The Role of Intravitreal Corticosteroids in the Treatment of DME: Predictive OCT Biomarkers

Abstract: This work aims to summarize predictive biomarkers to guide treatment choice in DME. Intravitreal anti-VEGF is considered the gold standard treatment for centers involving DME, while intravitreal steroid treatment has been established as a second-line treatment in DME. However, more than 1/3 of the patients do not adequately respond to anti-VEGF treatment despite up to 4-weekly injections. Not surprisingly, insufficient response to anti-VEGF therapy has been linked to low-normal VEGF levels in the serum and aqueous humor. These patients may well benefit from an early switch to intravitreal steroid treatment. In these patients, morphological biomarkers visible in OCT may predict treatment response and guide treatment decisions. Namely, the presence of a large amount of retinal and choroidal hyperreflective foci, disruption of the outer retinal layers and other signs of chronicity such as intraretinal cysts extending into the outer retina and a lower choroidal vascular index are all signs suggestive of a favorable treatment response of steroids compared to anti-VEGF. This paper summarizes predictive biomarkers in DME in order to assist individual treatment decisions in DME. These markers will help to identify DME patients who may benefit from primary dexamethasone treatment or an early switc

East Asia Today

East Asia attracts growing interest in the West. Th e region is the world’s hotbed of economic growth, led by burgeoning China aided by more advanced Asian economies investing heavily in manufacturing and trading networks involving China. Western entrepreneurs clamor to join the China wave

Investigation of mTOR-independent regulation of macroautophagy

Investigation of mTOR-independent regulation of macroautophagy Richard Ian Odle Macroautophagy is a critical catabolic response to cellular stress, enabling lysosomal mediated breakdown of cytosolic cargo. The nutrient-responsive mTORC1 kinase complex has been described as a master regulator of cellular metabolism. Indeed, mTORC1 inhibits autophagy via repressive phosphorylation of the key autophagy regulators ATG13, ULK1, ATG14 and TFEB. Consequently, mTORC1 has become a candidate therapeutic target in neurodegeneration and cancer; however, its essential role in other cellular programs has prompted the investigation of mTORC1-independent regulation of autophagy. This thesis explores the role of CMGC kinase family members ERK1/2 and CCNB1-CDK1 in the regulation of autophagy. The ERK1/2 signalling cascade is activated in a high proportion of cancers. ERK2 has been proposed as a regulatory kinase of TFEB; however, we found little evidence to suggest that ERK1/2 was a direct kinase responsible for TFEB phosphorylation, including at the putative site S142. Furthermore, whilst we observed that hyperactivation of the ERK1/2 pathway did lead to increases in total TFEB protein levels in HEK293, this appeared to be a cell line specific finding. We therefore concluded ERK1/2 was not likely to be a critical regulator of TFEB. It has been proposed that autophagy must be repressed during mitosis, otherwise nuclear envelope breakdown will expose the genome to the cytosolic autophagy machinery. Here we show that autophagy initiation, as measured by markers of the omegasome, is indeed repressed throughout mitosis. Furthermore, autophagy regulators undergo mitotic hyperphosphorylation, including at known repressive sites, in a manner dependent on CDK1 but not mTORC1. Indeed, we find mTORC1 is likely inactive as a result of CDK1-dependent hyperphosphorylation of RAPTOR. Thus, we conclude that mTORC1 is substituted by CDK1, as the master repressor of autophagy during mitosis. These results suggest that autophagy regulation is uncoupled from nutrient status during nuclear envelope breakdown as a mechanism to prevent genomic instability, a hallmark of cancer.Funded by a Medical Research Council PhD studentship, the Frank Edward Elmore Fund, and the James Baird Fun

