A comparison of three methods of Mendelian randomization when the genetic instrument, the risk factor and the outcome are all binary.

The method of instrumental variable (referred to as Mendelian randomization when the instrument is a genetic variant) has been initially developed to infer on a causal effect of a risk factor on some outcome of interest in a linear model. Adapting this method to nonlinear models, however, is known to be problematic. In this paper, we consider the simple case when the genetic instrument, the risk factor, and the outcome are all binary. We compare via simulations the usual two-stages estimate of a causal odds-ratio and its adjusted version with a recently proposed estimate in the context of a clinical trial with noncompliance. In contrast to the former two, we confirm that the latter is (under some conditions) a valid estimate of a causal odds-ratio defined in the subpopulation of compliers, and we propose its use in the context of Mendelian randomization. By analogy with a clinical trial with noncompliance, compliers are those individuals for whom the presence/absence of the risk factor X is determined by the presence/absence of the genetic variant Z (i.e., for whom we would observe X = Z whatever the alleles randomly received at conception). We also recall and illustrate the huge variability of instrumental variable estimates when the instrument is weak (i.e., with a low percentage of compliers, as is typically the case with genetic instruments for which this proportion is frequently smaller than 10%) where the inter-quartile range of our simulated estimates was up to 18 times higher compared to a conventional (e.g., intention-to-treat) approach. We thus conclude that the need to find stronger instruments is probably as important as the need to develop a methodology allowing to consistently estimate a causal odds-ratio.

A comparison of the performance of modern screen-film and digital mammography systems.

This work compares the detector performance and image quality of the new Kodak Min-R EV mammography screen-film system with the Fuji CR Profect detector and with other current mammography screen-film systems from Agfa, Fuji and Kodak. Basic image quality parameters (MTF, NPS, NEQ and DQE) were evaluated for a 28 kV Mo/Mo (HVL = 0.646 mm Al) beam using different mAs exposure settings. Compared with other screen-film systems, the new Kodak Min-R EV detector has the highest contrast and a low intrinsic noise level, giving better NEQ and DQE results, especially at high optical density. Thus, the properties of the new mammography film approach those of a fine mammography detector, especially at low frequency range. Screen-film systems provide the best resolution. The presampling MTF of the digital detector has a value of 15% at the Nyquist frequency and, due to the spread size of the laser beam, the use of a smaller pixel size would not permit a significant improvement of the detector resolution. The dual collection reading technology increases significantly the low frequency DQE of the Fuji CR system that can at present compete with the most efficient mammography screen-film systems.

Comparison of the proliferative activity of neuroblasts from chick embryo cerebral hemispheres of different ages in culture.

Dissociated cerebral hemisphere cells from 4- to 7-day-old chick embryos were cultured either on a collagen or a polylysine substrate in a serum-containing medium. Neurons were characterized by the demonstration of acetylcholinesterase, the presence of D2/N-CAM glycoprotein and neurofilament proteins. The proliferation of neuronal precursor cells was shown by morphological observations, autoradiographic analysis and measurements of [3H]-thymidine incorporation. Neuronal precursors derived from the 6-day-old embryos showed the highest proliferative activity. Neuroblast proliferation was found to be dependent on the culture substrates (i.e. polylysine or collagen), which yielded either isolated cells or cell aggregates, and the latter favored the mitogenic effect.

Direct in vitro comparison of six three-dimensional positive contrast methods for susceptibility marker imaging.

PURPOSE: To compare different techniques for positive contrast imaging of susceptibility markers with MRI for three-dimensional visualization. As several different techniques have been reported, the choice of the suitable method depends on its properties with regard to the amount of positive contrast and the desired background suppression, as well as other imaging constraints needed for a specific application. MATERIALS AND METHODS: Six different positive contrast techniques are investigated for their ability to image at 3 Tesla a single susceptibility marker in vitro. The white marker method (WM), susceptibility gradient mapping (SGM), inversion recovery with on-resonant water suppression (IRON), frequency selective excitation (FSX), fast low flip-angle positive contrast SSFP (FLAPS), and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) were implemented and investigated. RESULTS: The different methods were compared with respect to the volume of positive contrast, the product of volume and signal intensity, imaging time, and the level of background suppression. Quantitative results are provided, and strengths and weaknesses of the different approaches are discussed. CONCLUSION: The appropriate choice of positive contrast imaging technique depends on the desired level of background suppression, acquisition speed, and robustness against artifacts, for which in vitro comparative data are now available.

Flow targeted 3D steady-state free-precession coronary MR angiography: comparison of three different imaging approaches.

