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Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over-expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over-expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration.

Objectives: To measure uptake and disposal kinetics and absolute absorption of vitamin K(1) using two stable isotope-labelled forms of vitamin K(1).Subjects: Ten subjects (nine women and one man) aged between 22 and 31 years, with a mean (+/-standard deviation) body mass index of 22.5+/-2.4 kg/m(2). Subjects took capsules containing 3 microg of methyl-(13)C vitamin K(1), three times a day for six days to reach a steady state for plasma vitamin K(1) isotopic enrichment. On day seven, subjects were given an intravenous dose of Konakion MM to measure disposal kinetics and at the same time, a capsule containing 4 microg of ring-D(4) vitamin K(1) to measure absorption. Plasma vitamin K(1) concentration was measured by high-performance liquid chromatography and isotopic composition by gas chromatography mass spectrometry.Results: The disposal kinetics of the intravenous dose of vitamin K(1) were resolved into two exponentials with half-times of 0.22 (+/-0.14) and 2.66 (+/-1.69) h. Absorption of oral, deuterated vitamin K(1) was 13 (+/-9)%.Conclusions: Two-compartmental kinetic parameters observed in this study are similar to those obtained previously using radioactive tracers, but there may be additional slow-turnover body pools acting as stores of vitamin K(1). The kinetic parameters determined from the intravenous dose allowed determination of the absolute absorption of vitamin K(1) from a bolus oral dose. [ABSTRACT FROM AUTHOR]

Objective: We determined whether memory for hyperlinks improved when they represented relations between the contents of the Web pages.Background: J. S. Farris (2003) found that memory for hyperlinks improved when they represented relations between the contents of the Web pages. However, Farris's (2003) participants could have used their knowledge of site content to answer questions about relations that were instantiated via the site's content and its hyperlinks.Method: In Experiment 1, users navigated a Web site and then answered questions about relations that were instantiated only via content, only via hyperlinks, and via content and hyperlinks. Unlike Farris (2003), we split the latter into two sets. One asked whether certain content elements were related, and the other asked whether certain Web pages were hyperlinked. Experiment 2 replicated Experiment 1 with one modification: The questions that were asked about relations instantiated via content and hyperlinks were changed so that each question's wrong answer was also related to the question's target.Results: Memory for hyperlinks improved when they represented relations instantiated within the content of the Web pages. This was true when (a) questions about content and hyperlinks were separated (Experiment 1) and (b) each question's wrong answer was also related to the question's target (Experiment 2).Conclusion: The accuracy of users' mental representations of local architecture depended on whether hyperlinks were related to the site's content.Application: Designers who want users to remember hyperlinks should associate those hyperlinks with content that reflects the relation between the contents on the Web pages. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteochondritis dissecans of the capitellum of the humerus usually occurs in adolescence and is caused by the valgus forces associated with excessive throwing. HYPOTHESIS: Arthroscopic surgery is an appropriate procedure for this condition. STUDY DESIGN: Retrospective cohort study. METHODS: Arthroscopic surgery was performed on 10 baseball players (average age, 13.8 years) with osteochondritis dissecans whose symptoms had been apparent for an average of 9 months before the operation. Follow-up at an average of 3.9 years included use of a standard rating scale, radiographs, and a questionnaire regarding return to sport. RESULTS: There were two grade I, one grade II, two grade IV, and five grade V lesions. Symptoms and objective findings correlated poorly with the grade of the lesion. The postoperative score averaged 195, reflecting excellent results. Radiographically, the primary lesion was still apparent in one patient, secondary degenerative changes were evident in one patient, and, in one patient, the lesion was still evident and degenerative changes had occurred. Only four athletes returned to organized baseball. CONCLUSIONS: Arthroscopic surgery for symptomatic osteochondritis dissecans of the capitellum in adolescent baseball players can provide excellent rating scores with intermediate follow-up but does not assure return to baseball. [ABSTRACT FROM AUTHOR]

This Letter presents results from a combination of searches for Higgs boson pair production using 126-140  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.4 assuming no Higgs boson pair production. Constraints on the Higgs boson self-coupling modifier κ&#95;{λ}=λ&#95;{HHH}/λ&#95;{HHH}^{SM}, and the quartic HHVV coupling modifier κ&#95;{2V}=g&#95;{HHVV}/g&#95;{HHVV}^{SM}, are derived individually, fixing the other parameter to its SM value. The observed 95% CL intervals are -1.2<κ&#95;{λ}<7.2 and 0.6<κ&#95;{2V}<1.5, respectively, while the expected intervals are -1.6<κ&#95;{λ}<7.2 and 0.4<κ&#95;{2V}<1.6 in the SM case. Constraints obtained for several interaction parameters within Higgs effective field theory are the strongest to date, offering insights into potential deviations from SM predictions.

