Systems Factorial Analysis of Item and Associative Retrieval

Using hierarchical Bayesian estimation of RT distributions, wepresent a novel application of Systems Factorial Technology(Townsend & Nozawa, 1995) to the retrieval of item and asso-ciative information from episodic memory. We find that itemand associative information are retrieved concurrently, withpositive memory evidence arising from a holistic match be-tween the test pair and the contents of memory, in which bothitem and associative matches are pooled together into a sin-gle source. This retrieval architecture is inconsistent with bothstrictly serial processing and independence of item and asso-ciative information. Pooling of item and associative matchesimplies that while item and associative information may beseparable, they are not qualitatively different, nor are quali-tatively different processes (e.g., familiarity vs. recollection)used to retrieve these kinds of information

As Time Goes by: Understanding Child and Family Factors Shaping Behavioral Outcomes After Traumatic Brain Injury

Objective: To model pre-injury child and family factors associated with the trajectory of internalizing and externalizing behavior problems across the first 3 years in children with pediatric traumatic brain injury (TBI) relative to children with orthopedic injuries (OI). Parent-reported emotional symptoms and conduct problems were expected to have unique and shared predictors. We hypothesized that TBI, female sex, greater pre-injury executive dysfunction, adjustment problems, lower income, and family dysfunction would be associated with less favorable outcomes. Methods: In a prospective longitudinal cohort study, we examined the level of behavior problems at 12 months after injury and rate of change from pre-injury to 12 months and from 12 to 36 months in children ages 4–15 years with mild to severe TBI relative to children with OI. A structural equation model framework incorporated injury characteristics, child demographic variables, as well as pre-injury child reserve and family attributes. Internalizing and externalizing behavior problems were indexed using the parent-rated Emotional Symptoms and Conduct Problems scales from the Strengths and Difficulties questionnaire. Results: The analysis cohort of 534 children [64% boys, M (SD) 8.8 (4.3) years of age] included 395 with mild to severe TBI and 139 with OI. Behavior ratings were higher after TBI than OI but did not differ by TBI severity. TBI, higher pre-injury executive dysfunction, and lower income predicted the level and trajectory of both Emotional Symptoms and Conduct Problems at 12 months. Female sex and poorer family functioning were vulnerability factors associated with greater increase and change in Emotional Symptoms by 12 months after injury; unique predictors of Conduct Problems included younger age and prior emotional/behavioral problems. Across the long-term follow-up from 12 to 36 months, Emotional Symptoms increased significantly and Conduct Problems stabilized. TBI was not a significant predictor of change during the chronic stage of recovery. Conclusions: After TBI, Emotional Symptoms and Conduct Problem scores were elevated, had different trajectories of change, increased or stayed elevated from 12 to 36 months after TBI, and did not return to pre-injury levels across the 3 year follow-up. These findings highlight the importance of addressing behavioral problems after TBI across an extended time frame

Innovation Challenges in the Air Force SBIR Program: From the Small Businesses\u27 Perspective

Every year the United States invests $3.2 billion in the Small Business Innovation Research (SBIR) program to promote innovation among the nation’s small businesses. Half of this investment is from the DoD. This research considers the challenges faced by small businesses innovating with the DoD, particularly those awarded SBIR contracts with the United States Air Force. The authors surveyed 286 unique small businesses that were previously awarded an Air Force SBIR contract. By asking the survey respondents open-ended questions and categorizing their responses, they pinpoint unaddressed challenges from the small business perspective. By categorizing survey responses through Qualitative Content Analysis, they further identify five categories of challenges: Solver- Seeker Disconnect, Funding, Engagement, Processes, and Seeker Education. With this new insight, the authors seek to inform SBIR policies and improve the program’s effectiveness

Tailoring Messages to Individual Differences in Monitoring- Blunting Styles to Increase Fruit and Vegetable Intake

Objective To examine whether messages matched to individuals\u27 monitoring-blunting coping styles (MBCS) are more effective in increasing fruit and vegetable intake than mismatched messages. MBCS refers to the tendency to either attend to and amplify, or distract oneself from and minimize threatening information. Design/Setting Randomly assigned messages were tailored to resonate with either monitors or blunters and delivered at baseline, 1 week, 2 months, and 3 months later. Surveys were conducted at baseline and 2 and 4 months later. Participants 531 callers to a cancer information hotline who did not meet the 5 A Day guideline. Intervention A brief telephone-delivered message and 3 mailings of booklets and promotional items encouraging fruit and vegetable intake, tailored for either monitors or blunters. Main Outcome Measure Fruit and vegetable intake 2 and 4 months post-baseline. Analysis Hierarchical regression modeling. Results Messages matched to MBCS were more effective than mismatched messages, particularly for the monitor message, in increasing intake at 2 months but not at 4 months. Conclusions and Implications These minimal interventions influenced fruit and vegetable intake. MBCS may be a promising target for developing tailored messages aimed at increasing intake, although additional research is needed to verify the robustness of these findings

Genome-Wide Local Ancestry Approach Identifies Genes and Variants Associated with Chemotherapeutic Susceptibility in African Americans

Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5′-deoxyfluorouridine (5′-DFUR)-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10−4). Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5′-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10−3). Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (pTP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information.</p

The effect of metabolic phenotype on sociability and social group size preference in a coral reef fish

