scholarly journals The role of multimodal imaging and vision function testing in ABCA4-related retinopathies and their relevance to future therapeutic interventions

2021 ◽  
Vol 13 ◽  
pp. 251584142110563
Author(s):  
Saoud Al-Khuzaei ◽  
Mital Shah ◽  
Charlotte R. Foster ◽  
Jing Yu ◽  
Suzanne Broadgate ◽  
...  
Keyword(s):  
Multimodal Imaging ◽  
Retinal Dystrophy ◽  
Rate Of Change ◽  
Therapeutic Interventions ◽  
Tissue Loss ◽  
Stargardt Disease ◽  
Phenotypic Characterisation ◽  
Wide Range ◽  
Abca4 Gene ◽  
The Future

The aim of this review article is to describe the specific features of Stargardt disease and ABCA4 retinopathies (ABCA4R) using multimodal imaging and functional testing and to highlight their relevance to potential therapeutic interventions. Standardised measures of tissue loss, tissue function and rate of change over time using formal structured deep phenotyping in Stargardt disease and ABCA4R are key in diagnosis, and prognosis as well as when selecting cohorts for therapeutic intervention. In addition, a meticulous documentation of natural history will be invaluable in the future to compare treated with untreated retinas. Despite the familiarity with the term Stargardt disease, this eponymous classification alone is unhelpful when evaluating ABCA4R, as the ABCA4 gene is associated with a number of phenotypes, and a range of severity. Multimodal imaging, psychophysical and electrophysiologic measurements are necessary in diagnosing and characterising these differing retinopathies. A wide range of retinal dystrophy phenotypes are seen in association with ABCA4 mutations. In this article, these will be referred to as ABCA4R. These different phenotypes and the existence of phenocopies present a significant challenge to the clinician. Careful phenotypic characterisation coupled with the genotype enables the clinician to provide an accurate diagnosis, associated inheritance pattern and information regarding prognosis and management. This is particularly relevant now for recruiting to therapeutic trials, and in the future when therapies become available. The importance of accurate genotype-phenotype correlation studies cannot be overemphasised. This approach together with segregation studies can be vital in the identification of causal mutations when variants in more than one gene are being considered as possible. In this article, we give an overview of the current imaging, psychophysical and electrophysiological investigations, as well as current therapeutic research trials for retinopathies associated with the ABCA4 gene.

Features of optative modality in Macedonian language (with emphasis on the functionalities of independent da-construction)

2020 ◽  
pp. 301-323
Author(s):  
Natalya I. Kikilo ◽  
Keyword(s):  
Detailed Analysis ◽  
Present Article ◽  
Literary Language ◽  
Natural Context ◽  
Wide Range ◽  
Verb Forms ◽  
Text Types ◽  
The Future ◽  
The Subject ◽  
Ritual Context

In the Macedonian literary language the analytic da-construction used in an independent clause has a wide range of possible modal meanings, the most common of which are imperative and optative. The present article offers a detailed analysis of the semantics and functions of the Macedonian optative da-construction based on fiction and journalistic texts. The first part of the article deals with the specificities of the optative as a category which primarily considers the subject of a wish. In accordance with the semantic characteristics of this category, optative constructions are used in those discourse text types where the speakers are explicitly designated (the most natural context for the optative is the dialogue). The analysis of the Macedonian material includes instances of atypical usage of the optative da-construction, in which the wish of the subject is not apparent and thereby produces new emotional tonalities perceptible to the reader of a fiction/journalistic text. The study describes Macedonian constructions involving two different verb forms: 1) present tense form (da + praes) and 2) imperfective form (da + impf). These constructions formally designate the hypothetical and counterfactual status of the optative situation, respectively. Thus, the examples in the analysis are ordered according to two types of constructions, which reflect the speaker’s view on the probability of the realisation of his/her wish. Unrealistic wishes can be communicated through the present da-construction, while the imperfective construction denotes situations in which the wish can be realised in the future. The second part of the article is devoted to performative optative da-constructions, which express formulas of speech etiquette, wishes and curses. The analysis demonstrates that these constructions lose their magical functions, when used outside of the ritual context, and begin to function as interjections.

Cognitive Impact of Cerebellar Damage: Is There a Future for Cognitive Rehabilitation?