Background: The logistics of timely processing of blood specimens remains a barrier in population health studies to the generation of micronutrient status data., Objectives: To test a blood specimen processing protocol that includes overnight postage with cooling and its effect on nutritional biomarker concentrations., Methods: This study was embedded within the United Kingdom National Diet and Nutrition Survey. Paired specimens were collected from 64 participants (16 y+). One set of specimens were processed within 2 h of collection ["field"] and paired samples were mailed in an insulated box with cold packs using an overnight postal service to a central laboratory ["postal"]. Specimen processing protocols were aligned across field sites and the central laboratory. Specimens were frozen and later analyzed using established methods for vitamins, minerals, lipids, ferritin, and C-reactive protein (CRP). Percent difference was calculated between protocols and compared with quality specifications determined from intra- and interindividual variation., Results: In the postal protocol, ferritin [geometric mean percent difference (95% confidence interval)] [6% (3, 8)] (P = 0.002) and zinc [4% (1, 6)] (P = 0.004) were higher compared with the field protocol. Retinol [-3% (-4, -1)] (P < 0.0001) and selenium [-3% (-5, -1)] (P = 0.003) concentrations were lower in the postal protocol, whereas total [2% (1, 3)] and HDL [4% (2, 5)] cholesterol were higher (P < 0.0001) than in the field protocol. Percent differences were within the optimum quality specification for the majority of biomarkers, but ferritin, zinc, and selenium fell outside of the optimum limits. Higher ferritin concentration in the postal protocol led to a decrease in the proportion of specimens with ferritin concentration <15 μg/L from 13% to 9%., Conclusions: The majority of micronutrient biomarkers, serum lipids, and CRP were minimally affected by delayed processing when cooled. The study suggests acceptable stability of nutritional biomarkers within the described protocol, which can provide accurate data for nutritional biomarkers commonly measured in studies and surveys., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To report the outcomes of endoscopic repair in a consecutive series of patients with follow-up ranging from 5 to 10 years., Methods: Sixty-five consecutive hips in 63 patients (2 bilateral) undergoing endoscopic abductor tendon repair with minimum 5-year follow-up were assessed with the modified Harris Hip Score. The minimal clinically important difference (MCID) was determined as one-half the standard deviation of the amount of improvement., Results: The mean age was 56.6 years (standard deviation [SD], 11.3 years), with 58 female and 5 male patients. Follow-up was obtained on 64 hips (98.5%) at a mean of 85 months (SD, 15.7 months). There were 33 full-thickness and 32 partial-thickness tears, with 40 gluteus medius tears, 23 medius and minimus tears, and 2 isolated minimus tears. Concomitant arthroscopy of the hip joint was performed in 50 patients (52 hips), including 15 with correction of femoroacetabular impingement. The mean modified Harris Hip Score was 48.4 (SD, 15.7) preoperatively and 83.4 (SD, 15.9) postoperatively, reflecting a mean improvement of 34.9 (95% confidence interval, 34.9 ± 4.3), with 92.2% of patients achieving the MCID of 8.7. There were no complications. Three patients underwent further surgery: One underwent total hip replacement at 11 months after abductor repair, one underwent repeated arthroscopy for joint debridement at 12 months after repair, and one underwent revision abductor repair at 6 years postoperatively., Conclusions: Collectively, with 5- to 10-year follow-up, patients undergoing endoscopic abductor tendon repair can respond exceptionally well, with 92.2% achieving the MCID, even among a heterogeneous group of partial- and full-thickness tears with single- and 2-tendon involvement undergoing single- and double-row repair., Level of Evidence: Level IV, case series., Competing Interests: Disclosures The authors report the following potential conflicts of interest or sources of funding: J.W.T.B. is a consultant for Smith & Nephew and receives research support from Smith & Nephew, outside the submitted work. All other authors (K.S.J., S.D.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches., Objective: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD., Methods: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA., Conclusion: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose., Trial Registration: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SDE is a Data Safety Monitoring Board statistician for clinical trials performed by Janssen Research & Development LLC and Suven. For this manuscript, HHF reports grant funding from the National Institute of Aging (R01AG076634) with no personal funds received and all payments to UC San Diego. HHF also discloses grant funding from Annovis (QR Pharma), Vivoryon (Probiodrug), Biohaven Pharmaceuticals, AC Immune, and LuMind Foundation; service agreements for consulting activities with LuMind, Genentech (DSMB), Roche/Banner (DMC), Tau Consortium (SAB), Axon Neuroscience, Biosplice Therapeutics, Janssen Research & Development LLC (DMC), Arrowhead Pharmaceuticals, Samus Therapeutics; Advisory Board activities: Translating Research in Elder Care (TREC), Association for Frontotemporal Dementia, Tau Consortium and Rainwater Charitable Foundation; support for travel from Novo Nordisk, Royal Society of Canada, Tau Consortium, Canadian Consortium for Neurodegeneration in Aging (CCNA), Translating Research in Elder Care (TREC), World Events Forum (ADDF); and a philanthropic donation for the Epstein Family Alzheimer Research Collaboration. For these activities, no personal funds have been received with all payments to UC San Diego. HHF personally receives royalties for patent: Feldman HH (filed November 26, 2008). Detecting and Treating Dementia Serial Number 12/3-2691 U.S. Patent No. PCT/US2007/07008. Washington, DC: U.S. Patent and Trademark Office. DMJ reports support from grants to UC San Diego from NIH/NIA, Vivoryon Therapeutics, Biohaven Pharmaceuticals, and the Epstein Family Foundation. SAF reports grant funding from the NIH. GEG reports a pending patent. KJ received funding from BBSRC and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre. AK receives funding from the UKRI (MRC & BBSRC), the Wellcome Trust, and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre and is a paid consultant for the company Juvenescence. JAL was a consultant for Merck KGaA in 2022 (no longer active); receives drug/placebo from EMD Serono, Merck Subsidiary, for another clinical trial; and receives a stipend from Wolters Kluwer as Editor In Chief of the journal Alzheimer’s Disease and Associated Disorders. KEY, PBV, and VV are employed by and have equity interests in C2N Diagnostics. C2N Diagnostics has received support from the NIH (grant No. R44 AG059489), BrightFocus Foundation (grant No. CA2016636), The Gerald and Henrietta Rauenhorst Foundation, and the Alzheimer’s Drug Discovery Foundation (grant No. GC-201711-2013978). HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work)., (Copyright: © 2024 Feldman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency., Objectives: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine., Methods: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework., Results: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children ( P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 μg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine., Conclusions: Although ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337., (© 2024 The Author(s).)

