Targeting CYP51 in the treatment of Acanthamoeba keratitis

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially fill that gap. The most common EBIs are of the azole drug class, which inhibit CYP51 (sterol 14α-demethylase). This study reviews the clinical usage of azole inhibitors of CYP51 in the management of Acanthamoeba keratitis. Keywords: Amoebic keratitis, Cornea, Ergosterol biosynthesis inhibitors, Eukaryotic pathogen, Eye infectio

Sex Differences in Collateral Circulation and Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke

Background: Collateral circulation is known to lead to smaller infarct volume and better functional outcome after mechanical thrombectomy (MT), but studies examining sex differences in collateral circulation are scarce. The aim of this study was to investigate if collateral circulation has a different impact on outcome in women and men.Methods: A single-center retrospective study of 487 patients (230 men and 257 women) treated with MT for acute ischemic stroke in the anterior cerebral circulation. Collateral circulation was assessed on computed tomography angiography images. The outcome was evaluated at 90 days according to the modified Rankin Scale (mRS).Results: Women were older, median age 76 years (IQR 68-83) vs. 71 years (IQR 63–78). Stroke severity and time to recanalization were comparable. More women had moderate or good collaterals in 58.4 vs. 47.0% for men (p = 0.01). Among patients with moderate and good collaterals significantly more men (61%) were functionally independent (mRS 0–2) than women (41.5%) (p = < 0.01). This difference remained significant after correcting for age by linear weighting, 60.4 vs. 46.8% (p = 0.03).Conclusion: Women had better collateral flow but showed worse functional outcomes, while good collateral flow led to better outcomes in men, even after correcting for age. Further clinical studies on peri- and post-interventional care, factors affecting recovery after hospital discharge as well as basic research on the neurovascular unit are needed to find modifiable targets to improve clinical outcomes for women

Multi-objective time-cost optimization using Cobb-Douglas production function and hybrid genetic algorithm

 Existing research on construction time-cost tradeoff issues rarely explore the origin of the crashing cost. Crashing cost function was either assumed without much justification, or came from historical data of some real pro­jects. As a result the conclusions of the papers can hardly be used to guide allocations of labor and equipment resources respectively. The authors believe Cobb-Douglas function provides a much-needed piece to modeling the cost functions in the construction time-cost tradeoff problem during the crashing process. We believe this new perspective fills a gap of existing time-cost tradeoff research by considering project duration, labor and equipment cost as parameters of the Cobb- Douglas production function. A case study was presented to show how the proposed framework works. Our conclusion is that introducing Cobb-Douglas function into time-cost tradeoff problem provides us extra capacity to further identify the optimal allocations of labor and equipment resources during crashing

Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing

Pain is a prevalent symptom of Parkinson's disease, and is effectively treated by deep brain stimulation of the subthalamic nucleus (STN). However, the link between pain and the STN remains unclear. In the present work, we report that STN neurons exhibit complex tonic and phasic responses to noxious stimuli using in vivo electrophysiology in rats. We also show that nociception is altered following lesions of the STN, and characterize the role of the superior colliculus and the parabrachial nucleus in the transmission of nociceptive information to the STN, physiologically from both structures and anatomically in the case of the parabrachial nucleus. We show that STN nociceptive responses are abnormal in a rat model of PD, suggesting their dependence on the integrity of the nigrostriatal dopaminergic system. The STN-linked nociceptive network we reveal is likely to be of considerable clinical importance in neurological diseases involving a dysfunction of the basal ganglia

Applications of Cobb-Douglas Production Function in Construction Time-Cost Analysis

Cobb-Douglas Production Function was widely used in economics and productivity studies across many sectors. The function’s quantitative modeling of resource inputs and production outputs is appealing to the research domain of construction management. In this thesis we explored this function’s application in construction schedule crashing and project risk analysis related to duration of construction projects. Existing research on construction time-cost tradeoff issues rarely explore the origin of the crashing cost which is defined as the cost needed to shorten the project to the desired duration. In the existing literature crashing cost function was either assumed without much justification, or came from ad-hoc regression analysis of historical data of some actual projects. Cobb-Douglas production function, which defines the portion of labor and equipment needed based on the production rate, provides a much-needed piece to modeling the cost functions in the construction time-cost tradeoff problem during the schedule crashing process. This new perspective fills a gap of existing time-cost tradeoff research by considering project duration, labor and equipment cost as parameters of the Cobb-Douglas production function. A case study was presented to show how the proposed framework works. Case results are presented based on deterministic values of Cobb-Douglas function’s parameters (and ). Presented results show each of labor and equipment’s portion in total cost. Here, more than that we had earlier, we can analyze different options based on just one of these factors to find the optimum solution. Not only, the total labor and total equipment cost of a project is available, labor and equipment cost of each activity’s option can be calculated and compared with other options. After that, sensitivity analysis on the mentioned parameters was conducted to further explore the model’s sensitivities to these parameters. Inflation factors in labor and equipment cost were incorporated in the sensitivity analysis based on assumed costs’ fluctuation range. The results show that the total cost highly depends on the summation of and . The conclusion of the thesis is that utilizing Cobb-Douglas production function in construction crashing cost analysis expands our understanding of crashing cost sources and the portion of each of elements. Moreover, from sensitivity analysis results, it is concluded that labor and equipment efficiencies have significant effects on total cost of a project. Cost inflation analysis makes managers aware of uncertain market which influences total cost and duration of a project. Advisor: Zhigang She

