Antenatal testing--benefits and costs

Antenatal testing is a common component of care for the high-risk pregnancy. The goals of antenatal testing include the prevention of stillbirth and the detection of the hypoxic fetus to allow intervention before acidosis and long-term damage. Data regarding the efficacy of antenatal testing are limited by a lack of randomized controlled trials. The majority of available data hinge on observational studies with the inherent potential for bias. There is also a paucity of data comparing the various testing modalities and addressing the issue of the optimal timing of initiation of testing. As well, data are limited regarding the various conditions most likely to benefit from testing and the frequency with which testing should be performed. The issue of cost relating to antenatal testing is an important one. Central to the issue of estimating cost is an understanding of the efficacy of the test. Given our current limitations, we have significant difficulty accurately estimating the cost of antenatal testing; however, rough estimates of cost are made.     

Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling

OBJECTIVE: We studied hypophosphatasia (HP) mutations in 19 cases prenatally detected by ultrasonography without familial history of HP. We correlated the mutations with the reported ultrasound signs, and discussed genetic counseling with regard to the particular dominantly inherited prenatal benign form of HP. METHOD: The coding sequence of the tissue nonspecific alkaline phosphatase (TNSALP) gene was analyzed by DNA sequencing, and 3D modeling was used to locate the mutated amino acids with regard to the functional domains of TNSALP. RESULTS: Although reported ultrasound signs were heterogeneous, two mutated alleles were found in 18 of the 19 cases studied, indicating recessive transmission of the disease. Functional domains of TNSALP were affected by 74% of missense mutations. In all the cases, including one with only a heterozygous mutation, molecular, biological, and familial data do not corroborate the hypothesis of prenatal benign HP. The mutation c.1133A>T observed in the prenatal benign form of HP and common in USA was not found in this series. CONCLUSION: The results point out the prenatally detectable allelic heterogeneity of HP. The nature of the detected mutations and the evidence of recessive inheritance do not support these cases being affected with prenatal benign HP.     

Coordinating Canada's research response to global health challenges: the Global Health Research Initiative

The Global Health Research Initiative (GHRI) involving the Canadian International Development Agency, the Canadian Institutes of Health Research, Health Canada and the International Development Research Centre seeks to coordinate Canada's research response to global health challenges. In light of numerous calls to action both nationally and internationally, an orientation to applied health policy and systems research, and to public health research and its application is required to redress global inequalities in wealth and health and to tackle well-documented constraints to achieving the United Nations Millennium Development Goals. Over the last four years, the GHRI has funded close to 70 research program development and pilot projects. However, longer-term investment is needed. The proposed dollars 100 million Teasdale-Corti Global Health Research Partnership Program is such a response, and is intended to support teams of researchers and research users to develop, test and implement innovative approaches to strengthening institutional capacity, especially in low- and middle-income countries; to generating knowledge and its effective application to improve the health of populations, especially those most vulnerable; and to strengthen health systems in those countries. While Canada stands poised to act, concerted leadership and resources are still required to support "research that matters" for health and development in low- and middle-income countries.     

Concentration gradients in evaporating binary droplets probed by spatially resolved Raman and NMR spectroscopy

Understanding the evaporation process of binary sessile droplets is essential for optimizing various technical processes, such as inkjet printing or heat transfer. Liquid mixtures whose evaporation and wetting properties may differ significantly from those of pure liquids are particularly interesting. Concentration gradients may occur in these binary droplets. The challenge is to measure concentration gradients without affecting the evaporation process. Here, spectroscopic methods with spatial resolution can discriminate between the components of a liquid mixture. We show that confocal Raman microscopy and spatially resolved NMR spectroscopy can be used as complementary methods to measure concentration gradients in evaporating 1-butanol/1-hexanol droplets on a hydrophobic surface. Deuterating one of the liquids allows analysis of the local composition through the comparison of the intensities of the C–H and C–D stretching bands in Raman spectra. Thus, a concentration gradient in the evaporating droplet was established. Spatially resolved NMR spectroscopy revealed the composition at different positions of a droplet evaporating in the NMR tube, an environment in which air exchange is less pronounced. While not being perfectly comparable, both methods—confocal Raman and spatially resolved NMR experiments—show the presence of a vertical concentration gradient as 1-butanol/1-hexanol droplets evaporate.

