Grid-texture mechanisms in human vision:contrast detection of regular sparse micro-patterns requires specialist templates

Previous work has shown that human vision performs spatial integration of luminance contrast energy, where signals are squared and summed (with internal noise) over area at detection threshold. We tested that model here in an experiment using arrays of micro-pattern textures that varied in overall stimulus area and sparseness of their target elements, where the contrast of each element was normalised for sensitivity across the visual field. We found a power-law improvement in performance with stimulus area, and a decrease in sensitivity with sparseness. While the contrast integrator model performed well when target elements constituted 50–100% of the target area (replicating previous results), observers outperformed the model when texture elements were sparser than this. This result required the inclusion of further templates in our model, selective for grids of various regular texture densities. By assuming a MAX operation across these noisy mechanisms the model also accounted for the increase in the slope of the psychometric function that occurred as texture density decreased. Thus, for the first time, mechanisms that are selective for texture density have been revealed at contrast detection threshold. We suggest that these mechanisms have a role to play in the perception of visual textures

Low-level mediation of directionally specific motion after-effects: motion perception is not necessary

Previous psychophysical experiments with normal human observers have shown that adaptation to a moving dot stream causes directionally specific repulsion in the perceived angle of a subsequently viewed, moving probe. In this paper, we used a 2AFC task with roving pedestals to determine the conditions necessary and sufficient for producing directionally specific repulsion with compound adaptors, each ofwhich contains two oppositely moving, differently colored, component streams. Experiment 1 provides a demonstration of repulsion between single-component adaptors and probes moving at approximately 90° or 270°. In Experiment 2 oppositely moving dots in the adaptor were paired to preclude the appearance of motion. Nonetheless, repulsion remained strong when the angle betweeneach probe stream and one component was approximately 30°. In Experiment 3 adapting dot-pairs were kept stationary during their limited lifetimes. Their orientation content alone proved insufficient for producing repulsion. In Experiments 4-6 the angle between probe and both adapting components was approximately 90°or 270°. Directional repulsion was found when observers were asked to visually track one of the adapting components (Experiment 6), but not when observers were asked to attentionally track it (Experiment 5), nor while passively viewing the adaptor (Experiment 4). Our results are consistent with a low-level mechanism for motion adaptation. It is not selective for stimulus color and it is not susceptible to attentional modulation.The most likely cortical locus of adaptation is area V1

Atypical Development of Broca’s Area in a Large Family with Inherited Stuttering

Developmental stuttering is a condition of speech dysfluency, characterised by pauses, blocks, prolongations, and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene-brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering. We studied a four-generation family, sixteen family members were included in genotyping analysis. T1-weighted and diffusion weighted MRI scans were conducted on seven family members (6 male; aged 9–63 years) with two age and sex matched controls without stuttering (N = 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography. We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca’s area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold of p < 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (left p = 0.017; right p=0.037), and a larger right globus pallidus was associated with more severe stuttering (rho =0.86, p=0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype. Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca’s area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies

Prediction of photoperiodic regulators from quantitative gene circuit models

Photoperiod sensors allow physiological adaptation to the changing seasons. The external coincidence hypothesis postulates that a light-responsive regulator is modulated by a circadian rhythm. Sufficient data are available to test this quantitatively in plants, though not yet in animals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their lightsensitive proteins are thought to form an external coincidence sensor. We use 40 timeseries of molecular data to model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, the models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modelling makes this complexity explicit and may thus contribute to crop improvement

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Novel interactions of transglutaminase-2 with heparan sulphate proteoglycans: reflection on physiological implications

This mini-review brings together information from publications and recent conference proceedings that have shed light on the biological interaction between transglutaminase-2 and heparan sulphate proteoglycans. We subsequently draw hypothesis of possible implications in the wound healing process. There is a substantial overlap in the action of transglutaminase-2 and the heparan sulphate proteoglycan syndecan-4 in normal and abnormal wound repair. Our latest findings have identified syndecan-4 as a possible binding and signalling partner of fibronectinbound TG2 and support the idea that transglutaminase-2 and syndecan-4 acts in synergy

Femoral revision knee Arthroplasty with Metaphyseal sleeves: the use of a stem is not mandatory of a structural point of view

Purpose Metaphyseal sleeves are an option for patients with severe metaphyseal bony defects requiring TKA revision. Although sleeves are usually used with stems, little is known about the exact contribution/need of the stem for the initial sleeve-bone interface stability, particularly in the femur, if the intramedullary canal is deformed or bowed. It is hypothesised that diaphyseal-stem addition increases the sleeve-femur interface stability and the strain-shielding effect on the metaphyseal femur relatively to the stemless condition. Material and methods Synthetic-femur was used to measure cortex strain behaviour and implant cortex micromotions for three techniques: only femoral-component, stemless-sleeve and stemmed-sleeve. Paired t-tests were performed to evaluate the statistical significance of the difference between mean principal strains and implant-cortex micromotions. Finite-element models were developed to assess the cancellous-bone strain behaviour and sleeve-bone interface micromotions; these models were validated against the measurements. Results Cortex strains are reduced significantly (p<0.05) in 83% of strain gauges on stemmed-sleeve, which compares with 33% in stemless condition. Both techniques presented a cancellous bone strain reduction of 50% at the distal region and an increase of nearly four times at the sleeve proximal region relative to the model only with the femoral component. Both techniques presented sleeve-bone micromotions amplitude below 50-150μm, suitable for bone ingrowth. Conclusions The use of a supplemental diaphyseal-stem potentiates the risk of cortex bone resorption compared with the stemless-sleeve condition; however, the stem is not vital for increasing the initial sleeve-bone stability and has a minor effect on the cancellous-bone strain behaviour. Of a purely structural point view, appears that the use of a diaphyseal-femoral-stem with the metaphyseal sleeve is not mandatory in the revision TKA which is particularly relevant in cases where the use of stems is impracticable.publishe