Same, But Different: Testing Government Expenditure Shock Measures

In this study we test whether different government expenditure innovation measures proposed in the literature are good proxies for government spending shocks. We compare five government spending shock measures: forecast error of survey of professional forecasters (SPF), forecast error of forecast of Federal Reserve published in Greenbook (GB), military news, Fisher-Peters measure, Ben Zeev-Pappa measure. To compare these measures, we utilize the reliability estimator of a proxy, R², and F statistics which are proposed by [1]. We find that SPF and GB constitute the best proxy variable for government spending shocks with regard to different reliability estimators. SPF and military news proxies have the highest multipliers comparing to the others. Their both multipliers are greater than 1. Multiplier for Ben Zeev-Pappa and Fisher-Peters measures are less than zero. GB also has a positive multiplier but less than one

Post-Acute Care Facilities: Capacity Planning and Selection Procedure

Health care services received after discharge from an acute care are called post-acute care (PAC). These services improve patient functioning and help patients for better transition from hospitals to the community. PAC can be delivered in different settings such as long-term care (LTC). LTC is vital for people with functional limitations. In the U.S., most LTC is financed by state Medicaid programs. These are administered by states and jointly financed with state and federal funding. There are two main types of LTC delivery: institutionalized care, dominated by the nursing home industry (NHC), and outpatient care, provided through home and community based organizations (HCBS). HCBS is primarily funded through Medicaid “waiver” programs that allow states to allocate some LTC funding to non-institutionalized settings. While HCBS is the less costly option, participation is limited by capacity shortages, and many state waiver programs have long waiting lists. As the population ages, the demand for LTC is projected to grow significantly, and thus HCBS capacity problems constitute a significant policy concern. This work investigates this by formulating a bi-level stochastic game model in which a Medicaid program (the leader) specifies the size of its waiver program, and then HBCS organizations (the followers) respond by specifying their capacity, with LTC service demand being uncertain. We characterize the problem and design an approximation algorithm that exploits a piecewise linear function for computing the followers’ response function to the leader’s decision. We use a case study based on data from the state of Texas. Another important question in PAC studies is how to select the best providers. In addition, it is vital to determine the factors that play roles in this decision making procedure. Acute care managers are always looking for the best PAC providers, while they are willing not to pay too much. In order to determine a set of best PAC’s, a multi-objective decision making approach is developed for Post-Acute Care Provider (PACP) selection. PCAP selection, similar to other subcontracting problems, depends on multiple criteria. Besides the cost metrics, considering service coverage requirements, readmission rate, and service quality make the decision making more complicated. The proposed approach provides the decision making procedure for acute care providers subcontracting with PAC providers. This approach includes two phases. In the first phase, providers are evaluated and assigned a comparable value based on a set of criteria. These quality metrics are used to calculate closeness coefficients of each candidate PACP for both short-stay and long-stay patients. These patient categories are determined by the Medicaid. In the second phase, using the computed coefficients, we develop a multi-objective problem that considers cost, service quality, and readmission to the hospital as objectives. The novelty of this procedure is introducing a new view toward the provider selection problem. The proposed approach is implemented for the PACP selection problem in the city of Houston, TX

MULTI-OBJECTIVE TIME-COST OPTIMIZATION USING COBB-DOUGLAS PRODUCTION FUNCTION AND HYBRID GENETIC ALGORITHM

Existing research on construction time-cost tradeoff issues rarely explore the origin of the crashing cost. Crashing cost function was either assumed without much justification, or came from historical data of some real projects. As a result the conclusions of the papers can hardly be used to guide allocations of labor and equipment resources respectively. The authors believe Cobb-Douglas function provides a much-needed piece to modeling the cost functions in the construction time-cost tradeoff problem during the crashing process. We believe this new perspective fills a gap of existing time-cost tradeoff research by considering project duration, labor and equipment cost as parameters of the Cobb- Douglas production function. A case study was presented to show how the proposed framework works. Our conclusion is that introducing Cobb-Douglas function into time-cost tradeoff problem provides us extra capacity to further identify the optimal allocations of labor and equipment resources during crashing