A reconfigurable real-time compressive-sampling camera for biological applications

Many applications in biology, such as long-term functional imaging of neural and cardiac systems, require continuous high-speed imaging. This is typically not possible, however, using commercially available systems. The frame rate and the recording time of high-speed cameras are limited by the digitization rate and the capacity of on-camera memory. Further restrictions are often imposed by the limited bandwidth of the data link to the host computer. Even if the system bandwidth is not a limiting factor, continuous high-speed acquisition results in very large volumes of data that are difficult to handle, particularly when real-time analysis is required. In response to this issue many cameras allow a predetermined, rectangular region of interest (ROI) to be sampled, however this approach lacks flexibility and is blind to the image region outside of the ROI. We have addressed this problem by building a camera system using a randomly-addressable CMOS sensor. The camera has a low bandwidth, but is able to capture continuous high-speed images of an arbitrarily defined ROI, using most of the available bandwidth, while simultaneously acquiring low-speed, full frame images using the remaining bandwidth. In addition, the camera is able to use the full-frame information to recalculate the positions of targets and update the high-speed ROIs without interrupting acquisition. In this way the camera is capable of imaging moving targets at high-speed while simultaneously imaging the whole frame at a lower speed. We have used this camera system to monitor the heartbeat and blood cell flow of a water flea (Daphnia) at frame rates in excess of 1500 fps

Guiding Brain Tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-Held Raman Scanner

The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold-silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room

Common ADRB2 Haplotypes Derived from 26 Polymorphic Sites Direct β2-Adrenergic Receptor Expression and Regulation Phenotypes

The beta2-adrenergic receptor (beta2AR) is expressed on numerous cell-types including airway smooth muscle cells and cardiomyocytes. Drugs (agonists or antagonists) acting at these receptors for treatment of asthma, chronic obstructive pulmonary disease, and heart failure show substantial interindividual variability in response. The ADRB2 gene is polymorphic in noncoding and coding regions, but virtually all ADRB2 association studies have utilized the two common nonsynonymous coding SNPs, often reaching discrepant conclusions.We constructed the 8 common ADRB2 haplotypes derived from 26 polymorphisms in the promoter, 5'UTR, coding, and 3'UTR of the intronless ADRB2 gene. These were cloned into an expression construct lacking a vector-based promoter, so that beta2AR expression was driven by its promoter, and steady state expression could be modified by polymorphisms throughout ADRB2 within a haplotype. "Whole-gene" transfections were performed with COS-7 cells and revealed 4 haplotypes with increased cell surface beta2AR protein expression compared to the others. Agonist-promoted downregulation of beta2AR protein expression was also haplotype-dependent, and was found to be increased for 2 haplotypes. A phylogenetic tree of the haplotypes was derived and annotated by cellular phenotypes, revealing a pattern potentially driven by expression.Thus for obstructive lung disease, the initial bronchodilator response from intermittent administration of beta-agonist may be influenced by certain beta2AR haplotypes (expression phenotypes), while other haplotypes may influence tachyphylaxis during the response to chronic therapy (downregulation phenotypes). An ideal clinical outcome of high expression and less downregulation was found for two haplotypes. Haplotypes may also affect heart failure antagonist therapy, where beta2AR increase inotropy and are anti-apoptotic. The haplotype-specific expression and regulation phenotypes found in this transfection-based system suggest that the density of genetic information in the form of these haplotypes, or haplotype-clusters with similar phenotypes can potentially provide greater discrimination of phenotype in human disease and pharmacogenomic association studies

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

available in PMC 2011 February 3.MCL-1 has emerged as a major oncogenic and chemoresistance factor. A screen of stapled peptide helices identified the MCL-1 BH3 domain as selectively inhibiting MCL-1 among the related anti-apoptotic Bcl-2 family members, providing insights into the molecular determinants of binding specificity and a new approach for sensitizing cancer cells to apoptosis.National Institutes of Health (U.S.) (NIH award 5RO1GM084181)National Institutes of Health (U.S.) (NIH grant 5P01CA92625)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F31CA144566)Burroughs Wellcome Fund (Career Award