PURPOSE: To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P < 0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P < 0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P < 0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time. CONCLUSION: Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.

A comparison of rapid bioassessment protocols used in 2 regions with Mediterranean climates, the Iberian Peninsula and South Africa

Abstract. The ability of 2 Rapid Bioassessment Protocols (RBPs) to assess stream water quality was compared in 2 Mediterranean-climate regions. The most commonly used RBPs in South Africa (SAprotocol) and the Iberian Peninsula (IB-protocol) are both multihabitat, field-based methods that use macroinvertebrates. Both methods use preassigned sensitivity weightings to calculate metrics and biotic indices. The SA- and IB-protocols differ with respect to sampling equipment (mesh size: 1000 lm vs 250 300 lm, respectively), segregation of habitats (substrate vs flow-type), and sampling and sorting procedures (variable time and intensity). Sampling was undertaken at 6 sites in South Africa and 5 sites in the Iberian Peninsula. Forty-four and 51 macroinvertebrate families were recorded in South Africa and the Iberian Peninsula, respectively; 77.3% of South African families and 74.5% of Iberian Peninsula families were found using both protocols. Estimates of community similarity compared between the 2 protocols were .60% similar among sites in South Africa and .54% similar among sites in the Iberian Peninsula (BrayCurtis similarity), and no significant differences were found between protocols (Multiresponse Permutation Procedure). Ordination based on Non-metric Multidimensional Scaling grouped macroinvertebrate samples on the basis of site rather than protocol. Biotic indices generated with the 2 protocols at each site did not differ. Thus, both RBPs produced equivalent results, and both were able to distinguish between biotic communities (mountain streams vs foothills) and detect water-quality impairment, regardless of differences in sampling equipment, segregation of habitats, and sampling and sorting procedures. Our results indicate that sampling a single habitat may be sufficient for assessing water quality, but a multihabitat approach to sampling is recommended where intrinsic variability of macroinvertebrate assemblages is high (e.g., in undisturbed sites in regions with Mediterranean climates). The RBP of choice should depend on whether the objective is routine biomonitoring of water quality or autecological or faunistic studies.

A comparison of the energy budgets of two freshwater Pulmonates: Lymnaea peregra (Müller) and Physa acuta (Drap.)

The energy budgets of two freshwater gastropds, Lymnae peregra and Physa acuta, were compared in similar experimental conditions (20ºC, fed ad libitum with 24h-decayed lettuce), and found to differ in several ways. 1) L. Peregra has a higher assimilation efficiency than P. acuta (72% vs 60%). 2) These species assimilate different components of the ingested food: P. acuta uses a smaller, but more energetic part (probably mainly bacteria), whereas L. peregra assimilate a larger, but less energetic part (probably mainly cellulose). 3) L. peregra allocates more of its assimilated energy to oxygene consumption and mucus production (maintenance investments), wheras P. acuta invest more in growth and reproduction (production investments). Such differences are relevant to the natural habitat of these two species: P. acuta colonizes warm, eutrophic and temporary pools, where decaying material constitue the main part of available resources, and where adult mortality is high and impredictible. By contrast, L. peregra is frequently found in colder, oligotrophic and predictible environements, where living primary producers constitute the main part of available resources, and where biotic interactions are important factors of mortality.

Comparison of human and rhesus macaque T-cell responses elicited by boosting with NYVAC encoding human immunodeficiency virus type 1 clade C immunogens.

Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-gamma) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4(+) and CD8(+) T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-gamma, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-gamma T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.

Alcohol may not cause partner violence but it seems to make it worse: a cross national comparison of the relationship between alcohol and severity of partner violence.

This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13 countries as part of the GENACIS collaboration. Respondents described the most physically aggressive act done to them by a partner in the past 2 years, rated the severity of aggression on a scale of 1 to 10, and reported whether either partner had been drinking when the incident occurred. Severity ratings were significantly higher for incidents in which one or both partners had been drinking compared to incidents in which neither partner had been drinking. The relationship did not differ significantly for men and women or by country. We conclude that alcohol consumption may serve to potentiate violence when it occurs, and this pattern holds across a diverse set of cultures. Further research is needed that focuses explicitly on the nature of alcohol's contribution to intimate partner aggression. Prevention needs to address the possibility of enhanced dangers of intimate partner violence when the partners have been drinking and eliminate any systemic factors that permit alcohol to be used as an excuse. Clinical services for perpetrators and victims of partner violence need to address the role of drinking practices, including the dynamics and process of aggressive incidents that occur when one or both partners have been drinking.