Multimodal imaging in age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness and affects approximately one in seven Australians aged 50 years and above. Currently, this complex condition is not easily and uniformly assessed. The signs of AMD differ between eyes and also occur in other macular disorders. This hinders accurate diagnosis and classification, which is fundamental to optimal patient care. Ocular imaging and visual function assessment have the potential to minimise the devastating consequences of disease through early detection. However, multiple devices are now commercially available and the impact of these technologies in clinical practice may not be straightforward. For instance, their usefulness may depend on accessibility and the operator’s knowledge and clinical skills. The impact on patient management, as well as alternative models of eye-care delivery, requires clarification. This thesis aims to explore the current and potential utility of imaging technologies (optical coherence tomography, infrared imaging, monochromatic retinal photography and fundus autofluorescence) in the assessment and management of AMD and other diseases of retinal pigment epithelium dysfunction. The findings show that optometrists self-describe high levels of practice competency and make ready use of imaging in everyday practice. However, they also unwittingly demonstrated low awareness of the evidence base in AMD. Furthermore, when their interpretation of images was tested using a series of case vignettes, their diagnostic accuracy as a group improved by only five per cent (from 61 per cent to 66 per cent); their tendency to refer increased by four per cent. These factors might be improved through education. A series of open-access, chair-side reference charts were consequently devised to help optometrists use imaging technologies more effectively in clinical practice. The additive contribution of multimodal structural and functional testing was particularly emphasised. Finally, a novel model of intermediate-tier eye-care in Australia was shown to substantially reduce the number of false positive cases or cases without a specific diagnosis. Interestingly, this model was acclaimed by reviewers as “scoring highly for originality and of international relevance”. Most excitingly, the thesis concludes with future directions regarding collaborative care and multimodal imaging, where detection of disease might be facilitated via a computational approach

Molecular Therapies for Inherited Retinal Diseases

Following the implementation of next-generation sequencing technologies (e.g., exome and genome sequencing) in molecular diagnostics, the majority of genetic defects underlying inherited retinal disease (IRD) can readily be identified. In parallel, opportunities to counteract the molecular consequences of these defects are rapidly emerging, providing hope for personalized medicine. ‘Classical’ gene augmentation therapy has been under study for several genetic subtypes of IRD and can be considered a safe and sometimes effective therapeutic strategy. The recent market approval of the first retinal gene augmentation therapy product (LuxturnaTM, for individuals with bi-allelic RPE65 mutations) by the FDA has not only demonstrated the potential of this specific approach, but also opened avenues for the development of other strategies. However, every gene—or even every mutation—may need a tailor-made therapeutic approach, in order to obtain the most efficacious strategy with minimal risks associated. In addition to gene augmentation therapy, other subtypes of molecular therapy are currently being designed and/or implemented, including splice modulation, DNA or RNA editing, optogenetics and pharmacological modulation. In addition, the development of proper delivery vectors has gained strong attention, and should not be overlooked when designing and testing a novel therapeutic approach. In this Special Issue, we aim to describe the current state of the art of molecular therapeutics for IRD, and discuss existing and novel therapeutic strategies, from idea to implementation, and from bench to bedside

NASA Tech Briefs, January 1992

Topics include: New Product Ideas; Electronic Components and Circuits; Electronic Systems; Physical Sciences; Materials; Computer Programs; Mechanics; Machinery/Automation; Fabrication; Mathematics and Information Sciences; Life Sciences

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 385)

This bibliography lists 536 reports, articles and other documents introduced into the NASA Scientific and Technical Information System Database. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance

Optically Induced Nanostructures

Nanostructuring of materials is a task at the heart of many modern disciplines in mechanical engineering, as well as optics, electronics, and the life sciences. This book includes an introduction to the relevant nonlinear optical processes associated with very short laser pulses for the generation of structures far below the classical optical diffraction limit of about 200 nanometers as well as coverage of state-of-the-art technical and biomedical applications. These applications include silicon and glass wafer processing, production of nanowires, laser transfection and cell reprogramming, optical cleaning, surface treatments of implants, nanowires, 3D nanoprinting, STED lithography, friction modification, and integrated optics. The book highlights also the use of modern femtosecond laser microscopes and nanoscopes as novel nanoprocessing tools

Dichotomic role of NAADP/two-pore channel 2/Ca2+ signaling in regulating neural differentiation of mouse embryonic stem cells

Poster Presentation - Stem Cells and Pluripotency: abstract no. 1866The mobilization of intracellular Ca2+stores is involved in diverse cellular functions, including cell proliferation and differentiation. At least three endogenous Ca2+mobilizing messengers have been identified, including inositol trisphosphate (IP3), cyclic adenosine diphosphoribose (cADPR), and nicotinic adenine acid dinucleotide phosphate (NAADP). Similar to IP3, NAADP can mobilize calcium release in a wide variety of cell types and species, from plants to animals. Moreover, it has been previously shown that NAADP but not IP3-mediated Ca2+increases can potently induce neuronal differentiation in PC12 cells. Recently, two pore channels (TPCs) have been identified as a novel family of NAADP-gated calcium release channels in endolysosome. Therefore, it is of great interest to examine the role of TPC2 in the neural differentiation of mouse ES cells. We found that the expression of TPC2 is markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebound during the late stages of neurogenesis. Correspondingly, perturbing the NAADP signaling by TPC2 knockdown accelerates mouse ES cell differentiation into neural progenitors but inhibits these neural progenitors from committing to the final neural lineage. Interestingly, TPC2 knockdown has no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Overexpression of TPC2, on the other hand, inhibits mouse ES cell from entering the neural lineage. Taken together, our data indicate that the NAADP/TPC2-mediated Ca2+signaling pathway plays a temporal and dichotomic role in modulating the neural lineage entry of ES cells; in that NAADP signaling antagonizes ES cell entry to early neural progenitors, but promotes late neural differentiation.postprin

Strategic Latency Unleashed: The Role of Technology in a Revisionist Global Order and the Implications for Special Operations Forces

The article of record may be found at https://cgsr.llnl.govThis work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory in part under Contract W-7405-Eng-48 and in part under Contract DE-AC52-07NA27344. The views and opinions of the author expressed herein do not necessarily state or reflect those of the United States government or Lawrence Livermore National Security, LLC. ISBN-978-1-952565-07-6 LCCN-2021901137 LLNL-BOOK-818513 TID-59693This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory in part under Contract W-7405-Eng-48 and in part under Contract DE-AC52-07NA27344. The views and opinions of the author expressed herein do not necessarily state or reflect those of the United States government or Lawrence Livermore National Security, LLC. ISBN-978-1-952565-07-6 LCCN-2021901137 LLNL-BOOK-818513 TID-5969

Senescence

The book "Senescence" is aimed to describe all the phenomena related to aging and senescence of all forms of life on Earth, i.e. plants, animals and the human beings. The book contains 36 carefully reviewed chapters written by different authors, aiming to describe the aging and senescent changes of living creatures, i.e. plants and animals