Objective: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting., Study Design: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve., Results: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86)., Conclusions: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement., Trial Registration: Clinicaltrials.gov NCT03626337., Competing Interests: Declaration of Competing Interest This work was supported by the Bill & Melinda Gates Foundation [grant number INV-009736]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Kenneth Brown provided technical support in the study design while working for the Bill & Melinda Gates Foundation. The sponsor had no role in the data collection, analysis, interpretation, or writing of this article. The spouse of S.Y.H. previously worked for and currently consults for the Bill & Melinda Gates Foundation. DJT has provided statistical consultations to International Flavors and Fragrances Inc. All other authors declare that they have no conflicts of interest. This research was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bull riders represent a microcosm of athletes in whom severe consequences of femoroacetabular impingement may challenge the limits of arthroscopic intervention. Observations of this cohort may provide meaningful insight into the treatment of other populations. All patients undergoing hip arthroscopy are prospectively assessed with a modified Harris Hip Score. Sixteen consecutive bull riders (21 hips) with minimum 2-year follow-up are reported. The average age was 26 years, duration of symptoms was 33 months, and follow-up was 57 months. Arc of rotational hip motion averaged 31°. All had femoroacetabular impingement (17 combined and 4 cam impingements). Among the cam impingements, 1 also had dysplasia and 1 also had borderline dysplasia. Radiographic Tönnis grades were as follows: 2 Tönnis 1; 18 Tönnis 2; and 1 Tönnis 3. All had acetabular articular damage (14 Outerbridge grade 4; 6 Outerbridge grade 3; and 1 Outerbridge grade 1). Nine underwent microfracture. Four had accompanying femoral chondral lesions (3 grade 3; 1 grade 4). There were 20 labral tears (14 repaired and 6 debrided). All but 1 (95%) improved after surgery. One bilateral case underwent conversion to resurfacing arthroplasty on one side and revision arthroscopy on the other. The average improvement was 21.3 points. Thirteen (81.25%) returned to bull riding at an average of 7 months. Among the 3 who did not return, each had undergone bilateral procedures. There were no complications. Femoroacetabular impingement can be a significant problem among bull riders. Limited range of motion, grade 4 articular damage, and Tönnis 2 radiographic changes may not preclude successful arthroscopic treatment, but advanced bilateral disease may be too much even for these hardened athletes. [ Orthopedics . 2024;47(2):79-82.].