2018 ◽  
Vol 17 (3) ◽  
pp. 199-206 ◽  
Author(s):  
Kim van Dun ◽  
Frank V. Overwalle ◽  
Mario Manto ◽  
Peter Marien
Keyword(s):  
Affective Disorders ◽  
Cognitive Rehabilitation ◽  
Therapeutic Interventions ◽  
Posterior Fossa Surgery ◽  
Daily Life Activities ◽  
Wide Range ◽  
Affective Deficits ◽  
Cerebellar Injury ◽  
Cognitive Therapies ◽  
The Impact

Background & Objective: During the past 3 decades, numerous neurophysiological, neuroimaging, experimental and clinical studies have evidenced a crucial role for the cerebellum in cognitive, affective and behavioral functions. As a result of the acknowledged modulatory role of the cerebellum upon remote structures such as the cerebral cortex, cerebellar injury may give rise to a constellation of behavioral, affective and cognitive symptoms (Schmahmann's Syndrome). In sharp contrast to the wide range of therapeutic interventions to treat cognitive and affective disorders following cerebral cortical lesions and despite the consequences of Schmahmann’s syndrome upon daily life activities, the literature is surprisingly only scantly documented with studies investigating the impact of cognitive therapies on cerebellar induced cognitive and affective disorders. This survey aims to present an overview of the therapeutic interventions available in the literature as a possible treatment for Schmahmann’s Syndrome after cerebellar injury, after posterior fossa surgery in children, and in children with neurodevelopmental disorders. Although systematical studies are clearly warranted, available evidence suggests that cerebellar-induced cognitive and affective disorders should be treated in a specific way. Approaches where the patients are explicitly made aware of their deficits and are considered to act as an “external cerebellum” are the most promising. Conclusion: The study of the anatomical connectivity of the cerebellar microcomplexes involved in cognitive/affective deficits is likely to play a major-role in the future.

scholarly journals Frequency Division Multiplexing of Terahertz Waves Realized by Diffractive Optical Elements

2021 ◽  
Vol 11 (14) ◽  
pp. 6246
Author(s):  
Paweł Komorowski ◽  
Patrycja Czerwińska ◽  
Mateusz Kaluza ◽  
Mateusz Surma ◽  
Przemysław Zagrajek ◽  
...  
Keyword(s):  
Frequency Division Multiplexing ◽  
Diffractive Optical Elements ◽  
Frequency Division ◽  
Terahertz Waves ◽  
Optical Elements ◽  
Telecommunication Systems ◽  
Wide Range ◽  
The Future ◽  
Wireless Telecommunication ◽  
Finite Distance

Recently, one of the most commonly discussed applications of terahertz radiation is wireless telecommunication. It is believed that the future 6G systems will utilize this frequency range. Although the exact technology of future telecommunication systems is not yet known, it is certain that methods for increasing their bandwidth should be investigated in advance. In this paper, we present the diffractive optical elements for the frequency division multiplexing of terahertz waves. The structures have been designed as a combination of a binary phase grating and a converging diffractive lens. The grating allows for differentiating the frequencies, while the lens assures separation and focusing at the finite distance. Designed structures have been manufactured from polyamide PA12 using the SLS 3D printer and verified experimentally. Simulations and experimental results are shown for different focal lengths. Moreover, parallel data transmission is shown for two channels of different carrier frequencies propagating in the same optical path. The designed structure allowed for detecting both signals independently without observable crosstalk. The proposed diffractive elements can work in a wide range of terahertz and sub-terahertz frequencies, depending on the design assumptions. Therefore, they can be considered as an appealing solution, regardless of the band finally used by the future telecommunication systems.

Digital Authoritarianism and the Future of Human Rights

2021 ◽  
pp. 1-27
Author(s):  
Tiberiu Dragu ◽  
Yonatan Lupu
Keyword(s):  
Human Rights ◽  
New Technologies ◽  
Theoretic Model ◽  
Human Rights Abuses ◽  
Human Rights Regime ◽  
Wide Range ◽  
The Future ◽  
Technological Developments ◽  
Game Theoretic ◽  
Strategic Context

Abstract How will advances in digital technology affect the future of human rights and authoritarian rule? Media figures, public intellectuals, and scholars have debated this relationship for decades, with some arguing that new technologies facilitate mobilization against the state and others countering that the same technologies allow authoritarians to strengthen their grip on power. We address this issue by analyzing the first game-theoretic model that accounts for the dual effects of technology within the strategic context of preventive repression. Our game-theoretical analysis suggests that technological developments may not be detrimental to authoritarian control and may, in fact, strengthen authoritarian control by facilitating a wide range of human rights abuses. We show that technological innovation leads to greater levels of abuses to prevent opposition groups from mobilizing and increases the likelihood that authoritarians will succeed in preventing such mobilization. These results have broad implications for the human rights regime, democratization efforts, and the interpretation of recent declines in violent human rights abuses.

