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Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
This project surveyed Veterans’ COVID-19 vaccination beliefs and status. 1,080 (30.8%) Veterans responded. Factors associated with being unvaccinated, identified using binomial logistic regression, included negative feelings about vaccines (OR = 3.88, 95%CI = 1.52, 9.90) and logistical difficulties such as finding transportation (OR = 1.95, 95%CI = 1.01, 3.45). This highlights the need for education about and access to vaccination.
Contracting delays remain a challenge to the successful initiation of multisite clinical research in the US. The Clinical and Translational Science Awards (CTSA) Contracts Processing Study showed average contract negotiation duration of > 100 days for industry-sponsored or investigator-initiated contracts. Such delays create enormous costs to sponsors and to patients waiting to use new evidence-based treatments. With support from the National Institutes of Health’s National Center for Advancing Translational Sciences, the Accelerated Clinical Trial Agreement (ACTA) was developed by 25 major academic institutions and medical centers engaged in clinical research in collaboration with the University-Industry Demonstration Partnership and with input from pharmaceutical companies. The ACTA also informed the development of subsequent agreements, including the Federal Demonstration Partnership Clinical Trial Subaward Agreement (FDP-CTSA); both ACTA and the FDP-CTSA are largely non-negotiable agreements that represent pre-negotiated compromises in contract terms agreed upon by industry and/or medical center stakeholders. When the involved parties agree to use the CTSA-developed and supported standard agreement templates as a starting point for negotiations, there can be significant time savings for trials. Use of the ACTA resulted in an average savings of 48 days and use of the FDP-CTSA saved an average of 57 days of negotiation duration.
In Chapter 11, we studied the forces in machine systems in which all forces on the bodies were in balance, and therefore the systems were in either static or dynamic equilibrium. However, in real machines this is seldom, if ever, the case except when the machine is stopped. We learned in Chapter 4 that although the input crank of a machine may be driven at constant speed, this does not mean that all points of the input crank have constant velocity vectors or that other links of the machine operate at constant speeds. In general, there will be accelerations, and therefore machines with moving parts having mass are not balanced.
The existence of vibrating elements in a mechanical system produces unwanted noise, high stresses, wear, poor reliability, and, frequently, premature failure of one or more of the parts. The moving parts of all machines are inherently vibration producers, and for this reason engineers must expect vibrations to exist in the devices they design. But there is a great deal they can do during the design of the system to anticipate a vibration problem and to minimize its undesirable effects.
Balancing is defined here as the process of correcting or eliminating unwanted inertia forces and moments in rotating machinery. In previous chapters, we have seen that shaking forces on the frame can vary significantly during a cycle of operation. Such forces can cause vibrations that at times may reach dangerous amplitudes. Even if they are not dangerous, vibrations increase component stresses and subject bearings to repeated loads that may cause parts to fail prematurely by fatigue. Thus, in the design of machinery, it is not sufficient merely to avoid operation near the critical speeds; we must eliminate, or at least reduce, the dynamic forces that produce these vibrations in the first place.
In the previous chapters we learned how to analyze the kinematic characteristics of a given mechanism. We were given the design of a mechanism, and we studied ways to determine its mobility, its posture, its velocity, and its acceleration, and we even discussed its suitability for given types of tasks. However, we have said little about how the mechanism is designed – that is, how the sizes and shapes of the links are chosen by the designer.
In our studies of kinematic analysis in the previous chapters, we limited ourselves to consideration of the geometry of the motions and of the relationships between displacement and time. The forces required to produce those motions or the motion that would result from the application of a given set of forces were not considered. We are now ready for a study of the dynamics of machines and systems. Such a study is usually simplified by starting with the statics of such systems.
The large majority of mechanisms in use today have planar motion, that is, the motions of all points produce paths that lie in a single plane or in parallel planes. This means that all motions can be seen in true size and shape from a single viewing direction and that graphic methods of analysis require only a single view. If the coordinate system is chosen with the x and y axes parallel to the plane(s) of motion, then all z values remain constant, and the problem can be solved, either graphically or analytically, with only two-dimensional methods. Although this is usually the case, it is not a necessity. Mechanisms having three-dimensional point paths do exist and are called spatial mechanisms. Another special category, called spherical mechanisms, have point paths that lie on concentric spherical surfaces.
Gears are machine elements used to transmit rotary motion between two shafts, usually with a constant speed ratio. In this chapter, we will discuss the case where the axes of the two shafts are parallel, and the teeth are straight and parallel to the axes of rotation of the shafts; such gears are called spur gears.
In Chapters 2, 3, and 4, we concentrated entirely on problems that exhibit a single degree of freedom, and can be analyzed by specifying the motion of a single input variable. This was justifiable, since, by far, the vast majority of practical mechanisms are designed to have only one degree of freedom so that they can be driven by a single power source. However, there are mechanisms that have multiple degrees of freedom and can only be analyzed if more than one input motion is given. In this chapter, we will look at how our methods can be used to find the positions, velocities, and accelerations of these mechanisms.
Since velocity is a vector quantity, the change in velocity, Δ𝐕P, and the acceleration, 𝐀P, are also vector quantities – that is, they have both magnitude and direction. Also, like velocity, the acceleration vector is properly defined only for a point; the term should not be applied to a line, a coordinate system, a volume, or any other collection of points, since the accelerations of different points may be different.