Age Deficits in Associative Memory are not Alleviated by Multisensory Paradigms.

OBJECTIVES: Age deficits in memory are widespread, this impacts individuals at a personal level, and investigating memory has been a key focus in cognitive ageing research. Age deficits occur in memory for an episode, where information from the environment is integrated through the senses into an episodic event via associative memory. Associating items in memory has been shown to be particularly difficult for older adults but can often be alleviated by providing support from the external environment. The current investigation explored the potential for increased sensory input (multimodal stimuli) to alleviate age deficits in associative memory. Here, we present compelling evidence, supported by Bayesian analysis, for a null age-by-modality interaction. METHODS: Across three pre-registered studies, young and older adults (n = 860) completed associative memory tasks either in single modalities or in multimodal formats. Study 1 used either visual text (unimodal) or video introductions (multimodal) to test memory for name-face associations. Studies 2 and 3 tested memory for paired associates. Study 2 used unimodal visual presentation or cross modal visual-auditory word pairs in a cued recall paradigm. Study 3 presented word pairs as visual only, auditory only or audiovisual and tested memory separately for items (individual words) or associations (word pairings). RESULTS: Typical age deficits in associative memory emerged, but these were not alleviated by multimodal presentation. DISCUSSION: The lack of multimodal support for associative memory indicates that perceptual manipulations are less effective than other forms of environmental support at alleviating age deficits in associative memory.

Evaluation of a Virtual Health Equity Training for Mid-Career Primary Healthcare Providers.

OBJECTIVES: Providing cultural competence training is recommended as a way to improve patient-centered care and reduce health disparities. Increasing awareness of implicit biases and understanding internal motivations for overcoming these biases can influence provider decisions and communications with patients. This study aims to provide a health equity and implicit bias training to healthcare providers and assess knowledge and attitude gains. METHODS: Mid-career primary healthcare providers (n = 21) with at least 5 years of primary care experience participated in the training as a prerequisite for providing patient care in a telehealth primary care practice that overwhelmingly serves patients of color. RESULTS: There was a significant increase in knowledge (p < .001) as well as attitudes (p < .001) in healthcare providers from pretest to posttest. Almost none (4.5%) of the providers were distracted during the training, which may be due to the interactive nature of the training that included group-based reflection discussions. CONCLUSION: A virtual training for primary healthcare providers on health equity and implicit bias improved knowledge and equitable attitudes and had high satisfaction. Additional research is needed to determine if this type of training can influence providers' ability to actively address known disparities in care.

The effect of unisensory and multisensory information on lexical decision and free recall in young and older adults.

Studies using simple low-level stimuli show that multisensory stimuli lead to greater improvements in processing speed for older adults than young adults. However, there is insufficient evidence to explain how these benefits influence performance for more complex processes such as judgement and memory tasks. This study examined how presenting stimuli in multiple sensory modalities (audio-visual) instead of one (audio-only or visual-only) may help older adults to improve their memory and cognitive processing compared to young adults. Young and older adults completed lexical decision (real word vs. pseudoword judgement) and word recall tasks, either independently, or in combination (dual-task), with and without perceptual noise. Older adults were better able to remember words when encoding independently. In contrast, young adults were better able to remember words when encoding in combination with lexical decisions. Both young and older adults had better word recall in the audio-visual condition compared with the audio-only condition. The findings indicate significant age differences when dealing with multiple tasks during encoding. Crucially, there is no greater multisensory benefit for older adults compared to young adults in more complex processes, rather multisensory stimuli can be useful in enhancing cognitive performance for both young and older adults.

Investigating the outcomes of virus coinfection within and across host species.

