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كتاب دراسات في حضارة الإسلام هاملتون جب، ما إن يذكر هاملتون جيب (1895-1971 م) إلا وتصاحبه أوصاف الثناء والتبجيل بصورة تلفت الانتباه بقوة لأسمه، ولطبيعة دوره المعرفي، وتميز هذا الدور في مجال الدراسات الإسلامية والمعارف الاستشراقية، والشهرة الفائقة التي اكتسبها جيب جعلت منه شخصية مؤثرة في العالم الإسلامي، ومهابة في العالم الغربي، ومحورية في حقل الدراسات الإسلامية هناك.

Intuitively, combining multiple sources of evidence should lead to more accurate decisions than considering single sources of evidence individually. In practice, however, the proper computation may be difficult, or may require additional data that are inaccessible. Here, based on the concept of conditional independence, we consider expressions that can serve either as recipes for integrating evidence based on limited data, or as statistical benchmarks for characterizing evidence integration processes. Consider three events, A , B , and C . We find that, if A and B are conditionally independent with respect to C , then the probability that C occurs given that both A and B are known, P ( C | A , B ), can be easily calculated without the need to measure the full three-way dependency between A , B , and C . This simplified approach can be used in two general ways: to generate predictions by combining multiple (conditionally independent) sources of evidence, or to test whether separate sources of evidence are functionally independent of each other. These applications are demonstrated with four computer-simulated examples, which include detecting a disease based on repeated diagnostic testing, inferring biological age based on multiple biomarkers of aging, discriminating two spatial locations based on multiple cue stimuli (multisensory integration), and examining how behavioral performance in a visual search task depends on selection histories. Besides providing a sound prescription for predicting outcomes, this methodology may be useful for analyzing experimental data of many types.

Key Points Having information from multiple senses converge onto the same neurons allows the neurons to work in concert so that their combined product can enhance the physiological salience of an event, increase the ability to render a judgment about its identity, and initiate responses faster than would otherwise be possible. This interactive synergy among the senses, or 'multisensory integration', is manifested in individual neurons, by enhancing or degrading their responses, and in behaviour, by producing corresponding alterations in performance. Multisensory integration is guided by principles that relate to the spatial and temporal relationship among cross-modal stimuli, as well as to the vigor of the neuron's responses to their individual component stimuli. The spatial principle of multisensory integration relies on faithful register among a neuron's different receptive fields and this register must be maintained in spite of independent movement of the sense organs (such as the eyes). Recent studies suggest that compensation for such movement is less than perfect, and occurs to varying degrees in different neurons and brain regions. Degradation in receptive-field register has strong implications for multisensory integration, but these remain to be examined empirically. Multisensory integration is crucial for high-level cognitive functions in which considerations such as semantic congruence might determine its neural products and the perceptions and behaviours that depend on them. Multiple approaches have demonstrated the impact of multisensory integration in different brain structures in different species, including single-neuron and event-related-potential recordings and brain-imaging techniques. Primary, sensory-specific areas of the brain have now been shown to receive inputs from other senses. The functional role of these other inputs is not yet known, but they might facilitate the processing of information in the native sense. Multisensory integration allows information from multiple senses to be combined, with benefits for nervous-system processing. Stein and Stanford discuss the principles of multisensory integration in single neurons in the CNS and consider the questions that the field must address. For thousands of years science philosophers have been impressed by how effectively the senses work together to enhance the salience of biologically meaningful events. However, they really had no idea how this was accomplished. Recent insights into the underlying physiological mechanisms reveal that, in at least one circuit, this ability depends on an intimate dialogue among neurons at multiple levels of the neuraxis; this dialogue cannot take place until long after birth and might require a specific kind of experience. Understanding the acquisition and usage of multisensory integration in the midbrain and cerebral cortex of mammals has been aided by a multiplicity of approaches. Here we examine some of the fundamental advances that have been made and some of the challenging questions that remain.

