Will the introduction of non-invasive prenatal diagnostic testing erode informed choices? An experimental study of health care professionals

Objective

Informed choice is a fundamental concept within prenatal care. The present study assessed the extent to which the introduction of non-invasive prenatal diagnosis (NIPD) of Down's syndrome may undermine the process of making informed choices to undergo prenatal testing or screening for Down's syndrome by altering the quality and quantity of pre-test counselling.

Methods

231 obstetricians and midwives were randomly allocated one of three vignettes, each describing a different type of test: (a) invasive prenatal diagnosis (IPD), (b) non-invasive prenatal diagnosis (NIPD) or (c) Down's syndrome screening (DSS). Participants were then asked to complete a questionnaire assessing (1) the information considered important to communicate to women, (2) whether test offer and uptake should take place on different days, and (3) whether signed consent forms should be obtained prior to testing.

Results

Across the three test types, five out of the seven presented topics were considered equally important to communicate, including the information that testing is the woman's choice. Compared with participants receiving the IPD vignette, those receiving the NIPD and DSS vignettes were less likely to report that counselling and testing should occur on different days (IPD 94.7% versus 74.1% and 73.9% for NIPD and DSS respectively, p = .001) and that written consent was a necessity (IPD 96.1% versus 68.3% and 75.4% for NIPD and DSS respectively, p < .001).

Conclusion

This study provides the first empirical evidence to demonstrate that practitioners may view the consent process for NIPD differently to IPD. There is potential for the introduction of NIPD to undermine women making informed choices in the context of prenatal diagnostic testing for conditions like DS.

Practice implications

Given the importance of informed choice in reproductive decision-making, implementation of any programme based on NIPD should be designed to facilitate this.     

No evidence that a common pesticide impairs female mate choice in a freshwater amphipod

Sublethal concentrations of pesticides may drastically alter the evolutionary trajectories of populations by interfering with mating behaviors. We used a median lethal concentration (LC50) experiment to test the sensitivity of three amphipod (Hyalella sp.) classes (females, small males, and large males) to five concentrations [10.4, 1.52, 0.16, 0.05, none detected (ND) μg/L] of the most commonly applied pesticide (malathion) in the United States. We then tested the sensitivity of female mate choice to sublethal concentrations (0.55, 0.38, and 0.05 μg/L) of malathion using a dichotomous choice test. Mortality was relatively high at low concentrations for all three amphipod classes with LC50s ranging from 0.06 μg/L in females to 0.19 μg/L in small males. There was overlap in the 95% CI of these estimates across amphipod classes suggesting no class‐specific differences in sensitivity to malathion. We found no evidence that malathion interferes with female choice in this species, suggesting that mating behavior may not always be a good indicator of sublethal pesticide contamination. © 2009 Wiley Periodicals, Inc. Environ Toxicol 2010.     

Electrophysiological measures of conflict and reward processing are associated with decisions to engage in physical effort

Anterior cingulate cortex (ACC), a key brain region involved in cognitive control and decision making, is suggested to mediate effort- and value-based decision making, but the specific role of ACC in this process remains debated. Here we used frontal midline theta (FMT) and the reward positivity (RewP) to examine ACC function in a value-based decision making task requiring physical effort. We investigated whether (1) FMT power is sensitive to the difficulty of the decision or to selecting effortful actions, and (2) RewP is sensitive to the subjective value of reward outcomes as a function of effort investment. On each trial, participants chose to execute a low-effort or a high-effort behavior (that required squeezing a hand-dynamometer) to obtain smaller or larger rewards, respectively, while their brainwaves were recorded. We replicated prior findings that tonic FMT increased over the course of the hour-long task, which suggests increased application of control in the face of growing fatigue. RewP amplitude also increased following execution of high-effort compared to low-effort behavior, consistent with increased valuation of reward outcomes by ACC. Although neither phasic nor tonic FMT were associated with decision difficulty or effort selection per se, an exploratory analysis revealed that the interaction of phasic FMT and expected value of choice predicted effort choice. This interaction suggests that phasic FMT increases specifically under situations of decision difficulty when participants ultimately select a high-effort choice. These results point to a unique role for ACC in motivating and persisting at effortful behavior when decision conflict is high.     

