51 research outputs found
Assesment [sic] of cement augmentation and screw trajectory on pedicle screw fixation in osteoporotic vertebrae
Internal fixation of osteoporotic spines for fracture or deformity is currently difficult, owing to failure at the bone- implant interface. This study aims to ascertain whether pedicle screw trajectory and pedicle cortex retention can independently significantly affect fixation strength in osteoporotic vertebrae."MU Grant #00029187
Aging infrastructure creates opportunities for cost-efficient restoration of aquatic ecosystem connectivity
A hallmark of industrialization is the construction of dams for water management and roads for transportation, leading to fragmentation of aquatic ecosystems. Many nations are striving to address both maintenance backlogs and mitigation of environmental impacts as their infrastructure ages. Here, we test whether accounting for road repair needs could offer opportunities to boost conservation efficiency by piggybacking connectivity restoration projects on infrastructure maintenance. Using optimization models to align fish passage restoration sites with likely road repair priorities, we find potential increases in conservation return-on-investment ranging from 17% to 25%. Importantly, these gains occur without compromising infrastructure or conservation priorities; simply communicating openly about objectives and candidate sites enables greater accomplishment at current funding levels. Society embraces both reliable roads and thriving fisheries, so overcoming this coordination challenge should be feasible. Given deferred maintenance crises for many types of infrastructure, there could be widespread opportunities to enhance the cost-effectiveness of conservation investments by coordinating with infrastructure renewal efforts
Pet Project or Best Project? Online Decision Support Tools for Prioritizing Barrier Removals in the Great Lakes and Beyond
Structures that block movement of fish through river networks are built to serve a variety of societal needs, including transportation, hydroelectric power, and exclusion of exotic species. Due to their abundance, road crossings and dams reduce the amount of habitat available to fish that migrate from the sea or lakes into rivers to breed. The benefits to fish of removing any particular barrier depends on its location within the river network, its passability to fish, and the relative position of other barriers within the network. Balancing the trade-offs between ecological and societal values makes choosing among potential removal projects difficult. To facilitate prioritization of barrier removals, we developed an online decision support tool (DST) with three functions: (1) view existing barriers at various spatial scales; (2) modify information about barriers, including removal costs; and (3) run optimization models to identify portfolios of removals that provide the greatest amount of habitat access for a given budget. A survey of available DSTs addressing barrier removal prioritization indicates that barrier visualization is becoming widespread but few tools allow dynamic calculation of connectivity metrics, scenario analysis, or optimization. Having these additional functions, our DST enables organizations to develop barrier removal priorities based on
cost-effectiveness in restoring aquatic connectivity
BMQ
BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Sources of professional staff turnover in public accounting firms: Some further evidence
A comparison of V-I-E model predictions: A cross-national study in professional accounting firms
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Session C1: Prioritizing Barrier Removals in Great Lakes Tributaries: Balancing Tradeoffs Between Native and Invasive Fish Species
Abstract
Tributaries to the Great Lakes are highly fragmented by dams and road crossings that act as potential barriers to migratory fishes, restricting their access to historical riverine spawning grounds. There is growing investment in removing or modifying barriers to restore native fish migrations and ecosystem function, but these efforts may also increase available habitat for invasive sea lamprey. The restoration community lacks a systematic method for comparing these costs and benefits to assess which barrier removal projects would offer the greatest return on investment. To address this problem, we developed a basin-scale mathematical optimization model to prioritize barriers for removal on the basis of upstream breeding habitat for both native and invasive fishes. We parameterized the model using an extensive database of dams and road crossings; economic models of projected barrier removal and lampricide application costs; and historical data describing distributions of native and invasive species. We describe trade-offs resulting from increased habitat access for native migratory fishes and sea lamprey that would accompany different barrier removal scenarios. We further discuss the sensitivity of the model to uncertainty in estimates of tributary suitability for native and invasive species and investigate the benefit of simultaneously planning barrier removal and lamprey management actions
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