Biosensor-based fragment screening using FastStep injections.

We have developed a novel analyte injection method for the SensíQ Pioneer surface plasmon resonance-based biosensor referred to as "FastStep." By merging buffer and sample streams immediately prior to the reaction flow cells, the instrument is capable of automatically generating a two- or threefold dilution series (of seven or five concentrations, respectively) from a single analyte sample. Using sucrose injections, we demonstrate that the production of each concentration within the step gradient is highly reproducible. For kinetic studies, we developed analysis software that utilizes the sucrose responses to automatically define the concentration of analyte at any point during the association phase. To validate this new approach, we compared the results of standard and FastStep injections for ADP binding to a target kinase and a panel of compounds binding to carbonic anhydrase II. Finally, we illustrate how FastStep can be used in a primary screening mode to obtain a full concentration series of each compound in a fragment library.

Calibration and error analysis of metal-oxide-semiconductor field-effect transistor dosimeters for computed tomography radiation dosimetry.

PURPOSE: Metal-oxide-semiconductor field-effect transistors (MOSFETs) serve as a helpful tool for organ radiation dosimetry and their use has grown in computed tomography (CT). While different approaches have been used for MOSFET calibration, those using the commonly available 100 mm pencil ionization chamber have not incorporated measurements performed throughout its length, and moreover, no previous work has rigorously evaluated the multiple sources of error involved in MOSFET calibration. In this paper, we propose a new MOSFET calibration approach to translate MOSFET voltage measurements into absorbed dose from CT, based on serial measurements performed throughout the length of a 100-mm ionization chamber, and perform an analysis of the errors of MOSFET voltage measurements and four sources of error in calibration. METHODS: MOSFET calibration was performed at two sites, to determine single calibration factors for tube potentials of 80, 100, and 120 kVp, using a 100-mm-long pencil ion chamber and a cylindrical computed tomography dose index (CTDI) phantom of 32 cm diameter. The dose profile along the 100-mm ion chamber axis was sampled in 5 mm intervals by nine MOSFETs in the nine holes of the CTDI phantom. Variance of the absorbed dose was modeled as a sum of the MOSFET voltage measurement variance and the calibration factor variance, the latter being comprised of three main subcomponents: ionization chamber reading variance, MOSFET-to-MOSFET variation and a contribution related to the fact that the average calibration factor of a few MOSFETs was used as an estimate for the average value of all MOSFETs. MOSFET voltage measurement error was estimated based on sets of repeated measurements. The calibration factor overall voltage measurement error was calculated from the above analysis. RESULTS: Calibration factors determined were close to those reported in the literature and by the manufacturer (~3 mV/mGy), ranging from 2.87 to 3.13 mV/mGy. The error σV of a MOSFET voltage measurement was shown to be proportional to the square root of the voltage V: σV=cV where c = 0.11 mV. A main contributor to the error in the calibration factor was the ionization chamber reading error with 5% error. The usage of a single calibration factor for all MOSFETs introduced an additional error of about 5-7%, depending on the number of MOSFETs that were used to determine the single calibration factor. The expected overall error in a high-dose region (~30 mGy) was estimated to be about 8%, compared to 6% when an individual MOSFET calibration was performed. For a low-dose region (~3 mGy), these values were 13% and 12%. CONCLUSIONS: A MOSFET calibration method was developed using a 100-mm pencil ion chamber and a CTDI phantom, accompanied by an absorbed dose error analysis reflecting multiple sources of measurement error. When using a single calibration factor, per tube potential, for different MOSFETs, only a small error was introduced into absorbed dose determinations, thus supporting the use of a single calibration factor for experiments involving many MOSFETs, such as those required to accurately estimate radiation effective dose.

Use of an Accelerated Diagnostic Pathway allows rapid and safe discharge of 70% of chest pain patients from the emergency department.

INTRODUCTION: The majority of patients who present to the Emergency Department (ED) with chest pain, do not have Acute Coronary Syndrome (ACS). Rapid, safe discharge home for this large group is hampered by clinical uncertainty. A pragmatic Accelerated Diagnostic Pathway (ADP) used in our ED achieves this goal. AiIM: To demonstrate the safety and utility of a locally developed ADP. The primary outcome for patients who were identified as non-high risk by our ADP was death or acute myocardial infarction (AMI) at 30 days. Secondary outcomes were ED length of stay, discharge rates, provocative testing and revascularisation rates. METHOD: This is a prospective observational convenience cohort study of chest pain patients presenting to a regional ED excluding ST-elevation myocardial infarction (STEMI). Using a locally derived ADP, patients were classified as high risk or non-high risk for 30-day death or AMI. Patients could be classified as high risk on the basis of ECG change, troponin elevation, or senior clinician "gestalt" irrespective of negative serial ECGs and troponins. All others were classified non-high risk and were followed up at 30 days. RESULTS: There were 452 patient events with the ADP identifying 75% as non-high-risk (93% of these patients were actually discharged). All patients were successfully followed up for 30-day outcomes. The sensitivity and negative predictive value of the ADP was 100% (95% CI: 99-100%). Specificity was 83% (95% CI: 79-87%). The average ED length of stay was 4 hours 5 minutes. There were low rates of revascularisation (1.5%) and provocative testing (6.2%) in the non-high risk group. CONCLUSION: This ED ADP for chest pain rapidly and safely identified patients who were not at high risk of a short-term AMI or death.

Tutu toxicity: three case reports of Coriaria arborea ingestion, review of literature and recommendations for management.

We describe three cases of tutu berry (Coriaria arborea) ingestion resulting in tonic-clonic seizures in two individuals and mild symptoms in the third. Tutu poisoning in humans appears to be a rare occurrence; the last reported case in the medical literature being over 40 years ago. We review the literature on tutu poisoning and recommend extending the period of observation for poisoned individuals from 8 hours to 12 hours or longer. We also recommend that prophylactic benzodiazepine use should be considered in those with mild to moderate symptoms of poisoning.

Interprofessional initiatives at the University of Washington.

Pharmacists must collaborate with other health professionals to promote the optimal use of medications, relying on coordinated, interprofessional communication and care to do so. In 2003, the Institute of Medicine (IOM) recommended "all health professionals should be educated to deliver patient-centered care as members of an interdisciplinary team, emphasizing evidence-based practice, quality improvement approaches, and informatics." At the University of Washington, the Center for Health Sciences Interprofessional Education (CHSIE) was established in 1997 to promote interprofessional curricular and clinical innovation in education, faculty development, and student activities, and to conduct evaluative research regarding the impact of interprofessional innovations. In this manuscript, we will describe the Center for Health Sciences Interprofessional Education, and highlight key projects that serve as examples of pharmacy involvement in interprofessional education, research, and service.