Although individuals within social groups experience reduced predation risk and find food patches more consistently, there can be competition for food among groupmates. Individuals with a higher standard metabolic rate (SMR) may be less social, to prioritize food acquisition over defense, while a greater maximum metabolic rate (MMR) may modulate sociability through increased competitive ability. Therefore, in theory, individuals with a higher SMR may prefer smaller groups and those with greater MMR may prefer larger groups. We examined links among metabolic phenotype, sociability, and choice of group size in the redbelly yellowtail fusilier Caesio cuning. Individuals were exposed to three association tests: (a) a choice between two fish or zero fish; (b) a choice between five fish or zero fish; and (c) a choice between two fish and five fish. The first two tests quantified sociability while the third measured relative group size choice. Although there was no link between SMR and sociability, fish with a higher MMR were more social than those individuals with a lower MMR. While no correlation was found between MMR and group size choice, there was weak evidence that, if anything, individuals with a higher SMR preferred larger groups, contrary to our hypothesis. As C. cuning is an active fish that spends a large proportion of time operating above SMR, this result could suggest that the links between sociability and SMR may shift depending on a species’ routine behavior. Links between sociability and MMR may arise if competitive ability allows individuals to obtain resources within groups. Although metabolic traits had no significant influence on group size choice, variation in food availability or predation risk could alter the effects of metabolism on group size choice

Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes

Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.</p

Single-molecule live-cell imaging reveals RecB-dependent function of DNA polymerase IV in double strand break repair

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. Several functions have been proposed for the Escherichia coli DNA polymerase IV (pol IV). Although much research has focused on a potential role for pol IV in assisting pol III replisomes in the bypass of lesions, pol IV is rarely found at the replication fork in vivo. Pol IV is expressed at increased levels in E. coli cells exposed to exogenous DNA damaging agents, including many commonly used antibiotics. Here we present live-cell single-molecule microscopy measurements indicating that double-strand breaks induced by antibiotics strongly stimulate pol IV activity. Exposure to the antibiotics ciprofloxacin and trimethoprim leads to the formation of double strand breaks in E. coli cells. RecA and pol IV foci increase after treatment and exhibit strong colocalization. The induction of the SOS response, the appearance of RecA foci, the appearance of pol IV foci and RecA-pol IV colocalization are all dependent on RecB function. The positioning of pol IV foci likely reflects a physical interaction with the RecA* nucleoprotein filaments that has been detected previously in vitro. Our observations provide an in vivo substantiation of a direct role for pol IV in double strand break repair in cells treated with double strand break-inducing antibiotics

Multi-state models and arthroplasty histories after unilateral total hip arthroplasties: Introducing the Summary Notation for Arthroplasty Histories

Background and purpose: An increasing number of patients have several joint replacement procedures during their lifetime. We investigated the use and suitability of multi-state model techniques in providing a more comprehensive analysis and description of complex arthroplasty histories held in arthroplasty registries than are allowed for with traditional survival methods. Patients and methods: We obtained data from the Australian Orthopaedic Association National Joint Replacement Registry on patients (n = 84,759) who had undergone a total hip arthroplasty for osteoarthritis in the period 2002–2008. We set up a multi-state model where patients were followed from their first recorded arthroplasty to several possible states: revision of first arthroplasty, either a hip or knee as second arthroplasty, revision of the second arthroplasty, and death. The Summary Notation for Arthroplasty Histories (SNAH) was developed in order to help to manage and analyze this type of data. Results: At the end of the study period, 12% of the 84,759 patients had received a second hip, 3 times as many as had received a knee. The estimated probabilities of having received a second arthroplasty decreased with age. Males had a lower transition rate for receiving a second arthroplasty, but a higher mortality rate. Interpretation: Multi-state models in combination with SNAH codes are well suited to the management and analysis of arthroplasty registry data on patients who experience multiple joint procedures over time. We found differences in the progression of joint replacement procedures after the initial total hip arthroplasty regarding type of joint, age, and sex.Marianne H Gillam, Philip Ryan, Amy Salter, Stephen E Grave

Different competing risks models applied to data from the Australian Orthopaedic Association National Joint Replacement Registry

Purpose: Here we describe some available statistical models and illustrate their use for analysis of arthroplasty registry data in the presence of the competing risk of death, when the influence of covariates on the revision rate may be different to the influence on the probability (that is, risk) of the occurrence of revision. Patients and methods: Records of 12,525 patients aged 75–84 years who had received hemiarthroplasty for fractured neck of femur were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. The covariates whose effects we investigated were: age, sex, type of prosthesis, and type of fixation (cementless or cemented). Extensions of competing risk regression models were implemented, allowing the effects of some covariates to vary with time. Results: The revision rate was significantly higher for patients with unipolar than bipolar prostheses (HR = 1.38, 95% CI: 1.01–1.89) or with monoblock than bipolar prostheses (HR = 1.45, 95% CI: 1.08–1.94). It was significantly higher for the younger age group (75–79 years) than for the older one (80–84 years) (HR = 1.28, 95% CI: 1.05–1.56) and higher for males than for females (HR = 1.37, 95% CI: 1.09–1.71). The probability of revision, after correction for the competing risk of death, was only significantly higher for unipolar prostheses than for bipolar prostheses, and higher for the younger age group. The effect of fixation type varied with time; initially, there was a higher probability of revision for cementless prostheses than for cemented prostheses, which disappeared after approximately 1.5 years. Interpretation: When accounting for the competing risk of death, the covariates type of prosthesis and sex influenced the rate of revision differently to the probability of revision. We advocate the use of appropriate analysis tools in the presence of competing risks and when covariates have time-dependent effects.Marianne H Gillam, Amy Salter, Philip Ryan, and Stephen E Grave