Bone substitutes in orthopaedic surgery: from basic science to clinical practice

Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.     

A Fast and Accurate Technique for Mapping Parallel Applications on Stream-Oriented MPSoC Platforms with Communication Awareness

The problem of allocating and scheduling precedence-constrained tasks on the processors of a distributed real-time system is NP-hard. As such, it has been traditionally tackled by means of heuristics, which provide only approximate or near-optimal solutions. This paper proposes a complete allocation and scheduling framework, and deploys an MPSoC virtual platform to validate the accuracy of modelling assumptions. The optimizer implements an efficient and exact approach to the mapping problem based on a decomposition strategy. The allocation subproblem is solved through Integer Programming (IP) while the scheduling one through Constraint Programming (CP). The two solvers interact by means of an iterative procedure which has been proven to converge to the optimal solution. Experimental results show significant speed-ups w.r.t. pure IP and CP exact solution strategies as well as high accuracy with respect to cycle-accurate functional simulation. Two case studies further demonstrate the practical viability of our framework for real-life applications.     

Reactive Power Adequacy in Distribution Networks with Embedded Distributed Energy Resources

This paper addresses reactive power adequacy problems in distribution networks that include a significant number of distributed energy resources. The voltage profile of the distribution network is analyzed under increasing amounts of generation provided by the distributed energy resources. Both static and dynamic voltage disruption phenomena resulting from increasing distributed generation are described and the need for remedial actions identified. Different reactive power control schemes are then proposed to keep both an appropriate voltage profile and an appropriate voltage stability margin. Finally, an economic appraisal of remedial actions is carried out and the responsible parties identified. Results from a realistic case study are presented and discussed. Conclusions are duly drawn.     

Percutaneous umbilical blood sampling in the management of immune thrombocytopenic purpura during pregnancy

Severe neonatal thrombocytopenia occurs in about 15% of deliveries from women with immune thrombocytopenic purpura (ITP). Conflicting data exist about the real usefulness of percutaneous umbilical blood sampling (PUBS) in evaluating the fetal platelet count. We report successful experience, using PUBS, in the management of 12 pregnant women with ITP.     

An intelligent approach to welding robot selection

In a shipyard where multiple stationary and mobile workcells are employed in the fabrication of components of complex sub-assemblies,efficient operation requires an intelligent method of scheduling jobs and selecting workcells based on optimum throughput and cost. The achievement of this global solution requires the successful organization of resource availability,process requirements,and process constraints. The Off-line Planner (OLP) of the Programmable Automated Weld Systemd (PAWS) is capable of advanced modeling of weld processes and environments as well as the generation of complete weld procedures. These capabilities involve the integration of advanced Computer Aided Design (CAD), path planning, and obstacle detection and avoidance techniques as well as the synthesis of complex design and process information. These existing capabilities provide the basis of the functionality required for the successful implementation of an intelligent weld robot selector and material flow planner. Current efforts are focused on robot selection via the dynamic routing of components to the appropriate work cells. It is proposed that this problem is a variant of the “Traveling Salesman Problem” (TSP) that has been proven to belong to a larger set of optimization problems termed nondeterministic polynomial complete (NP complete). In this paper, a heuristic approach utilizing recurrent neural networks is explored as a rapid means of producing a near optimal, if not optimal, bdweld robot selection.     

Analysis of retinoic acid receptor beta expression in normal and malignant laryngeal mucosa by a sensitive and routine applicable reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay method

We have developed two assays for complete analysis of hemoglobins (Hbs) in the field of hemoglobinopathies: a high-performance cation-exchange liquid chromatography (HPLC) assay on the weak cation-exchanger Poly Cat A and a two-step capillary isoelectric focusing (CIEF) assay on the neutral-coated capillary from Beckman in a narrow pH gradient. The resolution was satisfactory for both HPLC and CIEF and allowed separation of normal and common abnormal Hbs, i.e., Hb A, Hb F, Hb A2, Hb S, Hb C, and Hb E; slight differences were shown for the resolution of unusual variants such as Hb C-Harlem and Hb D-Punjab. The reproducibility of retention times was satisfactory as well for HPLC (CV 3.3%) and CIEF (CV 4.9%). The imprecision of quantification of Hb A2, evaluated at two concentrations, and of Hb F and Hb S was < 5%, except for low concentrations of Hb A2 quantified by CIEF. Quantitative data obtained for these three Hb forms were highly correlated between the two assays. These results suggest that the new CIEF assay can be competitive with HPLC for complete routine analysis of Hb variants.     

Cisplatin nephrotoxicity: a multivariate analysis of potential predisposing factors

STUDY OBJECTIVE: To evaluate the usefulness of biologic and pharmacologic parameters for early identification of cisplatin-induced renal dysfunction. DESIGN: Prospective evaluation of 62 consecutively admitted patients with cancer. SETTING: Cancer center. PATIENTS: Sixty-two consecutive patients with cancer (52 men, 10 women; mean age 61.9 yrs). INTERVENTIONS: Patients received cisplatin as a single short intravenous infusion every 3 weeks. One hundred twenty-one cycles were analyzed. The dosage in the first cycle ranged between 61 and 105 mg/m2 (mean 84 mg/m2). All patients received a standard hydration protocol. MEASUREMENTS AND MAIN RESULTS: Renal function was evaluated for each cycle before treatment (day 0) and before next cycle (day 21) based on the estimated creatinine clearance (Clcr). For each cycle, the weighted relative decrease (WD) of Clcr was calculated (WDClcr = 100 x [Clcr (day 0) - Clcr (day 21)]/[Clcr (day 0)](2). Total and ultrafilterable (UF) platinum were measured as a single-sample assay taken 16 hours after the end of cisplatin administration. The mean WDClcr was 0.07 min/100 ml (range -1.0 to +1.7 min/100 ml). The intensity of renal dysfunction evaluated by WDClcr was independent of cisplatin dosage, age, sex, body surface area, initial Clcr, and cycle number. Of interest, total and UF platinum concentrations were significantly correlated to WDClcr: the higher the platinum concentration, the greater the intensity of renal dysfunction. In stepwise regression analysis, UF platinum concentration was the only selected factor. The best prediction of UF platinum was obtained by stepwise regression including cisplatin dosage, initial Clcr, and cycle number (r=0.58, p<0.0001). CONCLUSION: We consider our results to be a first step toward a clinical strategy to identify patients at risk for renal dysfunction after cisplatin treatment.