Antimicrobial Resistance (AMR) and Multidrug Resistance (MDR): Overview of Current Approaches, Consortia and Intellectual Property Issues

The supply of new diagnostics and treatments is insufficient to keep up with the increase in antimicrobial resistance (AMR) and multidrug resistance (MDR) as older medicines are used more widely and microbes develop resistance to them. At the same time, significant quantities of antibiotics are used on patients and animals that do not need them, while others who do need them lack access. Effective responses to AMR/MDR require effort by both the public and private sectors to develop and disseminate new diagnostics, vaccines and treatments on a global scale, as well as to adapt them to local needs. This calls for good governance to identify priorities, raise awareness and ensure effective stewardship at global, regional and national levels to minimize the development of resistance. Failure to act appropriately in one country will adversely impact all countries as resistance travels fast. Based on a review of recent literature, this WIPO Global Challenges Report includes a broad overview of current approaches and consortia designed to meet the challenge of research and development (R&D) investment for new treatments. It also examines patent applications by both the public and the private sectors as an indicator of innovative activity. This report finds that there is a need to address the unique market challenges and specific uncertainties associated with the development of new diagnostics and treatments, where current approaches are not optimal. An effective global framework that achieves the necessary political support while ensuring effective local implementation is crucial. There is an opportunity to complement this work by formulating mechanisms that drive innovation for results to incentivize success, while feeding expertise and experience into stewardship and access efforts. Intellectual property (IP) could be used in a constructive manner as one element in any reward or prize system for AMR/MDR R&D – both in terms of providing an incentive and governance

A User Study of the Hunter College Library Online Catalog System

Discusses the online catalog at the main Hunter College Library

An investigation of the fluorescence emitted by arterial intimas during irradiation by a XeCl excimer laser

Laser angioplasty of occluded arteries has been limited by the unacceptably high rate of vessel wall perforation. To overcome this limitation, fluorescence spectroscopy of arterial wall tissue has been proposed as a technique to discriminate between normal and atherosclerotic arteries and thereby prevent arterial wall perforation during laser angioplasty

Inactivity/sleep in two wild free-roaming African elephant matriarchs - Does large body size make elephants the shortest mammalian sleepers?

The current study provides details of sleep (or inactivity) in two wild, free-roaming African elephant matriarchs studied in their natural habitat with remote monitoring using an actiwatch subcutaneously implanted in the trunk, a standard elephant collar equipped with a GPS system and gyroscope, and a portable weather station. We found that these two elephants were polyphasic sleepers, had an average daily total sleep time of 2 h, mostly between 02:00 and 06:00, and displayed the shortest daily sleep time of any mammal recorded to date. Moreover, these two elephants exhibited both standing and recumbent sleep, but only exhibited recumbent sleep every third or fourth day, potentially limiting their ability to enter REM sleep on a daily basis. In addition, we observed on five occasions that the elephants went without sleep for up to 46 h and traversed around 30 km in 10 h, possibly due to disturbances such as potential predation or poaching events, or a bull elephant in musth. They exhibited no form of sleep rebound following a night without sleep. Environmental conditions, especially ambient air temperature and relative humidity, analysed as wet-bulb globe temperature, reliably predict sleep onset and offset times. The elephants selected novel sleep sites each night and the amount of activity between sleep periods did not affect the amount of sleep. A number of similarities and differences to studies of elephant sleep in captivity are noted, and specific factors shaping sleep architecture in elephants, on various temporal scales, are discussed

Numerical Simulation of UVA Ramjet/Scramjet Hypersonic Engine with Hydrogen-Air Combustion Using Wind-US

The internal flowpath of University of Virginia\u27s Mach 5, direct-connect, dual-mode scramjet engine was simulated using Wind-US, a density-based Reynolds-Averaged Navier-Stokes flow solver. Detailed flowfield simulation results are directly compared to experimental data to evaluate the accuracy of the numerical model and to provide insight into the flowfield behavior. Four hydrogen-air reaction mechanisms were initially assessed using the Burrows-Kurkov case. An Evans-Schexnayder, 7-specie, 8-reaction set with third body efficiencies was then selected for the scramjet simulations. The scramjet simulations included one fuel-off case and two reacting cases with different equivalence ratios, all with clean, non-vitiated air supply. The strong sensitivity of the simulation results to the choice of turbulent Schmidt number is demonstrated. For low equivalence ratio, excellent agreement with experimental data is achieved. For high equivalence ratio, the results agree with that of experiment, however, this case shows large numerical and combustion instabilities

