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Objectives: Training in emotion management is not a standard part of medical education. This study's objective was to understand physicians' challenges navigating emotion (their own and their patients') and identify areas for intervention to support physician wellness and enhance patient care., Methods: In 2019, we surveyed 103 physicians in emergency medicine, internal medicine, family medicine, and neurology. Participants quantitatively reported emotion training, emotions that were challenging, and barriers to addressing emotion. They provided qualitative examples of emotion challenges and successes that we analyzed using an inductive thematic analysis., Results: There were no significant differences in responses by specialty. Only 10% reported receiving emotion management training, with no evidence that more recently trained physicians received more. Those who had received training on emotion reported greater comfort in dealing with patients' emotions and were more likely to engage in teaching on emotion. There were gender and career stage differences regarding which emotions physicians found most challenging. The authors identified central themes of emotion-related challenges and successes., Conclusions: Targeted educational initiatives are needed to advance physicians' ability to navigate emotion in clinical encounters., Practice Implications: Developing strategies for managing patients' emotions may better prepare physicians for navigating the emotional demands of practicing medicine., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: Accurate delineation of the seizure-onset zone (SOZ) in focal drug-resistant epilepsy often requires stereo-EEG (SEEG) recordings. Our aims were to propose a truly objective and quantitative comparison between EEG/magnetoencephalography (MEG) source imaging (EMSI), EEG/fMRI responses for similar spikes with primary irritative zone (PIZ) and SOZ defined by SEEG and to evaluate the value of EMSI and EEG/fMRI to predict postsurgical outcome., Methods: We identified patients with drug-resistant epilepsy who underwent EEG/MEG, EEG/fMRI, and subsequent SEEG at the Epilepsy Service from the Montreal Neurological Institute and Hospital. We quantified multimodal concordance within the SEEG channel space as spatial overlap with PIZ/SOZ and distances to the spike-onset, spike maximum amplitude and seizure core intracerebral channels by applying a new methodology consisting of converting EMSI results into SEEG electrical potentials (EMSIe-SEEG) and projecting the most significant fMRI response on the SEEG channels (fMRIp-SEEG). Spatial overlaps with PIZ/SOZ (AUC PIZ , AUC SOZ ) were assessed by using the area under the receiver operating characteristic curve (AUC). Here, AUC represents the probability that a randomly picked active contact exhibited higher amplitude when located inside the spatial reference than outside., Results: Seventeen patients were included. Mean spatial overlaps with the PIZ and SOZ were 0.71 and 0.65 for EMSIe-SEEG and 0.57 and 0.62 for fMRIp-SEEG. Good EMSIe-SEEG spatial overlap with the PIZ was associated with smaller distance from the maximum EMSIe-SEEG contact to the spike maximum amplitude channel (median distance 14 mm). Conversely, good fMRIp-SEEG spatial overlap with the SOZ was associated with smaller distances from the maximum fMRIp-SEEG contact to the spike-onset and seizure core channels (median distances 10 and 5 mm, respectively). Surgical outcomes were correctly predicted by EEG/MEG in 12 of 15 (80%) patients and EEG/fMRI in 6 of 11(54%) patients., Discussion: With the use of a unique quantitative approach estimating EMSI and fMRI results in the reference SEEG channel space, EEG/MEG and EEG/fMRI accurately localized the SOZ and the PIZ. Precisely, EEG/MEG more accurately localized the PIZ, whereas EEG/fMRI was more sensitive to the SOZ. Both neuroimaging techniques provide complementary localization that can help guide SEEG implantation and select good candidates for surgery., (© 2022 American Academy of Neurology.)

Study Question: Does maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the first trimester affect the risk of miscarriage before 13 week's gestation?, Summary Answer: Pregnant women with self-reported diagnosis of SARS-CoV-2 in the first trimester had a higher risk of early miscarriage., What Is Known Already: Viral infections during pregnancy have a broad spectrum of placental and neonatal pathology. Data on the effects of the SARS-CoV-2 infection in pregnancy are still emerging. Two systematic reviews and meta-analyses reported an increased risk of preterm birth, caesarean delivery, maternal morbidity and stillbirth. Data on the impact of first trimester infection on early pregnancy outcomes are scarce. This is the first study, to our knowledge, to investigate the rates of early pregnancy loss during the SARS-CoV-2 outbreak among women with self-reported infection., Study Design, Size, Duration: This was a nationwide prospective cohort study of pregnant women in the community recruited using social media between 21 May and 31 December 2020. We recruited 3545 women who conceived during the SARS-CoV-2 pandemic who were <13 week's gestation at the time of recruitment., Participants/materials, Setting, Methods: The COVID-19 Contraception and Pregnancy Study (CAP-COVID) was an on-line survey study collecting longitudinal data from pregnant women in the UK aged 18 years or older. Women who were pregnant during the pandemic were asked to complete on-line surveys at the end of each trimester. We collected data on current and past pregnancy complications, their medical history and whether they or anyone in their household had symptoms or been diagnosed with SARS-CoV-2 infection during each trimester of their pregnancy. RT-PCR-based SARS-CoV-2 RNA detection from respiratory samples (e.g. nasopharynx) is the standard practice for diagnosis of SARS-CoV-2 in the UK. We compared rate of self-reported miscarriage in three groups: 'presumed infected', i.e. those who reported a diagnosis with SARS-CoV-2 infection in the first trimester; 'uncertain', i.e. those who did not report a diagnosis but had symptoms/household contacts with symptoms/diagnosis; and 'presumed uninfected', i.e. those who did not report any symptoms/diagnosis and had no household contacts with symptoms/diagnosis of SARS-CoV-2., Main Results and the Role of Chance: A total of 3545 women registered for the CAP-COVID study at <13 weeks gestation and were eligible for this analysis. Data for the primary outcome were available from 3041 women (86%). In the overall sample, the rate of self-reported miscarriage was 7.8% (238/3041 [95% CI, 7-9]). The median gestational age (GA) at miscarriage was 9 weeks (interquartile range 8-11). Seventy-seven women were in the 'presumed infected' group (77/3041, 2.5% [95% CI 2-3]), 295/3041 were in the uncertain group (9.7% [95% CI 9-11]) and the rest in the 'presumed uninfected' (87.8%, 2669/3041 [95% CI 87-89]). The rate of early miscarriage was 14% in the 'presumed infected' group, 5% in the 'uncertain' and 8% in the 'presumed uninfected' (11/77 [95% CI 6-22] versus 15/295 [95% CI 3-8] versus 212/2669 [95% CI 7-9], P = 0.02). After adjusting for age, BMI, ethnicity, smoking status, GA at registration and the number of previous miscarriages, the risk of early miscarriage appears to be higher in the 'presumed infected' group (relative rate 1.7, 95% CI 1.0-3.0, P = 0.06)., Limitations, Reasons for Caution: We relied on self-reported data on early pregnancy loss and SARS-CoV-2 infection without any means of checking validity. Some women in the 'presumed uninfected' and 'uncertain' groups may have had asymptomatic infections. The number of 'presumed infected' in our study was low and therefore the study was relatively underpowered., Wider Implications of the Findings: This was a national study from the UK, where infection rates were one of the highest in the world. Based on the evidence presented here, women who are infected with SARS-CoV-2 in their first trimester may be at an increased risk of a miscarriage. However, the overall rate of miscarriage in our study population was 8%. This is reassuring and suggests that if there is an effect of SARS-CoV-2 on the risk of miscarriage, this may be limited to those with symptoms substantial enough to lead to a diagnostic test. Further studies are warranted to evaluate a causal association between SARS-CoV-2 infection in early pregnancy and miscarriage risk. Although we did not see an overall increase in the risk of miscarriage, the observed comparative increase in the presumed infected group reinforces the message that pregnant women should continue to exercise social distancing measures and good hygiene throughout their pregnancy to limit their risk of infection., Study Funding/competing Interest(s): This study was supported by a grant from the Elizabeth Garrett Anderson Hospital Charity (G13-559194). The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. J.A.H. is supported by an NIHR Advanced Fellowship. A.L.D. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi&#95;disclosure.pdf and declare: support to J.A.H. and A.L.D. as above; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