Interactions between coinfecting pathogens have the potential to alter the course of infection and can act as a source of phenotypic variation in susceptibility between hosts. This phenotypic variation may influence the evolution of host-pathogen interactions within host species and interfere with patterns in the outcomes of infection across host species. Here, we examine experimental coinfections of two Cripaviruses-Cricket Paralysis Virus (CrPV), and Drosophila C Virus (DCV)-across a panel of 25 Drosophila melanogaster inbred lines and 47 Drosophilidae host species. We find that interactions between these viruses alter viral loads across D. melanogaster genotypes, with a ~3 fold increase in the viral load of DCV and a ~2.5 fold decrease in CrPV in coinfection compared to single infection, but we find little evidence of a host genetic basis for these effects. Across host species, we find no evidence of systematic changes in susceptibility during coinfection, with no interaction between DCV and CrPV detected in the majority of host species. These results suggest that phenotypic variation in coinfection interactions within host species can occur independently of natural host genetic variation in susceptibility, and that patterns of susceptibility across host species to single infections can be robust to the added complexity of coinfection.

Heterogeneities in infection outcomes across species: sex and tissue differences in virus susceptibility.

Species vary in their susceptibility to pathogens, and this can alter the ability of a pathogen to infect a novel host. However, many factors can generate heterogeneity in infection outcomes, obscuring our ability to understand pathogen emergence. Such heterogeneities can alter the consistency of responses across individuals and host species. For example, sexual dimorphism in susceptibility means males are often intrinsically more susceptible than females (although this can vary by host and pathogen). Further, we know little about whether the tissues infected by a pathogen in one host are the same in another species, and how this relates to the harm a pathogen does to its host. Here, we first take a comparative approach to examine sex differences in susceptibility across 31 species of Drosophilidae infected with Drosophila C Virus (DCV). We found a strong positive inter-specific correlation in viral load between males and females, with a close to 1:1 relationship, suggesting that susceptibility to DCV across species is not sex specific. Next, we made comparisons of the tissue tropism of DCV across seven species of fly. We found differences in viral load between the tissues of the seven host species, but no evidence of tissues showing different patterns of susceptibility in different host species. We conclude that, in this system, patterns of viral infectivity across host species are robust between males and females, and susceptibility in a given host is general across tissue types.

Transcriptomic Analysis of Glycosylation and Neuroregulatory Pathways in Rodent Models in Response to Psychedelic Molecules.

The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging knowledge-based gene-set information analysis has been adopted to explore the potential impact of psychedelic molecules on both glycosylation, (a post-translational modifications (PTM)) and on neuro-regulatory pathways. Though limitations and restrictions rise from the scarcity of publicly available 'omics' data, targeted analysis enabled us to identify a number of key glycogenes (Hexb, Hs6st2, Col9a2, B3gat2, Mgat5, Bgn) involved the structural organization of extracellular matrix and neuroprotective factors (Kl, Pomc, Oxt, Gal, Avp, Cartpt) which play vital roles in neuron protection, development as well as synaptic stability. In response to psychedelic molecules, we found that these genes and associated pathways are transcriptional altered in rodent models. The approach used indicates the potential to exploit existing datasets for hypothesis generation and testing for the molecular processes which play a role in the physiological response to psychedelic molecule effects. These reported findings, which focused on alterations in glycogenes and neuro-regulatory factors may provide a novel range of biomarkers to track the beneficial, as well as potential toxicological effects of psychedelic molecules.

Psychological adjustment to initial treatment for low-risk thyroid cancer: Preliminary study.

BACKGROUND: Low-risk papillary thyroid carcinoma (LR-PTC) can be managed by immediate surgery (IS) or active surveillance (AS). We compare the psychological impact of these treatments on patients with LR-PTC. METHODS: Psychological data were collected over 1 year, with assessments at the time of treatment decision (T1), at 6 months (T2) and 12 months (T3) follow-up. Assessments included 13 validated psychological tools. RESULTS: Of 27 enrolled patients, 20 chose AS and 7 chose IS. The average times to T2 and T3 were 5.7 and 11.3 months, respectively. For both groups, Impact of Events Scale scores significantly decreased (p = 0.001) at T2, and depressive/anxiety symptoms remained low. CONCLUSIONS: This study demonstrates the feasibility of assessing psychological outcomes among patients treated for LR-PTC. Further studies are needed to evaluate the impact of AS versus IS on quality of life and changes that patients experience over longer time periods following their treatment decision.