In terrestrial vertebrates, the olfactory system is divided into main (MOS) and accessory (AOS) components that process both volatile and nonvolatile cues to generate appropriate behavioral responses. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the vomeronasal organ (VNO), the accessory olfactory bulb (AOB), and the medial amygdala (MeA), we reveal that populations of neurons in the AOS can be molecularly subdivided based on their ongoing or prior expression of the transcription factors Foxp2 or Dbx1, which delineate separate populations of GABAergic output neurons in the MeA. We show that a majority of AOB neurons that project directly to the MeA are of the Foxp2 lineage. Using single-neuron patch-clamp electrophysiology, we further reveal that in addition to sex-specific differences across lineage, the frequency of excitatory input to MeA Dbx1- and Foxp2-lineage neurons differs between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons, and lineage and sex differences in patterns of connectivity., (© 2024 Wiley Periodicals LLC.)

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children., (© 2023 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Riboflavin (vitamin B2) is a component of the co-enzyme flavin adenine dinucleotide (FAD). The activity coefficient of erythrocyte glutathione reductase (EGRAC), a FAD-dependent enzyme, is a biomarker of riboflavin status. Here, we describe a protocol for measuring unstimulated (basal) and FAD-stimulated (activated) erythrocyte glutathione reductase activity to calculate EGRAC. We describe the steps for preparing washed red blood cells and hemolysates; preparing reagents; loading, incubating, and reading the 96-well plate; and calculating the results. For complete details on the use and execution of this protocol, please refer to Hess et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD). Following concern around folate status in the United Kingdom, the United Kingdom government announced in 2021 the intention to introduce mandatory folic acid fortification., Objective: This study aimed to describe folate status in the United Kingdom population prior to the implementation of mandatory folic acid fortification of non-whole wheat (non-wholemeal) flour and to assess trends in folate status, including in females of reproductive age (FRA)., Methods: Data were from the United Kingdom National Diet and Nutrition Survey Rolling Program (2008-2019), a cross-sectional, nationally representative survey of children and adults aged 1.5+ (n = 5792 with folate result). Serum folate concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and red blood cell (RBC) folate concentration by microbiological assay. Concentration data were compared against method-specific cut-offs and thresholds, and relationships were explored against demographic and lifestyle characteristics., Results: RBC and serum folate concentration significantly decreased by ∼3 percentage points per year between 2008 and 2019 in all age/sex groups. Prevalence of deficiency (RBC folate < 305 nmol/L) was highest in children aged 11 to 18 y (17% in 2016-2019). The proportion of FRA below the cut-off for increased risk of NTD (RBC folate < 748 nmol/L) increased from 69% to 89% between 2008 and 2019. Ethnicity, smoking status, and income were significant determinants of RBC and serum folate concentrations., Conclusions: These data reveal a decline in population folate status in the United Kingdom between 2008 and 2019 and a high prevalence of folate deficiency. A high proportion of FRA had RBC folate concentrations below the cut-off for increased risk of NTD. These data provide information on folate status in a population not currently exposed to mandatory folic acid fortification and are essential to model and assess its impact., (Copyright © 2023. Published by Elsevier Inc.)

Vitamin D is essential for optimal bone health, and vitamin D deficiency has been associated with an increased risk of adverse pregnancy, growth and developmental outcomes. In early life, and in the absence of endogenous vitamin D production from UVB light, infants are reliant on vitamin D stores established in utero and the vitamin D supply from human milk (HM). However, comprehensive data on vitamin D in HM is lacking. Thus, in this review we explore the application of liquid-chromatography tandem mass spectrometry (LC-MS/MS) to the assessment of vitamin D in HM. We discuss the challenges of extracting and measuring multiple vitamin D metabolites from HM including the frequent requirement for a large sample volume, and inappropriate poor sensitivity. Shortcomings in the reporting of experimental procedures and data analysis further hinder advances in the field. Data collated from all studies that have applied LC-MS/MS reveal that, in general, cholecalciferol concentration is greater and more variable than 25-hydroxyvitamin D concentration, and that the vitamin D content of HM is low and less than the currently recommended dietary requirement of infants, although maternal supplementation can increase the vitamin D content of HM. Improvements in analytical methods and their validation and larger, more representative studies are required to better characterize HM milk vitamin D metabolite concentrations and their relationship with maternal status. These data are essential to understand relationships with infant health and to inform public health policies around vitamin D fortification and supplementation., 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 © 2023 Jones, Meadows and Koulman.)

