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The content and organization of hyaluronan (HA) in the extracellular matrix (ECM) have been identified as strong indicators of inflammation in joint disease, although the source and role of HA as an effector of inflammation is not clear. In this study, we established co-cultures of activated human CD4 T cells with fibroblast-like synoviocytes (FLS) from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects and examined the role of HA in promoting inflammatory events. Co-cultures of RA FLS with activated CD4 T cells generated an HA-enriched ECM that promoted enhanced monocyte adhesion compared to co-cultures of OA FLS with activated CD4 T cells. In addition, both OA FLS and RA FLS co-cultures with activated CD4 T cells elicited significant increases in the expression of IL1β, TNF, and IL6, with the increase in IL6 expression most prominent in RA co-cultures. Blocking HA synthesis and accumulation with 4-methylumbelliferone reduced expression of IL6, IL1β, and TNF in both OA FLS and RA FLS co-cultures. The increase in HA synthesis in the co-cultures was mimicked by IL6 trans-signaling of FLS in the absence of CD4 T cells. Inhibition of HA synthesis blocked the increase in IL6 by RA FLS mediated by IL6 trans-signaling, suggesting that the HA synthetic pathway may be a key mediator in IL6 expression by FLS. Overall, our study indicates that HA-enriched ECM generated by co-cultures of activated CD4 T cells with FLS from human joints creates a pathogenic microenvironment by promoting adhesion of leukocytes and expression of inflammatory cytokines including IL6.

Locating and identifying viruses in in vitro optical measurements is desirable for disease control; however, the sub-diffraction-limit dimensions and low refractive index contrast of viruses make this challenging. Here, we introduce a 3D positional nanometrology for a virus-like 100 nm polystyrene sphere that can reveal the position of the nanoparticle with deeply sub-wavelength accuracy using topologically structured light illumination and machine learning. Scattering of topologically structured light is highly sensitive to the position of a nano-object. Exploiting this, our experiments demonstrate deeply sub-wavelength (λ) precision reaching 5 nm (λ/91). Our findings indicate a route toward label-free in vitro nanometrology of viruses and similar nano-objects with precision far beyond the Abbe–Rayleigh diffraction limit. [ABSTRACT FROM AUTHOR]

The Number 2 Dairy (No. 2 Dairy) unit at Ruakura, Hamilton, New Zealand was established as a dairy research farm in 1943 and became recognised globally as one of the leading institutes for farm systems science. The research undertaken was fundamental to the 'systemisation' of component research into replicable, efficient, competitive, and sustainable dairy systems. From McMeekan's seminal research in the 1950s on rotational grazing to the experiments of Carter, Campbell, Bryant, Penno and others, who brought greater resolution to the key principles influencing successful outcomes on-farm, the more than 60 years of experimental research led to 'good practice' rules that were to transcend geographical, climatic, and system-level interactions. Much of the research can only be found in Annual Reports or in summary form in conference proceedings and not in an electronic form. Our objective was to collate and discuss the research undertaken, thereby ensuring that the legacy of this great work and the wisdom amassed are not lost. To this end, we have compiled a compendium of the research undertaken at No. 2 Dairy, with the hope that it be used to inform the scientific rationale for system design and to stimulate future hypotheses for system improvement. [ABSTRACT FROM AUTHOR]

With the advent of large scale chip multiprocessors, there is growing interest in the design and analysis of on-chip networks. Full-system simulation is the most accurate way to perform such an analysis, but unfortunately it is very slow and thus limits design space exploration. To overcome this problem researchers frequently use trace-based simulation to study different network topologies and properties, which can be done much faster. Unfortunately, unless the traces that are used include information about dependencies between packets, trace-based simulations can lead one to draw incorrect conclusions about network performance metrics such as average packet latency and overall execution time. The primary contributions of this work are to demonstrate the importance of including dependency information in traces, and to present PDG-GEN, an inference-based technique for identifying and including dependencies in traces. This technique uses traces obtained from multiple full-system simulations of an application of interest to infer dependency information between packets and augment traces with this information. On the SPLASH-2 benchmark suite, PDG-GEN is 2.3 times more accurate at predicting overall execution time and almost 4,000 times more accurate at predicting average packet latency than traditional trace-based methods. © 1968-2012 IEEE.

Studies suggest that visual short-term memory (VSTM) is a continuous resource that can be flexibly allocated using probabilistic cues that indicate test likelihood (i.e., goal-directed attentional priority to those items). Previous studies using simultaneous cues have not examined this flexible allocation beyond two distinct levels of priority. Moreover, previous studies have not examined whether there are individual differences in the ability to flexibly allocate VSTM resources, as well as whether this ability benefits from practice. The current study used a continuous report procedure to examine whether participants can use up to three levels of attentional priority to allocate VSTM resources via simultaneous probabilistic spatial cues. Three experiments were performed with differing priority levels, cues, and cue presentation times. Group level analysis demonstrated flexible allocation of VSTM resources; however, there was limited evidence that participants could use three goal-directed priority levels. A temporal analysis suggested that task fatigue, rather than practice effects, may interact with item priority. A Bayesian individual-differences analysis revealed that a minority of participants were using three levels of attentional priority, demonstrating that, while possible, it is not the predominant pattern of behaviour. Thus, we provided evidence that flexible allocation to three attention levels is possible under simultaneous cuing conditions for a minority of participants. Flexible allocation to three categories may be interpreted as a skill of high-performing participants akin to high memory capacity. [ABSTRACT FROM AUTHOR]

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This article contrasts policy intent and policy implementation in school autonomy and accountability. The analysis uses a conceptual framework based on the interaction between school autonomy, student assessment, and accountability as elements of a closed system. The article analyzes the implementation of school autonomy and accountability policy, using data collected from 226 schools in Thailand that participated in the 2009 PISA survey. To understand how autonomy and accountability relate to student achievement, the study estimates a linear regression with PISA reading achievement as the dependent variable and indicators of autonomy and accountability (and control variables) as the independent variables. The estimates suggest that students at schools exercising a higher level of operational autonomy than the level ascribed by regulation tend to have PISA reading scores 6.0-8.6 points higher than students at schools that behave less autonomously. These results are consistent with other research findings.

Marriage practices in Northwest Europe are unique among societies with intensive agriculture. Critically, married couples were freely chosen non-relatives who set up their households independently of their parents and their extended families; households typically including non- relatives and were established only after achieving economic viability. This in turn required greater planning and self-control prior to marriage, and resulted in greater husband-wife partnership than is typical when marriage is embedded within extended kinship networks (i.e., joint family structure--a form of collectivism paradigmatically occurring in the Middle East). A standard view among historians is that this marriage regime was a response to the unique context after the fall of the Roman Empire in which lords were forced to give incentives to laborers. This hypothesis is rejected for several reasons: 1. there are strong currents of individualism in Indo-European culture long predating the post-Roman period; 2. the manorial system of the post-Roman world was remarkably similar to the prevailing practices of Germanic tribes during the Roman period; 3. individualist families have several disadvantages compared to collectivist families, including later generation time, uncertain inheritance, greater likelihood of sexual assault prior to marriage in households composed of non-relatives--thus making it unlikely to be freely chosen because of incentives provided by lords. This is compatible with a theory that European individualism results from genetically based tendencies resulting in a misfit with medieval environments compared to collectivist family structure. Data are reviewed indicating that the most extreme forms of individualism occur in Scandinavian societies, implying a cline in individualism from southeast to northwest. In conclusion, an ethnically based northwest-southeast gradient is proposed as the main variable in explaining variation in family structure within Western Europe. However, viewed in broader terms-in comparison, say, to the Middle East--all of Europe, including Eastern Europe, is relatively individualistic. Keywords: Individualist family; Collectivist family; Manorial system; Indo-European culture; Germanic tribes; Extended kinship; Eugenic selection, There is a consensus among historians of the family that the family structure of Northwest Europe is unique. However, there is dispute about exactly when this family pattern can be [...]

Recent advances in molecular genetics and epigenetics are reviewed that have major implications for the bio-behavioral sciences and for understanding how organisms adapt to their environments at both phylogenetic and ontogenic levels. From a post-genomics perspective, the environment is as crucial as the DNA sequence for constructing the phenotype, and as a source of information in trying to predict phenotypes. The review is organized with respect to four basic processes by which phenotypes adapt to environmental challenges, with an emphasis on the data for humans: (1) developmental plasticity, (2) epigenetic mechanisms, (3) genotype-environment correlations, and (4) gene x environment interactions.