Aspects of the neuroanatomy and physiology of sleep in African mole rats

Ph.D., Faculty of Science, University of the Witwatersrand, 2011Mole rats are a unique family of the rodent order and are known for a subterranean lifestyle, reduced eye size, regressed visual system and unusual patterns of circadian rhythmicity (co-existence of rhythmic and arrhythmic chronotypes within a species has been documented). Such dramatic changes especially that of phenotype, may lead to the prediction of significant differences in organisation of the brain and physiology, therefore these unusual phenotypic features form the core rationale providing the impetus for the present series of studies. Neuroanatomical examination of the mole rat brain for immunohistochemical markers of the cholinergic, catecholaminergic, serotonergic, orexinergic, and histaminergic systems revealed neuronal organisation that was remarkably similar to those previously reported in other rodents and mammals, despite the notable differences in lifestyle and phenotype. These results indicate a strong phylogenetic constraint acting at the systems level of neuronal organisation. The study of sleep and wake in rhythmic and arrhythmic chronotypes of a species of mole rat indicated the arrhythmic chronotype spent more time awake with a longer average duration of a waking episode and less time in sleep with a shorter average duration of a SWS episode. While remaining somewhat similar between mole rat chronotypes, total sleep time in the mole rats was significantly reduced in comparison to other rodents. These results also indicate independence of circadian rhythmicity and sleep homeostasis and possible alteration of specific genes involved in the sleep-wake cycle of the mole rats examined. Stereological assessment of absolute numbers of orexinergic neurons revealed that the arrrhythmic chronotype tends to have more orexinergic neurons per gram of body mass that the rhythmic chronotype, leading to the conclusion that enhanced vigilance and peripheral metabolism of the arrhythmic chronotype may underlie this difference. Immunohistochemical identification of nuclei involved with the sleep-wake cycle, showed no difference in the distribution of these nuclei between circadian chronotypes and no major differences when compared to other rodents. Some interesting and potentially functionally important homogeneities were observed in the distribution of GABAergic interneurons within the pontine region. Furthermore differential orexinergic terminal network densities were observed between chronotypes within the arcuate nucleus and the intergeniculate leaflet. Therefore despite unusual features in lifestyle and phenotype, the organisation of the mole rat brain remains remarkably similar to other rodents; however, distinctions of circadian chronotype consistently produced subtle differences in both the anatomy and physiology of these rodents

Multivariate Extreme Value Theory with an application to climate data in the Western Cape Province

An understanding of past and current weather conditions can aid in identifying trends and changes that have occurred in weather patterns. This is particularly important as certain weather conditions can have both a positive and a negative impact on various activities in any region. Together with an ever-changing climate it has become markedly noticeable that there is an upward trend in extreme weather conditions. The aim of this study is to evaluate the efficacy of univariate and multivariate extreme value theory models on climate data in the Western Cape province of South Africa. Data collected since 1965 from five weather stations viz. Cape Town International Airport, George Airport, Langebaanweg, Plettenberg Bay and Vredendal was modelled and analysed. In the multivariate analysis, multiple variables are modelled at a single location. Block maxima, threshold excess and point process approaches are used on the weather data, specifically on rainfall, wind speed and temperature maxima. For the block maxima approach, the data is grouped in n-length blocks and the maxima of each block form the dataset to be modelled. The threshold excess and point process approaches use a suitably chosen threshold whereby observations above the threshold are considered as extreme and therefore form the dataset used in the models. Under the threshold excess approach, only observations that exceed the threshold in all components are able to be modelled, whereas exceedances in one and all components simultaneously can be handled by the point process approach. While the probability of experiencing high levels of rainfall, wind speed and temperature individually and jointly are low, a few conclusions were drawn based on the comparison of the performance of the models. It was found that models under the block maxima approach did not perform well in modelling the weather variables at the five stations in both the univariate and multivariate case as many useful observations are discarded. The threshold excess and point process approaches performed better in modelling the weather extremes. Similar results are achieved between these two approaches in the univariate analysis and there is no outright distinction that favours one approach over the other. In terms of the multivariate case, which is restricted to two variables, the point process approach was able to provide estimates with increased accuracy as in many cases there are more extremes in one component individually than in both components. Specifically, the negative logistic and negative bilogistic models suitably capture the dependence structure between maximum wind speed versus maximum rain- fall and maximum wind speed versus maximum temperature at the five weather stations. The results from the point process models showed very weak dependence between wind speed and rainfall maxima as well as between wind speed and temperature maxima which may warrant the inclusion of additional variables into the analysis and even a spatial component which is not included in this study

Sociality Affects REM Sleep Episode Duration Under Controlled Laboratory Conditions in the Rock Hyrax, Procavia capensis.

The rock hyrax, Procavia capensis, is a highly social, diurnal mammal. In the current study several physiologically measurable parameters of sleep, as well as the accompanying behavior, were recorded continuously from five rock hyraxes, for 72 h under solitary (experimental animal alone in the recording chamber), and social conditions (experimental animal with 1 or 2 additional, non-implanted animals in the recording chamber). The results revealed no significant differences between solitary and social conditions for total sleep times, number of episodes, episode duration or slow wave activity (SWA) for all states examined. The only significant difference observed between social and solitary conditions was the average duration of rapid eye movement (REM) sleep episodes. REM sleep episode duration was on average 20 s and 40 s longer under social conditions daily and during the dark period, respectively. It is hypothesized that the increase in REM sleep episode duration under social conditions could possibly be attributed to improved thermoregulation strategies, however considering the limited sample size and design of the current study further investigations are needed to confirm this finding. Whether the conclusions and the observations made in this study can be generalized to all naturally socially sleeping mammals remains an open question