Evaporating droplets occur in various contexts such as inkjet printing (1, 2), heat transfer, or daily phenomena such as drying coffee stains (3, 4). In many applications, such as painting (5), cleaning, gluing, or printing (6), where liquid mixtures are used, the evaporation of a droplet is a complex process because the concentration profile within the droplet varies over time. To improve the controllability and predictability of the technical processes, it is essential to characterize the transport phenomena during the drying process. The measurement of the droplet composition is a crucial element and has to be carried out with sufficient spatial and temporal resolution. In particular, spectroscopic methods are promising tools for contactless concentration measurements of liquid mixtures.The evaporation of a droplet is governed by physical properties such as surface tension (7), density (8–10), vapor pressure (11), and boiling temperature. Additionally, concentration gradients can evolve in liquid mixtures (12). These gradients are driven by thermal gradients due to the enthalpy of evaporation (droplet cooling) or on heated surfaces, by surface tension gradients induced by preferential evaporation of one component or by density gradients for droplets composed of liquids with different densities like water and glycerol (13). The evaporation rates of the components can vary over the droplet surface. For sessile droplets with contact angles smaller than 90°, for example, the evaporation rates are higher at the three-phase contact line (14). These thermal or surface tension gradients can induce flow inside the droplet called Marangoni flow. This flow leads to concentration gradients across the droplet (7–10). The direction of the gradient depends on the density and surface tension. A direct application of this principle is, for instance, Marangoni cleaning in semiconductor technology (15).The investigation of the composition of sessile drops on the microliter scale, as they occur in inkjet printing or other technical processes, poses a challenge because the typical length scales of interest are smaller than the capillary length. In bulk samples, the composition can be examined in a straightforward manner with chromatographic methods such as gas chromatography and high-performance liquid chromatography or spectroscopic methods such as NMR spectroscopy, infrared spectroscopy, and Raman spectroscopy. However, for the investigation of sessile droplets, a high spatial and temporal resolution is required. For this purpose, confocal Raman spectroscopy and spatially resolved NMR spectroscopy are powerful tools. For both techniques, concentration determination is straightforward if at least two signals of the components of interest are baseline-separated. NMR is intrinsically calibration-free, whereas Raman spectroscopy requires calibration through reference experiments (16–18). Both approaches allow the quantification of concentration gradients in sessile droplets, as is shown here.In Raman microscopy, good spatial resolution can be achieved in a confocal setup. The components of mixtures can be distinguished via specific vibrations for different functional groups or through a careful analysis of the Raman signals in the fingerprint region (<1,500 cm⁻¹). For example, binary mixtures of ethanol and water can be characterized in a straightforward manner (17). If, however, both liquids have a similar chemical structure, the discrimination of the components might be hampered by signal overlap in the C–H stretching region (2,800 to 3,000 cm⁻¹); e.g., in such cases, Raman signals in the fingerprint region (<1,500 cm⁻¹) might be used for the identification of the species. However, these signals often provide a poor signal-to-noise ratio, which makes large integration times necessary. Thus, the image rate or resolution is so low that even slow diffusion processes are hardly resolved. Here, Raman stable isotope probing (SIP), which has been developed to monitor metabolic processes in microbiology, offers a solution (19). The basic idea of Raman SIP is to replace the proton in the C–H with deuterium in one of the mixture components such that the C–D stretching region occurs at roughly 1/2 times the C–H stretching and falls into a region with very weak or even without signals from the protonated liquid component. Thus, the concentration in a binary mixture can be calculated in a straightforward manner from the ratio of the integrated Raman intensities ICD/ICH of the respective stretching vibrations.Compared to Raman microscopy, where localization is achieved by scanning the focal point across the region of interest, in NMR experiments localization is achieved by using magnetic field gradients. Usually, one avoids phase boundaries (especially liquid–gas interfaces) in NMR experiments because they disturb the magnetic field homogeneity and reduce the spectral quality in terms of line shape and baseline separation of the resonances. Nevertheless, it has been shown that MRI can be used to characterize freezing water droplets (20), the infiltration of water into asphalts (21), and the evaporation of sessile droplets from porous surfaces (22–24). Additionally, NMR can be used to quantify the composition of binary droplets during evaporation (25).Thus, the use of both complementary approaches to characterize evaporating binary droplets may be beneficial. In this article, we discuss the capabilities of Raman SIP and NMR techniques to analyze the evolution of the composition of an evaporating sessile binary droplet. As a model system, a binary mixture of 1-butanol and 1-hexanol was used. This mixture shows a low volatility such that the evaporation process can be captured with both Raman and NMR spectroscopies. With Raman spectroscopy, it was possible to observe concentration gradients of 1-butan-d₉-ol over the height of the droplet during evaporation. NMR techniques were examined in terms of the capability to observe the evaporation of 1-butanol and yield time-dependent droplet composition with spatially resolved ¹H-NMR spectra. Furthermore, the contours of the evaporating droplets were tracked by optical measurements to characterize the time-dependent changes in the droplet dimensions. Flows induced by the concentration gradients were confirmed by astigmatic particle tracking velocimetry.     