We previously reported that feeding Se-biofortified alfalfa hay to weaned beef calves in a preconditioning program increases whole-blood Se (WB-Se) concentrations and nasal microbiome abundance and diversity during the preconditioning period, decreases morbidity and mortality during the feedlot period, and increases carcass weight and quality at slaughter. The objective of the current study was to see whether similar improvements can be achieved through Se supplementation of dams during various pregnancy trimesters. In a two-year experimental study, 80 Angus-cross cows received once-weekly Se-yeast boluses containing 105 mg of Se, during either the first (TR-1), second (TR-2), or third (TR-3) pregnancy trimester, or were not bolused (CTR). Whole-blood Se concentrations were higher from CTR, to TR-1, to TR-2, and to TR-3 in newborn calves (all p < 0.01). At weaning, only calves from TR-3 mothers had higher WB-Se concentrations compared with calves from CTR mothers (p = 0.02), and no significant differences in nasal microbiome abundance and diversity or nasal microbiota were observed. In the feedlot period, morbidity was low, and no differences were observed. At slaughter, no differences in carcass weight and quality were observed. In conclusion, Se supplementation of pregnant cows is effective for increasing WB-Se concentration of newborn calves, and the increase can be sustained until weaning for calves born to TR-3 dams. However, the increase in WB-Se concentrations is small and does not result in beneficial changes in the nasal microbiome. Thus, calves should be fed Se-biofortified forages again at weaning in a preconditioning program in order to diversify the nasal microbiome prior to entering the feedlot.

Cats with chronic kidney disease (CKD) have a decreased ability to maintain body weight. As CKD advances, loss of body weight contributes to morbidity and mortality. The goal of this study was to evaluate the combined effects of feeding betaine and prebiotics on body weight of both CKD and healthy cats. The pre-trial food (control food) was a complete and balanced dry food designed to aid in the management of CKD. Test food was the control food supplemented with betaine (0.500%) and prebiotics: long-chain oat beta-glucan (0.586%) and 0.407% short chain fructooligosaccharides (scFOS). The CKD cats (n = 7) were fed pre-trial food for 28 days and then randomly assigned to control food or test food. Each food was fed for 8 weeks in a cross-over study design. In a second study, healthy cats received control food or test food for 8 weeks (n = 8 each group). Blood, urine, and fecal samples were collected to evaluate concentrations of relevant kidney function biomarkers and metabolites at the end of each feeding period for CKD cats, and blood samples were collected monthly to evaluate concentrations of plasma metabolites for healthy cats. Body weight and composition were measured using dual-energy X-ray absorptiometry (DEXA) scan at baseline and after each feeding period. Total body mass was significantly higher in CKD cats after consuming test food compared with control food (P = 0.004), with no significant difference in food intake while consuming test or control food (P = 0.34). Test food did not affect total body mass or composition of healthy cats. Indole compounds produced by bacterial metabolism were decreased in urine and increased in feces of CKD cats fed test food, and plasma concentrations were negatively correlated with the level of kidney function, indicating a potential benefit of consuming test food. In healthy cats, consuming test food resulted in significantly decreased concentrations of plasma P-cresol sulfate (P = 0.004) and increased concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA; both P < 0.05), despite the fact that both control and test foods had similar concentrations of these long-chain fatty acids, 0.03% and 0.02%, respectively. These results suggest that the addition of betaine and prebiotics to the control food formula may have increased total body mass in CKD cats by enhancing one-carbon metabolism and by modulating the gut microbiome., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: two of the authors have an affiliation (EE) or formerly had an affiliation (DEJ) to the commercial funders of this research, as employees of Hill’s Pet Nutrition, Inc. (http://www.hillspet.com/our-company.html). This does not alter our adherence to PLOS ONE policies on sharing data and materials. Data is freely available upon request. The funder provided support in the form of salaries for authors (EE, DEJ), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”

Objectives: Recent literature documents a trend of gradual decline in temporal lobe (resective) epilepsy surgery over the past decade. Amongst these, a large scale, comprehensive survey done in selected European, Australian and American centres documents trends of resective temporal epilepsy surgery across two decades. Montreal Neurological Institute has been the leading epilepsy surgery centre for more than 50 years now. It has been at the forefront of investigating and managing epilepsy in Canada. We have looked into the trends of epilepsy surgery in our institute in the past 44 years., Methods: The records of all adult epilepsy surgery procedures (excluding reoperations) performed by the senior authors were analysed from 1971 to 2015. Data retrieved for analysis included type of surgery (intracranial recording, resective, and neuromodulatory) and the specific surgical target for resection. Procedures were grouped into temporal resective, extratemporal (ET) resective and placement of intracranial electrodes (stereotactic electroencephalogram (SEEG))., Results: A total of 2,078 new procedures were performed from 1971 to 2015 at the Montreal Neurological Institute. Temporal procedures constituted the bulk of the proportion of all procedures each year and the entire study period. SEEG group shows linear increase in the number of cases over the years catching up with the total number of temporal procedures., Conclusions: Our study involving a homogenous dataset spanning nearly 50 years shows a decline in temporal lobe surgeries and an increase in intracranial investigations despite the class I evidence of its effectiveness. This corroborates the trends in epilepsy surgery practice profiles in tertiary centres of developed countries.

This study was completed to evaluate a genotype-specific nutritional intervention for reducing the risk of calcium oxalate stone formation. Serum metabolomic profiles and genotypes of 445 cats in the colony at Hill’s Pet Nutrition, Inc (Topeka, KS, USA)were assessed in a genome-wide association study, and revealed an association between genetic variants of alanine-glyoxylate aminotransferase 2 (AGXT2) and 2-oxoarginine. The most significant single nucleotide polymorphisms (SNP) associated with 2-oxoarginine was at position chrA1:212069607, [G/A] (p < 3.687 × 10−17). This SNP explained approximately 15% of the variance in 2-oxoarginine concentrations. The distribution of genotype frequencies was 0.07 AA, 0.39 AG, and 0.54 GG, with a mean relative 2-oxoarginine concentration for each genotype of 0.45 AA, 0.92 AG, and 1.27 GG, indicating a subtractive effect of the minor allele (A). Serum concentrations of two AGXT2 substrates, symmetric/asymmetric dimethylarginines (SDMA/ADMA) and β-aminoisobutyrate (BAIB) were also strongly associated with SNP chrA1:212069607 (p < 1.43 × 10−12 and p < 2.30 × 10−14, respectively). These two AGXT2 substrates were increased with the minor allele (A), indicating that the variant of the AGXT2 gene results in decreased aminotransferase activity. Additionally, the lifetime history of stone incidence showed that cats with the AA variant of AGXT2 SNP had a 2.515× increased incidence of stones compared with cats having the GG variant (p = 0.019). In a subsequent study assessing AGXT2 genotypes, cats (n = 10 GG, 4 AG, 9 AA) were fed control or test food (containing betaine at 0.500%, and the botanicals green tea, fenugreek and tulsi at 0.25, 0.025, and 0.0015%, respectively) in a cross-over study design. Stone risk analysis was conducted on urine samples after feeding control or test food for 28 days each. A calcium oxalate titration test (COT) was performed to assess the amount of added Ox−2 (per L) required to initiate calcium oxalate crystal formation. Cats with the GG variant of the AGXT2 SNP required more added oxalate to initiate urine crystal formation after consuming test food compared with control food, indicating a decreased risk of oxalate crystal formation in GG cats. In addition, urine oxalate concentrations showed an overall effect of test food independent of genotype (p = 0.0009), which resulted in lower oxalate concentrations after consuming test food compared with control food. These data indicate that cats with the GG-specific variant of AGXT2 should benefit from a reduced risk of calcium oxalate stone formation after consuming a betaine and botanical dietary enhancement.