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25-55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmol/L overall, with higher levels in men (14·4 ± 2·9 µmol/l) than in women (13·2 ± 2·6 µmol/l), P -value < 0·0001. There was an inverse relationship between tertiles of plasma Zn and 2-h glucose concentrations ( P -value for linear trend = 0·002). The difference in 2-h glucose between those in the highest tertile of plasma Zn compared to the lowest was -0·63 (95 % CI - 1·02, -0·23) mmol/l. This remained significant after adjusting for age, sex, smoking status, alcohol intake, education level, area of residence, adiposity and objectively measured physical activity -0·43(-0·82, -0·04). Similar inverse associations were observed between plasma Zn concentrations and fasting glucose and homeostatic model assessment of insulin resistance when adjusted for socio-demographic and health-related behavioural characteristics. The current findings of an inverse association between plasma Zn concentrations and several markers of glucose homeostasis, together with growing evidence from intervention studies, suggest a role for Zn in glucose metabolism. If supported by further evidence, strategies to improve Zn status in populations may provide a cheap public health prevention approach for diabetes.

Knowing that an antibody's sensitivity and specificity is accurate is crucial for reliable data collection. This certainty is especially difficult to achieve for antibodies (Abs) which bind post-translationally modified proteins. Here we describe two validation methods using surrogate proteins in western blot and ELISA. The first method, which we termed "MILKSHAKE" is a modified maltose binding protein, hence the name, that is enzymatically conjugated to a peptide from the chosen target which is either modified or non-modified at the residue of interest. The surety of the residue's modification status can be used to confirm Ab specificity to the target's post-translational modification (PTM). The second method uses a set of surrogate proteins, which we termed "Sundae". Sundae consists of a set of modified maltose binding proteins with a genetically encoded target sequence, each of which contains a single amino acid substitution at one position of interest. With Sundae, Abs can be evaluated for binding specificities to all twenty amino acids at a single position. Combining MILKSHAKE and Sundae methods, Ab specificity can be determined at a single-residue resolution. These data improve evaluation of commercially available Abs and identify off-target effects for Research-Use-Only and therapeutic Abs., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card ('nurse collection') or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card ('self-collection'). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk., (© 2023. Springer Nature Limited.)

γ-Band oscillations (GBOs) are generated by fast-spiking interneurons (FSIs) and are critical for cognitive functions. Abnormalities in GBOs are frequently observed in schizophrenia and bipolar disorder and are strongly correlated with cognitive impairment. However, the underlying mechanisms are poorly understood. Studying GBOs in ex vivo preparations is challenging because of high energy demands and the need for continuous oxygen delivery to the tissue. As a result, GBOs are typically studied in brain tissue from very young animals or in experimental setups that maximize oxygen supply but compromise spatial resolution. Thus, there is a limited understanding of how GBOs interact within and between different brain structures and in brain tissue from mature animals. To address these limitations, we have developed a novel approach for studying GBOs in ex vivo hippocampal slices from mature animals, using 60-channel, perforated microelectrode arrays (pMEAs). pMEAs enhance oxygen delivery and increase spatial resolution in electrophysiological recordings, enabling comprehensive analyses of GBO synchronization within discrete brain structures. We found that transecting the Schaffer collaterals, a neural pathway within the hippocampus, impairs GBO coherence between CA1 and CA3 subfields. Furthermore, we validated our approach by studying GBO coherence in an Ank3 mutant mouse model exhibiting inhibitory synaptic dysfunction. We discovered that GBO coherence remains intact in the CA3 subfield of these mutant mice but is impaired within and between the CA1 subfield. Overall, our approach offers significant potential to characterize GBOs in ex vivo brain sections of animal models, enhancing our understanding of network dysfunction in psychiatric disorders., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Rodríguez Díaz et al.)

