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This systematic literature review aims to examine the different immersive technologies used to support autistic groups and determine the degree to which designers and researchers have taken into account the views and perspectives of autistic groups in the design and execution of related immersive learning research studies.

Objective: To evaluate the safety and efficacy of Cellular Matrix™, a new medical device designed for one-step preparation of platelet-rich plasma in presence of hyaluronic acid, for the management of tibiofemoral knee osteoarthritis in patients who had failed to respond adequately to previous treatment with hyaluronic acid alone. Methods: Multicentre, open-label, uncontrolled, pilot study in 77 patients with grade II or III knee osteoarthritis and a pain at walking score between 3 and 8 on a Numeric Rating Scale. The treatment consisted of a series of 3 intra-articular injections scheduled at D0, D60 and D180 into the affected knee of a combination of platelet-rich plasma and hyaluronic acid prepared with the device Cellular Matrix. The primary efficacy criterion was the variation of pain at walking, as assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (A1 score) between baseline and D270. Results: Treatment with the combination of platelet-rich plasma and hyaluronic acid prepared with Cellular Matrix significantly reduced pain at walking between baseline and D270. The percentage of responders according to the criteria of the Outcome Measures in Rheumatology Clinical Trial and Osteoarthritis Research Society International was 94.4%. The treatment provided long-lasting benefits for half of the patients and allowed avoiding surgery for almost 80% of them at four years. Conclusion: A 3-injection course of a combination of platelet-rich plasma and hyaluronic acid prepared with Cellular Matrix was well tolerated and effective in the long-term to relieve pain associated with symptomatic knee osteoarthritis.

Objective: To analyze the potential modulatory effect of Cellular Matrix, a new medical device designed for the one-step preparation of platelet-rich plasma in presence of hyaluronic acid, on the structure of articular cartilage in patients suffering from knee osteoarthritis using high-field Magnetic Resonance Imaging measurements of longitudinal relaxation time after gadolinium injection. Methods: The treatment consisted of a series of 3 intra-articular injections scheduled at D0, D60 and D180 into the affected knee of six patients with Kellgren-Lawrence grades of 1.5 to 3. Magnetic Resonance Imaging acquisitions were performed before the first injection at D0 (baseline), at D180 (just after the third injection) and at D270 (3 months after the third injection). The efficacy criterion was the variation of T1 relaxation time in different selected cartilage regions. Results: Our study reveals a positive" time-dependent" structural effect of the combination of PRP and HA obtained with Cellular Matrix on the proteoglycan content of the knee joint cartilage. At D180, the weight-bearing areas were involved in two patients with Kellgren-Lawrence grades equal to or greater than 2. At D270, 5 patients showed an initial improvement in the weight-bearing area; only one patient with early external femoropatellar osteoarthritis (with a Kellgren-Lawrence grade of 1.5) had no improvement. Conclusion: This pilot study demonstrates for the first time the modulatory effect on the structure of the knee joint cartilage of a combination of platelet-rich plasma and hyaluronic acid prepared with a specially dedicated medical device (Cellular Matrix) during the course treatment. Cellular Matrix could therefore be considered a Disease Modifying Osteoarthritis Device.

Purpose: Therapeutic evaluation of all-in-one intra-articular (IA) injections of autologous platelet rich plasma (PRP) combined with hyaluronic acid (HA) for knee degenerative disorders. Material and methods: The protocol consisted in one or three IA injections, generally ultrasound guided, of a combination of PRP and HA prepared with the innovative Cellular Matrix device (CM-PRP- HA) on three cohorts of patients: A first cohort of 202 patients with meniscal lesions, comprising 93 patients with grade II or III stable meniscal tear, 59 patients after meniscal suture and 50 patients with meniscal cyst, a second cohort of 20 patients with Grade II or III osteoarthritis (OA) and a third cohort of 40 patients presenting post traumatic bone marrow edema (BME) comprising 20 patients with post-traumatic algodystrophy (PTA) and 20 patients with post-traumatic osteoarthritis (PTOA). The International Knee Documentation Committee (IKDC) subjective knee score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale as well as magnetic resonance imaging (MRI) and ultrasounds were used to assess results. Results: Patients with meniscal lesion were treated with one injection of CM-PRP-HA. The follow up evaluation was done after one year. Significant improvement in the IKDC score (79.6/100 vs. 42/100 before treatment) was observed for patients with meniscal tears. Patients with meniscal suture presented no failure, while the success rate for patients treated for meniscal cysts was 70%. Patients with degenerative OA received 3 IA injections of CM-PRP-HA at day 0, at 2 months and at 6 months. Significant difference in the WOMAC pain scale was observed during the final evaluation at 9 months compared with value at day 0 (2.45 vs. 5.65). Patients presenting post traumatic bone marrow edema were treated with one IA injection of CM-PRP-HA and evaluated after one month. The pain score decreases from 8 to 4 for PTA and PTOA patients. This result was correlated with a reduction of bone marrow edema observed with MRI. Conclusions: The Cellular Matrix device has been designed to prepare intra-articular injections of a combination of PRP and HA for symptomatic treatment of articular pain and mobility improvement, essentially for patient suffering from knee OA. In this study, other indications for this innovative treatment are also proposed. CM-PRP-HA appears to be a more efficient alternative to visco-supplementation with HA for the symptomatic treatment of knee articular disorders, including pain reduction and increase of knee functionality for patients suffering of osteoarthritis, post traumatic bone marrow edema, meniscal tears, healing of meniscal suture and size reduction of meniscal cysts. Further investigations will determine the optimal frequency of IA injections with CM-PRP-HA, and whether this innovative product would represent not only a conservative treatment for various knee articular disorders but also a preventive treatment for OA, thus delaying the need for knee surgery.