Conceptual flaws can undermine even rigorous test development efforts, especially in the broad empathy and social cognition domains, which are characterized by measure proliferation and inconsistently used construct terms. We discuss these issues, focusing on a new instrument of "mentalizing" as a case study. Across several studies, Clutterbuck et al. (2021a) developed the Four-Item Mentalising Index (FIMI). They described it as the first self-report measure of mentalizing ability and suggested that it offers substantial advances for research and assessment. As we demonstrate with conceptual arguments and empirical data, the FIMI embodies several major problems that are common in this area of research. Using the FIMI as a case study, we underline the importance for test developers of attending to the nonnegotiable necessity of discriminant validity analyses, the challenge of choosing appropriate convergent validity measures, and the difficulties of navigating the jingle-jangle jungle of empathy and social cognition construct terms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Orthopaedic injuries may lead to an increased incidence of intimate partner violence (IPV) during recovery as people dependent on others' help are at a higher risk for abuse. Additionally, there is a lack of understanding of how IPV affects injury recovery. In women being treated for an orthopaedic injury, we aimed to determine the number of new IPV disclosures in the 12 months after an injury and to explore the impact of IPV on recovery., Methods: We enrolled 250 female participants from 6 orthopaedic fracture clinics in Canada, the Netherlands, Spain, and Finland. IPV disclosure and clinical outcomes were assessed at the initial visit and during the 12-month follow-up period., Results: Of 250 participants, 81 (32.4% [95% confidence interval (CI), 26.6% to 38.2%]) had a history of IPV in their lifetime and disclosed this at their initial orthopaedic clinic appointment. Twenty-one participants (12.4% [95% CI, 7.5% to 17.8%]) who did not disclose abuse at the initial visit disclosed IPV during the follow-up. In our a priori unadjusted analysis, disclosure of IPV at the initial appointment or a subsequent follow-up appointment was associated with a 32% lower likelihood of returning to a pre-injury level of function with no restrictions regarding responsibilities at home (hazard ratio, 0.68 [95% CI, 0.46 to 0.99]; p = 0.046). Participants disclosing IPV had lower health-related quality of life on the EuroQol-5 Dimensions (EQ-5D) at the 6-month-follow-up, with adjusted mean differences of -5.3 (95% CI, -10.2 to -0.4, p = 0.04) for the visual analog scale and -0.06 (95% CI, -0.11 to -0.01; p = 0.02) for the Function Index. They also had lower Function Index scores at the final 12-month follow-up visit, with an adjusted mean difference of -0.06 (95% CI, -0.10 to -0.02; p = 0.006)., Conclusions: A surprisingly high percentage of women disclosed IPV within 12 months after the injury. Our exploratory results suggest that women who disclose IPV may have lower health-related quality of life. This study supports the need to optimize orthopaedic clinics to provide appropriate support for asking about and assisting individuals who experienced IPV. Additional research is warranted to further explore these findings., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G888)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Despite growing evidence of pregnancy preparation benefits, there is little knowledge on how women in developing countries prepare for pregnancy and factors influencing their preparedness for pregnancy. Here, we determine how women in Malawi prepare for pregnancy and factors associated with pregnancy preparation., Methods: We used data from a previous cohort study comprising 4,244 pregnant mothers, recruited between March and December 2013 in Mchinji district, Malawi. Associations of pregnancy preparation with socio-demographic and obstetric factors were tested for using mixed effects ordinal regression, with the likelihood ratio and Wald's tests used for variable selection and independently testing the associations., Results: Most mothers (63.9%) did not take any action to prepare for their pregnancies. For those who did (36.1%), eating more healthily (71.9%) and saving money (42.8%) were the most common forms of preparation. Mothers who were married (adjusted odds-ratio (AOR 7.77 (95% CI [5.31, 11.25]) or with no or fewer living children were more likely to prepare for pregnancy (AOR 4.71, 95% CI [2.89,7.61]. Mothers with a period of two to three years (AOR 2.51, 95% CI [1.47, 4.22]) or at least three years (AOR 3.67, 95%CI [2.18, 6.23]) between pregnancies were more likely to prepare for pregnancy than women with first pregnancy or shorter intervals. On the other hand, teenage and older (≥ 35 years old) mothers were less likely to prepare for pregnancy (AOR 0.61, 95%CI [0.47, 0.80]) and AOR 0.49 95%CI [0.33, 0.73], respectively)., Conclusion: While preconception care may not be formally available in Malawi, our study has revealed that over a third of mothers took some action to prepare for pregnancy before conception. Although this leaves around two thirds of women who did not make any form of pregnancy preparation, our findings form a basis for future research and development of a preconception care package that suits the Malawian context., Competing Interests: The authors have declared that no competing interests exist.

Objective: Myelin regeneration in the human central nervous system relies on progenitor cells within the tissue parenchyma, with possible contribution from previously myelinating oligodendrocytes (OLs). In multiple sclerosis, a demyelinating disorder, variables affecting remyelination efficiency include age, severity of initial injury, and progenitor cell properties. Our aim was to investigate the effects of age and differentiation on the myelination potential of human OL lineage cells., Methods: We derived viable primary OL lineage cells from surgical resections of pediatric and adult brain tissue. Ensheathment capacity using nanofiber assays and transcriptomic profiles from RNA sequencing were compared between A2B5+ antibody-selected progenitors and mature OLs (non-selected cells)., Results: We demonstrate that pediatric progenitor and mature cells ensheathed nanofibers more robustly than did adult progenitor and mature cells, respectively. Within both age groups, the percentage of fibers ensheathed and ensheathment length per fiber were greater for A2B5+ progenitors. Gene expression of OL progenitor markers PDGFRA and PTPRZ1 were higher in A2B5+ versus A2B5- cells and in pediatric A2B5+ versus adult A2B5+ cells. The p38 MAP kinases and actin cytoskeleton-associated pathways were upregulated in pediatric cells; both have been shown to regulate OL process outgrowth. Significant upregulation of "cell senescence" genes was detected in pediatric samples; this could reflect their role in development and the increased susceptibility of pediatric OLs to activating cell death responses to stress., Interpretation: Our findings identify specific biological pathways relevant to myelination that are differentially enriched in human pediatric and adult OL lineage cells and suggest potential targets for remyelination enhancing therapies. ANN NEUROL 2022;91:178-191., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Robust forms of measurement such as the London Measure of Unplanned Pregnancy (LMUP), which recognise the complexity of the construct of pregnancy planning/intention, are being adopted worldwide. The aim of this study was to evaluate the psychometric properties of the Mozambican Portuguese version of the LMUP. The Brazilian Portuguese interviewer-administered LMUP was culturally adapted for use in Mozambique and pre-tested with 28 women. Field testing included 524 women aged 16-42. Completion rates of LMUP items were 100%. LMUP scores 0-12 were captured. In terms of reliability (internal consistency), Cronbach's alpha was 0.90, item-rest correlations were <0.2, and all inter-item correlations were positive. In terms of construct validity, principal components analysis showed that measurement was unidimensional, confirmatory factor analysis showed good model fit, and all hypotheses were met. We conclude that the Mozambican Portuguese LMUP is reliable, valid and suitable to use in Mozambique.