Characterizing the role of the pre‐SMA in the control of speed/accuracy trade‐off with directed functional connectivity mapping and multiple solution reduction

Several plausible theories of the neural implementation of speed/accuracy trade‐off (SAT), the phenomenon in which individuals may alternately emphasize speed or accuracy during the performance of cognitive tasks, have been proposed, and multiple lines of evidence point to the involvement of the pre‐supplemental motor area (pre‐SMA). However, as the nature and directionality of the pre‐SMA's functional connections to other regions involved in cognitive control and task processing are not known, its precise role in the top‐down control of SAT remains unclear. Although recent advances in cross‐sectional path modeling provide a promising way of characterizing these connections, such models are limited by their tendency to produce multiple equivalent solutions. In a sample of healthy adults (N = 18), the current study uses the novel approach of Group Iterative Multiple Model Estimation for Multiple Solutions (GIMME‐MS) to assess directed functional connections between the pre‐SMA, other regions previously linked to control of SAT, and regions putatively involved in evidence accumulation for the decision task. Results reveal a primary role of the pre‐SMA for modulating activity in regions involved in the decision process but suggest that this region receives top‐down input from the DLPFC. Findings also demonstrate the utility of GIMME‐MS and solution‐reduction methods for obtaining valid directional inferences from connectivity path models.     

Choosing the pacemaker; a rational approach to the use of modern pacemaker technology

Sophisticated pacemakers now afford greater benefit than only relief of syncope for patients with symptomatic bradyarrhythmia. For clinical reasons it is inappropriate to implant ventricular demand (VVI) pacemakers in every patient, but for both clinical and economic reasons it is also undesirable to use dual-lead or rate-responsive systems indiscriminately. However, the published guidelines for pacemaker choice and investigation are inadequate. We have analysed the clinical assessment and the investigations required in a series of 150 patients with various electrophysiological disorders, considered consecutively for pacemaker implantation using an algorithm to assist decisions. Holter electrocardiography in 77.3%, exercise testing--formal (in 9.3%) or informal (during Holter electrocardiography), electrophysiology study (EPS)--full in 15.3% and partial in 29.3%, and trial of pacing (10.7%) were all used to characterize dysfunction and to define appropriate pacing mode. 142 patients were paced--57.0% with single lead modes (12.7%) AAI, 44.3% VVI) and 43.0% dual-lead (2.8% DVI, 23.9% VDD or VAT, 16.2% DDD). Three patients received rate-responsive systems (VVIR) which, if available, would have been used in nine; four would have been suitable for AAIR and four for dual-lead responsive pacing (DVIR, DDIR or DDDR). We offer a rational approach based on published data for investigation and pacemaker choice in the management of patients with bradyarrhythmia.     

Implementation of three‐dimensional wavelet encoding spectroscopic imaging: In vivo application and method comparison

We have recently proposed a two‐dimensional Wavelet Encoding‐Spectroscopic Imaging (WE‐SI) technique as an alternative to Chemical Shift Imaging (CSI), to reduce acquisition time and crossvoxel contamination in magnetic resonance spectroscopic imaging (MRSI). In this article we describe the extension of the WE‐SI technique to three dimensions and its implementation on a clinical 1.5 T General Electric (GE) scanner. Phantom and in vivo studies are carried out to demonstrate the usefulness of this technique for further acquisition time reduction with low voxel contamination. In wavelet encoding, a set of dilated and translated prototype functions called wavelets are used to span a localized space by dividing it into a set of subspaces with predetermined sizes and locations. In spectroscopic imaging, this process is achieved using radiofrequency (RF) pulses with profiles resembling the wavelet shapes. Slice selective excitation and refocusing RF pulses, with single‐band and dual‐band profiles similar to Haar wavelets, are used in a modified PRESS sequence to acquire 3D WE‐SI data. Wavelet dilation and translation are achieved by changing the strength of the localization gradients and frequency shift of the RF pulses, respectively. The desired spatial resolution in each direction sets the corresponding number of dilations (increases in the localization gradients), and consequently, the number of translations (frequency shift) of the Haar wavelets (RF pulses), which are used to collect magnetic resonance (MR) signals from the corresponding subspaces. Data acquisition time is reduced by using the minimum recovery time (TR_min), also called effective time, when successive MR signals from adjacent subspaces are collected. Inverse wavelet transform is performed on the acquired data to produce metabolite maps. The proposed WE‐SI method is compared in terms of acquisition time, pixel bleed, and signal‐to‐noise ratio to the CSI technique. The study outcome shows that 3D WE‐SI provides accurate results while reducing both acquisition time and voxel contamination. Magn Reson Med 61:6–15, 2009. © 2008 Wiley‐Liss, Inc.     

Altered supraspinal motor networks in survivors of poliomyelitis: A cortico-muscular coherence study

ObjectivePoliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio.MethodsSurface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of cortico-muscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task.ResultsA pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30–47 Hz) was observed in frontal and parietal regions.ConclusionThese findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network.SignificanceThis research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions.     

PSD-95 in CA1 Area Regulates Spatial Choice Depending on Age

Cognitive processes that require spatial information rely on synaptic plasticity in the dorsal CA1 area (dCA1) of the hippocampus. Since the function of the hippocampus is impaired in aged individuals, it remains unknown how aged animals make spatial choices. Here, we used IntelliCage to study behavioral processes that support spatial choices of aged female mice living in a group. As a proxy of training-induced synaptic plasticity, we analyzed the morphology of dendritic spines and the expression of a synaptic scaffold protein, PSD-95. We observed that spatial choice training in young adult mice induced correlated shrinkage of dendritic spines and downregulation of PSD-95 in dCA1. Moreover, long-term depletion of PSD-95 by shRNA in dCA1 limited correct choices to a reward corner, while reward preference was intact. In contrast, old mice used behavioral strategies characterized by an increased tendency for perseverative visits and social interactions. This strategy resulted in a robust preference for the reward corner during the spatial choice task. Moreover, training decreased the correlation between PSD-95 expression and the size of dendritic spines. Furthermore, PSD-95 depletion did not impair place choice or reward preference in old mice. Thus, our data indicate that while young mice require PSD-95-dependent synaptic plasticity in dCA1 to make correct spatial choices, old animals observe cage mates and stick to a preferred corner to seek the reward. This strategy is resistant to the depletion of PSD-95 in the CA1 area. Overall, our study demonstrates that aged mice combine alternative behavioral and molecular strategies to approach and consume rewards in a complex environment.SIGNIFICANCE STATEMENT It remains poorly understood how aging affects behavioral and molecular processes that support cognitive functions. It is, however, essential to understand these processes to develop therapeutic interventions that support successful cognitive aging. Our data indicate that while young mice require PSD-95-dependent synaptic plasticity in dCA1 to make correct spatial choices (i.e., choices that require spatial information), old animals observe cage mates and stick to a preferred corner to seek the reward. This strategy is resistant to the depletion of PSD-95 in the CA1 area. Overall, our study demonstrates that aged mice combine alternative behavioral and molecular strategies to approach and consume rewards in a complex environment. Second, the contribution of PSD-95-dependent synaptic functions in spatial choice changes with age.     

Cueing the personal future to reduce discounting in intertemporal choice: Is episodic prospection necessary?

How does the ability to imagine detailed future experiences (i.e., episodic prospection) contribute to choices between immediate and delayed rewards? Individuals with amnesia do not show abnormally steep discounting in intertemporal choice, suggesting that neither medial temporal lobe (MTL) integrity nor episodic prospection is required for the valuation of future rewards (Kwan et al. ( ), Hippocampus, 22:1215‐1219; Kwan et al. (2013), J Exp Psychol, 142:1355‐1369 2013). However, hippocampally mediated episodic prospection in healthy adults reduces the discounting of future rewards (Peters and Büchel (2010), Neuron, 66:138‐148; Benoit et al. (2011), J Neurosci, 31:6771‐6779), raising the possibility that MTL damage causes more subtle impairments to this form of decision‐making than noted in previous patient studies. Intertemporal choice appears normal in amnesic populations, yet they may be unable to use episodic prospection to adaptively modulate the value assigned to future rewards. To investigate how the extended hippocampal system, including the hippocampus and related MTL structures, contributes to the valuation of future rewards, we compared the performance of six amnesic cases with impaired episodic prospection to that of 20 control participants on two versions of an intertemporal choice task: a standard discounting task, and a cued version in which cues prompted them to imagine specific personal future events temporally contiguous with the receipt of delayed rewards. Amnesic individuals' intertemporal choices in the standard condition were indistinguishable from those of controls, replicating previous findings. Surprisingly, performance of the amnesic cases in the cued condition indicates that amnesia does not preclude flexible modulation of choices in response to future event cues, even in the absence of episodic prospection. Cueing the personal future to modulate decisions appears to constitute a less demanding or a qualitatively different (e.g., personal semantic) form of prospection that is not as sensitive to MTL damage as prospective narrative generation. © 2015 Wiley Periodicals, Inc.     

基于非冗余平移不变小波变换的磁共振图像降噪**☆

背景：MRI成像机制决定了其时间/空间分辨率和信噪比之间存在矛盾,因此图像降噪变得十分必要。目前基于离散小波变换的降噪方法广泛应用,然而存在平移敏感性的缺陷。目前已出现了克服平移敏感性的离散小波变换,但其冗余性导致计算复杂度的快速增加。目的：针对图像降噪设计小波滤波器,减小降采样过程的影响,保持离散小波变换的非冗余性,并针对MRI图像Rician噪声的降噪进行分析。方法：由于平移敏感性主要是由于离散小波变换分解时降采样产生的混叠项带来的,在保证非冗余的前提下,提出了通过减小混叠项的影响来减小平移敏感性。在此基础上,设计了一个双正交小波。最后,将其以常见的阈值降噪方法应用到磁共振图像Rician噪声的降噪中。结果与结论：文章提出了设计小波滤波器的新方法,即满足严格重构条件外满足一些附加要求,最后将设计过程简化为一个有约束条件的最优化过程。将设计的双正交小波应用于MR图像,仿真结果表明降噪效果较通常小波有所改善,间接表明了设计思路和方法的有效性。