A perceptual judgment is typically characterized by constructing psychometric and chronometric functions, i.e., by mapping the accuracies and reaction times of motor choices as functions of a sensory stimulus feature dimension. Here, we show that various saccade metrics (e.g., peak velocity) are similarly modulated as functions of sensory cue viewing time during performance of an urgent-decision task. Each of the newly discovered functions reveals the dynamics of the perceptual evaluation process inherent to the underlying judgment. Remarkably, saccade peak velocity correlates with statistical decision confidence, suggesting that saccade kinematics reflect the degree of certainty with which an urgent perceptual decision is made. The data were explained by a race-to-threshold model that also replicates standard performance measures and cortical oculomotor neuronal activity in the task. The results indicate that, although largely stereotyped, saccade metrics carry subtle but reliable traces of the underlying cognitive processes that give rise to each oculomotor choice. Saccades have been extensively used to report choices in perceptual decision making studies yet little is known about the influence of covert decision-related processes on saccade metrics. Here, the authors demonstrate that saccade kinematics is a reliable tell about the degree of decision certainty.

The lateral intraparietal area (LIP) contains spatially selective neurons that help guide eye movements and, according to numerous studies, do so by accumulating sensory evidence in favor of one choice (e.g., look left) or another (look right). To examine this functional link, we trained two monkeys on an urgent motion discrimination task, a task with which the evolution of both the recorded neuronal activity and the subject’s choice can be tracked millisecond by millisecond. We found that while choice accuracy increased steeply with increasing sensory evidence, at the same time, the LIP selection signal became progressively weaker, as if it hindered performance. This effect was consistent with the transient deployment of spatial attention to disparate locations away from the relevant sensory cue. The results demonstrate that spatial selection in LIP is dissociable from, and may even conflict with, evidence accumulation during informed saccadic choices. In primate area LIP, target selection and the accumulation of sensory evidence are considered a single process. Here, the authors use urgent choice tasks to show that spatial selection in LIP is distinct from, and may even conflict with, evidence accumulation.

The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genome-wide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts. We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published. We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended meta-analysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3. We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our knowledge of genetic associations and BD, and provide further justification for pursuing collective initiatives in genetic studies given the low prevalence of this and other rare diseases.

The neural mechanisms that willfully direct attention to specific locations in space are closely related to those for generating targeting eye movements (saccades). However, the degree to which the voluntary deployment of attention to a location necessarily activates a corresponding saccade plan remains unclear. One problem is that attention and saccades are both automatically driven by salient sensory events; another is that the underlying processes unfold within tens of milliseconds only. Here, we use an urgent task design to resolve the evolution of a visuomotor choice on a moment-by-moment basis while independently controlling the endogenous (goal-driven) and exogenous (salience-driven) contributions to performance. Human participants saw a peripheral cue and, depending on its color, either looked at it (prosaccade) or looked at a diametrically opposite, uninformative non-cue (antisaccade). By varying the luminance of the stimuli, the exogenous contributions could be cleanly dissociated from the endogenous process guiding the choice over time. According to the measured time courses, generating a correct antisaccade requires about 30 ms more processing time than generating a correct prosaccade based on the same perceptual signal. The results indicate that saccade plans elaborated during fixation are biased toward the location where attention is endogenously deployed, but the coupling is weak and can be willfully overridden very rapidly. You are attending a talk at a conference, eyes straight ahead and fixed on the speaker… yet you may in fact also be covertly monitoring your phone, hoping for a long-awaited message to flash on the screen. This ability to focus on something without directly looking at it is called spatial attention. It plays an essential role in everyday tasks, such as spotting keys on a cluttered desk or noticing when a traffic light changes. Overlapping brain circuits control spatial attention and eye movements, creating tight links between the two processes. For example, shifting your gaze towards a specific location automatically leads you to pay at least partial attention to what unfolds at this spot. Whether the reverse is true, however, is less clear. In other words: when we are paying attention to something without looking at it, is our brain set to move our eyes towards this location? To explore this question, Goldstein et al. designed a visual task that allowed them to track human participants’ attention and eye movements moment by moment, and to unpick various factors affecting these processes. The volunteers fixed their gaze on the center of a screen, knowing that they also needed to pay attention to a certain location at the periphery where a cue was set to appear. The color of the cue determined whether the participants would then need to shift their gaze either towards or away from it – for example, they were instructed to look directly at a green cue but away from a magenta one. These analyses showed that participants needed about 30 milliseconds less time to program an eye movement toward the cue – that is, to shift their gaze towards the location that they were already covertly monitoring. Such difference in processing time suggests that eye movements are biased towards the location on which attention is directed, but that this preference can still be overridden quickly. By refining our understanding of the mechanisms underpinning attention, the findings by Goldstein et al. may help us better understand conditions like attention deficit hyperactivity disorder, where the brain struggles to engage and disengage with stimuli effectively.

