132 research outputs found
Genetics of age-related hearing loss
No full textAge‐related hearing loss (ARHL) has recently been confirmed as a common complex trait, that is, it is heritable with many genetic variants each contributing a small amount of risk, as well as environmental determinants. Historically, attempts to identify the genetic variants underlying the ARHL have been of limited success, relying on the selection of candidate genes based on the limited knowledge of the pathophysiology of the condition, and linkage studies in samples comprising related individuals. More recently genome‐wide association studies have been performed, but these require very large samples having consistent and reliable phenotyping for hearing loss (HL), and early attempts suffered from lack of reliable replication of their findings. Replicated variants shown associated with ARHL include those lying in genes GRM7, ISG20, TRIOBP, ILDR1, and EYA4. The availability of large biobanks and the development of collaborative consortia have led to a breakthrough over the last couple of years, and many new genetic variants associated with ARHL are becoming available, through the analysis publicly available bioresources and electronic health records. These findings along with immunohistochemistry and mouse models of HL look set to help disentangle the genetic architecture of ARHL, and highlight the need for standardization of phenotyping methods to facilitate data sharing and collaboration across research networks
Vertebral bone marrow (Modic) changes
No full textModic changes (MCs) are bone marrow changes in the spine, and they are classified into three categories (types 1, 2, and 3) based on magnetic resonance imaging (MRI) appearance. They share several determinants with bone marrow changes at other sites of the body. The precise pathology of MCs is still unclear but includes structural disc damage and the inflammatory response to it, atypical mechanical loading, and possible bacterial etiology. In particular, Modic type 1 change (MC1) is thought to be associated with low back pain (LBP) but may also occur among the normal, asymptomatic population. However, MC1 may play a role, especially among patients with chronic, troublesome LBP. Clinically, MCs are diagnosed using MRI with no evident clinical tests or diagnostic algorithms. Unfortunately, no evidence-based treatment options exist yet for patients with pain and MCs although fusion surgery, antibiotic, and nerve ablation treatment are being explored. Overall, MCs are clinically important structural spine phenotypes, with varied etiology and prognostics and a need for refined classification.</p
Genetic predisposition to chronic pain:from evolutionary advantage to a debilitating disease spectrum?
No full text
OLSIA: Open Lumbar Spine Image Analysis - A 3D Slicer Extension for Segmentation, Grading, and Intervertebral Disc Height Index with Multi-Dataset Validation
Full text linkAbstract
Study Design:
Retrospective and cross-sectional study
Objective:
The study aims to develop an open software for lumbar spine image analysis enabling no-code approach to lumbar spine segmentation, grading, and intervertebral disc height index (DHI) calculations with robust evaluation of the application on six external datasets from diverse geographical regions.
Summary of data:
The datasets used include NFBC1966 (Finland), HKDDC (Hong Kong), TwinsUK (UK), CETIR (Spain), NCSD (Hungary), SPIDER (Netherlands), and Mendeley (global). Thirty participants from each dataset were sampled for external evaluation and NFBC1966 was used for training. Annotation was performed on T2-weighted mid-sagittal slices of vertebral bodies L1-S1 and intervertebral discs L1/2-L5/S1.
Materials and Methods:
Open Lumbar Spine Image Analysis (OLSIA) application was developed to include no-code approach tools for automated segmentation, grading, DHI calculation, and batch processing capabilities by integrating the deep learning (DL) models. DL models were trained on the NFBC1966 dataset with augmentation (histogram clipping, median filtering, geometric scaling) to improve generalization. Inter-rater agreement was assessed using Dice similarity coefficient (DSC), Bland-Altman (BA) analysis for DHI measurements and a paired t-test for statistical significance.
Results:
Our application demonstrated 222-fold improvement in processing time compared to performing manually lumbar spine segmentation, grading and DHI calculation tasks. OLSIA’s segmentation performance exhibited close correspondence with the inter-rater agreement across all six external datasets. Inter-rater reliability was high (mean DSC>90). Although paired t-test on DHI measurements is significant (P<0.05), the mean difference (0.02) of DHI from the BA plots indicates low systematic bias.
Conclusion:
We introduced OLSIA, a user-friendly interface for lumbar spine segmentation, grading, and intervertebral DHI calculation. OLSIA empowers researchers from diverse backgrounds to efficiently use the no-code tools to accelerate their radiomics and lumbar spine image analysis workflows.Abstract
Study Design:
Retrospective and cross-sectional study
Objective:
The study aims to develop an open software for lumbar spine image analysis enabling no-code approach to lumbar spine segmentation, grading, and intervertebral disc height index (DHI) calculations with robust evaluation of the application on six external datasets from diverse geographical regions.
Summary of data:
The datasets used include NFBC1966 (Finland), HKDDC (Hong Kong), TwinsUK (UK), CETIR (Spain), NCSD (Hungary), SPIDER (Netherlands), and Mendeley (global). Thirty participants from each dataset were sampled for external evaluation and NFBC1966 was used for training. Annotation was performed on T2-weighted mid-sagittal slices of vertebral bodies L1-S1 and intervertebral discs L1/2-L5/S1.