Comparing patients’ and other stakeholders’ preferences for outcomes of integrated care for multimorbidity: a discrete choice experiment in eight European countries

Objectives To measure relative preferences for outcomes of integrated care of patients with multimorbidity from eight European countries and compare them to the preferences of other stakeholders within these countries. Design A discrete choice experiment (DCE) was conducted in each country, asking respondents to choose between two integrated care programmes for persons with multimorbidity. Setting Preference data collected in Austria (AT), Croatia (HR), Germany (DE), Hungary (HU), the Netherlands (NL), Norway (NO), Spain (ES), and UK. Participants Patients with multimorbidity, partners and other informal caregivers, professionals, payers and policymakers. Main outcome measures Preferences of participants regarding outcomes of integrated care described as health/well-being, experience with care and cost outcomes, that is, physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centredness, continuity of care and total costs. Each outcome had three levels of performance. Results 5122 respondents completed the DCE. In all countries, patients with multimorbidity, as well as most other stakeholder groups, assigned the (second) highest preference to enjoyment of life. The patients top-three most frequently included physical functioning, psychological well-being and continuity of care. Continuity of care also entered the top-three of professionals, payers and policymakers in four countries (AT, DE, HR and HU). Of the five stakeholder groups, preferences of professionals differed most often from preferences of patients. Professionals assigned lower weights to physical functioning in AT, DE, ES, NL and NO and higher weights to person-centredness in AT, DE, ES and HU. Payers and policymakers assigned higher weights than patients to costs, but these weights were relatively low. Conclusion The well-being outcome enjoyment of life is the most important outcome of integrated care in multimorbidity. This calls for a greater involvement of social and mental care providers. The difference in opinion between patients and professionals calls for shared decision-making, whereby efforts to improve well-being and person-centredness should not divert attention from improving physical functioning

Multi-centred mixed-methods PEPFAR HIV care & support public health evaluation: study protocol

BACKGROUND: A public health response is essential to meet the multidimensional needs of patients and families affected by HIV disease in sub-Saharan Africa. In order to appraise current provision of HIV care and support in East Africa, and to provide evidence-based direction to future care programming, and Public Health Evaluation was commissioned by the PEPFAR programme of the US Government. METHODS/DESIGN: This paper described the 2-Phase international mixed methods study protocol utilising longitudinal outcome measurement, surveys, patient and family qualitative interviews and focus groups, staff qualitative interviews, health economics and document analysis. Aim 1) To describe the nature and scope of HIV care and support in two African countries, including the types of facilities available, clients seen, and availability of specific components of care [Study Phase 1]. Aim 2) To determine patient health outcomes over time and principle cost drivers [Study Phase 2]. The study objectives are as follows. 1) To undertake a cross-sectional survey of service configuration and activity by sampling 10% of the facilities being funded by PEPFAR to provide HIV care and support in Kenya and Uganda (Phase 1) in order to describe care currently provided, including pharmacy drug reviews to determine availability and supply of essential drugs in HIV management. 2) To conduct patient focus group discussions at each of these (Phase 1) to determine care received. 3) To undertake a longitudinal prospective study of 1200 patients who are newly diagnosed with HIV or patients with HIV who present with a new problem attending PEPFAR care and support services. Data collection includes self-reported quality of life, core palliative outcomes and components of care received (Phase 2). 4) To conduct qualitative interviews with staff, patients and carers in order to explore and understand service issues and care provision in more depth (Phase 2). 5) To undertake document analysis to appraise the clinical care procedures at each facility (Phase 2). 6) To determine principle cost drivers including staff, overhead and laboratory costs (Phase 2). DISCUSSION: This novel mixed methods protocol will permit transparent presentation of subsequent dataset results publication, and offers a substantive model of protocol design to measure and integrate key activities and outcomes that underpin a public health approach to disease management in a low-income setting

From open radical hysterectomy to robot-assisted laparoscopic radical hysterectomy for early stage cervical cancer: aspects of a single institution learning curve

We analysed the introduction of the robot-assisted laparoscopic radical hysterectomy in patients with early-stage cervical cancer with respect to patient benefits and surgeon-related aspects of a surgical learning curve. A retrospective review of the first 14 robot-assisted laparoscopic radical hysterectomies and the last 14 open radical hysterectomies in a similar clinical setting with the same surgical team was conducted. Patients were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and open radical hysterectomy (RH) before August 2006 and were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and robot-assisted laparoscopic radical hysterectomy (RALRH) after August 2006. Overall, blood loss in the open cases was significantly more compared with the robot cases. Median hospital stay after RALRH was 5 days less than after RH. The median theatre time in the learning period for the robot procedure was reduced from 9 h to less that 4 h and compared well to the 3 h and 45 min for an open procedure. Three complications occurred in the open group and one in the robot group. RALRH is feasible and of benefit to the patient with early stage cervical cancer by a reduction of blood loss and reduced hospital stay. Introduction of this new technique requires a learning curve of less than 15 cases that will reduce the operating time to a level comparable to open surgery

Social network and dominance hierarchy analyses at Chimpanzee Sanctuary Northwest

Different aspects of sociality bear considerable weight on the individual- and group-level welfare of captive nonhuman primates. Social Network Analysis (SNA) is a useful tool for gaining a holistic understanding of the dynamic social relationships of captive primate groups. Gaining a greater understanding of captive chimpanzees through investigations of centrality, preferred and avoided relationships, dominance hierarchy, and social network diagrams can be useful in advising current management practices in sanctuaries and other captive settings. In this study, we investigated the dyadic social relationships, group-level social networks, and dominance hierarchy of seven chimpanzees (Pan troglodytes) at Chimpanzee Sanctuary Northwest. We used focal-animal and instantaneous scan sampling to collect 106.75 total hours of associative, affiliative, and agonistic data from June to September 2016. We analyzed our data using SOCPROG to derive dominance hierarchies and network statistics, and we diagrammed the group\u27s social networks in NetDraw. Three individuals were most central in the grooming network, while two others had little connection. Through agonistic networks, we found that group members reciprocally exhibited agonism, and the group\u27s dominance hierarchy was statistically non-linear. One chimpanzee emerged as the most dominant through agonism but was least connected to other group members across affiliative networks. Our results indicate that the conventional methods used to calculate individuals\u27 dominance rank may be inadequate to wholly depict a group\u27s social relationships in captive sanctuary populations. Our results have an applied component that can aid sanctuary staff in a variety of ways to best ensure the improvement of group welfare

Strengthening the evidence-base of integrated care for people with multi-morbidity in Europe using Multi-Criteria Decision Analysis (MCDA).

Background: Evaluation of integrated care programmes for individuals with multi-morbidity requires a broader evaluation framework and a broader definition of added value than is common in cost-utility analysis. This is possible through the use of Multi-Criteria Decision Analysis (MCDA). Methods and results: This paper presents the seven steps of an MCDA to evaluate 17 different integrated care programmes for individuals with multi-morbidity in 8 European countries participating in the 4-year, EU-funded SELFIE project. In step one, qualitative research was undertaken to better understand the decision-context of these programmes. The programmes faced decisions related to their sustainability in terms of reimbursement, continuation, extension, and/or wider implementation. In step two, a uniform set of decision criteria was defined in terms of outcomes measured across the 17 programmes: physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centeredness, continuity of care, and total health and social care costs. These were supplemented by programme-type specific outcomes. Step three presents the quasi-experimental studies designed to measure the performance of the programmes on the decision criteria. Step four gives details of the methods (Discrete Choice Experiment, Swing Weighting) to determine the relative importance of the decision criteria among five stakeholder groups per country. An example in step five illustrates the value-based method of MCDA by which the performance of the programmes on each decision criterion is combined with the weight of the respective criterion to derive an overall value score. Step six describes how we deal with uncertainty and introduces the Conditional Multi-Attribute Acceptability Curve. Step seven addresses the interpretation of results in stakeholder workshops. Discussion: By discussing our solutions to the challenges involved in creating a uniform MCDA approach for the evaluation of different programmes, this paper provides guidance to future evaluations and stimulates debate on how to evaluate integrated care for multi-morbidity