To generate the next eye movement, oculomotor circuits take into consideration the physical salience of objects in view and current behavioral goals, exogenous and endogenous influences, respectively. However, the interactions between exogenous and endogenous mechanisms and their dynamic contributions to target selection have been difficult to resolve because they evolve extremely rapidly. In a recent study (Salinas et al., 2019), we achieved the necessary temporal precision using an urgent variant of the antisaccade task wherein motor plans are initiated early and choice accuracy depends sharply on when exactly the visual cue information becomes available. Empirical and modeling results indicated that the exogenous signal arrives ∼80 ms after cue onset and rapidly accelerates the (incorrect) plan toward the cue, whereas the informed endogenous signal arrives ∼25 ms later to favor the (correct) plan away from the cue. Here, we scrutinize a key mechanistic hypothesis about this dynamic, that the exogenous and endogenous signals act at different times and independently of each other. We test quantitative model predictions by comparing the performance of human participants instructed to look toward a visual cue or away from it under high urgency. We find that, indeed, the exogenous response is largely impervious to task instructions; it simply flips its sign relative to the correct choice, and this largely explains the drastic differences in psychometric performance between the two tasks. Thus, saccadic choices are strongly dictated by the alignment between salience and behavioral goals.

Falls are an important health issue. They cause significant morbidity and mortality particularly in older people, and also have marked psychological effects on the individual. The literature focuses particularly on older adults, an age group in which both visual impairment and falls are more prevalent, as is the associated morbidity. In this review, we summarise the current literature and point to further studies which need to be undertaken. The consequences of falls are well recognised, and there has been considerable work into identifying risk factors. Changes in visual components such as visual field, acuity, contrast sensitivity and stereopsis all have a part and the co-existence of other sensory impairments certainly increases the risk of falls. However there remain considerable gaps in our knowledge of the relationship between visual loss and falls, for example in patients with diabetic eye disease. Furthermore, there is also conflicting data as to the importance of different visual components. Various interventions, such as programmed inter-disciplinary involvement, have shown promise, however these need further confirmation of their efficacy and cost effectiveness. An added confounder may be that an intervention (eg, cataract extraction) paradoxically affects an individual's future activity level and behaviour, thereby increasing the risk of falling. With an ageing population the importance of this topic is likely to increase, as will the potential benefits of optimising our assessment and management of these patients.

Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to the Golgi before being sorted for delivery to their final destination. Although ER-to-Golgi trafficking is highly conserved among eukaryotes, several layers of complexity have been added to meet the increased demands of complex cell types in metazoans. The specialized morphology of neurons and the necessity for precise spatiotemporal control over membrane and secretory protein localization and function make them particularly vulnerable to defects in trafficking. This review summarizes the general mechanisms involved in ER-to-Golgi trafficking and highlights mutations in genes affecting this process, which are associated with neurological diseases in humans.