Implementation of an Online External Ventricular Drain Training Module-An Educational Initiative to Improve Proficiency of Perioperative Health Care Providers: Results of a Retrospective Study.

BACKGROUND: An external ventricular drain (EVD) training module may improve the knowledge and proficiency of perioperative health care providers (HCPs). METHODS: We examined knowledge gaps, self-reported comfort in managing EVDs, and improvement in self-assessment scores among HCPs from 7 academic medical centers based on an online EVD training module. RESULTS: Of the 326 HCPs who completed the module, 207 (70.6%) reported being uncomfortable managing EVDs. The median pretest scores were 6 (interquartile range=2), and posttest scores were 8 (interquartile range=1), out of a maximum possible score of 9. The most frequent incorrectly answered questions were: (a) maximum allowed hourly cerebrospinal fluid volume drainage (51%), (b) the components of a normal intracranial pressure waveform (41%), and (c) identifying the correct position of the stopcock for accurate measurement of intracranial pressure (41%). The overall gain in scores was 2 (interquartile range=2) and highest among HCPs who had managed 1 to 25 EVDs (2.51, 95% confidence interval: 2.23-2.80), and without self-reported comfort in managing EVDs (2.26, 95% confidence interval: 1.96-2.33, P <0.0001). The majority of participants (312, 95.7%) reported that the training module helped them understand how to manage EVDs, and 276 (84.7%) rated the module 8 or more out of 10 in recommending it to their colleagues. CONCLUSIONS: This online EVD training module was well-received by participants. Overall, improved scores reflect enhanced knowledge among HCPs following completion of the module. The greatest benefit was observed in those reporting less experience and feeling uncomfortable in managing EVDs. The impact on the reduction in EVD-associated adverse events deserves further examination.

New York State 1115 Demonstration Independent Evaluation: Interim Report.

The broad goals of New York State's Medicaid Section 1115 Waiver are to enroll a majority of Medicaid beneficiaries into managed care, increase access and service quality, and expand coverage to more low-income New Yorkers. The RAND Corporation was competitively selected as the independent evaluator to assess two components under this 1115 Demonstration Waiver: the Managed Long-Term Care (MLTC) program and the 12-month continuous eligibility policy, which guarantees enrollees Medicaid coverage regardless of changes in income in the 12 months after eligibility determination and enrollment. This final interim evaluation examines whether these two components have helped achieve the program's goals. The RAND team's analyses show that the Demonstration has expanded access to managed care through mandatory MLTC enrollment and 12-month continuous eligibility. The team found no evidence of a significant change in patient safety or quality of care. The authors note that, although this means that there is no evidence the Demonstration achieved the goal of improving quality of care, increasing access without compromising quality of care is a success in its own right.

Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity.

