Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison.

Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate.

Using consensus methods to develop a Social Prescribing Learning Needs Framework for practitioners in Wales.

AIMS: Social prescribing is being widely implemented in Wales, but there is no consensus on the necessary learning, training and education needs for people delivering social prescribing. The purpose of the study was to develop an education and training needs conceptual framework for social prescribers in Wales, which could be used by commissioners and providers for the development of social prescribing curricula. METHODS: This study used two consensus methods. First, Group Concept Mapping using Concept Systems Global MaxTM software which identified the important and available learning needs of 18 (n = 18) geographically spread social prescribing practitioners. Second, a world café style workshop asked 85 (n = 85) social prescribers to identify when training and support would be most appropriate and valuable in developing their role and skills. RESULTS: A Social Prescribing Learning Needs Framework was developed identifying important learning needs and their availability across a timeline from induction onwards. This was conceptualised from a group concept mapping cluster map and go-zone report. The map comprises five clusters of statements (compassion, interpersonal relationships, socioeconomic disadvantage, networking and monitoring data) from the original 120 statements of learning needs identified by participants. The Go-Zone report displayed how each learning need was rated by participants on scales of importance and availability. A large number of training needs (45%) that were identified as important, are not currently available to social prescribers. All training needs were placed within the first year of the social prescriber working timeline, with 39% placed in an induction period. CONCLUSION: The use of two different consensus methods enabled social prescribers geographically spread across Wales to engage with the study. The Social Prescribing Learning Needs Framework will be used to inform the commissioning and decommissioning of training for people delivering social prescribing in Wales.

Real-time active suppression of directional acoustic wave components in tubular acoustic systems.

Acoustic pulse reflectometry is a method of non-destructive testing used for locating and characterising features and defects in gas-filled objects such as tubes, pipes, and ducts. A sound wave is emitted into the waveguide and travels in the axial direction until it is partially or fully reflected at changes in cross-section. The recorded reflection sequence is analysed to reveal time-of-flight, amplitude, and reflection shape. Analysis of reflection sequences is problematic due to the presence of multiple repeated echoes. The principal contribution is the introduction and demonstration of a method of actively suppressing unwanted echoes by modifying the signal emitted by the speaker in real-time. Unlike previous work, the proposed system accounts for inter-transducer attenuation and does not require re-calibration for each test object. The proposed real-time active absorbing termination is implemented using a programmable embedded controller and shown to function effectively. A quantitative evaluation of available wave separation techniques is provided using a known metric for quantifying the performance of absorbing terminations is introduced.

Stimulated Brillouin scatter in a magnetized ionospheric plasma.

High power electromagnetic waves transmitted from the HAARP facility in Alaska can excite low-frequency electrostatic waves by magnetized stimulated Brillouin scatter. Either an ion-acoustic wave with a frequency less than the ion cyclotron frequency (f(CI)) or an electrostatic ion cyclotron (EIC) wave just above f(CI) can be produced. The coupled equations describing the magnetized stimulated Brillouin scatter instability show that the production of both ion-acoustic and EIC waves is strongly influenced by the wave propagation relative to the background magnetic field. Experimental observations of stimulated electromagnetic emissions using the HAARP transmitter have confirmed that only ion-acoustic waves are excited for propagation along the magnetic zenith and that EIC waves can only be detected with oblique propagation angles. The ion composition can be obtained from the measured EIC frequency.

Prescription drug samples--does this marketing strategy counteract policies for quality use of medicines?

Prescription drug samples, as used by the pharmaceutical industry to market their products, are of current interest because of their influence on prescribing, and their potential impact on consumer safety. Very little research has been conducted into the use and misuse of prescription drug samples, and the influence of samples on health policies designed to improve the rational use of medicines. This is a topical issue in the prescription drug debate, with increasing costs and increasing concerns about optimizing use of medicines. This manuscript critically evaluates the research that has been conducted to date about prescription drug samples, discusses the issues raised in the context of traditional marketing theory, and suggests possible alternatives for the future.

The nematode Anisakis simplex in American shad (Alosa sapidissima) in two Oregon rivers.

