Receptors on phaeochromocytoma cells for two members of the PP-fold family — NPY and PP

AbstractPancreatic polypeptide (PP) and neuropeptide Y (NPY) belong to a family of regulatory peptides which hold a distinct tertiary structure, the PP-fold, even in dilute aqueous solution. High-affinity receptors, specific for both PP and NPY, are described on the rat phaeochromocytoma cell line, PC-12. The binding of [125I-Tyr36]PP to PC-12 cells was inhibited by concentrations of unlabeled PP which correspond to physiological concentrations of the hormone, 10−11-10−9 mol/1. The affinity of the receptor for the neuropeptide, NPY, was 102-times lower than that of the PP receptor. C-terminal fragments of both PP (PP24–36) and NPY (NPY13–36) were between 102 - and 103-times less potent in displacing the radiolabeled 36-amino-acid peptides from their respective receptors. It is concluded that PC-12 cells are suited for structure-function studies of the PP-fold peptides and studies on the cellular events following cellular binding of PP-fold peptides

Delivering precision antimicrobial therapy through closed-loop control systems

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients

K-Space at TRECVID 2008

In this paper we describe K-Space’s participation in TRECVid 2008 in the interactive search task. For 2008 the K-Space group performed one of the largest interactive video information retrieval experiments conducted in a laboratory setting. We had three institutions participating in a multi-site multi-system experiment. In total 36 users participated, 12 each from Dublin City University (DCU, Ireland), University of Glasgow (GU, Scotland) and Centrum Wiskunde and Informatica (CWI, the Netherlands). Three user interfaces were developed, two from DCU which were also used in 2007 as well as an interface from GU. All interfaces leveraged the same search service. Using a latin squares arrangement, each user conducted 12 topics, leading in total to 6 runs per site, 18 in total. We officially submitted for evaluation 3 of these runs to NIST with an additional expert run using a 4th system. Our submitted runs performed around the median. In this paper we will present an overview of the search system utilized, the experimental setup and a preliminary analysis of our results

Adaptive Appointment Systems with Patient Preferences

Patients\u27 satisfaction with an appointment system when they attempt to book a nonurgent appointment is affected by their ability to book with a doctor of choice and to book an appointment at a convenient time of day. For medical conditions requiring urgent attention, patients want quick access to a familiar physician. For such instances, it is important for clinics to have open slots that allow same-day (urgent) access. A major challenge when designing outpatient appointment systems is the difficulty of matching randomly arriving patients\u27 booking requests with physicians\u27 available slots in a manner that maximizes patients\u27 satisfaction as well as clinics\u27 revenues. What makes this problem difficult is that booking preferences are not tracked, may differ from one patient to another, and may change over time. This paper describes a framework for the design of the next generation of appointment systems that dynamically learn and update patients\u27 preferences and use this information to improve booking decisions. Analytical results leading to a partial characterization of an optimal booking policy are presented. Examples show that heuristic decision rules, based on this characterization, perform well and reveal insights about trade-offs among a variety of performance metrics important to clinic managers

CAMKII as a therapeutic target for growth factor-induced retinal and choroidal neovascularisation

This study was supported by grants from the British Heart Foundation (PG/11/99/29207 and PG/11/94/29169), Fight for Sight, UK (1387/88), Health & Social Care R&D Division, Northern Ireland (STL/4748/13) and the Medical Research Council (MC_PC_15026). We would like to thank Gordon Revolta for excellent assistance with colony management and genotyping.Peer reviewedPublisher PD

Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

A new efficient trial design for assessing reliability of ankle-brachial index measures by three different observer groups

BACKGROUND: The usual method of assessing the variability of a measure such as the ankle brachial index (ABI) as a function of different observer groups is to obtain repeated measurements. Because the number of possible observer-subject combinations is impractically large, only a few small studies on inter- and intraobserver variability of ABI measures have been carried out to date. The present study proposes a new and efficient study design. This paper describes the study methodology. METHODS: Using a partially balanced incomplete block design, six angiologists, six primary-care physicians and six trained medical office assistants performed two ABI measurements each on six individuals from a group of 36 unselected subjects aged 65–70 years. Each test subject is measured by one observer from each of the three observer groups, and each observer measures exactly six of the 36 subjects in the group. Each possible combination of two observers occurs exactly once per patient and is not repeated on a second subject. The study involved four groups of 36 subjects (144), plus standbys. RESULTS: The 192 volunteers present at the study day were similar in terms of demographic characteristics and vascular risk factors: mean age 68.6 ± 1.7; mean BMI 29.1 ± 4.6; mean waist-hip ratio 0.92 ± 0.09; active smokers 12%; hypertension 60.9%; hypercholesterolemia 53.4%; diabetic 17.2%. A complete set of ABI measurements (three observers performing two Doppler measurements each) was obtained from 108 subjects. From all other subjects at least one ABI measurement was obtained. The mean ABI was 1.08 (± 0.13), 15 (7.9%) volunteers had an ABI <0.9, and none had an ABI >1.4, i.e. a ratio that may be associated with increased stiffening of the arterial walls. CONCLUSION: This is the first large-scale study investigating the components of variability and thus reliability in ABI measurements. The advantage of the new study design introduced here is that only one sixth of the number of theoretically possible measurements is required to obtain information about measurement errors. Bland-Altman plots show that there are only small differences and no systematic bias between the observers from three occupational groups with different training backgrounds

Predicting healthcare employees' participation in an office redesign program: Attitudes, norms and behavioral control

<p>Abstract</p> <p>Background</p> <p>The study examined the extent to which components based on a modified version of the theory of planned behavior explained employee participation in a new clinical office program designed to reduce patient waiting times in primary care clinics.</p> <p>Methods</p> <p>We regressed extent of employee participation on attitudes about the program, group norms, and perceived behavioral control along with individual and clinic characteristics using a hierarchical linear mixed model.</p> <p>Results</p> <p>Perceived group norms were one of the best predictors of employee participation. Attitudes about the program were also significant, but to a lesser degree. Behavioral control, however, was not a significant predictor. Respondents with at least one year of clinic tenure, or who were team leaders, first line supervisor, or managers had greater participation rates. Analysis at the clinic level indicated clinics with scores in the highest quartile clinic scores on group norms, attitudes, and behavioral control scores were significantly higher on levels of overall participation than clinics in the lowest quartile.</p> <p>Conclusion</p> <p>Findings suggest that establishing strong norms and values may influence employee participation in a change program in a group setting. Supervisory level was also significant with greater responsibility being associated with greater participation.</p