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This paper describes the development and validation of a new 32-item test of knowledge of good clinical practice (GCP) administered to 625 clinical research coordinators. GCP training is mandated by study sponsors including the US National Institutes of Health. The effectiveness of training is rarely assessed, and the lack of validated tests is an obstacle to assessment. The GCP knowledge test was developed following evaluation of two existing widely used GCP tests to ensure it accurately reflects the content of current training. The final GCP knowledge test demonstrated good reliability (α = 0.69). It is a valid and reliable instrument for measuring knowledge of GCP. The test will be useful in assessing the effectiveness of GCP training programs as well as individuals’ mastery of GCP content.
This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
There is a lack of evidence pointing to specific dietary elements related to weight gain and obesity prevention in childhood and adulthood. Dietary intake and obesity are both inherited and culturally transmitted, but most prospective studies on the association between diet and weight status do not take genetics into consideration. The objective of this study was to document the association between dietary intake at 9 years and subsequent Body Mass Index (BMI) in adolescent monozygotic boy and girl twin pairs. This research used data from 152 twin pairs. Dietary data were collected from two 24-hour-recall interviews with a parent and the child aged 9 years. Height and weight were obtained when the twins were aged 9, 12, 13, and 14 years. Intrapair variability analysis was performed to identify dietary elements related to BMI changes in subsequent years. BMI-discordant monozygotic twin pairs were also identified to analyze the dietary constituents that may have generated the discordance. After eliminating potential confounding genetic factors, pre-adolescent boys who ate fewer grain products and fruit and consumed more high-fat meat and milk had higher BMIs during adolescence; pre-adolescent girls who consumed more grain products and high-fat meat and milk had higher BMIs during adolescence. Energy intake (EI) at 9 years was not related to BMI in subsequent years. Our study suggests that messages and interventions directed at obesity prevention could take advantage of sex-specific designs and‚ eventually‚ genetic information.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
This paper reports on the study of a subsidy programme that was established in Quebec for alternate housing models (AHMs), which allows private and community organisations to offer housing services within the framework of a partnership with public health-care services. The research objectives were: (a) to compare how facility characteristics and services provided by AHMs and nursing homes (NHs) differ; (b) to examine the personal characteristics of residents living in AHMs; and (c) to compare residents with similar characteristics within AHMs and NHs in terms of unmet needs, quality of care, satisfaction with care and services, and psycho-social adaptation to the residence. A cross-sectional study was undertaken with individually matched groups to assess whether AHMs meet the needs of elders in a way similar to NHs. Overall, residents in both groups had moderate to severe levels of disability and about 60 per cent had mild to severe cognitive problems. While their general features were heterogeneous, the AHMs were more comfortable and homelike than the NHs. The quality of and satisfaction with care was appropriate in both settings, although AHMs performed better. Only one-quarter of residents in both settings, however, evidenced a good level of psycho-social adaptation to their residence. This partnership approach is a good strategy to provide a useful range of housing types in communities that can respond to the needs of elders with moderate to severe disabilities.
Early disruptive behaviors, such as aggressive and hyperactive behaviors, known to be influenced by genetic factors, have been found to predict early school peer relation difficulties, such as peer rejection and victimization. However, there is no consensus regarding the developmental processes underlying this predictive association. Genetically informative designs, such as twin studies, are well suited for investigating the underlying genetic and environmental etiology of this association. The main goal of the present study was to examine the possible establishment of an emerging gene–environment correlation linking disruptive behaviors to peer relationship difficulties during the first years of school. Participants were drawn from an ongoing longitudinal study of twins who were assessed with respect to their social behaviors and their peer relation difficulties in kindergarten and in Grade 1 through peer nominations measures and teacher ratings. As predicted, disruptive behaviors were concurrently and predictively associated with peer relation difficulties. Multivariate analyses of these associations indicate that they were mainly accounted for by genetic factors. These results emphasize the need to adopt an early and persistent prevention framework targeting both the child and the peer context to alleviate the establishment of a negative coercive process and its consequences.
The Quebec Newborn Twin Study (QNTS) is an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early bio-social determinants, as well as their putative role in later social-emotional adjustment, school and health outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS has 14 waves of data collected or planned, including 5 in preschool. Over the past 15 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multi-method measurements. QNTS also entails extended and detailed multi-level assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child's environment. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene-environment transactions in development.
Ever since the beginning of the history of computer systems, the demand for more performance has been the most important driving force for evolution in computer architecture. In particular, many important applications demand more performance than a single (serial) processor core can provide, and historically have pushed parallel architecture technology. A good example is numerical programs used in computer simulation to analyze and solve problems in science and engineering, such as climate modeling, weather forecasting, or computer-aided design. Another example is commercial systems in which a large pool of independent queries must be executed to meet the growing demands of the information age. Over the years, another driving force for parallel architectures has been the fear of impending technological barriers that would eventually stall the performance growth of serial computers. These two forces have fueled from the beginning a keen interest in multiprocessor architecture research. While scientific computing needs made these research efforts relevant early on in the market place, multiprocessor technology hit the mainstream with the shift to multi-core computers at the beginning of the twenty-first century.