Objective: The integration of high-frequency oscillations (HFOs; ripples [80-250 Hz], fast ripples [250-500 Hz]) in epilepsy evaluation is hampered by physiological HFOs, which cannot be reliably differentiated from pathological HFOs. We evaluated whether defining abnormal HFO rates by statistical comparison to region-specific physiological HFO rates observed in the healthy brain improves identification of the epileptic focus and surgical outcome prediction., Methods: We detected HFOs in 151 consecutive patients who underwent stereo-electroencephalography and subsequent resective epilepsy surgery at two tertiary epilepsy centers. We compared how HFOs identified the resection cavity and predicted seizure-free outcome using two thresholds from the literature (HFO rate > 1/min; 50% of the total number of a patient's HFOs) and three thresholds based on normative rates from the Montreal Neurological Institute Open iEEG Atlas (https://mni-open-ieegatlas., Research: mcgill.ca/): global Atlas threshold, regional Atlas threshold, and regional + 10% threshold after regional Atlas correction., Results: Using ripples, the regional + 10% threshold performed best for focus identification (77.3% accuracy, 27% sensitivity, 97.1% specificity, 80.6% positive predictive value [PPV], 78.2% negative predictive value [NPV]) and outcome prediction (69.5% accuracy, 58.6% sensitivity, 76.3% specificity, 60.7% PPV, 74.7% NPV). This was an improvement for focus identification (+1.1% accuracy, +17.0% PPV; p < .001) and outcome prediction (+12.0% sensitivity, +1.0% PPV; p = .05) compared to the 50% threshold. The improvement was particularly marked for foci in cortex, where physiological ripples are frequent (outcome: +35.3% sensitivity, +5.3% PPV; p = .014). In these cases, the regional + 10% threshold outperformed fast ripple rate > 1/min (+3.6% accuracy, +26.5% sensitivity, +21.6% PPV; p < .001) and seizure onset zone (+13.5% accuracy, +29.4% sensitivity, +17.0% PPV; p < .05-.01) for outcome prediction. Normalization did not improve the performance of fast ripples., Significance: Defining abnormal HFO rates by statistical comparison to rates in healthy tissue overcomes an important weakness in the clinical use of ripples. It improves focus identification and outcome prediction compared to standard HFO measures, increasing their clinical applicability., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The concept of empathy as it is used in scholarly discourse has been challenged for over 50 years, yet the same ambiguities and controversies associated with the concept persist and, indeed, have accelerated with the accumulation of definitions, subconstructs that are included under the empathy umbrella, and measuring instruments. In this article we address the following interrelated problems: many definitions, authors not offering definitions, authors using instruments that do not match their definitions, authors not specifying definitions and measurements in cited studies, the jingle-jangle problem, and the persistent need for more construct validity research. In this Special Issue on empathy and its problems, authors bring new theoretical insights, creative research designs, and a critical focus on the empathy concept itself.

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified., Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated., Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021., Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample., Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity., Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

Objective: The authors' objective was to report postsurgical seizure outcome of temporal lobe epilepsy (TLE) patients with normal or subtle, nonspecific MRI findings and to identify prognostic factors related to seizure control after surgery., Methods: This was a retrospective study of patients who underwent surgery from 1999 to 2014 at two comprehensive epilepsy centers. Patients with a clear MRI lesion according to team discussion and consensus were excluded. Presurgical information, surgery details, pathological data, and postsurgical outcomes were retrospectively collected from medical charts. Multiple logistic regression analysis was used to assess the effect of clinical, surgical, and neuroimaging factors on the probability of Engel class I (favorable) versus class II-IV (unfavorable) outcome at last follow-up., Results: The authors included 73 patients (59% were female; median age at surgery 35.9 years) who underwent operations after a median duration of epilepsy of 13 years. The median follow-up after surgery was 30.6 months. At latest follow-up, 44% of patients had Engel class I outcome. Favorable prognostic factors were focal nonmotor aware seizures and unilateral or no spikes on interictal scalp EEG., Conclusions: Favorable outcome can be achieved in a good proportion of TLE patients with normal or subtle, nonspecific MRI findings, particularly when presurgical investigation suggests a rather circumscribed generator. Presurgical factors such as the presence of focal nonmotor aware seizures and unilateral or no spikes on interictal EEG may indicate a higher probability of seizure freedom.

Molecular excitons play a foundational role in chromophore aggregates found in light-harvesting systems and offer potential applications in engineered excitonic systems. Controlled aggregation of chromophores to promote exciton delocalization has been achieved by covalently tethering chromophores to deoxyribonucleic acid (DNA) scaffolds. Although many studies have documented changes in the optical properties of chromophores upon aggregation using DNA scaffolds, more limited work has investigated how structural modifications of DNA via bridged nucleotides and chromophore covalent attachment impact scaffold stability as well as the configuration and optical behavior of attached aggregates. Here we investigated the impact of two types of bridged nucleotides, LNA and BNA, as a structural modification of duplex DNA-templated cyanine (Cy5) aggregates. The bridged nucleotides were incorporated in the domain of one to four Cy5 chromophores attached between adjacent bases of a DNA duplex. We found that bridged nucleotides increase the stability of DNA scaffolds carrying Cy5 aggregates in comparison with natural nucleotides in analogous constructs. Exciton coupling strength and delocalization in Cy5 aggregates were evaluated via steady-state absorption, circular dichroism, and theoretical modeling. Replacing natural nucleotides with bridged nucleotides resulted in a noticeable increase in the coupling strength (≥10 meV) between chromophores and increased H-like stacking behavior (i.e., more face-to-face stacking). Our results suggest that bridged nucleotides may be useful for increasing scaffold stability and coupling between DNA templated chromophores.

Objective: To explore the experiences of women who had used an Early Pregnancy Assessment Unit (EPAU) service in the UK and make recommendations for their improvement., Design: Qualitative interview study., Setting: Early Pregnancy Assessment Units in the UK., Sample: A maximum variation sample of women who had consented to be interviewed having attended one of 26 EPAUs involved in the VESPA study in 2018., Methods: In-depth telephone interviews with 38 women. A thematic framework analysis was conducted, with a focus on how experiences varied according to EPAU service configuration and clinical pathway., Main Outcome Measures: Women's experiences of EPAU services., Results: We found that EPAUs are highly valued, and women's experiences were generally positive. However, women reported a range of issues that negatively affected their experience. These included difficulties accessing the service, insensitive management of the investigation and treatment options of pregnancy loss, poor communication, insufficient information and a lack of support for their psychological health. These issues were not strongly associated with EPAU configuration or clinical pathway., Conclusions: Recommendations to improve women's experiences include the separation of EPAUs from general maternity services, and we make suggestions on how to remove barriers to access by reviewing opening hours, how to provide sensitive patient management, such as automatically cancelling appointments and scans following pregnancy loss, and how to improve communication, both with women and their partners as well as with other parts of the health service., Tweetable Abstract: Early Pregnancy Assessment Units are highly valued by women but aspects of their care experiences, particularly around sensitive management of pregnancy loss, could be improved., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: To evaluate the differences in patient outcomes after operative or nonoperative treatment of displaced, type II distal clavicle fractures., Design: Multicenter, prospective, randomized controlled trial., Setting: Level I trauma centers., Patients/participants: Patients with completely displaced type II distal clavicle fractures were included. Fifty-seven patients were randomized: 27 to the operative group and 30 to the nonoperative group., Intervention: Patients randomized to nonoperative care received a standard shoulder sling, followed by pendulum or gentle range of motion shoulder exercises at any time as directed by the attending surgeon. Patients randomized to the operative group received plate fixation with a precontoured distal clavicular plate or a "hook" plate within 28 days from injury., Main Outcome Measure: Disabilities of the Arm, Shoulder and Hand scores at 1 year., Results: There were no between-group differences in Disabilities of the Arm, Shoulder and Hand or Constant scores at 1 year. More patients in the operative group went on to union (95% vs. 64%, P = 0.02) within 1 year. Twelve patients in the operative group underwent a second operation for implant removal (12/27, 44%). In the nonoperative group, 6 patients (6/30, 20%) subsequently underwent 8 operative procedures., Conclusion: Although this study failed to demonstrate a difference in functional outcomes between operative and nonoperative treatment of Neer type II distal clavicle fractures, nonoperative management led to more complications including a moderate rate of nonunion, which often required secondary surgery to correct, a higher rate of early dissatisfaction with shoulder appearance, and a delayed return to activities in the first 6 months. Operative management provided a safe and reliable treatment option with few complications, but often required secondary implant removal, especially with hook plate fixation., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: M. D. McKee and E. H. Schemitsch are consultants and receive royalties from Stryker for design of clavicle plates. The remaining authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Selenium (Se) is an essential micronutrient for growth and immune function in beef cattle. We previously showed that supranutritional maternal organic Se supplementation during late pregnancy improves immune function in their newborn calves; however, the effects of maternal organic Se-supplementation on fetal programming during different pregnancy stages have yet to be elucidated. Herein, we investigated the effects of supranutritional maternal organic Se-supplementation in different pregnancy trimesters on their beef calf's genome-wide transcriptome profiles. Within 12 to 48 h of birth, whole blood and Longissimus dorsi (LD) muscle biopsies were collected from calves born to 40 crossbred Angus cows that received, except for the control group (CTR), Se-yeast boluses (105 mg of Se/wk) during the first (TR1), second (TR2), or third (TR3) trimester of gestation. Whole-blood Se concentrations of newborn calves increased from CTR, TR1, TR2 to TR3, whereas muscle Se concentrations of newborn calves were only increased in TR3 group. We identified 3048 unique differentially expressed genes (DEGs) across all group comparisons (FDR ≤ 0.05 and |log2FC| ≥ 1.5). Furthermore, we predicted 237 unique transcription factors that putatively regulate the DEGs. Independent of supplementation trimester, supranutritional maternal organic Se supplementation downregulated genes involved in adaptive immunity in all trimesters. Dependent on supplementation trimester, genes involved in muscle development were upregulated by TR3 Se supplementation and downregulated by TR1 Se-supplementation, and genes involved in collagen formation were downregulated by TR2 Se-supplementation. Supranutritional maternal organic Se supplementation in the last trimester of pregnancy resulted in upregulation of myosin and actin filament associated genes, potentially allowing for optimal muscle function and contraction. Our findings suggest a beneficial effect of supranutritional maternal organic Se supplementation during late gestation on Se-status and muscle development and function of newborn calves.

