Myoblast-mediated gene transfer to the joint

Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression. In this study, data were investigated regarding the use of muscle cells as an alternative gene-delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra-articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post-mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post-mitotic myofibers in the knee joint raises the possibility of long-term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene-delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.     

4- and 13-GHz tuned amplifiers implemented in a 0.1-μm CMOStechnology on SOI, SOS, and bulk substrates

Four- and 13-GHz tuned amplifiers have been implemented in a partially scaled 0.1-1 μm CMOS technology on bulk, silicon-on-insulator (SOI), and silicon-on-sapphire (SOS) substrates. The 4-GHz bulk, SOI, and SOS amplifiers exhibit forward gains of 14, 11, and 12.5 dB and F_min's of 4.5 (bulk) and 3.5 db (SOS). The 13-GHz SOS and SOI amplifiers exhibit gains of 15 and 5.3 dB and F_unn's of 4.9 and 7.8 dB. The 4-GHz bulk amplifier has the highest resonant frequency among reported bulk CMOS amplifiers, while the 13-GHz SOS and SOI amplifiers are the first in a CMOS technology to have tuned frequencies greater than 10 GHz. These and other measurement results suggest that it may be possible to implement 20-GHz tuned amplifiers in a fully scaled 0.1-1 μm CMOS process     

Antiretroviral drugs as a public health intervention for pregnant HIV-infected women in rural South Africa: an issue of cost-effectiveness and capacity

OBJECTIVE: To estimate cost-effectiveness and capacity requirements for providing antiretroviral drugs to pregnant HIV-infected women in rural South Africa. SETTING: Hlabisa health district, where HIV prevalence among pregnant women was 26.0% in 1997. METHODS: Calculation of the number of paediatric HIV infections averted under three scenarios, and their cost. No intervention was compared with scenario A (zidovudine delivered within current infrastructure), scenario B (zidovudine delivered through enhanced infrastructure), and scenario C (short-course zidovudine plus lamivudine delivered through enhanced infrastructure). Cost-effectiveness was defined as cost per infection averted and cost per potential life-year gained. Capacity was determined in terms of staff and infrastructure required to effectively implement the scenarios. RESULTS: With no intervention, 657 paediatric HIV infections were projected for 1997. In scenario A this could be reduced by 15% at a cost of US$ 574 825, in scenario B by 42% at US$ 1520770, and in scenario C by 47% at US$ 764901. In scenario C, drugs accounted for 76% of costs, whereas additional staff accounted for 18%. Cost per infection averted was US$ 2492 and cost per potential life-year gained (discounted at 3%) was US$ 88. Cost of scenario C was equivalent to 14% of the 1997 district health budget. At least 12 extra counsellors and nurses and one laboratory technician, together with substantial logistical and managerial support, would be needed to deliver an effective intervention. CONCLUSION: Although antiretrovirals may be relatively cost-effective in this setting, the budget required is currently unaffordable. Developing the capacity required to deliver the intervention would pose both a major challenge, and an opportunity, to improve health services.     

Aliphatic heterocyclic polymers

Aliphatic polybenzoxazoles, polybenzothiazoles, and polybenzimidazoles have been prepared by three methods: in poly(phosphoric acid), by the polyamide precursor, and by melt polymerization. The melt polymerization method was found to be the most satisfactory. All of the aliphatic heterocyclic polymers had excellent thermal stability, resistance to alkaline hydrolysis, high glass transition temperatures, and a high degree of flexibility. The only class of polymer found having any degree of solubility, however, was the polybenzimidazoles. Aliphatic polybenzimidazole films were prepared by solution casting. These films were found to be extremely flexible at ambient and cryogenic temperatures. The films were unaffected by alkaline hydrolysis, even in an oxidizing medium. A molding prepared from the aliphatic polybenzimidazole had excellent physical properties at both cryogenic and room temperature.     

