Photocurable Bioink for the Inkjet 3D Pharming of Hydrophilic Drugs.

Novel strategies are required to manufacture customized oral solid dosage forms for personalized medicine applications. 3D Pharming, the direct printing of pharmaceutical tablets, is an attractive strategy, since it allows for the rapid production of solid dosage forms containing custom drug dosages. This study reports on the design and characterization of a biocompatible photocurable pharmaceutical polymer for inkjet 3D printing that is suitable for hydrophilic active pharmaceutical ingredients (API). Specifically, hyaluronic acid was functionalized with norbornene moieties that, in the presence of poly(ethylene) glycol dithiol, Eosin Y as a photoinitiator, and a visible light source, undergoes a rapid step-growth polymerization reaction through thiol-ene chemistry. The engineered bioink was loaded with Ropinirole HCL, dispensed through a piezoelectric nozzle onto a blank preform tablet, and polymerized. Drug release analysis of the tablet resulted in 60% release within 15 min of tablet dissolution. The study confirms the potential of inkjet printing for the rapid production of tablets through the deposition of a photocurable bioink designed for hydrophilic APIs

From a different angle: A novel approach to health valuation

The value of a health state is typically described relative to the value of an optimal state, specifically as a ratio ranging from unity (equal to optimal health) to negative infinity. Incorporating potentially infinite values is a challenging issue in the econometrics of health valuation. In this paper, we apply a directional statistics approach based on the assumption of wavering preference. Unlike ratio statistics, directional statistics are based on polar coordinates (angle, radius). The range of angles is bounded between 45 degrees (unity) and negative 90 degrees (i.e., negative infinity); therefore, mean angles are well behaved and negate the impetus behind arbitrary data manipulations. Using time trade-off (TTO) responses from the seminal Measurement and Valuation of Health study, we estimate 243 EQ-5D health state values by minimizing circular variance with and without radial weights. For states with published values greater than zero (i.e., better-than-death), the radially weighted estimates are nearly identical to the published values (Mean Absolute Difference 0.07; Lin’s rho 0.94). For worse-than-death states, the estimates are substantially lower than the published values (Mean Absolute Difference 0.186; Lin’s rho 0.576). For the worst EQ-5D state (33333), the published value is -0.59 and the directional estimate is -1.11. By taking a directional statistics approach, we circumvent problems inherent to ratio statistics and the systematic bias introduced by arbitrary data manipulations. The predictions suggest that published estimates overvalue severe states. This paper examines TTO responses; however, it may be extended to all forms of health valuation

Realization of a feedback controlled flashing ratchet

A flashing ratchet transports diffusive particles using a time-dependent, asymmetric potential. Particle speed is predicted to increase when a feedback algorithm based on particle positions is used. We have experimentally realized such a feedback ratchet using an optical line trap, and observed that use of feedback increases velocity by up to an order of magnitude. We compare two different feedback algorithms for small particle numbers, and find good agreement with simulations. We also find that existing algorithms can be improved to be more tolerant to feedback delay times

Valuation of Child Behavioral Problems from the Perspective of US Adults

To assess preferences between child behavioral problems and estimate their value on a quality-adjusted life year (QALYs) scale

Assessment of Stream Restoration Structures in Streams of North-Central Pennsylvania

Interest in stream restoration has increased over the last two decades, leading to a growth in the industry to the point that it has become a 1 billion dollar per year enterprise (Bernhart et al 2005, Thompson 2002). In north-central Pennsylvania alone, over $9 million has been spent since 1999 on stream restoration projects, from the designing stage to actual construction and reconstruction of the sites. Even though a extensive amount of money is being spent on the construction of these projects, very little to no post-monitoring is taking place. Without post-monitoring of the projects, it is unknown if they actually work. After a successful statewide stream restoration assessment was completed in North Carolina by the advisor of this project, it was discussed to undertake a similar one for the state of Pennsylvania starting with the north-central region. This includes Bradford, Cambria, Cameron, Centre, Columbia, Lycoming, McKean, Montour, Northumberland, Potter, Sullivan, Tioga, and Union Counties. Within these 13 counties over 60 restoration projects have been implemented since the 1990s ranging in type from FGM structures to Fish and Boat Commission habitat structures. Twenty-two of the restoration sites comprising of 58,255 feet of restoration work were selected for individual site assessment during March 2008-May 2009. Over 300 structures were assessed during this period of time for structural integrity and the degree to which the adjacent bed and banks had been affected by unintended erosion or deposition. Approximately 75% of the structures have sustained some structural damage (ranking \u3e1) or erosion or deposition (ranking \u3e1). Thirty-five percent of the structures have sustained significant damage (ranking \u3e2) or significant erosion or deposition (ranking \u3e3). Most of the damage (63% of all structures) is related to erosion or deposition which can impact the functionality of the structure. Many of the streams in north-central Pennsylvania are experiencing pulses of aggradation of gravel-cobble size clasts throughout the stream system. This pulse of gravel is contributing to the partial burial of individual structures and may fill in the pool that was created by the structure. Out of the four highly used structure types (cross vanes, j-hooks, log vanes, and rock vanes), j-hooks and rock vanes sustained the highest percentage of damage compared to the other two structures. Much more work needs to be completed in this region before we can fully grasp an understanding for failure of the various structures

Evaluating Bottom-Up and Top-Down Effects on Elk Survival and Recruitment: A Case Study in the Bitterroot Valley

Understanding the contribution of recruitment rates to overall growth rate in ungulate populations is a fundamental challenge in wildlife management. Ungulate populations with low recruitment rates may result in population level declines over time. In the southern Bitterroot Valley of western Montana, the decline of elk (Cervus elaphus) populations and calf recruitment occurred concurrently with wolf (Canis lupus) recovery. However, a multitude of abiotic, bottom-up and top-down factors likely affect recruitment rates and the relative affects of these factors on elk calf survival rate likely vary temporally throughout the first year. We studied cause-specific mortality of elk calves to understand the role of competing mortality risk on calf recruitment in the East Fork and West Fork of the Bitterroot Valley, Montana. A total of 66 neonatal elk calves were captured in spring 2011 and an additional 31 6-month olds in late November2011. We will analyze survival using a Weibull parametric survival model, and cause-specific mortality using a competing risks framework. Preliminary analyses suggest the potential for competing risks between black bears, mountain lions, and wolves. As the study progresses into the second year, we will evaluate the role of summer range nutritional resources on maternal condition, lactation performance, and calf birth weights and survival. Our study will fill a gap regarding the role of summer vs winter mortality in elk and the role of nutrition in first year survival. The study will complement previous studies on elk population dynamics and inform elk population management following carnivore recovery

Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: A review of the National Cancer Database

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival

Anticoagulant rodenticides on our public and community lands: spatial distribution of exposure and poisoning of a rare forest carnivore.

Anticoagulant rodenticide (AR) poisoning has emerged as a significant concern for conservation and management of non-target wildlife. The purpose for these toxicants is to suppress pest populations in agricultural or urban settings. The potential of direct and indirect exposures and illicit use of ARs on public and community forest lands have recently raised concern for fishers (Martes pennanti), a candidate for listing under the federal Endangered Species Act in the Pacific states. In an investigation of threats to fisher population persistence in the two isolated California populations, we investigate the magnitude of this previously undocumented threat to fishers, we tested 58 carcasses for the presence and quantification of ARs, conducted spatial analysis of exposed fishers in an effort to identify potential point sources of AR, and identified fishers that died directly due to AR poisoning. We found 46 of 58 (79%) fishers exposed to an AR with 96% of those individuals having been exposed to one or more second-generation AR compounds. No spatial clustering of AR exposure was detected and the spatial distribution of exposure suggests that AR contamination is widespread within the fisher's range in California, which encompasses mostly public forest and park lands Additionally, we diagnosed four fisher deaths, including a lactating female, that were directly attributed to AR toxicosis and documented the first neonatal or milk transfer of an AR to an altricial fisher kit. These ARs, which some are acutely toxic, pose both a direct mortality or fitness risk to fishers, and a significant indirect risk to these isolated populations. Future research should be directed towards investigating risks to prey populations fishers are dependent on, exposure in other rare forest carnivores, and potential AR point sources such as illegal marijuana cultivation in the range of fishers on California public lands