Background: Oncology patients and physicians value empathy because of its association with improved health outcomes. Common measures of empathy lack consistency and were developed without direct input from patients. Because of their intense engagement with health care systems, oncology patients may have unique perspectives on what behaviors signal empathy in a clinical setting., Methods: As part of a cross-sectional study of patient perspectives on clinician empathy at an academic cancer center in the northeastern United States, the authors solicited up to 10 free-text responses to an open-ended question about what clinician behaviors define empathy., Results: The authors categorized open-ended responses from 89 oncology patients into 5 categories representing 14 themes. These categories were relationship sensitivity, focus on the whole person, communication, clinician attributes, and institutional resources and care processes. Frequently represented themes, including listening, understanding, and attention to emotions and what matters most, aligned with existing measures of empathy; behaviors that were not well represented among existing measures included qualities of information sharing and other communication elements. Patients also associated clinician demeanor, accessibility, and competence with empathy., Conclusions: Oncology patients' perspectives on empathy highlight clinician behaviors and attributes that may help to refine patient experience measures and may be adopted by clinicians and cancer centers to enhance patient care and outcomes. High-quality communication skills training can promote active listening and paying attention to the whole person. A system-level focus on delivering empathic care may improve patients' experiences and outcomes., Lay Summary: Oncology patients' responses to an open-ended question about empathic clinician behavior have revealed insights into a variety of behaviors that are perceived as demonstrative of empathy. These include behaviors that imply sensitivity to the clinician-patient relationship, such as listening and understanding and attention to the whole person. Participants valued caring communication and demeanor and clinician accessibility. Perspective taking was not common among answers. Many existing measures of clinical care quality do not include the behaviors cited by patients as empathic. These results can inform efforts to refine quality measures of empathy-associated behaviors in clinical practice. Cancer centers can use skills training to improve elements of communication., (© 2021 American Cancer Society.)

Background and Objectives: To assess the utility of EEG-fMRI for epilepsy surgery, we evaluated surgical outcome in relation to the resection of the most significant EEG-fMRI response., Methods: Patients with postoperative neuroimaging and follow-up of at least 1 year were included. In EEG-fMRI responses, we defined as primary the cluster with the highest absolute t value located in the cortex and evaluated 3 levels of confidence for the results. The threshold for low confidence was t ≥ 3.1 ( p < 0.005); the one for medium confidence corresponded to correction for multiple comparisons with a false discovery rate of 0.05; and a result reached high confidence when the primary cluster was much more significant than the next highest cluster. Concordance with the resection was determined by comparison to postoperative neuroimaging., Results: We evaluated 106 epilepsy surgeries in 84 patients. An increasing association between concordance and surgical outcome with higher levels of confidence was demonstrated. If the peak response was not resected, the surgical outcome was likely to be poor: for the high confidence level, no patient had a good outcome; for the medium and low levels, only 18% and 28% had a good outcome. The positive predictive value remained low for all confidence levels, indicating that removing the maximum cluster did not ensure seizure freedom., Discussion: Resection of the primary EEG-fMRI cluster, especially in high confidence cases, is necessary to obtain a good outcome but not sufficient., Classification of Evidence: This study provides Class II evidence that failure to resect the primary EEG-fMRI cluster is associated with poorer epilepsy surgery outcomes., (© 2021 American Academy of Neurology.)

Objectives: To explore how physicians in neurology, family medicine, internal medicine, and emergency medicine characterize clinical empathy., Methods: Physicians (N = 94) were asked to describe up to 10 examples of empathic physician behavior. Data were analyzed using template analysis., Results: Physicians' descriptions of clinical empathy patterned into three themes: Clinical Performance and Professionalism, Interpersonal Communication, and Clinician Orientation. Clinical Performance and Professionalism subthemes included physician competency and accessibility; intersection with institutional resources; and spending/making/taking time with patients. Interpersonal Communication subthemes involved information sharing; verbal and nonverbal approaches; interpersonal sensitivity; physician self-disclosure; and attention to emotion. Clinician Orientation encompassed general physician demeanor and internal thoughts and feelings that might be unobservable by patients. Physicians varied widely in the themes they mentioned in their definition of empathy., Conclusion: Physicians hold diverse notions of clinical empathy. These extend beyond traditional affective and cognitive empathy definitions to include structural elements like team-based care and accessibility after hours. Communication behaviors were perceived as important for demonstrating empathy. Some physician descriptions of empathy may not be perceptible to patients., Practice Implications: Training physicians to engage in behaviors that both they and patients perceive as empathic may lead to higher patient and physician satisfaction., Competing Interests: Declaration of Competing Interest The authors declare they have no competing conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: The lack of underrepresented in medicine (UIM) physicians in academic plastic surgery is emerging as a critical issue. Lack of diversity has a negative effect on patient care and on the culture of our health care system. This study reports the current status of ethnically UIM physicians in the plastic surgery pipeline, starting from the medical student level and progressing to national leadership positions., Methods: The Electronic Residency Applications Service, National Resident Matching Program, Association of American Medical Colleges, and professional Web sites for journals and national societies were accessed for racial demographic information from 2008 to 2019., Results: Over the past decade, there has been no change or a slight decrease in representation of Blacks among plastic surgery residency applicants, trainees, and academic faculty, at half or less than expected, compared with US Census data. The first point of drop-off occurs at the resident (3.8% of integrated and 5.6% of independent residents) to faculty level (<2.8%). Two percent of program directors and department heads/division chiefs are Black. The next point of drop-off occurs at the national level: there has never been a Black president of American Society of Plastic Surgeons or Plastic Surgery Foundation, and there are no Black editors-in-chiefs of major plastic surgery journals.Following LatinX American surgeons down the pipeline over the past decade, there has been no change or a decrease in representation among plastic surgery residency applicants, resident physicians, and academic faculty, at one-third or less than expected, compared with US Census data. The first point of drop-off occurs at the faculty (4.8%) to local leadership level (0% of program directors and department heads/division chiefs) where there is no representation of LatinX. Once this drop-off occurs, there is no recovery at the national leadership level., Conclusions: In order for our profession to reflect our nation's demographics, academic plastic surgery is in need of a paradigm shift now. Attrition of UIM physicians in plastic surgery begins at medical school graduation and persists through surgical training, faculty appointments, and attainment of leadership positions. Creative and innovative commitment to diversity and inclusion is necessary., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Bilateral lambdoid and sagittal synostosis, or Mercedes Benz Syndrome, is a rare complex craniosynostosis resulting in frontal bossing, a tapered posterior fossa, and an anteriorly displaced cranial vertex. Its ideal surgical correction must result in posterior expansion, skull elongation, and caudal repositioning of the vertex. We present a craniometric analysis of skull changes with posterior-superior distraction and introduce a novel craniometric measure: vertex position. In this study, a retrospective review was performed to analyze outcomes of posterior cranial vault distraction osteogenesis (PVDO) using a posterior-superior distraction vector from 2016 to 2019. Cranial vertex position was measured as a fraction of the occipitofrontal diameter from rostral to caudal (0-1.0). Four patients underwent PVDO at mean age 10.61 ± 3.16 months utilizing a posterior-superior distraction vector. Linear distraction distance averaged 30.30 ± 0.90 mm with a mean consolidation period of 3.98 ± 0.72 months. Mean corrected change in intra-cranial volume was 236.30 ± 3.71 mL, at an average rate of 7.81 ± 2.00 mL/mm of distraction. Increases in anterior cranial height (7.83 ± 2.51 mm), middle cranial height (8.43 ± 4.21 mm), posterior cranial height (13.15 ± 7.45 mm), and posterior cranial fossa height (21.99 ± 8.55 mm) were observed. Cranial vertex demonstrated a mean posterior movement of 0.18 ± 0.13. PVDO utilizing a posterior-superior distraction vector for management of nonsyndromic bilateral lambdoid and sagittal synostosis effectively increases intracranial volume and height and provides an esthetic outcome with posterior movement of the cranial vertex., Competing Interests: The authors report no conflicts of interests., (Copyright © 2021 by Mutaz B. Habal, MD.)

