Molecular and cellular mechanisms of ultraviolet corneal crosslinking

In the presented mainly experimental work, the regularities and mechanisms of ultrastructural transformation and changes in corneal metabolism under ultraviolet exposure are established. High-quality saturation of the stroma with riboflavin is necessary to perform safe and effective UV crosslinking of the cornea, which can be achieved mainly due to a sufficient area of de-epithelization (at least 8-9 mm). It was found that UV crosslinking of the cornea with the use of developed riboflavin solutions (Dextralink, Ribolink and Khitolink) as photosensitizers increases its strength properties associated with changes in the structural state of collagen fibrils. It is proved that the riboflavin-UV effect on the optical shell of the eyeball is caused by a short-term local increase in free radical processes, a decrease in the overall antioxidant status, and the absence of necrotic and significant inflammatory reactions. It is shown that the lack of riboflavin in the stroma forms a cascade of pathomorphological events of an irreversible nature, leading to the loss of the native structure of the cornea. On the basis of the conducted studies, the necessity of a differentiated approach to the use of riboflavin-containing solutions during ultraviolet crosslinking of the cornea is justified. Key words: ultraviolet corneal crosslinking, molecular-cellular mechanisms, photosensitizers, riboflavin.

Worcester Educator Climate Assembly: Promoting Sustainability Leadership through Participation. A Community Approach to Education in Climate Emergency

Our urgent state of “Climate Emergency,” as declared by the UK Government on 1st May 2019, has done little to change our secondary education system or educational leadership. As we collectively begin to move into acceptance of the irreversible nature of a portion of the environmental damage and its long-term consequences, we need to explore the purpose and practice of education and educational leadership in climate emergency. How should we prepare teachers and educators to lead and develop young people in a time of climate crisis and who should be involved in making the decisions? This article reports on the findings of a Green Impact project, an online Educator Climate Assembly that took place on World Environment Day 2021, with West Midlands education stakeholder participants. The following themes are explored: responsibility, process complexity, confidence, sense of scale and communities of practice, with an invitation to readers to adapt this process and use it in their own education settings. Suggested further research includes trialing the process in a range of settings and a longitudinal approach to measuring the impacts.

ASSESSMENT OF GLAUCOMAAWARENESS AMONG PEOPLE ATTENDING HEALTHCARE REFERRAL CENTRE

Background: Glaucoma is a major public health problem in the India as well as world. Community based surveys reported that only 10% to 50% of people with glaucoma are aware about they have disease. Aim & Objective:The aim of this study to evaluate awareness about different aspect of glaucoma including symptoms, treatment. Methodology: This cross-sectional analytical study was done among people attending the Ophthalmology Out Patient Department at GMERS Medical College and Hospital Gandhinagar. Total 350 students were included in the study. Astructured interview with xed approach was used to collect data. The order of the questions was specied. Questionnaire has been validated by subject experts. Results: Mean age was 38.3 ± 13.8 years. Majority of the study participant were male (60.9%), literate (83.7%) and belonged to class III and above SE class (52.2%). Only 36.0% participants heard about glaucoma. Asymptomatic glaucoma and irreversible nature vision loss was known to 14.2% and 8.8% of participants. Awareness about glaucoma was signicantly low in participants of 21 to 60 year age group, education below secondary, SE class 4 & 5 and laborer. Conclusion:Awareness of glaucoma is very poor in persons attending GMERS medical college, Gandhinagar. There is need for community-based health education programmes to increase the level of awareness and knowledge about glaucoma

Timing of Auctions of Real Options

This paper endogenizes auction timing and initiation in auctions of real options. Because bidders have information rent, a seller faces a “virtual strike price” higher than the actual exercise cost. The seller inefficiently delays the auction to encourage bidder participation and uses the irreversible nature of time to gain partial control over option exercises. The seller’s private benefit at option exercise may restore efficient auction timing, but option exercises are always inefficiently late. When the seller lacks commitment to auction timing, bidders always initiate in equilibrium, resulting in earlier option exercise and higher welfare than auctions proscribing bidder initiation. Overall, auction timing modifies the distribution of the bidder valuations and has important implications for bidding strategies, auction design, and real outcomes. This paper was accepted by Gustavo Manso, finance.