The early intervention service (EIS) model for psychosis has been implemented with increasing frequency; yet, improving outcomes across domains for all patients remains challenging. Measurement-based care can strengthen outcomes by optimizing interventions and promoting alignment with standards, but it is still not widely deployed in EIS. The authors conducted a scoping review by systematically identifying and synthesizing measures used in EIS related to purpose (i.e., to assess patients, families, and programs), domains (e.g., symptoms, quality of life), and reporting perspectives (of patients, families, and clinicians). EMBASE, MEDLINE, PsycINFO, CINAHL, and Cochrane Library databases were searched for pertinent literature published between 2000 and 2020. Two reviewers independently screened titles, abstracts, and full texts and extracted data. Measures were classified as clinician-reported outcome measures (CROMs), patient-reported outcome or experience measures (PROMs/PREMs), or family-reported outcome or experience measures (FROMs/FREMs). In total, 172 measures of 27 domains were identified from 115 articles. Nineteen measures had been used to assess programs on fidelity, service engagement, and satisfaction; 136 to assess patients on duration of untreated psychosis, symptoms, functioning, quality of life, and others; and 17 to assess families on coping and burden, background, and others. Sixty percent were CROMs, 30% were PROMs/PREMs, and 10% were FROMs/FREMs. Greater inclusion of PROMs and FROMs is needed because they align with the EIS philosophy of patient and family engagement and may improve shared decision making and outcomes. A comprehensive, meaningfully synthesized archive of measures can advance measurement-based care, services research, and data harmonization in early psychosis. [ABSTRACT FROM AUTHOR]

Computer Assisted Instruction (CAI) has shown increased popularity recently and there are many studies showing promise for this approach for children with Autism Spectrum Disorders (ASD). However, there are no between-subject studies to date assessing the efficacy of CAI with this population. In this study, 47 preschool and K-1 students in ASD classrooms participated from Los Angeles Unified School District. "TeachTown: Basics", a CAI program which also includes supplementary off-computer activities, was implemented over 3 months for approximately 20 minutes per day on the computer and 20 minutes per day in supplementary "TeachTown: Basics" activities. Compared to the students in the control group, the "TeachTown: Basics" students showed more improvement overall on language and cognitive outcome measures. In addition, students who used "TeachTown: Basics" demonstrated significant progress overall in the software and those students who used the program for more time demonstrated larger gains within the software and in outcome measures. Although not conclusive, these findings offer possibilities for the use of CAI for remediating many deficits for children with ASD and other special needs. In addition, CAI may offer solutions to schools and parents with insufficient funds for more expensive treatments. (Contains 1 table and 3 figures.)

This article analyzes the effortful control of automatic processing related to social and emotional behavior, including control over evolved modules designed to solve problems of survival and reproduction that were recurrent over evolutionary time. The inputs to effortful control mechanisms include a wide range of nonrecurrent information--information resulting not from evolutionary regularities but from explicit appraisals of costs and benefits. Effortful control mechanisms are associated with the ventromedial prefrontal cortex and the ventral anterior cingulated cortex. These mechanisms are largely separate from mechanisms of cognitive control (termed executive function) and working memory, and they enable effortful control of behavior in the service of long range goals. Individual differences in effortful control are associated with measures of conscientiousness in the Five Factor Model of personality. Research in the areas of aggression, ethnocentrism, sexuality, reward seeking, and emotion regulation is reviewed indicating effortful control of automatic, implicit processing based on explicit appraisals of the context. Evidence is reviewed indicating that evolutionary pressure for cooperation may be a critical adaptive function accounting for the evolution of explicit processing.

Notes that rough-and-tumble play must be considered in the context of social values; has beneficial influences on children's cognitive and social development; and is distinguishable from aggression. Makes a case for the use of socializing techniques in conjunction with rough and tumble play. (LB)

Provides an evolutionary account of the human affectional system. Warmth is conceptualized as a reward system which evolved to facilitate cohesive family relationships and paternal investment in children. Warmth must be distinguished from security of attachment. Relationships based on warmth can coexist with relationships based on exploitation. (BC)

Islamization in Mande West Africa gradually accompanied the expansion of mercantile groups and was surprisingly accommodating via syncretic processes with local spiritual traditions. Elites of the Empire of Mali were amongst the first to embrace Islam and mediate between it and indigenous earth religions. Yet this process was patchy across different cultural sectors and from the seventeenth century onwards there were upswellings of Bamanaya, earth religions, in open conflict with waves of Islamic jihadism (e.g. the Umarian movement). Thus, historic polities could retain both mosques and non-Islamic shrines, and maraboutic practices incorporated forms of local magic. This article considers results from "Project Segou": historical and archaeological fieldwork undertaken between 2005 and 2013 in the Segou region of Mali, stretching approximately from Sinsanni in the east to Nyamina in the west. As a heartland of the Empire of Mali (c. AD 1235-1500) and the core of Bamana Segou (c. AD 1700-1861), its oral and archaeological sources inform our deep time appreciation of ideological and spiritual change at the margins of the Middle Niger from the thirteenth through nineteenth centuries AD. [ABSTRACT FROM AUTHOR]