Evaluation and study of advanced optical contamination, deposition, measurement, and removal techniques

A program is described to design, fabricate and install an experimental work chamber assembly (WCA) to provide a wide range of experimental capability. The WCA incorporates several techniques for studying the kinetics of contaminant films and their effect on optical surfaces. It incorporates the capability for depositing both optical and contaminant films on temperature-controlled samples, and for in-situ measurements of the vacuum ultraviolet reflectance. Ellipsometer optics are mounted on the chamber for film thickness determinations, and other features include access ports for radiation sources and instrumentation. Several supporting studies were conducted to define specific chamber requirements, to determine the sensitivity of the measurement techniques to be incorporated in the chamber, and to establish procedures for handling samples prior to their installation in the chamber. A bibliography and literature survey of contamination-related articles is included

A Triple-Masked, Randomized Controlled Trial Comparing Ultrasound-Guided Brachial Plexus and Distal Peripheral Nerve Block Anesthesia for Outpatient Hand Surgery

Background. For hand surgery, brachial plexus blocks provide effective anesthesia but produce undesirable numbness. We hypothesized that distal peripheral nerve blocks will better preserve motor function while providing effective anesthesia. Methods. Adult subjects who were scheduled for elective ambulatory hand surgery under regional anesthesia and sedation were recruited and randomly assigned to receive ultrasound-guided supraclavicular brachial plexus block or distal block of the ulnar and median nerves. Each subject received 15 mL of 1.5% mepivacaine at the assigned location with 15 mL of normal saline injected in the alternate block location. The primary outcome (change in baseline grip strength measured by a hydraulic dynamometer) was tested before the block and prior to discharge. Subject satisfaction data were collected the day after surgery. Results. Fourteen subjects were enrolled. Median (interquartile range [IQR]) strength loss in the distal group was 21.4% (14.3, 47.8%), while all subjects in the supraclavicular group lost 100% of their preoperative strength, P = 0.001. Subjects in the distal group reported greater satisfaction with their block procedures on the day after surgery, P = 0.012. Conclusion. Distal nerve blocks better preserve motor function without negatively affecting quality of anesthesia, leading to increased patient satisfaction, when compared to brachial plexus block

A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease

von Willebrand factor (VWF) is a multimeric glycoprotein that mediates platelet adhesion and is decreased in von Willebrand disease (VWD). 1-8 deamino-d-arginine vasopressin (DDAVP), the most common treatment for VWD, is limited by tachyphylaxis and inconvenience, and in 20% of the patients, unresponsiveness. Recombinant human interleukin-11 (rhIL-11), a gp-130 signalling cytokine with haematopoietic and anti-inflammatory activity, increases VWF antigen and its activity in heterozygous VWF+/− mice and dogs. To determine the biological efficacy and safety of rhIL-11 in non-bleeding human subjects with mild VWD, we conducted a phase II prospective open-label trial of rhIL-11 at 10, 25 and 50 μg kg−1 subcutaneously (s.c.), given daily for 7 days in nine subjects with mild VWD. VWF and factor VIII (FVIII) levels increased gradually and progressively after s.c. rhIL-11, which was sustained through 7 days of dosing to 1.5- to 3-fold over baseline. Following intravenous DDAVP, 0.3 μg kg−1, on day 7 there was a further boost in VWF and FVIII levels, suggesting that the mechanism of rhIL-11 differs from that of DDAVP. Platelet VWF mRNA expression measured by quantitative PCR increased from two- to eightfold over baseline, suggesting that the mechanism of rhIL-11 effect may be upregulation of VWF mRNA. VWF and FVIII levels returned to baseline by day 14. rhIL-11 was well tolerated with less than grade-1 hypertension, hypokalaemia and fluid retention. Recombinant IL-11 increases VWF levels in humans with mild VWD, justifying future clinical trials to determine its potential in preventing or reducing bleeding in this patient population

Status report on solid control in leachates

Sludge pretreatment will involve some combination of washing and leaching with sodium hydroxide solutions to remove soluble salts and amphoteric material such as alumina. It is of paramount importance to prevent gelation and uncontrolled solid formation in tanks, transfer lines, and process equipment. An evaluation of results of washing and caustic leaching indicates that washing is more effective in dissolving sludge solids than subsequent sodium hydroxide treatment. Only aluminum and chromium were removed more effectively by caustic leaching than by water washing

Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor VII Deficiency

Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders