Normative Template Research Articles

Synaptic loss pattern is associated with functional connectivity in Alzheimer’s disease

AbstractBackgroundSynaptic loss is identified as a strong correlate of cognitive impairment in Alzheimer’s disease (AD). Pathological tau can induce direct toxicity to synapse and spread trans‐synaptically across connected neurons. Recent neuroimaging evidence revealed that tau pathology propagates along interconnected brain regions throughout macroscale brain networks. However, whether synaptic loss propagates in AD follows a similar vein is unclear.MethodSeventy‐six amyloid‐positive (Aβ+) subjects across AD spectrum and 48 cognitively normal (CN) Aβ‐ controls characterized by cross‐sectional [18F]florbetapir amyloid‐PET were included in the current study. The density of synaptic vesicle glycoprotein 2A (SV2A) was measured by [18F]SynVesT‐1 PET. A normative template of functional connectome distance across 200 neocortical regions of interest (ROIs) was generated using resting‐state fMRI data from 1000 subjects of the Human Connectome Project. We assessed the association between synaptic loss and functional connectivity by correlating the cross‐subject inter‐regional covariance with the normative functional connectivity template. In a next step, we tested whether the functional distance to synaptic loss epicenter (i.e., top 10% ROIs with greatest synaptic loss) is associated with synaptic loss in connected regions at both group‐ and subject‐level.ResultAmong Aβ+ subjects, inter‐regional covariance of SV2A‐PET‐assessed synaptic loss was associated with inter‐regional functional connectivity (Figure 1), suggesting that higher functional connectivity may facilitate the propagation of synaptic loss. At both group‐ and subject‐level, we found that shorter functional distance to synaptic loss epicenters is associated with greater levels of synaptic loss in connected regions (Figure 2).ConclusionWe found that inter‐regional functional connectivity is associated with greater synaptic loss in AD, suggesting that synaptic loss may systematically propagate along brain connections.

Development of the Fetal Brain Corticocortical Structural Network during the Second-to-Third Trimester Based on Diffusion MRI.

During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the interwired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and postmortem fetal brains, the in utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in utero dMRI data from human fetuses of both sexes between 26 and 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intrahemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for Wernicke's area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development.

Patient-specific finite element modeling of scoliotic curve progression using region-specific stress-modulated vertebral growth

PurposeThis study describes the creation of patient-specific (PS) osteo-ligamentous finite element (FE) models of the spine, ribcage, and pelvis, simulation of up to three years of region-specific, stress-modulated growth, and validation of simulated curve progression with patient clinical angle measurements. Research Question: Does the inclusion of region-specific, stress-modulated vertebral growth, in addition to scaling based on age, weight, skeletal maturity, and spine flexibility allow for clinically accurate scoliotic curve progression prediction in patient-specific FE models of the spine, ribcage, and pelvis?MethodsFrontal, lateral, and lateral bending X-Rays of five AIS patients were obtained for approximately three-year timespans. PS-FE models were generated by morphing a normative template FE model with landmark points obtained from patient X-rays at the initial X-ray timepoint. Vertebral growth behavior and response to stress, as well as model material properties were made patient-specific based on several prognostic factors. Spine curvature angles from the PS–FE models were compared to the corresponding X-ray measurements.ResultsAverage FE model errors were 6.3 ± 4.6°, 12.2 ± 6.6°, 8.9 ± 7.7°, and 5.3 ± 3.4° for thoracic Cobb, lumbar Cobb, kyphosis, and lordosis angles, respectively. Average error in prediction of vertebral wedging at the apex and adjacent levels was 3.2 ± 2.2°. Vertebral column stress ranged from 0.11 MPa in tension to 0.79 MPa in compression.ConclusionIntegration of region-specific stress-modulated growth, as well as adjustment of growth and material properties based on patient-specific data yielded clinically useful prediction accuracy while maintaining physiological stress magnitudes. This framework can be further developed for PS surgical simulation.

Focused Ultrasound Thalamotomy Sensory Side Effects Follow the Thalamic Structural Homunculus.