Researchers in the healthcare communication field come from many different educational backgrounds. Such diversity generally strengthens a field, but sometimes a set of beliefs or a particular orthodoxy may predominate in ways that are negative. We discuss one such example, noting how the research culture deriving from training in schools of education treats the concepts of reliability and validity. We note that some researchers working in fields such as medical education and healthcare communication use the terms "reliable" and "valid" loosely or even incorrectly, often referring to them as a single catch-phrase. More importantly, we caution healthcare communication researchers against a tyranny of reliability and validity in which researchers feel pressure to avoid creating unique instruments to study new questions, instead using instruments with previously demonstrated reliability and validity even when these may not directly capture the concept of interest. This practice is motivated by realistic fears that reviewers and editors will disapprove of their work because the instruments used are not known to be "reliable and valid." We encourage the research community to take a more balanced approach wherein originality is not stifled, and in which creativity and rigor exist side by side., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Radiofrequency thermocoagulation (RF-TC) is a minimally invasive ablative option for refractory focal epilepsy., Methods: A retrospective chart review was conducted of all patients who underwent stereoelectroencephalography (SEEG)-guided RF-TC at our institution., Results: Fourteen patients underwent robot-guided electrode implantation and subsequent RF-TC. After RF-TC, one of the three patients with PVNH was seizure free, one had 18 months of seizure freedom (Engel 2b), and one required temporal neocortical/PVNH resection (Engel 1a). One of the four patients with focal cortical dysplasia (FCD) was seizure free (Engel 1a), two attained seizure freedom after resection (Engel 1a and 1b), while one continues to have significant seizures (Engel 4b). One patient with cavernoma and low central area epileptogenic zone (EZ) did not benefit from RF-TC and is planned for resection. Two of the MRI-negative patients achieved seizure freedom for 3 months and 1 year, respectively, subsequently requiring resection (Engel 1a). One remains seizure free at 4 weeks. Three had seizure recurrence immediately (Engel 4b). With RF-TC alone, two patients (14%) achieved Engel 1a, two were seizure free at 1 year, one had 3 months of seizure freedom, while the rest had recurrence immediately or within a few weeks. 7/14 patients underwent secondary interventions after RF-TC. Overall, seven patients achieved Engel 1a or 1b, one each 2b and 3a, and five Engel 4b., Conclusion: At our institution, RF-TC is a safe ablative procedure for refractory focal epilepsy. It can serve as a segue to secondary interventions and appears promising in PVNH cases. Its role in MRI-negative cases is less clear.

Objective: Drug-resistant temporal lobe epilepsy (TLE) is the most common type of epilepsy for which patients undergo surgery. Despite the best clinical judgment and currently available prediction algorithms, surgical outcomes remain variable. We aimed to build and to evaluate the performance of multidimensional Bayesian network classifiers (MBCs), a type of probabilistic graphical model, at predicting probability of seizure freedom after TLE surgery., Methods: Clinical, neurophysiological, and imaging variables were collected from 231 TLE patients who underwent surgery at the University of California, San Francisco (UCSF) or the Montreal Neurological Institute (MNI) over a 15-year period. Postsurgical Engel outcomes at year 1 (Y1), Y2, and Y5 were analyzed as primary end points. We trained an MBC model on combined data sets from both institutions. Bootstrap bias corrected cross-validation (BBC-CV) was used to evaluate the performance of the models., Results: The MBC was compared with logistic regression and Cox proportional hazards according to the area under the receiver-operating characteristic curve (AUC). The MBC achieved an AUC of 0.67 at Y1, 0.72 at Y2, and 0.67 at Y5, which indicates modest performance yet superior to what has been reported in the state-of-the-art studies to date., Significance: The MBC can more precisely encode probabilistic relationships between predictors and class variables (Engel outcomes), achieving promising experimental results compared to other well-known statistical methods. Multisite application of the MBC could further optimize its classification accuracy with prospective data sets. Online access to the MBC is provided, paving the way for its use as an adjunct clinical tool in aiding pre-operative TLE surgical counseling., (© 2021 International League Against Epilepsy.)

Environmental enteric dysfunction (EED) is a gastrointestinal inflammatory disease caused by malnutrition and chronic infection. EED is associated with stunting in children and reduced efficacy of oral vaccines. To study the mechanisms of oral vaccine failure during EED, we developed a microbiota- and diet-dependent mouse EED model. Analysis of E. coli-labile toxin vaccine-specific CD4 + T cells in these mice revealed impaired CD4 + T cell responses in the small intestine and but not the lymph nodes. EED mice exhibited increased frequencies of small intestine-resident RORγT + FOXP3 + regulatory T (Treg) cells. Targeted deletion of RORγT from Treg cells restored small intestinal vaccine-specific CD4 T cell responses and vaccine-mediated protection upon challenge. However, ablation of RORγT + FOXP3 + Treg cells made mice more susceptible to EED-induced stunting. Our findings provide insight into the poor efficacy of oral vaccines in EED and highlight how RORγT + FOXP3 + Treg cells can regulate intestinal immunity while leaving systemic responses intact., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific., Methods: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death., Results: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate., Conclusion: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool., (© Crown copyright 2021.)