BACKGROUND: Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries. METHODS: In this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry. We further integrated genetics, clinical and literature evidence to prioritise drug targets. Additional sensitivity analyses including multi-trait colocalization and phenome-wide MR were conducted to test for MR assumptions. FINDINGS: MR and colocalization prioritized four protein targets, FCRL3, ICAM5, ENTPD5 and OAS1 that showed effect on COVID-19 severity in European ancestry. One protein target, SERPINA1 showed a stronger effect in African ancestry but much weaker effect in European ancestry (odds ratio [OR] in Africans=0.369, 95%CI=0.203 to 0.668, P = 9.96 × 10-4; OR in Europeans=1.021, 95%CI=0.901 to 1.157, P = 0.745), which suggested that increased level of SERPINA1 will reduce COVID-19 risk in African ancestry. One protein, ICAM1 showed suggestive effect on COVID-19 severity in both ancestries (OR in Europeans=1.152, 95%CI=1.063 to 1.249, P = 5.94 × 10-4; OR in Africans=1.481, 95%CI=1.008 to 2.176; P = 0.045). The OAS1, SERPINA1 and ICAM1 effects were replicated using updated COVID-19 severity data in the two ancestries respectively, where alternative splicing events in OAS1 and ICAM1 also showed marginal effects on COVID-19 severity in Europeans. The phenome-wide MR of the prioritised targets on 622 complex traits provided information on potential beneficial effects on other diseases and suggested little evidence of adverse effects on major complications. INTERPRETATION: Our study identified six proteins as showing putative causal effects on COVID-19 severity. OAS1 and SERPINA1 were targets of existing drugs in trials as potential COVID-19 treatments. ICAM1, ICAM5 and FCRL3 are related to the immune system. Across the six targets, OAS1 has no reliable instrument in African ancestry; SERPINA1, FCRL3, ICAM5 and ENTPD5 showed a different level of putative causal evidence in European and African ancestries, which highlights the importance of more powerful ancestry-specific GWAS and value of multi-ancestry MR in informing the effects of drug targets on COVID-19 across different populations. This study provides a first step towards clinical investigation of beneficial and adverse effects of COVID-19 drug targets. FUNDING: No.

Comparison of Missing School Meals among Public Schools: How Did New York State Do during COVID-19?

BACKGROUND: The COVID-19 pandemic created barriers to participation in school meals. As a result, many students may have missed out on school meals. The objectives of this study are (1) to compare the number of school meals served by New York State public schools during the first spring and summer of the COVID-19 pandemic to the number served before the COVID-19 pandemic, and (2) to determine relationships between the number of meals served and the levels of school district need and urbanicity. METHODS: This study is a secondary analysis of administrative data. The percentage change in the number of school breakfasts and lunches served was calculated for each month and by school district need level and urbanicity level. RESULTS: The number of school meals served decreased during the first spring of the pandemic compared to the spring of the previous school year (-43% in April, -51% in May), while the number of school meals served increased during the first summer of the pandemic compared to the summer of the previous school year (+92% in July, +288% in August). CONCLUSIONS: Waivers may provide flexibility to increase participation in school meals, especially during the summer.

Methane emissions from US low production oil and natural gas well sites.

Eighty percent of US oil and natural gas (O&G) production sites are low production well sites, with average site-level production ≤15 barrels of oil equivalent per day and producing only 6% of the nation's O&G output in 2019. Here, we integrate national site-level O&G production data and previously reported site-level CH4 measurement data (n = 240) and find that low production well sites are a disproportionately large source of US O&G well site CH4 emissions, emitting more than 4 (95% confidence interval: 3-6) teragrams, 50% more than the total CH4 emissions from the Permian Basin, one of the world's largest O&G producing regions. We estimate low production well sites represent roughly half (37-75%) of all O&G well site CH4 emissions, and a production-normalized CH4 loss rate of more than 10%-a factor of 6-12 times higher than the mean CH4 loss rate of 1.5% for all O&G well sites in the US. Our work suggests that achieving significant reductions in O&G CH4 emissions will require mitigation of emissions from low production well sites.

Does audio-visual information result in improved health-related decision-making compared with audio-only or visual-only information? Protocol for a systematic review and meta-analysis.

INTRODUCTION: Making health-related decisions can be difficult due to the amount and complexity of information available. Audio-visual information may improve memory for health information but whether audio-visual information can enhance health-related decisions has not been explored using quantitative methods. The objective of this systematic review is to understand how effective audio-visual information is for informing health-related decision-making compared with audio-only or visual-only information. METHODS AND ANALYSIS: Randomised controlled trials (RCTs) will be included if they include audio-visual and either audio-only or visual-only information provision and decision-making in a health setting. Studies will be excluded if they are not reported in English. Twelve databases will be searched including: Ovid MEDLINE, PubMed and PsychINFO. The Cochrane Risk of Bias tool (V.7) will be used to assess risk of bias in included RCTs. Results will be synthesised primarily using a meta-analysis; where quantitative data are not reported, a narrative synthesis will be used. ETHICS AND DISSEMINATION: No ethical issues are foreseen. Data will be disseminated via academic publication and conference presentations. Findings may also be published in scientific newsletters and magazines. This review is funded by the Economic and Social Research Council. PROSPERO REGISTRATION NUMBER: CRD42021255725.