Focused ultrasound thalamotomy is an effective treatment for tremor; however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects and their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML). Sensory adverse effects were categorized into 4 groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemibody/limb paresthesia, and dysgeusia. Then, areas of significant risk (ASRs) for each category were defined using voxel-wise mass univariate analysis and overlaid on corresponding odds ratio maps. The ASR associated with the maximum risk was used as a region of interest in a normative functional connectome to determine side effect-specific functional connectivity. Finally, each ASR was overlaid on the ML derived from normative template. Of 103 patients, 17 developed sensory side effects after thalamotomy persisting 3 months after the procedures. Lesions producing sensory side effects extended posteriorly into the principle sensory nucleus of the thalamus or below the thalamus in the ML. The topography of sensory adverse effects followed the known somatotopy of the ML and the sensory nucleus. Functional connectivity patterns between each sensory-specific thalamic seed and the primary somatosensory areas supported the role of the middle insula in processing of gustatory information and in multisensory integration. Distinct regions in the sensory thalamus and its afferent connections rise to specific sensory disturbances. These findings demonstrate the relationship between the sensory thalamus, ML, and bilateral sensory cortical areas.

Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life.

Background:The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer’s disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition.Materials and Methods:One hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology.Results:The pattern of increasing perfusion (temporal lobe < parietal lobe < frontal lobe < insula/cingulate gyrus < occipital lobe; F(4,26) = 7.8, p = 0.0003) in young, healthy adults was not exactly identical to but approximated the pattern of increasing amyloid burden (temporal lobe < occipital lobe < frontal lobe < parietal lobe < insula/cingulate gyrus; F(4,26) = 5.0, p = 0.004) in older adults. However, investigating subregions within cortical lobes provided consistent agreement between ranked normative perfusion patterns and expected Thal staging of amyloid progression in AD (Spearman r = 0.39, p = 0.03).Conclusion:Our findings suggest that brain areas with normatively greater perfusion may be more susceptible to amyloid deposition in later life, possibly due to higher metabolic demand, and associated levels of oxidative stress and inflammation.

Corporate Law and the Myth of Efficient Market Control

In recent times, there has been an unprecedented shift in power from managers to shareholders, a shift that realizes the long-held theoretical aspiration of market control of the corporation. This Article subjects the market control paradigm to comprehensive economic examination and finds it wanting. The market control paradigm relies on a narrow economic model that focuses on one problem only, management agency costs. With the rise of shareholder power, we need a wider lens that also takes in market prices, investor incentives, and information asymmetries. General equilibrium theory (GE) provides that lens. Several lessons follow from reference to this higher-order economic theory. First, the presumption that markets can efficiently coordinate the economy is shown to be unfounded, unless one relies on heroic assumptions. Second, GE shows that shareholders suffer from misaligned incentives, undercutting any normative program grounded in shareholder empowerment. The third lesson is negative, as there are no economically-founded instructions for addressing the trade-offs between agency costs reduction and market inefficiency implied by the new shareholder corporation. Policy implications also follow. Given the lack of a clear normative template, only private ordering can be counted on to address each corporation’s specific tradeoffs between agency costs and market inefficiency. This conclusion leads to an endorsement of Delaware’s equitable adjudication system, the flexibility of which is well-suited to policing the bargaining process between managers and empowered shareholders.

Jeszcze o wątpliwościach dotyczących funkcjonowania spółki z ograniczoną odpowiedzialnością utworzonej za pomocą normatywnego wzorca umowy

SOME FURTHER DOUBTS ABOUT FUNCTIONING OF THE LIMITED LIABILITY COMPANY MADE BY NORMATIVE TEMPLATE OF ARTICLE OF ASSOCIATION AVAILABLE IN THE IT SYSTEMThe study contains comments on the issue of the sale of shares and an increase of the capital in the e-limited liability company resulting from the possibility of covering the share capital after the registration of the company, which is a solution different from the traditional model of a Polish limited liability company. The purpose of the paper is primarily to determine whether it is possible to sell shares before covering the share capital and to pass a resolution to increase the share capital before full coverage in the e-limited liability company.

The anatomy of the human medial forebrain bundle: Ventral tegmental area connections to reward-associated subcortical and frontal lobe regions.