Thiamine (vitamin B1) is an essential micronutrient required as a cofactor in many metabolic processes. Clinical symptoms of thiamine deficiency are poorly defined, hence biomarkers of thiamine status are important. The erythrocyte transketolase activity coefficient (ETKac) is a sensitive measure of thiamine status, but its interpretation may be confounded where the availability of the transketolase enzyme is limited. Basal ETK activity per gram of hemoglobin provides a complementary biomarker of thiamine status; however, its measurement and calculation are poorly described. Here, we describe in detail the assessment of basal ETK activity, including the calculation of path length in microplates and the molar absorption coefficient of NADH specific to the assay, and the measurement of hemoglobin in sample hemolysates. To illustrate the application of the methods, we present ETKac and basal ETK activity from women in The Gambia and UK. In conclusion, we present a clear protocol for the measurement of basal ETK activity that will permit the harmonization of methods to improve replication between laboratories., (© 2023 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Objective: To understand how aspects of vishing calls (phishing phone calls) influence perceived visher honesty., Background: Little is understood about how targeted individuals behave during vishing attacks. According to truth-default theory, people assume others are being honest until something triggers their suspicion. We investigated whether that was true during vishing attacks., Methods: Twenty-four participants read written descriptions of eight real-world vishing calls. Half included highly sensitive requests; the remainder included seemingly innocuous requests. Participants rated visher honesty at multiple points during conversations., Results: Participants initially perceived vishers to be honest. Honesty ratings decreased before requests occurred. Honesty ratings decreased further in response to highly sensitive requests, but not seemingly innocuous requests. Honesty ratings recovered somewhat, but only after highly sensitive requests., Conclusions: The present results revealed five important insights: (1) people begin vishing conversations in the truth-default state, (2) certain aspects of vishing conversations serve as triggers, (3) other aspects of vishing conversations do not serve as triggers, (4) in certain situations, people's perceptions of visher honesty improve, and, more generally, (5) truth-default theory may be a useful tool for understanding how targeted individuals behave during vishing attacks., Application: Those developing systems that help users deal with suspected vishing attacks or penetration testing plans should consider (1) targeted individuals' truth-bias, (2) the influence of visher demeanor on the likelihood of deception detection, (3) the influence of fabricated situations surrounding vishing requests on the likelihood of deception detection, and (4) targeted individuals' lack of concern about seemingly innocuous requests.

To develop reproducible results, it is critical that all reagents used in an experiment be validated in an alternative or independent method. We present two such independent methods for determining the specificity of antibodies: (1) "MILKSHAKE," which can be used to validate the liability and specificity of antibodies directed against post-translationally-modified epitopes, and (2) "Sundae," which is a more complete alanine-like scanning method that can be used to better understand the binding and bioactivity of specific residues of a protein. We apply both of these methods to the interaction between an antibody and its antigen., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Researchers can often successfully generate antibodies to predicted epitopes. Especially when the epitopes are on the surface of a protein or in a hydrophilic loop. But it is difficult to direct recombinant antibodies to bind either to- or near a specific amino acid on a protein or peptide. We have developed a unique immune-targeting strategy, that we call "Epivolve," that enables us to make site-specific antibodies (Abs). Epivolve technology leverages a highly immunogenic modified amino acid that acts as a "pseudo-hapten" immuno-target and takes advantage of Ab affinity maturation technologies to make high-affinity site-specific antibodies. Epivolve functions by the evolution of an Ab paratope to either synonymous or especially non-synonymous amino acid (aa) binding. Here we describe the use of Epivolve technology in phage display and the protocols for developing site-specific antibodies., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The majority of circulating 25-hydroxyvitamin D (25(OH)D) is protein bound and perhaps less available than the free fraction of 25(OH)D; therefore, researchers have proposed that the measurement of free 25(OH)D in human serum may be a better indicator of vitamin D health status than total 25(OH)D. The availability of a new enzyme-linked immunosorbent assay (ELISA) for the determination of free 25(OH)D provides a method for direct measurement of the low levels of non-protein bound 25(OH)D. As an initial step towards harmonization of measurements of free 25(OH)D, the ELISA was used to measure free 25(OH)D in three existing Standard Reference Materials (SRMs): SRM 972a Vitamin D Metabolites in Frozen Human Serum, SRM 2973 Vitamin D Metabolites in Frozen Human Serum (High Level), and SRM 1949 Frozen Prenatal Human Serum. Target values for free 25(OH)D in the nine SRM serum pools, obtained by combining the results from two laboratories, ranged from 3.76 ± 0.36 to 10.0 ± 0.58 pg/mL. Of particular significance is the assignment of free 25(OH)D target values to SRM 1949, which consists of four serum pools from non-pregnant female donors of reproductive age and pregnant women in each of the three trimesters and which also has values assigned for vitamin D binding protein, which increases during pregnancy. The availability of target values for free 25(OH)D in these SRMs will allow researchers to validate new analytical methods and to compare their results with other researchers as an initial step towards harmonization of measurements among different studies and laboratories., (© 2022. The Author(s).)