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome.

OBJECTIVE: To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT). METHODS: sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes. RESULTS: Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7-161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2-212.2) than in HC (10.7 pg/ml [IQR] 4.9-21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB-PT in the first 3 months (UVB-PT -10.6% vs non-UVB-PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall. CONCLUSIONS: Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro-axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB-PT.

Engineering alginate microparticles for optimized accumulation in fetal rat myelomeningocele.

INTRODUCTION: Intraamniotic microparticle injection is a novel technique for the treatment of myelomeningocele (MMC) in which microparticles are delivered in-utero in a minimally invasive fashion to bind to and protect the exposed spinal cord. This technique could offer earlier intervention and greater access to prenatal treatment of MMC. Here we demonstrate progress on the engineering of the microparticles to promote binding to the MMC defect. We hypothesized that when the particle's surface charge was decreased and delivery concentration increased, particles would bind to the MMC defect more frequently and more specifically. METHODS: Alginate microparticles underwent surface modification to alter the particle charge. Dye-loaded alginate, alginate- dextran sulfate, and alginate- chitosan were injected on e17 into the amnion of a rat model of MMC and the incidence of successful binding and specificity of particle binding to the MMC defect were calculated. Specificity of binding was described using a defect-to-skin brightness ratio based on specimen imaging. Comparisons were made with chi-square, p< 0.05 marked significance. RESULTS: There was no difference in the incidence of successful binding at e17 with 0.6 mg/fetal kg between the three tested alginate particles. However, alginate- dextran sulfate bound most specifically to the defect (p< 0.05). Alginate-dextran sulfate also demonstrated more frequent binding at higher doses than lower doses (79% at 1.2 mg/kg vs 38% at 0.6 mg/kg and 24% at 0.8 mg/kg, p< 0.01 for both). Specificity was not sacrificed at higher dose injections: defect-to-skin brightness ratio of 5.4 at 1.2 mg/kg vs 1.8 at 0.6 mg/kg (p< 0.05) CONCLUSION: We demonstrate that the intraamniotic injection of alginate-dextran sulfate microparticles at high concentration bind more frequently and more specifically to MMC defects than the previously tested unmodified alginate microparticles.

Between virus correlations in the outcome of infection across host species: Evidence of virus by host species interactions.

Virus host shifts are a major source of outbreaks and emerging infectious diseases, and predicting the outcome of novel host and virus interactions remains a key challenge for virus research. The evolutionary relationships between host species can explain variation in transmission rates, virulence, and virus community composition between hosts, but it is unclear if correlations exist between related viruses in infection traits across novel hosts. Here, we measure correlations in viral load of four Cripavirus isolates across experimental infections of 45 Drosophilidae host species. We find positive correlations between every pair of viruses tested, suggesting that some host clades show broad susceptibility and could act as reservoirs and donors for certain types of viruses. Additionally, we find evidence of virus by host species interactions, highlighting the importance of both host and virus traits in determining the outcome of virus host shifts. Of the four viruses tested here, those that were more closely related tended to be more strongly correlated, providing tentative evidence that virus evolutionary relatedness may be a useful proxy for determining the likelihood of novel virus emergence, which warrants further research.

Reliability of phenotype estimation and extended classification of ancestry using decedent samples.