IntroductionDespite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human medial forebrain bundle (MFB) and the connectivity of the ventral tegmental area (VTA). A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB) - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.). This work aims at a normative description of the human MFB (and more detailed the slMFB) anatomy with respect to distant prefrontal connections and microstructural features.Methods and materialHealthy subjects (n = 55; mean age ± SD, 40 ± 10 years; 32 females) underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments) of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB.ResultsThe MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right) and 98% (left) of the total relative fiber counts of the slMFB.DiscussionThe anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and cortical prefrontal regions - but not to emotion-related regions on the medial cortical surface - realized via the superolateral branch of the MFB. Local tractography approaches appear to be inferior in showing these far-reaching projections. Since these local approaches are typically used for surgical targeting of DBS procedures, the here established detailed map might - as a normative template - guide future efforts to target deep brain stimulation of the slMFB in depression and other disorders related to dysfunction of reward and reward-associated learning.

Social Justice and the Legitimacy of Slavery: The Role of Philosophical Asceticism from Ancient Judaism to Late Antiquity by Ilaria L. E. Ramelli

What then led Gregory to his conclusions that human nature cannot be divided into slavery and mastery, that the elimination of slavery in the eschatological situation should set a normative template for Christians and, consequently, that they should free their slaves (188–89)? The main thesis in Social Justice is that there is a strong relationship between asceticism and the rejection of slavery and a criticism of lavish wealth accumulated at the cost of the poor. [...]emerged the myth that Christianity planted the seed of slavery’s implosion.

Republican Non-Domination and Labour Law: New Normativity or Trojan Horse?

This article considers the prospects for a new normativity for labour law based upon neorepublican theories of non-domination. It argues that the neo-republican tradition is complex and contested, and that it does not generate a single normative template for labour law. Some neo-republican theorists prescribe a policy mix of enhanced ‘exit’ rights and labour market deregulation, whereas others advocate a radical programme of structural emancipation. It is important that labour lawyers scrutinize the details of neo-republicanism, to ask which neorepublicanism, before embracing it wholesale as a new foundation for the discipline.

Predicting individual contrast sensitivity functions from acuity and letter contrast sensitivity measurements.

Contrast sensitivity (CS) is widely used as a measure of visual function in both basic research and clinical evaluation. There is conflicting evidence on the extent to which measuring the full contrast sensitivity function (CSF) offers more functionally relevant information than a single measurement from an optotype CS test, such as the Pelli–Robson chart. Here we examine the relationship between functional CSF parameters and other measures of visual function, and establish a framework for predicting individual CSFs with effectively a zero-parameter model that shifts a standard-shaped template CSF horizontally and vertically according to independent measurements of high contrast acuity and letter CS, respectively. This method was evaluated for three different CSF tests: a chart test (CSV-1000), a computerized sine-wave test (M&S Sine Test), and a recently developed adaptive test (quick CSF). Subjects were 43 individuals with healthy vision or impairment too mild to be considered low vision (acuity range of −0.3 to 0.34 logMAR). While each test demands a slightly different normative template, results show that individual subject CSFs can be predicted with roughly the same precision as test–retest repeatability, confirming that individuals predominantly differ in terms of peak CS and peak spatial frequency. In fact, these parameters were sufficiently related to empirical measurements of acuity and letter CS to permit accurate estimation of the entire CSF of any individual with a deterministic model (zero free parameters). These results demonstrate that in many cases, measuring the full CSF may provide little additional information beyond letter acuity and contrast sensitivity.

Modeling 4D pathological changes by leveraging normative models

With the increasing use of efficient multimodal 3D imaging, clinicians are able to access longitudinal imaging to stage pathological diseases, to monitor the efficacy of therapeutic interventions, or to assess and quantify rehabilitation efforts. Analysis of such four-dimensional (4D) image data presenting pathologies, including disappearing and newly appearing lesions, represents a significant challenge due to the presence of complex spatio-temporal changes. Image analysis methods for such 4D image data have to include not only a concept for joint segmentation of 3D datasets to account for inherent correlations of subject-specific repeated scans but also a mechanism to account for large deformations and the destruction and formation of lesions (e.g., edema, bleeding) due to underlying physiological processes associated with damage, intervention, and recovery.In this paper, we propose a novel framework that provides a joint segmentation-registration framework to tackle the inherent problem of image registration in the presence of objects not present in all images of the time series. Our methodology models 4D changes in pathological anatomy across time and also provides an explicit mapping of a healthy normative template to a subject’s image data with pathologies. Since atlas-moderated segmentation methods cannot explain appearance and locality pathological structures that are not represented in the template atlas, the new framework provides different options for initialization via a supervised learning approach, iterative semisupervised active learning, and also transfer learning, which results in a fully automatic 4D segmentation method.We demonstrate the effectiveness of our novel approach with synthetic experiments and a 4D multimodal MRI dataset of severe traumatic brain injury (TBI), including validation via comparison to expert segmentations. However, the proposed methodology is generic in regard to different clinical applications requiring quantitative analysis of 4D imaging representing spatio-temporal changes of pathologies.