A recently discovered, enhanced Ge diffusion mechanism along the oxidizing interface of Si/SiGe nanostructures has enabled the formation of single-crystal Si nanowires and quantum dots embedded in a defect-free, single-crystal SiGe matrix. Here, we report oxidation studies of Si/SiGe nanofins aimed at gaining a better understanding of this novel diffusion mechanism. A superlattice of alternating Si/Si 0.7 Ge 0.3 layers was grown and patterned into fins. After oxidation of the fins, the rate of Ge diffusion down the Si/SiO 2 interface was measured through the analysis of HAADF-STEM images. The activation energy for the diffusion of Ge down the sidewall was found to be 1.1 eV, which is less than one-quarter of the activation energy previously reported for Ge diffusion in bulk Si. Through a combination of experiments and DFT calculations, we propose that the redistribution of Ge occurs by diffusion along the Si/SiO 2 interface followed by a reintroduction into substitutional positions in the crystalline Si.

Deep inspiration breath-hold (DIBH) is an advanced radiotherapy technique that has been shown to have dosimetric benefits in the treatment of patients with mediastinal lymphoma. Whilst there is much published data on the use of DIBH in breast radiotherapy, reports on the use of the technique in mediastinal lymphoma patients remain limited. As the first NHS centre in the UK to implement DIBH in this pt group, we have evaluated our experience and success in using this technique over a 5 year period., Competing Interests: 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., (Crown Copyright © 2022 Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)

Deep inspiration breath-hold, butterfly volumetric modulated arc therapy and daily imaging techniques for mediastinal lymphoma patients have been introduced in a single department. Whilst introducing these techniques, there were many practical lessons to be learned across the patient pathway, from pre-treatment through to treatment delivery.Therapeutic radiographers were key members of the multi-disciplinary team implementing these techniques. This work reflects on the experience of introducing these advanced techniques for mediastinal lymphoma patients and the lessons learnt., Competing Interests: 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., (Crown Copyright © 2022 Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)

The current research proposes to incorporate vocational interests into the study of adverse impact (i.e., differential hiring/selection rates between minority and majority groups in employment settings). In the context of high stakes testing (e.g., using cognitive and personality tests), we show how race gaps in vocational interests would correspond to differential rates of job attraction (the attraction process) and various personnel selection outcomes (the selection process), in patterns that are not always intuitive. Using findings from various meta-analyses, we construct a combined correlation matrix of race, vocational interests, cognitive ability, and Conscientiousness; and provide mathematical formulas to assess the role of vocational interests in determining subgroup differences on predictors in applicant pools. Results and empirical examples suggest: (a) applicant attraction based on vocational interests can reduce adverse impact potential when the interest favors the minority [majority] group and is negatively [positively] related to the predictor; (b) attraction effects of vocational interests on adverse impact potential are modest; (c) if the vocational interest subgroup mean difference is small relative to other predictors in use, personnel selection on the interest will reduce adverse impact potential; (d) attraction effects tend to dampen or remove the selection effects of vocational interests on adverse impact potential, due to variance restriction on interests in the applicant pool; and (e) selection effects tend to be much stronger than attraction effects. These findings have implications for how adverse impact might differ systematically across job types, partly due to attraction and selection effects involving race differences in vocational interests. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D 3 by endocytosis, placental metabolism of 25(OH)D 3 into 24,25-dihydroxyvitamin D 3 and active 1,25-dihydroxyvitamin D [1,25(OH) 2 D 3 ], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D 3 and synthesis of 1,25(OH) 2 D 3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D 3 . We demonstrate that 25(OH)D 3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy., Competing Interests: BA, CS, CJ, FH, JF, FR, EL, EH, LC, PM, RM, SC, HI, JH, KJ, RL, MB, JC No competing interests declared, AM AM is CSO of Proteas Bioanalytics Inc, BioLabs at the Lundquist Institute, CW Cory H White is affiliated with Merck Exploratory Science Centre, Merck Research Laboratories. The author has no financial interests to declare, SB SB part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone, EC EC reports honoraria/travel support from Eli Lilly, UCB, Pfizer and Amgen outside the submitted work, KG KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone, CC CC has received lecture fees and honoraria from Amgen, Danone, Eli Lilly, GSK, Kyowa Kirin, Medtronic, Merck, Nestle, Novartis, Pfizer, Roche, Servier, Shire, Takeda and UCB outside of the submitted work, MH MH has received an honorarium for presenting to Thornton and Ross, SG SG is President and CEO/CTO of Proteas Bioanalytics Inc, BioLabs at the Lundquist Institute, NH NCH reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, UCB, Consilient Healthcare, Kyowa Kirin and Internis Pharma, outside the submitted work, (© 2022, Ashley et al.)