Objectives: The incidence of pancreatic cancer is age dependent. Ninety percent of new diagnoses occur in patients older than 55 years. Despite the association with age and cancer, elderly patients are historically underrepresented in clinical trials. Thus, optimal management of elderly patients has a lack of data. The purpose of this retrospective study was to investigate the outcomes of palliative chemotherapy in elderly patients with pancreatic cancer compared with supportive care alone., Methods: Unicentric data were reviewed on all elderly patients (defined as age >65 years) with a diagnosis of pancreatic cancer from 2008 through 2019 to compare outcomes in those who received chemotherapy versus supportive care alone., Results: The study reviewed 665 patients with a median age of 75 years (mean, 75.7 years) and average Charlson Comorbidity Score of 5.74. Of them, 291 received chemotherapy and 363 received supportive care only. Chemotherapy was associated with a median overall survival of 250 versus 93 days with supportive care (P < 0.0001). Analysis showed improved survival for all age ranges, cancer stages, and Charlson Comorbidity Scores., Conclusions: Elderly pancreatic cancer patients can benefit from palliative chemotherapy, and it should be considered, especially in patients with fewer medical comorbidities and better functional status., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The objective of this study was to evaluate the benefits and inherent risks of dental cleaning procedures, based on serum and urine biomarkers for kidney function and tissue damage, in dogs and cats. Thirty-one asymptomatic, mostly older dogs (14 neutered male and 17 ovariohysterectomized female dogs of various breeds between 3 and 14 years old) and cats (19 neutered male and 12 ovariohysterectomized female domestic short hair cats between 2 and 16 years old) diagnosed with periodontal disease on physical exam, and recommended by their veterinarian to have dental cleaning under general anesthesia were evaluated in a prospective study. Serum and urine samples were collected from dogs and cats 1 week before, 6 hours after, and again 1 week after the dental cleaning procedure. Samples were analyzed for biomarkers of kidney function [serum creatinine (Cr), symmetric dimethylarginine (SDMA), and blood urea nitrogen (BUN), and urine for specific gravity (USG) and protein:creatinine (UPC) ratio]. A panel of biomarkers for renal tissue damage was also assessed [serum β-aminoisobutyric acid (BAIB), and urine cystatin B and clusterin]. Samples collected one week before dental cleaning procedures showed that increased age and severity of dental disease were linked to abnormal kidney function biomarker values (age: elevated SDMA and Cr concentrations and isosthenuric USG values; disease severity: elevated UPC ratios) as well as elevated urine cystatin B and clusterin concentrations. Directly after the dental cleaning procedure, an increased number of cats with elevated SDMA concentrations was observed (specifically in cats with longer duration of dental procedures). Extended duration of dental procedures (≥60 min) was linked to increased urine cystatin B and clusterin concentrations, whereas shorter duration procedures was linked to decreased urine cystatin B and clusterin. Higher SDMA concentrations persisted in cats one week after the dental cleaning procedures and were linked to elevated UPC ratios one week before cleaning procedures. In conclusion, the results of this study indicate a link between severity of dental disease, renal tissue injury, and impaired renal function. Longer duration dental procedures in cats may carry inherent risks of kidney injury and impaired renal function., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: two of the authors have an affiliation (GF, MY) to the commercial funders of this research, as employees of IDEXX Laboratories, Inc. (https://www.idexx.com/en/). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The purpose of this study is to determine if water with increased viscosity results in increased water intake, thus lowering the risk of urolithiasis in cats. Twelve healthy adult cats were fed pre-trial standard dry maintenance food for 1 week and then randomized into two groups for the study phase. The cats continued to receive the same food but were provided either control (deionized) water or viscous (1% methylcellulose) water for two months and then switched to the other water type for two months in a cross-over study design with repeated measures. Complete blood counts, serum chemistry profiles, and urinalysis were performed at the initiation of the study and again at 1, 2, 3, and 4 months. Daily water consumption and energy intake for each cat were recorded. Body weights were assessed weekly. Cats consuming 1% methylcellulose water with increased viscosity had increased water intake ( p < 0.001; 25% and 21% higher at 28 and 56 days, respectively). Increased consumption of water resulted in lower urine specific gravity ( p = 0.04), serum creatinine ( p = 0.02), and blood urea nitrogen ( p = 0.002) concentrations (without changing serum albumin, glucose, and calcium concentrations or serum osmolality) and decreased urine calcium concentration ( p = 0.01) compared with cats consuming control water. In addition, the increased water intake increased ( p = 0.05) resistance to oxalate crystal formation.

Introduction: Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia., Case Report: A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia.Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk., Discussion: Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors' knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.

Objective: Previous positron emission tomography (PET) studies using [ 11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [ 11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes., Methods: We obtained magnetic resonance imaging (MRI) and [ 11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [ 11 C]ABP688 nondisplaceable binding potential (BP ND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [ 11 C]ABP688-BP ND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [ 18 F]fluorodeoxyglucose (FDG) uptake in each clinical group., Results: MTLE [ 11 C]ABP688-BP ND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [ 11 C]ABP688-BP ND and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [ 11 C]ABP688-BP ND was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [ 11 C]ABP688-PET+[ 18 F]FDG-PET showed no between-group significant difference in [ 18 F]FDG uptake, whereas CA1-3 [ 11 C]ABP688-BP ND remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21)., Significance: Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [ 11 C]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [ 11 C]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients., (© 2021 International League Against Epilepsy.)

Objective: To investigate the psychometric properties of the validated Chichewa version of the London Measure of Unplanned Pregnancy in a large representative community-based sample in Malawi, a low-income country. We collected data on pregnancy intention from a cohort of 4244 pregnant women in Malawi using the validated Chichewa version of the London Measure of Unplanned Pregnancy (LMUP). We evaluated the psychometric properties of the Chichewa LMUP using classical test theory and confirmatory factor analysis to re-assess the performance of items one and six, which had weaker performance in the original smaller, facility-based validation sample., Results: The Chichewa version of the LMUP met all pre-set criteria for validation. There are now nine validations of the LMUP in different low-and-middle-income countries, confirming the validity and applicability of the LMUP in these settings.

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multidisciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined the following four major topics: 1 ) the science of wildland fire incidence and fire management, 2 ) the respiratory and cardiovascular health effects of wildland fire smoke exposure, 3 ) communication strategies to address these health risks, and 4 ) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication, and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease. Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults, and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and development of robust clinical and public health communication tools.

Objectives: To explore what undergraduates, community members, oncology patients, and physicians consider empathic behavior in a physician., Methods: 150 undergraduates, 152 community members, 95 physicians, and 89 oncology patients rated 49 hypothetical physician behaviors for how well they fit their personal definition of physician empathy. Dimensions of empathy were explored and compared across groups., Results: Three dimensions of empathy were Conscientious and Reassuring, Relationship Oriented, and Emotionally Involved. Relationship Oriented was the most strongly endorsed, followed by Emotionally Involved, with Conscientious and Reassuring coming in last. There were no group differences for Conscientious and Reassuring, but the Relationship Oriented factor was more endorsed by the clinical groups (physicians and patients) than the non-clinical groups. The Emotionally Involved factor was endorsed by physicians notably more than by patients., Conclusion: What is considered clinical empathy is not the same across individuals and stakeholder groups., Practice Implications: Physicians and patients differ in how much they include the physicians' emotionality and emotion-related actions in their definition of empathy. Communication training for physicians that emphasizes behaviors associated with empathy (listening, understanding a person's feelings and perspectives, and showing interest in and concern for the whole person) may enhance patients' perception of clinical empathy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Thin slices are used across a wide array of research domains to observe, measure, and predict human behavior. This article reviews the thin-slice method as a measurement technique and summarizes current comparative thin-slice research regarding the reliability and validity of thin slices to represent behavior or social constructs. We outline decision factors in using thin-slice behavioral coding and detail three avenues of thin-slice comparative research: (1) assessing whether thin slices can adequately approximate the total of the recorded behavior or be interchangeable with each other (representativeness); (2) assessing how well thin slices can predict variables that are different from the behavior measured in the slice (predictive validity), and (3) assessing how interpersonal judgment accuracy can depend on the length of the slice (accuracy-length validity). The aim of the review is to provide information researchers may use when designing and evaluating thin-slice behavioral measurement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Murphy and Hall.)

Abstract: The STarT Back approach comprises subgrouping patients with low back pain (LBP) according to the risk of persistent LBP-related disability, with appropriate matched treatments. In a 12-month clinical trial and implementation study, this stratified care approach was clinically and cost-effective compared with usual, nonstratified care. Despite the chronic nature of LBP and associated economic burden, model-based economic evaluations in LBP are rare and have shortcomings. This study therefore produces a de novo decision model of this stratified care approach for LBP management to estimate the long-term cost-effectiveness and address methodological concerns in LBP modelling. A cost-utility analysis from the National Health Service perspective compared stratified care with usual care in patients consulting in primary care with nonspecific LBP. A Markov state-transition model was constructed where patient prognosis over 10 years was dependent on physical function achieved at 12 months. Data from the clinical trial and implementation study provided short-term model parameters, with extrapolation using 2 cohort studies of usual care in LBP. Base-case results indicate this model of stratified care is cost-effective, delivering 0.14 additional quality-adjusted life years at a cost saving of £135.19 per patient over a time horizon of 10 years. Sensitivity analyses indicate the approach is likely to be cost-effective in all scenarios and cost saving in most. It is likely this stratified care model will help reduce unnecessary healthcare usage while improving the patient's quality of life. Although decision-analytic modelling is used in many conditions, its use has been underexplored in LBP, and this study also addresses associated methodological challenges., (Copyright © 2020 International Association for the Study of Pain.)