A primer for ZooMS applications in archaeology

Collagen peptide mass fingerprinting by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, also known as zooarchaeology by mass spectrometry (ZooMS), is a rapidly growing analytical technique in the fields of archaeology, ecology, and cultural heritage. Minimally destructive and cost effective, ZooMS enables rapid taxonomic identification of large bone assemblages, cultural heritage objects, and other organic materials of animal origin. As its importance grows as both a research and a conservation tool, it is critical to ensure that its expanding body of users understands its fundamental principles, strengths, and limitations. Here, we outline the basic functionality of ZooMS and provide guidance on interpreting collagen spectra from archaeological bones. We further examine the growing potential of applying ZooMS to nonmammalian assemblages, discuss available options for minimally and nondestructive analyses, and explore the potential for peptide mass fingerprinting to be expanded to noncollagenous proteins. We describe the current limitations of the method regarding accessibility, and we propose solutions for the future. Finally, we review the explosive growth of ZooMS over the past decade and highlight the remarkably diverse applications for which the technique is suited.     

Cortical basis for skilled vocalization

Marmosets display remarkable vocal motor abilities. Macaques do not. What is it about the marmoset brain that enables its skill in the vocal domain? We examined the cortical control of a laryngeal muscle that is essential for vocalization in both species. We found that, in both monkeys, multiple premotor areas in the frontal lobe along with the primary motor cortex (M1) are major sources of disynaptic drive to laryngeal motoneurons. Two of the premotor areas, ventral area 6 (area 6V) and the supplementary motor area (SMA), are a substantially larger source of descending output in marmosets. We propose that the enhanced vocal motor skills of marmosets are due, in part, to the expansion of descending output from these premotor areas.

Speech is a uniquely human form of communication which uses vocalization to express thoughts and feelings. Vocalization is built on the exquisitely coordinated control over respiration, phonation, and articulation. Historically, the enhanced vocal motor skills of humans have been attributed to alterations in the peripheral mechanisms for sound production (1, 2). However, recent studies of laryngeal biomechanics have ruled out this explanation (3). Instead, modifications in central neural circuits are the likely basis of the enhanced vocal abilities of humans (1). Here, we used a comparative approach to identify the adaptations in the cerebral cortex that provide a substrate for the enhanced vocal motor abilities of some monkeys.Our experiments compared the areas of the cerebral cortex that are involved in the control of a laryngeal muscle in macaques and marmosets. We selected these two monkey species because of the striking differences in their vocal behavior. Macaque vocalization is generally limited to spontaneous utterances of acoustically simple calls which relate the animal’s emotional and motivational state (4). In the laboratory setting, it is difficult for researchers to elicit macaque vocalizations and for the monkeys to suppress spontaneous calls (5, 6). In contrast, marmosets readily vocalize in the laboratory setting. These monkeys naturally exhibit vocal turn taking with multiple back-and-forth exchanges that entrain to each other just as in human conversation (7–10). Marmosets can modulate the amplitude (11), timing (9, 11), and pitch (12) of their calls to compensate not only for physical noise but also for physical distance between conspecifics. Overall, marmosets demonstrate vocal skills and experience-dependent vocal production not observed in macaques (13–15).To identify areas of the cerebral cortex that are involved in vocalization, we used retrograde transneuronal transport of rabies virus from the cricothyroid muscle. We selected the cricothyroid because it is the laryngeal muscle that is most specifically related to vocal motor control. The cricothyroid is an intrinsic laryngeal muscle that when active increases tension on the vocal folds (4). This muscle is unique in controlling vocal pitch while contributing little to other laryngeal functions, such as swallowing and airway regulation (4).