scholarly journals Phenotypic Characterisation for Growth and Nut Characteristics Revealed the Extent of Genetic Diversity in Wild Macadamia Germplasm

Agriculture ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 680
Author(s):  
Thuy T. P. Mai ◽  
Craig M. Hardner ◽  
Mobashwer M. Alam ◽  
Robert J. Henry ◽  
Bruce L. Topp
Keyword(s):  
Genetic Diversity ◽  
Growth Traits ◽  
Principal Component ◽  
Conservation Strategies ◽  
Wild Germplasm ◽  
Phenotypic Characterisation ◽  
Wide Range ◽  
Genetic And Environmental Factors ◽  
Positive Correlations ◽  
Wild Accessions

Macadamia is a recently domesticated Australian native nut crop, and a large proportion of its wild germplasm is unexploited. Aiming to explore the existing diversity, 247 wild accessions from four species and inter-specific hybrids were phenotyped. A wide range of variation was found in growth and nut traits. Broad-sense heritability of traits were moderate (0.43–0.64), which suggested that both genetic and environmental factors are equally important for the variability of the traits. Correlations among the growth traits were significantly positive (0.49–0.76). There were significant positive correlations among the nut traits except for kernel recovery. The association between kernel recovery and shell thickness was highly significant and negative. Principal component analysis of the traits separated representative species groups. Accessions from Macadamia integrifolia Maiden and Betche, M. tetraphylla L.A.S. Johnson, and admixtures were clustered into one group and those of M. ternifolia F. Muell were separated into another group. In both M. integrifolia and M. tetraphylla groups, variation within site was greater than across sites, which suggested that the conservation strategies should concentrate on increased sampling within sites to capture wide genetic diversity. This study provides a background on the utilisation of wild germplasm as a genetic resource to be used in breeding programs and the direction for gene pool conservation.

Report on CLEF 2019

2019 ◽  
Vol 53 (2) ◽  
pp. 108-118
Author(s):  
Martin Braschler ◽  
Linda Cappellato ◽  
Fabio Crestani ◽  
Nicola Ferro ◽  
Gundula Heinatz Bürki ◽  
...  
Keyword(s):  
Standard Test ◽  
Future Perspectives ◽  
Research Papers ◽  
Test Collections ◽  
Lessons Learnt ◽  
Wide Range ◽  
The Future ◽  
20Th Anniversary

This is a report on the tenth edition of the Conference and Labs of the Evaluation Forum (CLEF 2019), held from September 9--12, 2019, in Lugano, Switzerland. CLEF was a four day event combining a Conference and an Evaluation Forum. The Conference featured keynotes by Bruce Croft, Yair Neuman, and Miguel Martínez, and presentation of peer reviewed research papers covering a wide range of topics in addition to many posters. The Evaluation Forum consisted to nine Labs: CENTRE, CheckThat, eHealth, eRisk, ImageCLEF, LifeCLEF, PAN, PIR-CLEF, and ProtestNews, addressing a wide range of tasks, media, languages, and ways to go beyond standard test collections. CLEF 2019 marked the 20th anniversary of CLEF, which was celebrated with a dedicated session and a book on the lessons learnt in twenty years of evaluation activities and the future perspectives for CLEF. CLEF 2019 also introduced the Industry Days to further extend the reach and impact of CLEF.

scholarly journals Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1781
Author(s):  
Gustavo A. Arias-Pinilla ◽  
Helmout Modjtahedi
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Antibody Therapy ◽  
Therapeutic Targets ◽  
Poor Response ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Western World ◽  
Wide Range ◽  
Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

Practice Guidelines: How Good are Medicine's New Recipes?

1995 ◽  
Vol 23 (1) ◽  
pp. 47-48 ◽  
Author(s):  
Alexander Morgan Capron
Keyword(s):  
Health Care ◽  
Nonprofit Organizations ◽  
Medical Knowledge ◽  
Medical Specialty ◽  
Therapeutic Interventions ◽  
Medical Interventions ◽  
Practice Parameters ◽  
Wide Range ◽  
Standard Of Practice

Over the last decade, standards for when and how to undertake a wide range of medical interventions have poured forth from medical specialty groups, commercial and nonprofit organizations, and state and federal panels. Known by a variety of names—from practice parameters to clinical guidelines—and intended for a range of purposes—from diminishing the incidence of maloccurences in hospitals to cutting the costs of health care—these guidelines share one important feature: the intention of decreasing the range of variation in medical practice. Such standardization immediately appeals to anyone interested in improving the quality of health care and, in particular, reducing inappropriate medical interventions, in light of the difficulties for a conscientious physician today in adhering to the best standard of practice when faced with ever increasing medical knowledge and the growing number and complexity of diagnostic, preventive, and therapeutic interventions.