This chapter is devoted to design principles of multiprocessor systems. It focuses on two multiprocessor architectural styles: shared-memory and message-passing multiprocessor systems. Both styles use multiple processors with the goal of achieving a linear speedup of computational power with the number of processors. However, they differ in the method by which the processors exchange data. Processors in shared-memory multiprocessors share the same address space and can exchange data through shared-memory locations by regular load and store instructions.
This chapter is dedicated to the correct and reliable communication of values in shared-memory multiprocessors. Relevant correctness properties of the memory system of shared-memory multiprocessors include coherence, the memory consistency model (henceforth also referred to as the memory model), and the reliable execution of synchronization primitives. Since chip multiprocessors are designed as shared-memory multi-core systems, this chapter targets correctness issues not only in symmetric multiprocessors (SMPs) or large-scale cache coherent distributed shared-memory systems (cc-NUMAs and COMAs) covered in Chapter 5, but also in chip multiprocessors with core multi-threading (CMPs) covered in Chapter 8.
The correctness of a shared-memory multi-threaded program must be independent of the relative execution speed of its threads, because of the numerous unpredictable events that can disrupt the execution of any one thread, such as DVFS (dynamic voltage and frequency scaling), thermal emergencies, conflicts for hardware and software resources, interrupts, exceptions, kernel activity, thread scheduling, data allocation delays, and interactions with other running programs. If a multi-threaded program is written for a dedicated machine in which timing is highly predictable and the program is written in a way that takes timing into account for its correctness (such as, possibly, in real-time systems), many conclusions of this chapter should be revised. In other words, the target software throughout this chapter is portable shared-memory multi-threaded programs written for general-purpose or multi-purpose machines and includes the operating system kernel.
In this chapter we sharpen our focus on thread-level parallelism within a single die. Parallelism within a die comes in different forms. Within a single-core, multiple threads can be executed to improve resource utilization, an approach called core multi-threading. There are three approaches to core multi-threading depending on how and when instructions are fetched from multiple ready threads: block multi-threading, interleaved multi-threading and simultaneous multi-threading. We show the hardware additions and modifications necessary for each of these three multi-threading approaches to work within the contexts of traditional (single-threaded) in-order and out-of-order processors. We use example-driven approaches to show the performance advantages of finer-grain multi-threading over coarse-grain multithreading. The performance advantages come at additional hardware cost.
The next paradigm to provide on-die parallelism is exploiting multiple cores on the same chip. Chip multiprocessors (CMPs) are fast becoming ubiquitous in all walks of computing, from cell phones to datacenter servers. We explain the fundamental advantages of CMPs over traditional shared-memory multiprocessors (SMPs) mostly borne from the fact that all cores are tightly integrated on a single die by on-die interconnects.We describe three on-die interconnect topologies common today for building CMPs. When all cores on a CMP are identical, the CMP is said to be homogeneous. The cores in heterogeneous CMPs differ in their capabilities. We describe various heterogeneous CMP designs and the gamut of different performance and functionality possible.
Given the widening gaps between processor speed, main memory (DRAM) speed, and secondary memory (disk) speed, it has become more and more difficult in recent years to feed data and instructions at the speed required by the processor while providing the ever-expanding memory space expected by modern applications. Modern systems rely on a memory hierarchy based on speed, size, and cost, as illustrated in Figure 4.1. Left of the dotted line is the cache hierarchy. Right of the dotted line is the virtual memory hierarchy, which may include a disk cache (not shown).
It has been observed over the years that the speed gap between the processor (clocked at multiple gigahertz and executing multiple instructions per clock) and main memory (with access times in the tens or even hundreds of nanoseconds) is growing exponentially. This problem is commonly referred to as the memory wall. A hierarchy of multiple levels of caches with various sizes and access times are employed to bridge the speed gap. Moreover, caches at every level are becoming more and more complex to help reduce or hide the latency of cache misses. To support OoO dynamically scheduled processors, which may have more than ten memory accesses pending at any time, modern, lockup-free (non-blocking) caches are capable of handling multiple cache hits and misses at a time. Furthermore, data and instructions are prefetched in caches before they are needed. In this chapter we describe these enhancements to cache designs.
Teaching fundamental design concepts and the challenges of emerging technology, this textbook prepares students for a career designing the computer systems of the future. In-depth coverage of complexity, power, reliability and performance, coupled with treatment of parallelism at all levels, including ILP and TLP, provides the state-of-the-art training that students need. The whole gamut of parallel architecture design options is explained, from core microarchitecture to chip multiprocessors to large-scale multiprocessor systems. All the chapters are self-contained, yet concise enough that the material can be taught in a single semester, making it perfect for use in senior undergraduate and graduate computer architecture courses. The book is also teeming with practical examples to aid the learning process, showing concrete applications of definitions. With simple models and codes used throughout, all material is made open to a broad range of computer engineering/science students with only a basic knowledge of hardware and software.