Commissioned women soldiers and politics in Zimbabwe

Masters of ArtThe Zimbabwe National Army (ZNA) and the ruling party, the Zimbabwe African Union Patriotic Front (ZANU-PF), are strongly interlinked in politics since independence, that is, the Army largely functions as the military wing of the party (ZANU-PF) and the state. The ZNA is also deeply involved in civilian politics. This study examines the experiences of commissioned women soldiers, as well as their understandings of power and politics in the ZNA. While many male soldiers are in positions of power and authority in the military, party, state, and civilian politics, commissioned women soldiers are marginalised in all of these areas. The role and position of women soldiers in this regard nevertheless remain under-researched. In this thesis I interrogate the complex processes and relations of power which discipline women soldiers and exclude them from processes of power and politics in the ZNA. I argue that there are various practice and discourses which affect women soldiers’ roles in the military. To do so, I draw on Foucault’s (1977) work on power/ knowledge, particularly the concepts of practices, relations, power and panopticism to examine how woman soldiers’ aspirations regarding power and politics are monitored and restricted in the military. I also draw on Enloe’s (2000) work on power politics and Sasson-Levy’s (2003) work on military gendered practices as interpretive and critical paradigmatic approaches to analyse how women experience hegemonic military masculinities in- and outside the army. The study employed ethnographic methods such as life histories, in-depth interviews and informal conversations with ten commissioned women soldiers in the ZNA. These methods were triangulated to corroborate responses from research participants and the data was thematically analyse

Fictional Practices of Spirituality I: Interactive Media

"Fictional Practices of Spirituality" provides critical insight into the implementation of belief, mysticism, religion, and spirituality into worlds of fiction, be it interactive or non-interactive. This first volume focuses on interactive, virtual worlds - may that be the digital realms of video games and VR applications or the imaginary spaces of life action role-playing and soul-searching practices. It features analyses of spirituality as gameplay facilitator, sacred spaces and architecture in video game geography, religion in video games and spiritual acts and their dramaturgic function in video games, tabletop, or LARP, among other topics. The contributors offer a first-time ever comprehensive overview of play-rites as spiritual incentives and playful spirituality in various medial incarnations

A compact high-energy particle detector for low-cost deep space missions

Over the last few decades particle physics has led to many new discoveries, laying the foundation for modern science. However, there are still many unanswered questions which the next generation of particle detectors could address, potentially expanding our knowledge and understanding of the Universe. Owing to recent technological advancements, electronic sensors are now able to acquire measurements previously unobtainable, creating opportunities for new deep-space high-energy particle missions. Consequently, a new compact instrument was developed capable of detecting gamma rays, neutrons and charged particles. This instrument combines the latest in FPGA System-on-Chip technology as the central processor and a 3x3 array of silicon photomultipliers coupled with an organic plastic scintillator as the detector. Using modern digital pulse shape discrimination and signal processing techniques, the scintillator and photomultiplier combination has been shown to accurately discriminate between the di_erent particle types and provide information such as total energy and incident direction. The instrument demonstrated the ability to capture 30,000 particle events per second across 9 channels - around 15 times that of the U.S. based CLAS detector. Furthermore, the input signals are simultaneously sampled at a maximum rate of 5 GSPS across all channels with 14-bit resolution. Future developments will include FPGA-implemented digital signal processing as well as hardware design for small satellite based deep-space missions that can overcome radiation vulnerability

Retrying Leopold and Loeb: A Neuropsychological Perspective

They called it the crime of the century; in 1924 in Chicago two brilliant, well-educated, and wealthy young men kidnapped and murdered a 14-year-old boy and killed him for the thrill of it . Expert testimony was presented by several well-known psychiatrists and psychologists, but even with all their clinical insights, none could reach a conclusion about the causal relation between their disturbed childhoods and a violent senseless crime. In fact, the well-known criminal defense attorney Clarence Darrow made little mention of the extensive psychiatric and psychological workups, and the judge did not deal with it in his sentencing. A review of the findings does suggest a delusional disorder for one of the defendants and psychopathy for the other; the interaction of these two disordered personalities led to a perfect storm a confluence of factors that only in combination could result in the brutal crime. Recent developments in neuropsychology allow us to see how these two disordered personalities interacted; the neuropsychological basis of delusional disorder and of psychopathy will be explored in this presentation along with a re-imagined closing argument by their attorney

Occasional Papers: On Creativity in the Arts

Volume 3 of The Hollybush Series contains thirteen essays on creativity, and three photographs of visual artwork, by Rowan College of New Jersey faculty. The editor is Janice Rowan Poley and the authors of the works are Joseph Robinette, Antoinette Libro, Rodney Gates, William Morris, Kenneth Kaleta, William Travis, E. Michael Desilets, Donald Gephardt, Joseph Tishler, Bertram Greenspan, Daniel Chard, Richard Ambacher, Harold Oliver, N. Jeane Hartman, Richard Grupenhoff, and Joseph Bierman.https://rdw.rowan.edu/hollybushseries/1001/thumbnail.jp