The assessment and modeling of perceptual control: a transformation in research methodology to address the replication crisis

Replication in the behavioral sciences is a matter of considerable debate. We describe a series of fundamental interrelated conceptual and methodological issues with current research that undermine replication and we explain how they could be addressed. Conceptually, we need a shift (a) from verbally described theories to mathematically specified theories, (b) from lineal stimulus-cognition-response theories to closed-loop theories that model behavior as feeding back to sensory input via the environment, and (c) from theories that “chunk” responses to theories that acknowledge the continuous, dynamic nature of behavior. A closely related shift in methodology would involve studies that attempt to model each individual's performance as a continuous and dynamic activity within a closed-loop process. We explain how this shift can be made within a single framework—perceptual control theory (PCT)—that regards behavior as the control of perceptual input. We report evidence of multiple replication using this approach within visual tracking, and go on to demonstrate in practical research terms how the same overarching principle can guide research across diverse domains of psychology and the behavioral sciences, promoting their coherent integration. We describe ways to address current challenges to this approach and provide recommendations for how researchers can manage the transition

Editorial: Returning to Mechanisms in Psychological Therapies: Understand the Engine Before Steaming in

MRC Clinician Scientist Fellowshi

Disentangling surface and bulk transport in topological-insulator pp-nn junctions

By combining $n$-type $\mathrm{Bi_2Te_3}$ and $p$-type $\mathrm{Sb_2Te_3}$ topological insulators, vertically stacked $p$-$n$ junctions can be formed, allowing to position the Fermi level into the bulk band gap and also tune between $n$- and $p$-type surface carriers. Here we use low-temperature magnetotransport measurements to probe the surface and bulk transport modes in a range of vertical $\mathrm{Bi_2Te_3/Sb_2Te_3}$ heterostructures with varying relative thicknesses of the top and bottom layers. With increasing thickness of the $\mathrm{Sb_2Te_3}$ layer we observe a change from $n$- to $p$-type behavior via a specific thickness where the Hall signal is immeasurable. Assuming that the the bulk and surface states contribute in parallel, we can calculate and reproduce the dependence of the Hall and longitudinal components of resistivity on the film thickness. This highlights the role played by the bulk conduction channels which, importantly, cannot be probed using surface sensitive spectroscopic techniques. Our calculations are then buttressed by a semi-classical Boltzmann transport theory which rigorously shows the vanishing of the Hall signal. Our results provide crucial experimental and theoretical insights into the relative roles of the surface and bulk in the vertical topological $p$-$n$ junctions.Comment: 11 pages, 5 figure

Improving professional psychological practice through an increased repertoire of research methodologies : illustrated by the development of MOL.

Mental health problems present an increasing global disease burden making the development of effective and efficient psychological treatments an urgent public health priority. Despite the continued proliferation of treatments and large numbers of randomized controlled trials (RCTs), evidence suggests that pre-post effect sizes have been decreasing over time not increasing. Promoting RCTs as a gold standard of evidence has not been a useful strategy for advancing progress in the development of increasingly effective and efficient psychological treatments and has, in fact, created a divide between research and practice in professional psychology. To close this divide, other methodologies are needed that can assist in the rigorous development and evaluation of treatments in routine clinical practice. We outline some of the problems with using RCTs as the sole means of generating evidence for treatment effectiveness and efficiency and we use the development and evaluation of a transdiagnostic cognitive therapy to illustrate an alternative way of accumulating evidence through a much closer connection between research and practice. Ultimately, including other methodologies alongside RCTs that combine research and practice more seamlessly, will produce treatments of greater effectiveness and efficiency and help to reduce the global burden of mental health problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized

Topological states and phase transitions in Sb₂Te₃-GeTe multilayers

Topological insulators (TIs) are bulk insulators with exotic 'topologically protected' surface conducting modes. It has recently been pointed out that when stacked together, interactions between surface modes can induce diverse phases including the TI, Dirac semimetal, and Weyl semimetal. However, currently a full experimental understanding of the conditions under which topological modes interact is lacking. Here, working with multilayers of the TI Sb₂Te₃ and the band insulator GeTe, we provide experimental evidence of multiple topological modes in a single Sb₂Te₃-GeTe-Sb₂Te₃ structure. Furthermore, we show that reducing the thickness of the GeTe layer induces a phase transition from a Dirac-like phase to a gapped phase. By comparing different multilayer structures we demonstrate that this transition occurs due to the hybridisation of states associated with different TI films. Our results demonstrate that the Sb₂Te₃-GeTe system offers strong potential towards manipulating topological states as well as towards controlledly inducing various topological phases.T.-A.N., D.B., D.A.R. and V.N. acknowledge funding from the Leverhulme Trust, UK, T.-A.N., D.B., A.S., R.M., C.B., D.A.R. and V.N. acknowledge funding from EPSRC (UK). G.M., M.L. and D.G. acknowledge financial support from the DFG-funded priority programme SPP1666

MRI-based strain measurements reflect morphological changes following myocardial infarction:A study on the UK Biobank cohort

In a porcine experimental model of myocardial infarction, a localised, layer-specific, circumferential left ventricular strain metric has been shown to indicate chronic changes in ventricular function post-infarction more strongly than ejection fraction. This novel strain metric might therefore provide useful prognostic information clinically. In this study, existing clinical volume indices, global strains, and the novel, layer-specific strain were calculated for a large human cohort to assess variations in ventricular function and morphology with age, sex, and health status. Imaging and health data from the UK Biobank were obtained, including healthy volunteers and those with a history of cardiovascular illness. In total, 710 individuals were analysed and stratified by age, sex and health. Significant differences in all strain metrics were found between healthy and unhealthy populations, as well as between males and females. Significant differences in basal circumferential strain and global circumferential strain were found between healthy males and females, with males having smaller absolute values for both (all (Formula presented.) 0.001). There were significant differences in the functional variables left ventricular ejection fraction, end-systolic volume, end-systolic volume index and mid-ventricular circumferential strain between healthy and unhealthy male cohorts aged 65–74 (all (Formula presented.) 0.001). These results suggest that whilst regional circumferential strains may be useful clinically for assessing cardiovascular health, care must be taken to ensure critical values are indexed correctly to age and sex, due to the differences in these values observed here.</p

Comparison of the within-reader and inter-vendor agreement of left ventricular circumferential strains and volume indices derived from cardiovascular magnetic resonance imaging

PurposeVolume indices and left ventricular ejection fraction (LVEF) are routinely used to assess cardiac function. Ventricular strain values may provide additional diagnostic information, but their reproducibility is unclear. This study therefore compares the repeatability and reproducibility of volumes, volume fraction, and regional ventricular strains, derived from cardiovascular magnetic resonance (CMR) imaging, across three software packages and between readers.MethodsSeven readers analysed 16 short-axis CMR stacks of a porcine heart. Endocardial contours were manually drawn using OsiriX and Simpleware ScanIP and repeated in both softwares. The images were also contoured automatically in Circle CVI42. Endocardial global, apical, mid-ventricular, and basal circumferential strains, as well as end-diastolic and end-systolic volume and LVEF were compared.ResultsBland-Altman analysis found systematic biases in contour length between software packages. Compared to OsiriX, contour lengths were shorter in both ScanIP (-1.9 cm) and CVI42 (-0.6 cm), causing statistically significant differences in end-diastolic and end-systolic volumes, and apical circumferential strain (all pConclusionOsiriX and CVI42 gave consistent results for all strain and volume metrics, with no statistical differences found between OsiriX and ScanIP for mid-ventricular, global or basal strains, or left ventricular ejection fraction. However, volumes were influenced by the choice of contouring software, suggesting care should be taken when comparing volumes across different software