Materials and Methods:
Open Lumbar Spine Image Analysis (OLSIA) application was developed to include no-code approach tools for automated segmentation, grading, DHI calculation, and batch processing capabilities by integrating the deep learning (DL) models. DL models were trained on the NFBC1966 dataset with augmentation (histogram clipping, median filtering, geometric scaling) to improve generalization. Inter-rater agreement was assessed using Dice similarity coefficient (DSC), Bland-Altman (BA) analysis for DHI measurements and a paired t-test for statistical significance.
Results:
Our application demonstrated 222-fold improvement in processing time compared to performing manually lumbar spine segmentation, grading and DHI calculation tasks. OLSIA’s segmentation performance exhibited close correspondence with the inter-rater agreement across all six external datasets. Inter-rater reliability was high (mean DSC>90). Although paired t-test on DHI measurements is significant (P<0.05), the mean difference (0.02) of DHI from the BA plots indicates low systematic bias.
Conclusion:
We introduced OLSIA, a user-friendly interface for lumbar spine segmentation, grading, and intervertebral DHI calculation. OLSIA empowers researchers from diverse backgrounds to efficiently use the no-code tools to accelerate their radiomics and lumbar spine image analysis workflows
Multinational corporations in the Arab world with particular reference to the contribution of industrial joint ventures to development in the Gulf region
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis investigates the status and the role of Multinational Corporations in the Arab World. Its main hypothesis is that the Multinationals today represent a permanent feature as the major world-wide source of modern technology. As such, the Arab countries will continue relying, into the foreseeable future, upon technology produced, owned or controlled by these global firms.
The research finds that a century of increasing integration with the western industrialised countries, primarily shaped by the activities of the multinational corporations, has nevertheless left the Arab region less industrialised and more technologically and institutionally backward than many other parts of the world. The Arab Nation as a whole, in all its diversity of countries and regions, has failed to economically or industrially advance at the same rate as other newly industrialising regions. The lack of commitment to national and regional development needs in the Arab World on the part of most multinationals, is matched by an equal absence of any clear sense of purpose and dedication on the part of the Arab countries themselves.
Despite the proposition by some Arab professionals and elites that the Arab States must consider breaking with any development strategy that substantially relies on access to capital and technology provided by foreign multinationals, the research contends that, in view of the current underdeveloped state of indigenous technology in the Arab World, the contemplation of the option of "de-linking" from the multinationals is neither possible nor desirable. The fact is, that the Arab States, individually or as whole, are not as yet prepared for the challenges that such a go-it-alone development strategy would imply.
The research also finds that, as the multinational' behaviour is governed by diverse objectives, helping out the developing countries of the Arab World to build-up their technological base is not generally one of their distinctive goals. They have their own "growth" strategy while each of the individual Arab States has its own "development" policy. The objectives of each differ, as shown in this thesis, and are often incompatible. Yet, for a multinational corporation to secure profit, growth and security, it will need the goodwill of the Arab countries, while the latter, in order to start building their technological base, need the multinationals. Thus, objectively, they need each other and a fruitful cooperation between the two parties depends on the convergence of two strategies, which usually need to undergo many changes in order to accommodate each other's diverse interests.
This means that, what a foreign multinational can really offer depends on how much an Arab country, individually or in collaboration with other Arab countries, may actually be prepared or able to take. From the latter's viewpoint, the ability to take is dependent on the extent to which the Arab countries can cooperate effectively together. The recent trend in the region towards forging economic integration, in the form of regional groupings among neighbouring Arab countries, is widely heralded to be an essential step in the right direction. However, in view of the considerable variations in natural resource endowments which exist among the countries of the Arab World, it has been increasingly suggested by the Arab participants of our main survey, that inter-Arab multinational joint ventures constitute a highly desirable form of organising economic activity, and of accomplishing effective economic cooperation among the countries of the region.
Most importantly, the thesis demonstrates that there are many areas in which conventional economic theories are deficient in explaining multinationals' behaviour and impact on the Arab World. Deficiencies between theory and practice arc referred to throughout the work and discussed in particular detail in Chapters 4 and 12.
A major conclusion of this study is that, the Arab governments which once feared the multinationals are now actively interested in seeking to court and accommodate them more effectively to local development needs. There is increasing evidence that the Arab countries have learned to bargain with multinationals to make them better serve their specific objectives and interests. Through more contacts and interactions, previously contrasting positions have softened and a wave of pragmatic attitudes on both sides is emerging to promote greater recognition of the mutual interests involved.
It is the hope of the author of this thesis that his work will encourage even greater mutual understanding and cooperation between the Arab States and multinational partners in the future. Indeed it is only through such cooperation that joint efforts can be effectively used to promote beneficial development and growth for the future prosperity of the Arab Nation as a whole
Genetic and environmental correlational structure among metabolic syndrome endophenotypes
No full textAbstract: Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood. The present paper takes a multi-prong approach to examining the extent of this genetic overlap. This includes the quantitative genetic and additive Bayesian network modeling of the large TwinsUK project and examination of the results of genome-wide association study (GWAS) of UK Biobank data through use of LD score regression and examination of the number of genes and pathways identified in the GWASes which overlap across MetS traits. Results demonstrate a modest genetic overlap, and the genetic correlations obtained from TwinsUK and UK Biobank are nearly identical. However, these correlations imply more genetic dissimilarity than similarity. Furthermore, examination of the extent of overlap in significant GWAS hits, both at the gene and pathway level, again demonstrates only modest but significant genetic overlap. This lends support to the idea that in clinical treatment of MetS, treating each of the components individually may be an important way to address MetS.</p
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