Механізми вдосконалення управління інноваційною діяльністю в умовах економічної нестабільності

Розглядаються особливості глобально-постіндустріального розвитку. Досліджено методичні основи системи моніторингу, прогнозування, планування і забезпечення реалізації інноваційної діяльності та головні засади механізму її функціонування.Peculiarities of the global post-industrial development are reviewed. Methodical fundamentals of the system for monitoring, forecasting, planning and provision of innovation activity implementation and main principles of its functioning mechanisms are reviewed

Phenylbutazone in the horse: a review

Phenylbutazone is an acidic, lipophilic, nonsteroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, y-hydroxyphenylbutazone and y-hydroxyoxyphenbutazone. account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE?. It appears to act on prostaglalidin-H synthase and prostacyclin synthase, after conversion by prostaglandin-H synthase to reactive intermediates. It markedly reduces prostanoid-dependent swelling, edema, erythema, and hypersensitivity to pain in inflamed tissues. Its principal use in the horse is for treatment of soft tissue inflammation. Phenylbutazone is highly bound (\u3e 98%) to plasma protein. After i.v. injection, blood levels decline with an elimination half-life of 3-10 h. The plasma kinetics of phenylbutazone may be dose dependent, with the plasma half-life increasing as the drug dosage level increases. Plasma residues of the drug at 24 h after a single i.v. dose of 2 g/450 kg average about 0.9 pg/ml, but considerable variation occurs. If dosing is repeated, the plasma residue accumulates to give mean residual blood levels of approxiniately 4.5 pg/ml on Day 5 after 4 days of dosing. Approximately similar blood levels are found after a combination of oral and i.v. dosing. Experiments on large numbers of horses in training have been undertaken to ascertain the population distributions of residual blood levels after such dosing schedules. Absorption of phenylbutazone from the gastrointestinal tract is influenced by the dose administered and the relationship of dosing to feeding. Access to hay can delay the time of peak plasma concentration to 18 h or longer. Under optimal conditions, the bioavailability of oral phenylbutazone is probably in the region of 70%. Paste preparations may be more slowly absorbed than other preparations and yield higher residual plasma levels at 24 h after dosing, but further controlled studies are required. Phenylbutazone is easily detected in the plasma and urine of horses but concentrations in saliva are low. It is quantitated for forensic purposes by HPLC. The variability of this method between laboratories is about k 25%. Increasing urinary pH increases the urinary concentration of phenylbutazone and its metabolites up to 200-fold. However, urinary pH has little effect on the plasma half-life of phenylbutazone, which is determined mainly by hepatic metabolism and possibly by biliary secretion. Phenylbutazone has a narrow therapeutic index in the horse. If the administered dose is greater than recommended by the manufacturer, toxic effects may be produced, especially if high dose administration is maintained for more than a few days. Signs of toxicity include anorexia, depression, oral and GI ulcers, plasma protein losing enteropathy, and death from shock. Other side-effects include toxic neutropenia, hepatotoxicity and renal papillary necrosis; the latter may occur if access to water is restricted. If phenylbutazone is withdrawn in the early stages of toxicity, the prognosis is good. Late withdrawal is associated with delayed recovery. Death may occur up to 50 days after withdrawal of the drug. This toxicity can be antagonized by administration of prostaglandins

Novel adaptive beam-dependent margins for additional OAR sparing.

Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Unfortunately, whilst the use of margins can increase the probability that sufficient dose is delivered to the CTV, it can also result in delivering high dose of radiation to surrounding organs at risk (OARs). We expand on our previous work on beam-dependent margins and propose a novel adaptive margin concept, where margins are moulded away from selected OARs for better OAR-high-dose sparing, whilst maintaining similar dose coverage probability to the CTV. This, however, comes at a cost of a larger irradiation volume, and thus can negatively impact other structures. We investigate the impact of the adaptive margin concept when applied to prostate radiotherapy treatments, and compare treatment plans generated using our beam-dependent margins without adaptation, with adaption from the rectum and with adaptation from both the rectum and bladder. Five prostate patients were used in this planning study. All plans achieved similar dose coverage probability, and were able to ensure at least 90% population coverage with the target receiving at least 95% of the prescribed dose to [Formula: see text]. We observed overall better high-dose sparing to OARs that were considered when using the adapted beam-dependent PTVs, with the degree of sparing dependent on both the number of OARs under consideration as well as the relative position between the CTV and the OARs

Lung stereotactic body radiotherapy with an MR-linac - Quantifying the impact of the magnetic field and real-time tumor tracking.

Background and purpose There are concerns that radiotherapy doses delivered in a magnetic field might be distorted due to the Lorentz force deflecting secondary electrons. This study investigates this effect on lung stereotactic body radiotherapy (SBRT) treatments, conducted either with or without multileaf collimator (MLC) tumor tracking.Material and methods Lung SBRT treatments with an MR-linac were simulated for nine patients. Two different treatment techniques were compared: conventional, non-tracked deliveries and deliveries with real-time MLC tumor tracking, each conducted either with or without a 1.5T magnetic field.Results Slight dose distortions at air-tissue-interfaces were observed in the presence of the magnetic field. Most prominently, the dose to 2% of the skin increased by 1.4Gy on average. Regardless of the presence of the magnetic field, MLC tracking was able to spare healthy tissue, for example by decreasing the mean lung dose by 0.3Gy on average, while maintaining the target dose.Conclusions Accounting for the magnetic field during treatment plan optimization allowed for design and delivery of clinically acceptable lung SBRT treatments with an MR-linac. Furthermore, the ability of MLC tumor tracking to decrease dose exposure of healthy tissue, was not inhibited by the magnetic field