrence (KL) grade (18 with KL grade=0; four each with KL grades=1, 2 and 4; nine with grade 3). Electromyography (EMG) signals were simultaneously acquired using surface [surface EMG (S-EMG)] and intramuscular needle electrodes, and analyzed by decomposition-enhanced spike-triggered averaging to obtain estimates of size [surface-represented MU action potentials (S-MUAP) area], number [MU recruitment index (MURI)] and firing rates [MU firing rates (mFR)] of active MUs at 10%, 20%, 30% and 50% effort relative to maximum voluntary force [maximal voluntary isometric contraction (MVIC)] during isometric knee extension., Results: Knee extensor MVIC was lower in OA participants, especially at higher KL grades (P=0.05). Taking the observed force differences into account, OA was also associated with activation of larger MUs (S-MUAP area/MVICx%effort; P<0.0001). In contrast, the estimated number of active units (MURI/MVICx%effort) changed differently as effort increased from 10% to 50% and was higher with advanced OA (KL=3, 4) than controls (P=0.0002)., Conclusion: VM activation changes at the level of the MU with symptomatic knee OA, and this change is influenced by radiographic severity. Poor muscle quality may explain the pattern observed with higher KL grades, but alternative factors (e.g., nerve or joint injury, physical inactivity or muscle composition changes) should be examined in early OA.