Digital stress is believed to play a role in the association between social media use and psychosocial outcomes. However, the literature is limited by a lack of measures that conform to published theoretical models of the construct. The present investigation details the development of a new multidimensional measure of digital stress. Based on an earlier conceptualization of Digital Stress (Steele et al., 2020), Study 1 identified items from extant measures of digital stress, conducted a qualitative review of the literature to compose new items, and conducted focus groups with young adults and adolescents (N = 23) to improve item wording and interpretation. Study 2 conducted an exploratory factor analysis (EFA) of items with a young adult sample (N = 247) collected online, yielding support for four hypothesized factors (i.e., availability stress, approval anxiety, fear of missing out [FoMO], and connection overload) plus one unanticipated factor (i.e., online vigilance). In Study 3, college students (N = 174) completed paper-and-pencil surveys, and EFA results showed a similar structure as detected in Study 2. In Study 4, confirmatory factor analysis examining the five-factor model was conducted on data from adolescents (N = 163) and college students (N = 152). These procedures yielded 24 items measuring 5 components of digital stress: availability stress, approval anxiety, FoMO, connection overload, and online vigilance. Associations between digital stress and psychosocial distress and functioning are reported to demonstrate convergent and divergent validity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Problem and Background: The preconception period provides a significant opportunity to engage women in healthy behaviour change for improved maternal and child health outcomes. However, there is limited research exploring women's pregnancy planning in Australia., Aim: This study investigated associations between pregnancy planning, socio-demographics and preconception health behaviours in Australian women., Methods: A retrospective cross-sectional survey of pregnant women ≥18-years-of-age recruited through a Victorian public maternity service and a national private health insurer., Results: Overall 317 women (30±4.7 years) participated (public: n=225, private: n=92). Planned pregnancies were reported by 74% of women and were independently associated with marital status (AOR=5.71 95% CI 1.92-17.00, p=0.002); having ≤2 children (AOR=3.75 95% CI 1.28-11.05, p=0.016); and having private health insurance (AOR=2.51 95% CI 1.08-5.81, p=0.03). Overall, women reported preconception: any folic-acid supplementation (59%), up-to-date cervical screening (68%), weight management attempts (75%), accessing information from health professionals (57%) and immunisation reviews (47%). Pregnancy planners were more likely to use folic-acid (AOR=17.13 95% CI 7.67-38.26, p<0.001), review immunisations (AOR=2.09 95% CI 1.07-4.10, p=0.03) and access information (AOR=3.24 95% CI 1.75-6.00, p<0.001) compared to non-planners. Women <25-years-of-age were less likely to access information (AOR=0.38 95% CI 0.16-0.89, p=0.03) and take folic-acid (AOR=0.23 95% CI 0.09-0.59, p=0.002) and were more likely to smoke 3-months preconception (AOR=6.68 95% CI 1.24-36.12, p=0.03)., Conclusions: Women with planned and unplanned pregnancies reported variable preconception health behaviour uptake and limited healthcare engagement. Opportunities exist to improve awareness and healthcare engagement for optimising preconception health and pregnancy planning benefits including collaborative health promotion. Population-based and targeted approaches reaching pregnancy planners and non-planners are required., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Neuronavigation using pre-operative imaging data for neurosurgical guidance is a ubiquitous tool for the planning and resection of oncologic brain disease. These systems are rendered unreliable when brain shift invalidates the patient-image registration. Our previous review in 2015, Brain shift in neuronavigation of brain tumours: A review offered a new taxonomy, classification system, and a historical perspective on the causes, measurement, and pre- and intra-operative compensation of this phenomenon. Here we present an updated review using the same taxonomy and framework, focused on the developments of intra-operative ultrasound-based brain shift research from 2015 to the present (2020). The review was performed using PubMed to identify articles since 2015 with the specific words and phrases: "Brain shift" AND "Ultrasound" . Since 2015, the rate of publication of intra-operative ultrasound based articles in the context of brain shift has increased from 2-3 per year to 8-10 per year. This efficient and low-cost technology and increasing comfort among clinicians and researchers have allowed unique avenues of development. Since 2015, there has been a trend towards more mathematical advancements in the field which is often validated on publicly available datasets from early intra-operative ultrasound research, and may not give a just representation to the intra-operative imaging landscape in modern image-guided neurosurgery. Focus on vessel-based registration and virtual and augmented reality paradigms have seen traction, offering new perspectives to overcome some of the different pitfalls of ultrasound based technologies. Unfortunately, clinical adaptation and evaluation has not seen as significant of a publication boost. Brain shift continues to be a highly prevalent pitfall in maintaining accuracy throughout oncologic neurosurgical intervention and continues to be an area of active research. Intra-operative ultrasound continues to show promise as an effective, efficient, and low-cost solution for intra-operative accuracy management. A major drawback of the current research landscape is that mathematical tool validation based on retrospective data outpaces prospective clinical evaluations decreasing the strength of the evidence. The need for newer and more publicly available clinical datasets will be instrumental in more reliable validation of these methods that reflect the modern intra-operative imaging in these procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gerard, Kersten-Oertel, Hall, Sirhan and Collins.)

The effects of operational factors an on an electrokinetic-enhanced filtration (EKEF) application to dewater orange juice (OJ) and malt extract (ME) was investigated. EKEF improved dewatering of both foodstuffs and resulted in net dewatering efficiencies of 7.4% and 4.9% for OJ and 10.7% and 6.3% for ME after 5.5 h processing under 30 V and 15 V, respectively. Dry matter content was increased by 19.2% and 15.6% for OJ after 5.5 h and 14.8% and 12.8% for ME after 3.5 h under 30 V and 15 V, respectively, compared with 14.9% and 10.3% under the control conditions for OJ and ME, respectively. The EKEF process effectively improved dewatering of high moisture-content foods with positive impacts on process efficiency by increased voltage, pressure, and the pore size of filters. The initial distance between electrodes had a negative impact as the distance increased. EKEF is a useful adjunct to improve high pressure filtration of foodstuffs., 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.)

Objective: To identify differences in patient-physician interactions associated with improvements in GERD symptoms in a randomized controlled trial comparing integrative medicine and primary care/standard visits., Methods: We analyzed video recordings of 2-minute excerpts (thin slices) from the beginning, middle, and end of 21 study visits (11 standard, 10 integrative medicine)., Results: According to blind coders' analysis of the excerpts, prospective improvement in GERD symptoms was most highly correlated with patients appearing pleased (r = 0.71, p < 0.01) and friendly (r = 0.67, p < 0.01) at the end of the visit, controlling for visit type. The combination of patient and physician smiling at the end of the visit was associated with improvement in GERD symptoms (r 2 = 0.45, p = 0.004). The physician in the integrative visits was more engaged (p = 0.009), friendly (p = 0.005), relaxed (p = 0.002), smiled longer (p = 0.006), gazed longer (p = 0.02), and gestured more (p = 0.007), compared to standard visits. Patients in integrative visits also smiled longer (p = 0.004)., Conclusion: The expanded history-taking questions asked by integrative clinicians may enhance relationship building, modifying patients' responses and improving patient-centered behaviors from clinicians,ultimately facilitating symptom improvement., Practice Implications: Analysis of nonverbal behaviors may facilitate a better understanding of patient-clinician interactions in integrative medicine visits and yield insights to improve clinical interactions in conventional medicine., Competing Interests: Declaration of Competing interest MLD has received remuneration from Harvard Health Publishing for blogs and is an author for UpToDate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sterile neutrinos are natural extensions to the standard model of particle physics and provide a possible portal to the dark sector. We report a new search for the existence of sub-MeV sterile neutrinos using the decay-momentum reconstruction technique in the decay of ^{7}Be. The experiment measures the total energy of the ^{7}Li daughter atom from the electron capture decay of ^{7}Be implanted into sensitive superconducting tunnel junction (STJ) quantum sensors. This first experiment presents data from a single STJ operated at a low count rate for a net total of 28 days, and provides exclusion limits on sterile neutrinos in the mass range from 100 to 850 keV that improve upon previous work by up to an order of magnitude.