Haemorheological Effects on Thrombocyte Adhesion and Aggregation Found Under Controlled Flow Conditions

1979 ◽  
Author(s):  
P.D. Richardson
Keyword(s):  
Rate Of Change ◽  
Continuous Observation ◽  
Flow Conditions ◽  
Wide Range ◽  
Stream Migration ◽  
Local Shear ◽  
Videotape Recording ◽  
Controlled Flow ◽  
A Site

Thrombocyte adhesion and aggregation in a vessel or on a chamber wall can be measured most readily if the flow is controlled and steady, and continuous observation is used. Videotape recording is very helpful for subsequent quantification of the dynamics. The adhesion of each thrombocyte can occur for a finite time interval:this interval has been observed to have a wide range. Platelets which escape often leave open a site which attracts other platelets preferentially. The rate of change of adhesion density (platelets/mm2) is affected by the local shear rate and the shear history upstream. Aggregation is affected similarly, and also proceeds with some platelet turnover. The role of erythrocytes in facilitating cross-stream migration of thrombocytes (which can enhance the growth rate of large thrombi) appears due in part to convective flow fields induced by the motion of erythrocytes in a shear flow, which can be demonstrated theoretically and experimentally. Observations of the phenomenlogy of adhesion and aggregation under controlled flow conditions and comparison with fLu id-dynamically based theory allows representation in terras of a small number of parameters with prospects of prediction of behaviour over a wide range of haemodynamic conditions; biochemical changes lead to changes in values of the parameters, so that activating agents and inhibiting agents modify values in different directions.

The Australia and New Zealand v Japan Southern Bluefin Tuna (Jurisdiction and Admissibility) Award of the First Law of the Sea Convention Annex VII Arbitral Tribunal

2001 ◽  
Vol 16 (2) ◽  
pp. 239-293 ◽  
Author(s):  
Barbara Kwiatkowska
Keyword(s):  
New Zealand ◽  
Bluefin Tuna ◽  
Fundamental Principle ◽  
Law Of The Sea ◽  
Arbitral Tribunal ◽  
Compulsory Arbitration ◽  
Wide Range ◽  
The Future ◽  
Questions And Answers ◽  
Southern Bluefin Tuna

AbstractThe Southern Bluefin Tuna (Jurisdiction and Admissihilily) Award of 4 August 2000 marked the first instance of the application of compulsory arbitration under Part XV, Section 2 of the 1982 UN Law of the Sea Convention and of the exercise by the Annex VII Tribunal of la compétence de la compétence pursuant to Article 288(4) over the merits of the instant dispute. The 72-paragraph Award is a decision of pronounced procedural complexity and significant multifaceted impacts of which appreciation requires an in-depth acquaintance with procedural issues of peaceful settlement of disputes in general and the-law-of-the-sea-related disputes in particular. Therefore, the article surveys first the establishment of and the course of proceedings before the five-member Annex VII Arbitral Tribunal, presided over by the immediate former ICJ President, Judge Stephen M. Schwebel, and also comprising Judges Keith, Yamada. Feliciano and Tresselt. Subsequently, the wide range of specific paramount questions and answers of the Tribunal are scrutinised against the background of arguments advanced by the applicants (Australia and New Zealand) and the respondent (Japan) during both written and oral pleadings, including in reliance on the extensive ICJ jurisprudence and treaty practice concerned. On this basis, the article turns to an appraisal of the impacts of the Arbitral Tribunal's paramount holdings and its resultant dismissal of jurisdiction with the scrupulous regard for the fundamental principle of consensuality. Amongst such direct impacts as between the parties to the instant case, the inducements provided by the Award to reach a successful settlement in the future are of particular importance. The Award's indirect impacts concern exposition of the paramount doctrine of parallelism between the umbrella UN Convention and many compatible (fisheries, environmental and other) treaties, as well as of multifaceted, both substantial and procedural effects of that parallelism. All those contributions will importantly guide other courts and tribunals seised in the future under the Convention's Part XV, Section 2.

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