Study of meteoroid impact into ablative heat shield materials Final report

Meteoroid impact damage to Apollo and Gemini ablative heat shield

Oral drug delivery strategies for development of poorly water soluble drugs in paediatric patient population

Selecting the appropriate formulation and solubility-enabling technology for poorly water soluble drugs is an essential element in the development of formulations for paediatric patients. Different methodologies and structured strategies are available to select a suitable approach and guide formulation scientists for development of adult formulations. However, there is paucity of available literature for selection of technology and overcoming the challenges in paediatric formulation development. The need for flexible dosing, and the limited knowledge of the safety of many formulation excipients in paediatric subjects, impose significant constraints and in some instances require adaptation of the approaches taken to formulating these drugs for the adult population. Selection of the best drug delivery system for paediatrics requires an efficient, systematic approach that considers a drug's physical and chemical properties and the targeted patient population's requirements. This review is a step towards development of a strategy for the design of solubility enhancing paediatric formulations of highly insoluble drugs. The aim of this review is to provide an overview of different approaches and strategies to consider in order to assist development of paediatric formulation for poorly water-soluble drugs with the provision of examples of some marketed products. In addition, it provides recommendations to overcome the range of challenges posed by these strategies and adaptations of the adult approach/product presentation required to enable paediatric drug development and administration

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Effects of Exposure to Psychophysical Scaling on Lingual Vibrotactile Magnitude Estimation and Magnitude Production

The purpose of the present study was to determine if the results obtained by the scaling methods of magnitude estimation and magnitude production could be influenced by providing subjects with prior exposure to psychophysical scaling in the form of magnitude estimation or magnitude production. Group 1 ( n = 10, Mage = 21.1 yr.) performed lingual vibrotactile-magnitude estimation followed by lingual vibrotactile magnitude production. Group 2 ( n = 10, Mage = 19.7 yr.) performed lingual vibrotactile-magnitude production (using the magnitude-estimation responses provided by Group 1), followed by lingual vibrotactile-magnitude estimation. For the magnitude estimations there was no over-all statistically significant difference between the two groups, but there was for the magnitude-production values. Magnitude-estimation scaling was apparently not influenced by prior exposure to magnitude production, while magnitude-production scaling was influenced by prior exposure to magnitude estimation. The results are discussed in terms of how subjective scaling behavior in psychophysical experimentation may be influenced by the interaction between an absolute internal scaling mechanism and parameters set by the experimenter, such as scaling method and range of stimulus intensity. </jats:p

Effects of Psychophysical Scaling Method, Body Test-Site, and Skin-Contactor Surface Area on Vibrotactile Magnitude Functions

This study was designed to focus on possible interactive effects that scaling method, body test-site, and skin-contactor surface area might have on vibrotactile magnitude functions. The psychophysical scaling methods of magnitude estimation and magnitude production were used to apply vibrotactile stimulation to the anterior midline of the tongue and the thenar eminence of the hand through the use of three skin-contactor areas (.128, .320, and 1.30 cm3). Ten subjects, ranging in age from 19 to 21 yr. ( M age = 19.8 yr.) were employed. Data obtained from the 10 subjects suggested that the suprathreshold-scaling method chosen can be a significant determinant of the findings obtained. They further suggested that the tongue and hand may respond differently to suprathreshold vibrotactile stimulation and that the effects of varying skin-contactor area may be different for the two body-sites tested. </jats:p