Water Baptism and Spirit Baptism in Luke-Acts

Despite their disagreement on the interpretation of Acts regarding reception of the Spirit, both Evangelicals and Pentecostals operate from the assumption that the purpose of Acts is to provide a normative template of experience to be repeated in later Christians. Here it is argued that the purpose of Luke-Acts in reporting on the reception of the Spirit is not to provide an experiential norm at all, but rather to highlight the contrast between John’s water baptism without the Spirit and Christian water baptism with the Spirit. A careful reading of Luke-Acts reveals a consistent and at times strident distinction between John and Jesus, suggesting a long-forgotten struggle in the early church to ascertain where the otherwise identical practice of water baptism by John and by Jesus’s followers diverges. This interpretation is supported by consideration of the missional focus of Acts and the issue of the forgiveness of sins.

Cyber-Green: idealism in the information age

Purpose– This paper aims to retrieve relevant aspects of the work of idealist thinker T.H. Green to improve comprehension of, and policy responses to, various dilemmas facing contemporary “information societies”.Design/methodology/approach– The paper is an exercise in interdisciplinary conceptual research, seeking a new synthesis that draws upon a range of ethical, metaphysical, empirical and policy texts and ideas. It is an application of moral and political principles to post-industrial problems, part of an ongoing international effort to develop viable normative approaches to the emergent information society. The background research includedin situstudy of archival papers.Findings– Green’s version of idealism illuminates current, technologically induced shifts in our understandings of important categories such as self, substance and space. The paper finds that Green’s doctrine of the common good, his alternative to the (still prevalent) school of utilitarian welfarism, combined with his famously “positive” theory of the state, is highly relevant as a normative template for applied philosophy and policy. The article demonstrates its applicability to three vital contemporary issues: freedom of information, intellectual property and personal privacy. It concludes that Green’s work provides exceptional resources for an original, anti-technocratic, theory of the information society as good society.Practical implications– It is hoped that, as part of the wider rediscovery of the work of Green and other idealists, the paper will have some impact on public policy.Originality/value– The paper contains a new scholarly interpretation of Green’s theories of the common good and of the state. In addition, it is believed to be the first major attempt to apply idealism to the information society and its problems.

Living and Working Precariously with an Episodic Disability: Barriers in the Canadian Context

The organization of contemporary labour markets has radically altered the nature of work and its embodied or bodily performance. Changes from standard, permanent jobs to non-standard or precarious work arrangements have increasingly become the normative template for many workers, including persons with disabilities. Drawing on findings from 13 qualitative interviews associated with ‘Project EDGE,’ Episodic Disabilities in the Global Economy, I describe how Canadian workers with “episodic” or fluctuating disabilities experience and negotiate barriers to work within precarious work environments in Toronto, Ontario. Implications that consider the episodic dimension of disability for workforce participation and employment policy are considered.

Understanding My Culture Means Understanding Myself: The Function of Cultural Identity Clarity for Personal Identity Clarity and Personal Psychological Well‐Being

AbstractCulture is acknowledged to be a critical element in the construction of an individual's identity; however, in today's increasingly multicultural environments, the influence of culture is no longer straightforward. It is now important to explore cultural identity clarity—the extent to which beliefs about identity that arise from one's cultural group membership(s) are clearly and confidently understood. We describe a novel theoretical model to explain why having a clear and confident understanding of one's cultural identity is important for psychological well‐being, as it clarifies one's understanding of personal identity. We propose that a clear cultural identity clarifies one's personal existence, by providing a clear normative template, reducing personal uncertainty, providing an individual with a sense of continuity, and buffering an individual against the fear of death. We discuss the implications of this model within our complex cultural worlds.

