Opthalmic Teaching Problems: The Ayes Have It

The problems associated with the teaching of ophthalmology to medical students in today\u27s university setting are by no means unique to ophthalmology. However, these problems are more severe in small departments such as ophthalmology and are more disruptive to the teaching process than similar problems in larger departments. The purpose of this paper is to identify some of the more important teaching problems and propose solutions to them

Cogan-Guerry Microcystic Corneal Epithelial Dystrophy: A Clinical and Electron Microscopic Study

In summary, microcystic epithelial dystrophy of the cornea as described by Cogan and Guerry has become a well documented clinical entity. In this paper, a case report and preliminary electron microscopic findings of a patient with this dystrophy were presented. This case showed a thickened, two-layered basement membrane which was completely missing in some areas. The second characteristic change was that of cystic epithelial areas containing debris. The possible significance of these findings and a diagnostic technique for detecting of these corneal changes were discussed

A perpetual switching system in pulmonary capillaries

Of the 300 billion capillaries in the human lung, a small fraction meet normal oxygen requirements at rest, with the remainder forming a large reserve. The maximum oxygen demands of the acute stress response require that the reserve capillaries are rapidly recruited. To remain primed for emergencies, the normal cardiac output must be parceled throughout the capillary bed to maintain low opening pressures. The flow-distributing system requires complex switching. Because the pulmonary microcirculation contains contractile machinery, one hypothesis posits an active switching system. The opposing hypothesis is based on passive switching that requires no regulation. Both hypotheses were tested ex vivo in canine lung lobes. The lobes were perfused first with autologous blood, and capillary switching patterns were recorded by videomicroscopy. Next, the vasculature of the lobes was saline flushed, fixed by glutaraldehyde perfusion, flushed again, and then reperfused with the original, unfixed blood. Flow patterns through the same capillaries were recorded again. The 16-min-long videos were divided into 4-s increments. Each capillary segment was recorded as being perfused if at least one red blood cell crossed the entire segment. Otherwise it was recorded as unperfused. These binary measurements were made manually for each segment during every 4 s throughout the 16-min recordings of the fresh and fixed capillaries (>60,000 measurements). Unexpectedly, the switching patterns did not change after fixation. We conclude that the pulmonary capillaries can remain primed for emergencies without requiring regulation: no detectors, no feedback loops, and no effectors-a rare system in biology. NEW & NOTEWORTHY The fluctuating flow patterns of red blood cells within the pulmonary capillary networks have been assumed to be actively controlled within the pulmonary microcirculation. Here we show that the capillary flow switching patterns in the same network are the same whether the lungs are fresh or fixed. This unexpected observation can be successfully explained by a new model of pulmonary capillary flow based on chaos theory and fractal mathematics

Quantifying and Mitigating Motor Phenotypes Induced by Antisense Oligonucleotides in the Central Nervous System [preprint]

Antisense oligonucleotides (ASOs) are emerging as a promising class of therapeutics for neurological diseases. When injected directly into the cerebrospinal fluid, ASOs distribute broadly across brain regions and exert long-lasting therapeutic effects. However, many phosphorothioate (PS)-modified gapmer ASOs show transient motor phenotypes when injected into the cerebrospinal fluid, ranging from reduced motor activity to ataxia or acute seizure-like phenotypes. The effect of sugar and phosphate modifications on these phenotypes has not previously been systematically studied. Using a behavioral scoring assay customized to reflect the timing and nature of these effects, we show that both sugar and phosphate modifications influence acute motor phenotypes. Among sugar analogues, PS-DNA induces the strongest motor phenotype while 2’-substituted RNA modifications improve the tolerability of PS-ASOs. This helps explain why gapmer ASOs have been more challenging to develop clinically relative to steric blocker ASOs, which have a reduced tendency to induce these effects. Reducing the PS content of gapmer ASOs, which contain a stretch of PS-DNA, improves their toxicity profile, but in some cases also reduces their efficacy or duration of effect. Reducing PS content improved the acute tolerability of ASOs in both mice and sheep. We show that this acute toxicity is not mediated by the major nucleic acid sensing innate immune pathways. Formulating ASOs with calcium ions before injecting into the CNS further improved their tolerability, but through a mechanism at least partially distinct from the reduction of PS content. Overall, our work identifies and quantifies an understudied aspect of oligonucleotide toxicology in the CNS, explores its mechanism, and presents platform-level medicinal chemistry approaches that improve tolerability of this class of compounds

