A solute gradient in the tear meniscus I. A hypothesis to explain Marx's line

Marx's line is a line of mucosal staining behind the mucocutaneous junction. It can be demonstrated throughout life in all normal lids by staining with lissamine green and related dyes. Of all the body orifices, only the mucosae of the eye and mouth are directly exposed to the atmosphere. In this paper, we suggest that for the eye, this exposure leads to the formation of Marx's line. The tear meniscus thins progressively toward its apex, where it is pinned at the mucocutaneous junction of the lid. It also thins toward the black line, which segregates the meniscus from the tear film after the blink. We predict that, because of the geometry of the tear meniscus, evaporation generates a solute gradient across the meniscus profile in the anteroposterior plane, which peaks at the meniscus apices at the end of the interblink. One outcome would be to amplify the level of tear molarity at these sites so that they reach hyperosmolar proportions. Preliminary mathematical modeling suggests that dilution of this effect by advection and diffusion of solute away from the meniscus apex at the mucocutaneous junction will be restricted by spatial constraints, the presence of tear and surface mucins at this site, and limited fluid flow. We conclude that evaporative water loss from the tear meniscus may result in a physiological zone of hyperosmolar and related stresses to the occlusal conjunctiva, directly behind the mucocutaneous junction. We hypothesize that this stimulates a high epithelial cell turnover at this site, incomplete epithelial maturation, and a failure to express key molecules such as MUC 16 and galectin-3, which, with the tight junctions between surface epithelial cells, are necessary to seal the ocular surface and prevent penetration of dyes and other molecules into the epithelium. This is proposed as the basis for Marx's line. In Part II of this paper (also published in this issue of The Ocular Surface), we address additional pathophysiological consequences of this mechanism, affecting lid margins

A solute gradient in the tear meniscus II. implications for lid margin disease, including meibomian gland dysfunction

We have hypothesized previously that evaporation from the tears generates a solute gradient across the tear meniscus, which delivers hyperosmolar stress to the mucocutaneous junction (MCJ) of the lid margin. This is proposed as the basis for Marx's line, a line of staining with topically applied dyes that lies directly behind the MCJ. In this article, we consider the implications of this hypothesis for progressive damage to the lid margin as an age-related phenomenon, its amplification in dry eye states, and its possible role in the etiology of meibomian gland dysfunction (MGD). It is suggested that a hyperosmolar or related stimulus, acting behind the MCJ over a lifetime, promotes the anterior migration of the MCJ, which is a feature of the aging lid margin. This mechanism would be amplified in dry eye states, not only by reason of increased tear molarity at the meniscus apex but also by raising the concentration of inflammatory peptides at this site. This could explain the increased width and irregularity of Marx's line in dry eye. While the presence of stem cells at the lid margin may equip this region to respond to such stress, their depletion could be the basis of irreversible lid margin damage. It is further proposed, given the proximity of the MCJ to the meibomian gland orifices, that the solute gradient mechanism could play a role in the initiation of MGD by delivering hyperosmolar and inflammatory stresses to the terminal ducts and orifices of the glands. By the same token, the presence of a zone of increased epithelial permeability in this region may provide a back door route for the delivery of drugs in the treatment of MGD

A mass and solute balance model for tear volume & osmolarity in the normal and the dry eye

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye.\ud \ud The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity.\ud \ud Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable

Leaky vessels as a potential source of stromal acidification in tumours

Malignant tumours are characterised by higher rates of acid production and a lower extracellular pH than normal tissues. Previous mathematical modelling has indicated that the tumour-derived production of acid leads to a gradient of low pH in the interior of the tumour extending to a normal pH in the peritumoural tissue. This paper uses mathematical modelling to examine the potential of leaky vessels as an additional source of stromal acidification in tumours. We explore whether and to what extent increasing vascular permeability in vessels can lead to the breakdown of the acid gradient from the core of the tumour to the normal tissue, and a progressive acidification of the peritumoural stroma. We compare our mathematical simulations to experimental results found in vivo with a tumour implanted in the mammary fat pad of a mouse in a window chamber construct. We find that leaky vasculature can cause a net acidification of the normal tissue away from the tumour boundary, though not a progressive acidification over time as seen in the experiments. Only through progressively increasing the leakiness can the model qualitatively reproduce the experimental results. Furthermore, the extent of the acidification predicted by the mathematical model is less than as seen in the window chamber, indicating that although vessel leakiness might be acting as a source of acid, it is not the only factor contributing to this phenomenon. Nevertheless, tumour destruction of vasculature could result in enhanced stromal acidification and invasion, hence current therapies aimed at buffering tumour pH should also examine the possibility of preventing vessel disruption

A New Hybrid: Students’ Extensions of Integrated Communication Content

Using Bandura’s (1977) self-efficacy theory, this study examined student perceptions of changes in efficacy and affect toward a variety of communication skills (e.g., interpersonal, writing, visual, public speaking, group collaboration) over a sequence of two hybrid basic course classes. As part of a larger assessment initiative, both quantitative and qualitative data from the first course (n = 793) and the second course (n = 273) were analyzed. Students reported greater affect and efficacy during the second course when compared to the first course. Specifically, students reported six affective changes including expanded knowledge, enhanced collaborative skills, increased openness and acceptance, heightened awareness, increased confidence, and the ability to critically examine. The students referenced observing these changes in academic and work life, but most frequently felt that these skills would impact their everyday life. The results have implications for assignment sequences, incorporating visual communication into the basic course, and requiring two basic courses to maximize affect and efficacy changes in students

Characterization of Secondary Organic Aerosol (SOA) formed by the Reaction of β-caryophyllene, Soot and Ozone: Climate Impact

Diesel soot (black carbon, BC) is an important light absorbing aerosol component in atmosphere that can cause tropospheric heating. Laboratory studies have found it to be unreactive to ozone at ambient temperature. The low uptake coefficient i.e., γ 300 K = 2× 10-7 , of the soot-O3 reaction indicates a low probability of irreversible O3 loss from gas phase to surface-adsorbed product (Particle phase). This shows clearly that at low temperature soot is not reactive with atmospheric oxidants. In contrast, sesquiterpenes (SQT) such as β-caryophyllene (C15H24), which are produced primarily by plants, are extremely reactive with ozone. For example, the residence time of β- caryophyllene in the atmosphere is only 2 min in the presence of 60 ppb ozone. Thus, ozonolysis reaction of β-caryophyllene is expected to be a significant source of biogenic secondary organic aerosols. These oxidized products may condense onto soot particles, and a question arises as to how they will partition between the soot surface, vapor phase, and aqueous aerosol phases. Liquid chromatography- mass spectrometry (LC/MS), Fourier transform infrared (FTIR) and UVVis spectroscopies are being used to study the β- caryophyllene-dark ozonolysis reaction at low ozone levels (40-60 ppb). Products identified include low molecular weight highly volatile and water soluble products such as formaldehyde, acetaldehyde, acetone, and acetic acid. Also identified are high molecular weight components (~350 Dalton) with lower water solubility and vapor pressures. The SOA coatings of these SQTs on soot are being evaluated to determine their hygroscopicity. As these compounds absorb in the IR and UV-Vis they can add to radiative forcing by submicron aerosols and need to be better understood for climate modeling

Comparison of measurements of peroxyacyl nitrates and primary carbonaceous aerosol concentrations in Mexico City determined in 1997 and 2003