The Illumina® MiSeq FGx™, in conjunction with the ForenSeq™ DNA Signature Prep kit, produces genotypes of the CODIS-required short tandem repeats and provides phenotype and biogeographical ancestry estimations via phenotype-informative and ancestry-informative markers, respectively. Although both markers have been validated for use in forensic biology, there is little data to determine the practical utility of these estimations to assist in identifying missing persons using decedent casework samples. The accuracy and utility of phenotypic and ancestral estimations were investigated for 300 samples received by the Los Angeles County Department of Medical Examiner-Coroner. piSNP genotypes were translated into hair and eye colors using the Forenseq™ Universal Analysis Software (UAS) on the MiSeq FGx™ and the HIrisPlex System, and statistical accuracy was evaluated in context with the reported decedent characteristics. Similarly, estimates of each decedent's biogeographical ancestry were compared to assess the efficacy of these markers to predict ancestry correctly. The average UAS and the HIrisPlex system prediction accuracy for brown and blue eyes were 95.3% and 96.2%, respectively. Intermediate eye color could not be predicted with high accuracy using either system. Other than the black hair phenotype reporting an accuracy that exceeded 90% using either system, hair color was also too variable to be predicted with high accuracy. The FROG-kb database distinguishes decedents adequately beyond the Asian, African, European, and Admixed American global ancestries provided by the MiSeq FGx™ UAS PCA plots. FROG-kb correctly identified Middle Eastern, Pacific Islander, Latin American, or Jewish ancestries with accuracies of 70.0%, 81.8%, 73.8%, and 86.7%, respectively.

DNA methylation of decedent blood samples to estimate the chronological age of human remains.

Chronological age estimation may offer valuable investigative leads in human identification cases. Bisulfite pyrosequencing analysis of single CpG sites on five genes (KLF14, ELOVL2, C1orf132, TRIM59, and FHL2) was performed on 264 postmortem blood samples from individuals aged 3 months to 93 years. The goals were to develop age prediction models based on the correlation between the methylation profile and chronological age and to assess the accuracy of the prediction. Linear regression between methylation levels and age at each CpG site revealed that the five markers show a statistically significant correlation with age. The methylation data from a training set of 160 postmortem blood samples were used to develop an age prediction model with a correlation coefficient of 0.65, explaining 73.1% of age variation, with a mean absolute deviation from the chronological age of 7.60 years. The accuracy of the model was evaluated with a test set of 72 samples producing a mean absolute deviation of 7.42 years. The training and test sets were also categorized by specific age groups to assess accuracy and deviation from chronological age. The data for both sets revealed a lower prediction potential as an individual increases in age, particularly for the age categories above 50 years.

The Influence of the Type of Background Noise on Perceptual Learning of Speech in Noise.

OBJECTIVES: Auditory perceptual learning studies tend to focus on the nature of the target stimuli. However, features of the background noise can also have a significant impact on the amount of benefit that participants obtain from training. This study explores whether perceptual learning of speech in background babble noise generalizes to other, real-life environmental background noises (car and rain), and if the benefits are sustained over time. DESIGN: Normal-hearing native English speakers were randomly assigned to a training (n = 12) or control group (n = 12). Both groups completed a pre- and post-test session in which they identified Bamford-Kowal-Bench (BKB) target words in babble, car, or rain noise. The training group completed speech-in-babble noise training on three consecutive days between the pre- and post-tests. A follow up session was conducted between 8 and 18 weeks after the post-test session (training group: n = 9; control group: n = 7). RESULTS: Participants who received training had significantly higher post-test word identification accuracy than control participants for all three types of noise, although benefits were greatest for the babble noise condition and weaker for the car- and rain-noise conditions. Both training and control groups maintained their pre- to post-test improvement over a period of several weeks for speech in babble noise, but returned to pre-test accuracy for speech in car and rain noise. CONCLUSION: The findings show that training benefits can show some generalization from speech-in-babble noise to speech in other types of environmental noise. Both groups sustained their learning over a period of several weeks for speech-in-babble noise. As the control group received equal exposure to all three noise types, the sustained learning with babble noise, but not other noises, implies that a structural feature of babble noise was conducive to the sustained improvement. These findings emphasize the importance of considering the background noise as well as the target stimuli in auditory perceptual learning studies.