This paper represents the first report of the nematode Anisakis simplex in the American shad (Alosa sapidissima) in its introduced range in the American Pacific Northwest. All the adult shad sampled from spawning populations in the Willamette (n = 9) and Umpqua (n = 12) rivers were infected with A. simplex with intensities ranging from 6 to 89 worms per fish. This preliminary investigation contrasts sharply with previous studies in the native range of American shad and confirms that this fish may be an important intermediate host for A. simplex in the Pacific Northwest. It is suggested that this new parasite-host relationship has led to an ecological expansion into rivers and Anisakis may present an emerging health risk for wildlife and some human consumers.

Orthotopic liver transplantation for alcoholic liver disease: a retrospective analysis of survival, recidivism, and risk factors predisposing to recidivism.

The aim of this study performed at the Liver Unit at the Queen Elizabeth Hospital, Birmingham, UK, is to assess posttransplantation alcohol consumption and identify risk factors associated with recidivism. This retrospective case-control study used a self-report questionnaire to assess pretransplantation and posttransplantation drinking, and a retrospective cohort study used patient notes to analyze risk factors for recidivism. Of 64 patients who underwent transplantation for alcoholic liver disease (ALD) between May 1996 and November 1999, a total of 49 surviving patients (40 men, 9 women) were available for study. The comparison group consisted of 49 patients matched for age, sex, and date of transplantation who underwent transplantation for non-alcohol-induced chronic liver disease. Two-year patient survival rates were 82% in both study groups. The questionnaire response rate was 69.3% and 75.5% in patients with and without ALD, respectively. Data on recidivism (defined as any alcohol consumption after transplantation) were available in 46 of the 49 patients with ALD. Of these, 45.6% were drinking; 21.7% reported only occasionally drinking; 17.3%, moderate drinking; and 6.5%, heavy drinking. Information on alcohol consumption was available from 41 of the 49 controls. Of these, 52.5% consumed alcohol; 22.0% reported drinking only on special occasions; 24.4%, moderate drinking; and 4.9%, a return to heavy drinking. However, these differences were not statistically significant, and log-rank analysis found no significant difference in time to resumption of drinking. In the ALD cohort, no significant risk factors were identified to predict recidivism. No pretransplantation risk factors (including period of abstinence before transplantation) correlated with recidivism. Survival after transplantation for ALD is similar to that in other forms of chronic liver disease. Recidivism rates for patients with ALD are high, but patients with ALD do not drink more than their control counterparts posttransplantation. In most instances, alcohol consumption posttransplantation is minimal to moderate (<20 units/wk) and seems to be controlled.

Blood flow in composite arterial grafts and effect of native coronary flow.

BACKGROUND: Total arterial coronary revascularization can be achieved by joining arteries together as a composite graft with the proximal left internal mammary artery as the only source of blood inflow. Proof of the capacity of this composite conduit to provide adequate blood flow to the coronary circulation is required. METHODS: The radial artery was anastomosed to the left internal mammary artery as a Y graft in 17 patients and all coronary arteries grafted. Intraoperative blood flow through the composite grafts was evaluated by the transit-time Doppler technique. RESULTS: Against no resistance, blood flow in the left internal mammary artery alone was 99 +/- 9 mL/min and rose to 173 +/- 16 mL/min when the radial artery was anastomosed as a Y graft. Composite-graft flow following grafting was 88 +/- 9 mL/min, 49 +/- 6 mL/min when the aortic clamp was removed and native coronary flow restored and 82 +/- 13 mL/min following weaning from cardiopulmonary bypass. The maximal potential flow through the composite graft was 2.3-fold (95% CI 1.6 to 3.2) greater than that after cardiopulmonary bypass. CONCLUSIONS: Total arterial revascularization, using a composite graft, provided a 2.3-fold reserve of blood flow to the coronary vascular bed through the grafts.

Antihydrophobic cosolvent effects in organic displacement reactions.

[formula: see text] Rates of reactions in water can be modified by the presence of antihydrophobic cosolvents such as ethanol and DMSO, which lower the energies of nonpolar surfaces. The rate effects reflect changes both in the solvation of nonpolar surfaces and also in the solvation of polar groups. The effects have been sorted out for some displacement reactions, revealing the geometry of an interesting branching reaction whose two paths show different antihydrophobic effects.