Thiamine deficiency disorders are associated with a variety of clinical symptoms affecting the nervous and cardiovascular systems. There is growing recognition that thiamine deficiency can occur in populations well beyond the classical region of South Asia, and at-risk populations include those who receive a large proportion of their energy from polished white rice (or other low-thiamine staple foods) and with low dietary diversity. Reports of thiamine deficiency in West Africa over the last century have suggested that this has historically been an issue in this population, but in more recent decades, these reports have been limited to prison populations. To understand if thiamine deficiency might be an unrecognized problem in the communities of this region, erythrocyte samples collected during the wet and dry seasons from 226 women of reproductive age (mean age = 28 years old) were assessed for thiamine status by measuring the erythrocyte transketolase activity coefficient (ETKac). Overall, 35.8% of the sample was at high risk of thiamine deficiency (ETKac ≥ 1.25). Risk of thiamine deficiency was significantly higher in the wet (47.9%) compared with the dry season (22.9%) (P < 0.001). To our knowledge, this is the first report of biochemical thiamine deficiency in a free-living population in West Africa in the 21st century and suggests that further investigation is warranted., (© 2021 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Antibody (Ab) validation is the procedure in which an Ab is thoroughly assayed for sensitivity and specificity in a given application. Validation of Abs against post-translationally modified (PTM) targets is particularly challenging because it requires specifically prepared antigen. Here we describe a novel validation method using surrogate proteins in a Western blot. The surrogate protein, which we termed 'MILKSHAKE,' is a modified maltose binding protein enzymatically conjugated to a peptide from the chosen target that is either modified or nonmodified at the residue of interest. The certainty of the residue's modification status can be used to confirm Ab specificity. This method also allows for Ab validation even in the absence or limited availability of treated cell lysates.

Background: The measurement of micronutrient status is essential to understand the health of individuals and populations, but there are limited data on the stability of micronutrients in whole blood., Objectives: The objective was to investigate the effects of delayed processing of whole blood on the stability of 25 micronutrient and selected clinical biomarkers., Methods: Blood from 16 healthy adults was collected into EDTA, lithium heparin (LH), or serum tubes. Samples were processed within 2 hours of collection ("2-hour processed") or mailed overnight (boxed with frozen cold packs) before processing ("24-hour processed"). Micronutrient and clinical biomarker concentrations were quantified with validated methods. The concentration percentage difference between the 2- and 24-hour processed samples was calculated and was compared against quality specifications determined from intra- and interindividual variations., Results: All analytes had a sample type where the percentage difference concentration between 2-hour and 24-hour processed samples was ≤4% and was acceptable based on calculated limits, including for biomarkers of vitamin A, vitamin D, thiamin, folate, vitamin B-12, iron (ferritin), and zinc status and for selected clinical markers, C-reactive protein, HDL and total cholesterol, and triglycerides. EDTA plasma vitamin C was lower compared to the 2-hour processed sample (geometric mean, 43%; 95% CI: 36%-49%). Pyridoxal-5-phosphate (vitamin B-6 biomarker) decreased, with differences from the 2-hour processed samples of -8% (95% CI: -13% to -2%) and -14% (95% CI: -18% to -9%) in LH plasma and serum, respectively., Conclusions: In blood collected from adult participants, delayed processing of chilled whole blood for 24 hours did not materially affect the measured concentrations of the majority of micronutrients and selected clinical biomarkers. This suggests that for these analytes, adherence to a 2-hour processing protocol may be unnecessary. This knowledge is valuable and may help to simplify logistics for sample transport and processing of blood samples for micronutrient status assessment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The controlled fabrication of vertical, tapered, and high-aspect ratio GaN nanowires via a two-step top-down process consisting of an inductively coupled plasma reactive ion etch followed by a hot, 85% H 3 PO 4 crystallographic wet etch is explored. The vertical nanowires are oriented in the[0001]direction and are bound by sidewalls comprising of{336¯2}semipolar planes which are at a 12° angle from the [0001] axis. High temperature H 3 PO 4 etching between 60 °C and 95 °C result in smooth semipolar faceting with no visible micro-faceting, whereas a 50 °C etch reveals a micro-faceted etch evolution. High-angle annular dark-field scanning transmission electron microscopy imaging confirms nanowire tip dimensions down to 8-12 nanometers. The activation energy associated with the etch process is 0.90 ± 0.09 eV, which is consistent with a reaction-rate limited dissolution process. The exposure of the{336¯2}type planes is consistent with etching barrier index calculations. The field emission properties of the nanowires were investigated via a nanoprobe in a scanning electron microscope as well as by a vacuum field emission electron microscope. The measurements show a gap size dependent turn-on voltage, with a maximum current of 33 nA and turn-on field of 1.92 V nm -1 for a 50 nm gap, and uniform emission across the array., (© 2021 IOP Publishing Ltd.)