Long-acting parenteral formulations of antiretrovirals could facilitate maintenance and prophylactic treatment in HIV. Using the poorly water- and oil-soluble non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 (rilpivirine) as base or hydrochloride (HCl), nanosuspensions were prepared by wet milling (Elan NanoCrystal technology) in an aqueous carrier. Laser diffraction showed that the average particles size were (1) close to the targeted size proportionality (200-400-800 nm), with increasing distributions the larger the average particle size, and (2) were stable over 6 months. Following single-dose administration, the plasma concentration profiles showed sustained release of TMC278 over 3 months in dogs and 3 weeks in mice. On comparison of intramuscular and subcutaneous injection of 5mg/kg (200 nm) in dogs, the subcutaneous route resulted in the most stable plasma levels (constant at 25 ng/mL for 20 days, after which levels declined slowly to 1-3 ng/mL at 3 months); 200 nm nanosuspensions achieved higher and less variable plasma concentration profiles than 400 and 800 nm nanosuspensions. In mice, the pharmacokinetic profiles after a single 20mg/kg dose (200 nm) were similar with two different surfactants used (poloxamer 338, or d-alpha-tocopheryl polyethylene glycol 1000 succinate). In conclusion, this study provides proof-of-concept that 200-nm sized TMC278 nanosuspensions may act as long-acting injectable.

The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice-daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects were randomly assigned to receive 3 consecutive 4-day regimens of tipifarnib with different treatment sequences: a 100-mg 2-hour intravenous infusion, 200-mg oral administration twice daily, and a 200-mg/d continuous intravenous infusion. The systemic exposure to tipifarnib was comparable among these 3 regimens. The plasma concentration-time profile of 2-hour intravenous infusion more closely resembled the oral administration than did the continuous infusion. Glucuronidation is a metabolic pathway for tipifarnib with concentrations of the glucuronide conjugate greatly exceeding the parent compound after oral and intravenous administration. Analysis of plasma metabolites indicated that tipifarnib also undergoes dealkylation and loss of the imidazole group.

The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-beta-cyclodextrin (HPbetaCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPbetaCD. After pH adjustment, the itraconazole/HPbetaCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPbetaCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.

A self aligned complementary HIGFET technology has been developed for high speed/low power digital and microwave analog applications. The process uses 9 lithographic steps including two level of interconnect metal. Typical transconductances of 290 mS/mm and 65 mS/mm are acheived on lum gate length N and P-channel devices respectively. 0.5 um gate length N-HIGFET show a Ft of 40 GHz and an intrinsic Fc of 80 GHz. These devices show promise for incorporation in complementary digital, MMIC and RF power circuits.

We consider the effects of slowly varying depth and current on the evolution of a packet of Stokes waves. The lengthscale of one-dimensional depth variation is assumed to be much greater than that of the wave envelope, and the direction of the current is perpendicular to the depth contours. By the method of multiple scales, the wave envelope is found to satisfy a cubic Schrödinger equation with slowly varying coefficients The criterion of spatial instability to small sidebands is extended. Numerical integration shows that the nonlinear evolution of a wavepacket is directly related to the instability parameter, which depends strongly on the current and depth variation. The heuristic hypothesis of Djordjevic & Redekopp on the soliton evolution over a slope in the absence of current is assessed.

The present invention concerns novel formulations comprising an antifungal agent having a low solubility in aqueous media, a process for preparing said formulations and pharmaceutical dosage forms comprising said novel formulations for nasal administration.