International audiencePeroxyacetyl nitrate (PAN) concentrations in ambient air can be a good indicator of air quality and the effectiveness of control strategies for reducing ozone levels in urban areas. As PAN is formed by the oxidation of reactive hydrocarbons in the presence of nitrogen dioxide (NO2), it is a direct measure of the peroxyacyl radical levels produced from reactive organic emissions in the urban air shed. Carbon soot, known as black carbon or elemental carbon, is a primary atmospheric aerosol species and is a good indicator of the levels of combustion emissions, particularly from diesel engines, in major cities. Mexico City is the second largest megacity in the world and has long suffered from poor air quality. Reported here are atmospheric measurements of PAN and black carbon obtained in Mexico City during the Mexico Megacity 2003 field study. These results are compared with measurements obtained earlier during the Investigación sobre Materia Particulada y Deterioro Atmosférico ? Aerosol and Visibility Research (IMADA-AVER) campaign in 1997 to obtain an estimate of the changes in emissions in Mexico City and the effectiveness of control strategies adopted during that time. Concentrations of PAN in 1997 reached a maximum of 34 ppb with an average daily maximum of 15 ppb. The PAN levels recorded in 2003 were quite different, with an average daily maximum of 3 ppb. This dramatic reduction in PAN levels observed in 2003 indicate that reactive hydrocarbon emissions have been reduced in the city due to controls on olefins in liquefied petroleum gas (LPG) and also due to the significant number of newer vehicles with catalytic converters that have replaced older higher emission vehicles. In contrast, black/elemental carbon levels were similar in 1997 and 2003 indicating little improvement likely due to the lack of controls on diesel vehicles in the city. Thus, while air quality and ozone production has improved, Mexico City and other megacities continue to be a major source of black carbon aerosols, which can be an important species in determining regional radiative balance and climate

A roadmap for rapid decarbonization

Although the Paris Agreement's goals (1) are aligned with science (2) and can, in principle, be technically and economically achieved (3), alarming inconsistencies remain between science-based targets and national commitments. Despite progress during the 2016 Marrakech climate negotiations, long-term goals can be trumped by political short-termism. Following the Agreement, which became international law earlier than expected, several countries published mid-century decarbonization strategies, with more due soon. Model-based decarbonization assessments (4) and scenarios often struggle to capture transformative change and the dynamics associated with it: disruption, innovation, and nonlinear change in human behavior. For example, in just 2 years, China's coal use swung from 3.7% growth in 2013 to a decline of 3.7% in 2015 (5). To harness these dynamics and to calibrate for short-term realpolitik, we propose framing the decarbonization challenge in terms of a global decadal roadmap based on a simple heuristic—a “carbon law”—of halving gross anthropogenic carbon-dioxide (CO2) emissions every decade. Complemented by immediately instigated, scalable carbon removal and efforts to ramp down land-use CO2 emissions, this can lead to net-zero emissions around mid-century, a path necessary to limit warming to well below 2°C

Re-defining silence in unvoiced dialogues in storying-play: The sound of affects

This article chronicles three stories selected from a post-intentional phenomenological study conducted by the first author. The authors aim to investigate affective connections in children’s silent play by addressing three research questions:  (a) How do children engage in dialogue with the teacher, their peers, and the material environment without words? (b) What emotions are produced in silent play? and (c) What changes in children’s affective connections occur through silence? We drew on the notion of intentionality in post-intentional phenomenology to illuminate meanings of the phenomenon for individuals about what they felt and experienced. With a focus on intentionality, we delved into the ways children meaningfully communicated with others and connected to the environment in their unspeaking moments. We also took on a posthuman notion of intra-actions to rethink silence as an inaudible yet sensible sound communicated between children and things. The prior studies showed that children’s silence was a mode of expression. Through storying the silent play-stories, we offered two alternative meanings of silence––intra-active communication with people and things and inaudible inner wellbeing, in addition to a mode of nonverbal expression as identified in prior studies. The findings are significant in enriching and renewing our understanding of children’s silence in inclusive ECE environments. Silence is re-defined as a mode of embodied communication and affective connections. This article invites researchers and educators to genuinely “listen” to children’s stories, even in silent play