Surgical outcomes in craniosynostosis reconstruction: The use of prefabricated templates in cranial vault remodelling

Cranio-orbital reshaping for anterior cranial-vault deformities associated with craniosynostosis traditionally relies on the surgeon's subjective estimate of the shape and appearance of a normal forehead. Computer-aided design/computer-aided manufacture (CAD/CAM) bandeau templates to guide reconstruction were introduced in our centre to eliminate this subjectivity and to effect more reproducible surgical results. The aim of this study was to compare two groups of patients (template, n = 14 vs. no template, n = 23) to measure surgical outcomes. The virtual, computational version of the template was used as an outcome assessment tool. It was used to calculate an intervening area under the curve (AUC) between the normative template and the patient's reconstructed supra-orbital bar on a representative computed tomography (CT) axial section. A comprehensive chart review was conducted of patients in both groups to examine the preoperative and postoperative variables. Based on the analysis performed on the immediate postoperative CT scans, in the template group - as compared to the control, no-template group - the use of the bandeau template led to a greater reduction in AUC (74% vs. 56%, p = 0.016), indicating a better conformity between the reconstructed supra-orbital bar and the ideal, normal bandeau shape. The duration of operation was significantly reduced with the use of the template (212 vs. 258 min, p < 0.001). The application of prefabricated templates in cranio-orbital reshaping is highly useful for accurate preoperative planning; reproducible and efficient intra-operative correction of dysmorphology; and objective surgical outcomes assessment.

Barriers to Employment Among Women With Complex Episodic Disabilities

The expansion of the global economy, characterized by shifts in the organization of labor markets, has increased demands for flexible employment. Changes from standard, permanent employment relationships to nonstandard or “precarious” work arrangements have become the normative template in many work settings. Although significant scholarship explores precarious employment among the nondisabled, little work examines precarious work among persons with disabilities, especially women. Drawing on a secondary analysis of a series of longitudinal, semistructured interviews, this article explores the personal and structural barriers to employment that five women with complex episodic disabilities identify as welfare recipients within the context of precarious employment. Implications for practice relationships and policy that consider an alternative understanding of (dis)ability and employability as a contingent, fluid embodiment are considered.

Should We Elect the US Supreme Court?

Extensive political science research reveals that the decisions of the US Supreme Court are deeply political. And both advocates and critics of judicial elections concede that partisan elections are a democratic method of judicial selection. Does the value of democratic representation mean that US Supreme Court Justices should be selected through partisan elections? I argue not. Partisan judicial elections are actually far poorer institutional mechanisms for capturing the judgment of the people on legal matters than has been recognized. The role of parties in structuring a campaign distorts the deliberative environment surrounding judicial elections, creating significant barriers to voters expressing a judgment on matters of legal meaning. The kind of distortion is best understood through reference to aprocessualcriterion of deliberative democracy, which provides a fitting normative template to ground theoretical inquiry into the reason-giving possibilities of existing democratic institutions and practices. Hence, answering why the US Supreme Court should not be elected on democratic grounds also reveals new insights about the role of parties in sustaining (or subverting) deliberative democratic ideals.

China, Regional Trade Agreements and WTO Law

China’s policy towards regional trade agreements (RTAs) will have a major impact on the international trading system, the debate about regionalism and multilateralism, and the policy of the WTO concerning RTAs. This article analyses China’s RTAs, identifies many reasons underlying them, and proposes a three–fold typology for China’s RTAs: economic integration agreements, standard regional trade agreements with other countries in the Asia–Pacific region, and bilateral free trade agreements with non–Asian countries. It then compares rules of origin, safeguards, and dispute settlement mechanisms in selected RTAs and evaluates them from the standpoint of WTO law. The article concludes, first, that the basic three–fold typology helps us to understand the objectives, organisation, and operation of China’s RTAs and their relations to China’s domestic structures, policy processes, legal and political culture and international and regional policies. Second, China’s RTAs are generally WTO–compatible since they are drafted in the shadow of WTO law, even though WTO law does not always provide a detailed normative template. Finally, China has the challenge and the opportunity of contributing to the development of a new role for the WTO in managing RTAs.