The longitudinal impact of enterprise system users’ pre-adoption expectations and organizational support on post-adoption proficient usage

Although enterprise systems (ES) are ubiquitous, many firms report less than stellar payoffs from these costly investments, with underutilization often attributed to failures in the implementation process. Unfortunately, research has not provided sufficient insights into these failures, in part because it has focused on actual usage, as opposed to proficient usage, as the benchmark for successful implementation. Moreover, research has not generally examined how the adoption process unfolds over time, thus overlooking potential underlying mechanisms that may help explain how adopters achieve proficiency. To begin addressing these shortcomings, we study how adopters’ pre-adoption expectations, enacted over time, can influence their post-adoption proficiency, by shaping how and why they spend time using the system during the adoption period. We analyzed time-lagged survey data from 153 financial analysts, required to adopt new ES-based software, at a multinational bank. We found that adopters who hold pre-adoption expectations reflecting greater internal and external motives to adopt the system as well as systematically integrate it into their work routines are more apt to use the system in ways that enhance their cumulative knowledge of it, and subsequently develop higher levels of proficiency post-adoption. Moreover, greater organizational support enhanced the impact of adopters’ expectations on proficiency, except when their actual use is low in which case organizational support had an adverse effect.     

Transport of the dicyanogold(i) anion

We have shown that dicyanogold(I), [Au(CN)(2)](-) is a common metabolite found in blood and urine samples of patients treated with different gold based drugs. Some patients have high levels of gold within their red blood cells (RBCs). Size exclusion and C18 reversed phase chromatography show that the majority of the gold in RBC lysates is bound to protein, but small molecules such as dicyanogold(I) and gold-glutathione complexes are also present. Dicyanogold incubation with red blood cells in vitro leads to a rapid and complete uptake of gold. This uptake is unaffected by DIDS, an inhibitor of the anion channel, but is blocked by the addition of external cyanide. Dicyanogold is also readily taken up by H9 cells, a continuous CD(4+) cell line. This uptake is significantly inhibited by N-ethylmaleimide, suggesting a requirement for sulfhydryl groups. Dicyanogold inhibits the replication of the AIDS virus, HIV, in a cell culture model.     

A Multi-Criteria Decision Analysis Technique for Stochastic Task Criticality in Project Management

Inherent in project management is the risk that a project fails to meet planned completion deadlines due to delays experienced in individual tasks. As such, certain critical tasks may be candidates for risk management (e.g., the allocation of additional resources such as labor, materials, and equipment) to prevent delays. A common means to identify such critical tasks is with the critical path method (CPM), which identifies a path of tasks in a project network that, when delayed, result in project delays. This work offers a complementary, stochastic approach to CPM that ranks tasks according to their effect on the project completion time distribution, when the distributions of task completion time are delayed. The new hybrid approach is based on the use of a Monte Carlo simulation and a multi-criteria decision analysis technique. Monte Carlo simulation allows for approximating the cumulative distribution function of the total duration of the project, while the multi-criteria decision analysis technique is used to compare and rank the tasks across percentiles of the resulting project completion time distributions. Doing so allows for different percentile weighting schemes to represent decision maker risk preferences. The suggested approach is applied to two project network examples. The examples illustrate that the proposed approach highlights some tasks as risky, which may not always lie on the critical path as identified by CPM. This is valuable for practicing managers as it allows them to properly consider their risk preferences when determining task criticality based on the distribution of project completion time (e.g., emphasizing median vs. upper tail completion time).     

Comparison of methods for selecting personal protective equipment for arc flash hazards

In 1960, a large global chemical company began documenting and implementing requirements for preventing injuries from electric arc flash hazards, including appropriate personal protective equipment (PPE). Methods evolved from requiring a 100% natural fiber long-sleeve shirt for a specific task to a detailed analysis with multiple flame-resistant clothing options. This paper compares the PPE required by these methods, based on hazards analysis in more than 65 manufacturing and laboratory facilities. The total costs for the example company are estimated for each method.