Cholera forecast for Dhaka, Bangladesh, with the 2015-2016 El Nino: Lessons learned

A substantial body of work supports a teleconnection between the El Nino-Southern Oscillation (ENSO) and cholera incidence in Bangladesh. In particular, high positive anomalies during the winter (Dec-Feb) in sea surface temperatures (SST) in the tropical Pacific have been shown to exacerbate the seasonal outbreak of cholera following the monsoons from August to November. Climate studies have indicated a role of regional precipitation over Bangladesh in mediating this long-distance effect. Motivated by this previous evidence, we took advantage of the strong 2015-2016 El Nino event to evaluate the predictability of cholera dynamics for the city in recent times based on two transmission models that incorporate SST anomalies and are fitted to the earlier surveillance records starting in 1995. We implemented a mechanistic temporal model that incorporates both epidemiological processes and the effect of ENSO, as well as a previously published statistical model that resolves space at the level of districts (thanas). Prediction accuracy was evaluated with "out-of-fit" data from the same surveillance efforts (post 2008 and 2010 for the two models respectively), by comparing the total number of cholera cases observed for the season to those predicted by model simulations eight to twelve months ahead, starting in January each year. Although forecasts were accurate for the low cholera risk observed for the years preceding the 2015-2016 El Nino, the models also predicted a high probability of observing a large outbreak in fall 2016. Observed cholera cases up to Oct 2016 did not show evidence of an anomalous season. We discuss these predictions in the context of regional and local climate conditions, which show that despite positive regional rainfall anomalies, rainfall and inundation in Dhaka remained low. Possible explanations for these patterns are given together with future implications for cholera dynamics and directions to improve their prediction for the city

Spectral Typing of Late Type Stellar Companions to Young Stars from Low Dispersion Near-Infrared Integral Field Unit Data

We used the Project 1640 near-infrared coronagraph and integral field spectrograph to observe 19 young solar type stars. Five of these stars are known binary stars and we detected the late-type secondaries and were able to measure their JH spectra with a resolution of R\sim30. The reduced, extracted, and calibrated spectra were compared to template spectra from the IRTF spectral library. With this comparison we test the accuracy and consistency of spectral type determination with the low-resolution near-infrared spectra from P1640. Additionally, we determine effective temperature and surface gravity of the companions by fitting synthetic spectra calculated with the PHOENIX model atmosphere code. We also present several new epochs of astrometry of each of the systems. Together these data increase our knowledge and understanding of the stellar make up of these systems. In addition to the astronomical results, the analysis presented helps validate the Project 1640 data reduction and spectral extraction processes and the utility of low-resolution, near-infrared spectra for characterizing late-type companions in multiple systems.Comment: Accepted to Astronomical Journal, 25 pages, 8 figure

The Freedom Budget at 45: Functional Finance and Full Employment

Forty-five years ago, the A. Philip Randolph Institute issued The Freedom Budget, in which a program for economic transformation was proposed that included a job guarantee for everyone ready and willing to work, a guaranteed income for those unable to work or those who should not be working, and a living wage to lift the working poor out of poverty. Such policies were supported by a host of scholars, civic leaders, and institutions, including the Rev. Dr. Martin Luther King Jr.; indeed, they provided the cornerstones for King's Poor Peoples' Campaign and economic bill of rights. This paper proposes a New Freedom Budget for full employment based on the principles of functional finance. To counter a major obstacle to such a policy program, the paper includes a primer on three paradigms for understanding government budget deficits and the national debt: the deficit hawk, deficit dove, and functional finance perspectives. Finally, some of the benefits of the job guarantee are outlined, including the ways in which the program may serve as a vehicle for a variety of social policies