72 research outputs found
Building a collaborative Psychological Science: Lessons Learned from ManyBabies 1
The field of infancy research faces a difficult challenge: Some questions require samples that are simply too large for any 1 lab to recruit and test. ManyBabies aims to address this problem by forming large-scale collaborations on key theoretical questions in developmental science, while promoting the uptake of Open Science practices. Here, we look back on the first project completed under the ManyBabies umbrella—ManyBabies 1—which tested the development of infant-directed speech preference. Our goal is to share the lessons learned over the course of the project and to articulate our vision for the role of large-scale collaborations in the field. First, we consider the decisions made in scaling up experimental research for a collaboration involving 100+ researchers and 70+ labs. Next, we discuss successes and challenges over the course of the project, including the following: protocol design and implementation, data analysis, organisational structures and collaborative workflows, securing funding, and encouraging broad participation in the project. Finally, we discuss the benefits we see both in ongoing ManyBabies projects and in future large-scale collaborations in general, with a particular eye toward developing best practices and increasing growth and diversity in infancy research and psychological science in general. Throughout the article, we include first-hand narrative experiences to illustrate the perspectives of researchers playing different roles within the project. Although this project focused on the unique challenges of infant research, many of the insights we gained can be applied to large-scale collaborations across the broader field of psychology
Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells
Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells
Prion-specific and surrogate CSF biomarkers in Creutzfeldt-Jakob disease:diagnostic accuracy in relation to molecular subtypes and analysis of neuropathological correlates of p-tau and A beta 42 levels
The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrPSc). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82\u201396%) and virtually full specificity. In the present study, we investigated the diagnostic value of both prion RT-QuIC and surrogate protein markers in a large patient population with suspected CJD and then evaluated the influence on CSF findings of the CJD type, and the associated amyloid-\u3b2 (A\u3b2) and tau neuropathology. RT-QuIC showed an overall diagnostic sensitivity of 82.1% and a specificity of 99.4%. However, sensitivity was lower in CJD types linked to abnormal prion protein (PrPSc) type 2 (VV2, MV2K and MM2C) than in typical CJD (MM1). Among surrogate proteins markers (14-3-3, total (t)-tau, and t-tau/phosphorylated (p)-tau ratio) t-tau performed best in terms of both specificity and sensitivity for all sCJD types. Sporadic CJD VV2 and MV2K types demonstrated higher CSF levels of p-tau when compared to other sCJD types and this positively correlated with the amount of tiny tau deposits in brain areas showing spongiform change. CJD patients showed moderately reduced median A\u3b242 CSF levels, with 38% of cases having significantly decreased protein levels in the absence of A\u3b2 brain deposits. Our results: (1) support the use of both RT-QuIC and t-tau assays as first line laboratory investigations for the clinical diagnosis of CJD; (2) demonstrate a secondary tauopathy in CJD subtypes VV2 and MV2K, correlating with increased p-tau levels in the CSF and (3) provide novel insight into the issue of the accuracy of CSF p-tau and A\u3b242 as markers of brain tauopathy and \u3b2-amyloidosis
Quantifying Sources of Variability in Infancy Research Using the Infant-Directed-Speech Preference
Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure
Mathematical Modeling and Simulation of Ventricular Activation Sequences: Implications for Cardiac Resynchronization Therapy
Next to clinical and experimental research, mathematical modeling plays a crucial role in medicine. Biomedical research takes place on many different levels, from molecules to the whole organism. Due to the complexity of biological systems, the interactions between components are often difficult or impossible to understand without the help of mathematical models. Mathematical models of cardiac electrophysiology have made a tremendous progress since the first numerical ECG simulations in the 1960s. This paper briefly reviews the development of this field and discusses some example cases where models have helped us forward, emphasizing applications that are relevant for the study of heart failure and cardiac resynchronization therapy
Perceived managerial and leadership effectiveness in a Korean context: An indigenous qualitative study
Multinational corporations (MNCs) across the world have sent an increasing number of managers abroad to leverage unprecedented opportunities in the era of globalization. However, their failure rate has been above 33% for decades, resulting in substantial costs (Puck, Kittler, & Wright, 2008). One of the primary reasons for this failure is a lack of understanding of the national and organizational cultures within the host countries (Festing & Maletzky, 2011). For example, while a number of MNCs have entered the Korean market, several such as Yahoo, Motorola, and Walmart have failed and withdrawn due to the companies’ lack of adjustment to the Korean cultural context (Choe, 2006; Woo, 2013). In spite of the significance of culturally embedded practices, most researchers who have explored management and leadership in Asian countries, whether they were Western or indigenous researchers, have implemented studies using extant Western management and leadership theories derived within the Western cultural context (Leung, 2007; Tsui, 2006). Numerous scholars have claimed that this could be problematic because the findings of such studies may not be applicable to non-Western countries (Li, 2012; Liden & Antonakis, 2009), and may fail to provide insights and understanding of novel contexts or to reveal indigenous aspects of management and leadership (Tsui, 2007). Consequently, there have been increasing calls for indigenous management and leadership research within Asian countries (see Li et al., 2014; Lyles, 2009; Tsui, 2004; Wolfgramm, Spiller, & Voyageur, 2014). Over the past 30 years, managerial effectiveness and leadership effectiveness have been substantially neglected areas of management research (Noordegraaf & Stewart, 2000; Yukl, Gordon, & Taber, 2002). In addition, there has been little agreement on what specific behaviors distinguish effective managers from ineffective ones. Furthermore, more research is needed to examine the managerial and leadership behaviors that are critical for shaping the performance of individuals, groups and organizations (see Borman & Brush, 1993; Cammock, Nilakant & Dakin, 1995; Mumford, 2011; Noordegraaf & Stewart, 2000; Yukl et al., 2002). While most of the research related to managerial and leadership effectiveness has been conducted in the U.S., the few notable non-U.S. studies include that of Cammock et al. (1995) in New Zealand who developed a behavioral lay model of managerial effectiveness using the repertory grid technique. Another notable exception is the cumulative series of perceived managerial and leadership effectiveness studies conducted by Hamlin with various indigenous co-researchers in Western and non-Western countries (see Hamlin & Patel, 2012; Ruiz, Wang, & Hamlin, 2013) using Flanagan’s (1954) critical incident technique (CIT)
Role of Appetite-Regulating Peptides in the Pathophysiology of Addiction: Implications for Pharmacotherapy
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