Cellular senescence impairs the reversibility of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown. In this study, we used MCT+shunt-induced PAH in rats to identify a dichotomous reversibility response to HU, similar to the human situation. We compared vascular profiles of reversible and irreversible PAH using RNA sequencing. Cumulatively, we report that loss of reversibility is associated with a switch from a proliferative to a senescent vascular phenotype and confirmed markers of senescence in human PAH-CHD tissue. In vitro, we showed that human pulmonary endothelial cells of patients with PAH are more vulnerable to senescence than controls in response to shear stress and confirmed that the senolytic ABT263 induces apoptosis in senescent, but not in normal, endothelial cells. To support the concept that vascular cell senescence is causal to the irreversible nature of end-stage PAH, we targeted senescence using ABT263 and induced reversal of the hemodynamic and structural changes associated with severe PAH refractory to HU. The factors that drive the transition from a reversible to irreversible pulmonary vascular phenotype could also explain the irreversible nature of other PAH etiologies and provide new leads for pharmacological reversal of end-stage PAH.

Pathogenetic aspects of cachexia

The relevance of cachexia syndrome is determined by its high prevalence in clinical practice. It accompanies the course of not only oncological diseases, but also the majority of chronic somatic pathologies, such as chronic heart failure, renal failure, diabetes mellitus, chronic obstructive pulmonary disease, acquired immunodeficiency syndrome, rheumatoid arthritis, Alzheimers disease and others. It is known that even a slight weight loss in patients can determine an unfavorable prognosis of the underlying disease and reduce the effectiveness of therapy, and sometimes it becomes the direct cause of death of the patient. Cachexia is a complex metabolic syndrome, which is based on a violation of the central regulation of metabolism. The dangerous combination of decreased appetite (anorexia) and increased metabolism is the result of an imbalance in energy exchange. Treatment of cachexia syndrome is ineffective and limited in means. Given the progressive and irreversible nature of this syndrome, early diagnosis and prevention of its development are the primary task of the doctor. The article describes the main pathogenetic aspects of the development of cachexia syndrome. They can be common in different diseases. The article discusses the difficulties of diagnosing cachexia syndrome, the possibilities and prospects of treatment.

Exploratory Combinatorial Optimization with Reinforcement Learning

Many real-world problems can be reduced to combinatorial optimization on a graph, where the subset or ordering of vertices that maximize some objective function must be found. With such tasks often NP-hard and analytically intractable, reinforcement learning (RL) has shown promise as a framework with which efficient heuristic methods to tackle these problems can be learned. Previous works construct the solution subset incrementally, adding one element at a time, however, the irreversible nature of this approach prevents the agent from revising its earlier decisions, which may be necessary given the complexity of the optimization task. We instead propose that the agent should seek to continuously improve the solution by learning to explore at test time. Our approach of exploratory combinatorial optimization (ECO-DQN) is, in principle, applicable to any combinatorial problem that can be defined on a graph. Experimentally, we show our method to produce state-of-the-art RL performance on the Maximum Cut problem. Moreover, because ECO-DQN can start from any arbitrary configuration, it can be combined with other search methods to further improve performance, which we demonstrate using a simple random search.

Epistasis between cultural traits causes paradigm shifts in cultural evolution

Every now and then the cultural paradigm of a society changes. While current models of cultural shifts usually require a major exogenous or endogenous change, we propose that the mechanism underlying many paradigm shifts may just be an emergent feature of the inherent congruence among different cultural traits. We implement this idea through a population dynamics model in which individuals are defined by a vector of cultural traits that changes mainly through cultural contagion, biased by a ‘cultural fitness’ landscape, between contemporary individuals. Cultural traits reinforce or hinder each other (through a form of cultural epistasis) to prevent cognitive dissonance. Our main result is that abrupt paradigm shifts occur, in response to weak changes in the landscape, only in the presence of epistasis between cultural traits, and regardless of whether horizontal transmission is biased by homophily. A relevant consequence of this dynamics is the irreversible nature of paradigm shifts: the old paradigm cannot be restored even if the external changes are undone. Our model puts the phenomenon of paradigm shifts in cultural evolution in the same category as catastrophic shifts in ecology or phase transitions in physics, where minute causes lead to major collective changes.

Inherited neurodegenerative diseases

Many disorders of the nervous system, especially the degenerative conditions, have a genetic basis, which is usually due to a mutated gene resulting in decreased production of a critical structural or regulatory protein. Inherited neurodegenerative disorders present an enormous challenge because of the complexity of the nervous system, the broad clinical and genetic heterogeneity characteristic of these diseases, and the progressive and generally irreversible nature of their neuropathology. This chapter reviews and provides a guideline for inherited neurodegenerative disease. It is organized in a manner that a good neurological examination would be organized (i.e. systemic disorders followed by neurological disorders), discussed in a top-down manner (i.e. from cortex to muscle). Discussion of individual disorders starts with the molecular genetics, followed by molecular pathology, histology, clinical features, investigational findings, and management.