Debugging experiment machinery through time-course event sequence analysis

This application note describes an open-source web application software package for viewing and analysing time-course event sequences in the form of log files containing timestamps. Web pages allow the visualisation of time-course event sequences as time curves and the comparison of sequences against each other to visualise deviations between the timings of the sequences. A feature allows the analysis of the sequences by parsing selected sections with a support vector machine model that heuristically calculates a value for the likelihood of an error occurring based on the textual output in the log files. This allows quick analysis for errors in files with large numbers of log events. The software is written in ASP.NET with Visual Basic code-behind to allow it to be hosted on servers and integrated into web application frameworks

Observability Increases the Demand for Commitment Devices

Previous research often interprets the choice to restrict one’s future opportunity set as evidence for sophisticated time inconsistency. We propose an additional mechanism that may contribute to the demand for commitment technology: the desire to signal to others. We present a field experiment where participants can choose to give up money if they do not follow through with an action. When commitment choices are made public rather than kept private, we find significantly higher uptake rates

Complementary and Alternative Medicine Use in Musculoskeletal Disorders: Does Medical Skepticism Matter?

Medical skepticism is the reservation about the ability of conventional medical care to significantly improve health. Individuals with musculoskeletal disorders seeing specialists usually experience higher levels of disability; therefore it is expected they might be more skeptical of current treatment and thus more likely to try Complementary and Alternative Medicine (CAM). The goal of this study was to define these relationships. These data were drawn from a cross-sectional survey from two cohorts: those seeing specialists (n=1,344) and non-specialists (n=724). Site-level fixed effects logistic regression models were used to test associations between medical skepticism and 10 CAM use categories. Some form of CAM was used by 88% of the sample. Increased skepticism was associated with one CAM category for the non-specialist group and six categories for the specialist group. Increased medical skepticism is associated with CAM use, but medical skepticism is more often associated with CAM use for those seeing specialists

Going to scale: design and implementation challenges of a program to increase access to skilled birth attendants in Nigeria

This is the final version. Available from BMC via the DOI in this record.Background: The lack of availability of skilled providers in low- and middle- income countries is considered to be an important barrier to achieving reductions in maternal and child mortality. However, there is limited research on programs increasing the availability of skilled birth attendants in developing countries. We study the implementation of the Nigeria Midwives Service Scheme, a government program that recruited and deployed nearly 2,500 midwives to rural primary health care facilities across Nigeria in 2010. An outcome evaluation carried out by this team found only a modest impact on the use of antenatal care and no measurable impact on skilled birth attendance. This paper draws on perspectives of policymakers, program midwives, and community residents to understand why the program failed to have the desired impact. Methods: We conducted semi-structured interviews with federal, state and local government policy makers and with MSS midwives. We also conducted focus groups with community stakeholders including community leaders and male and female residents. Results: Our data reveal a range of design, implementation and operational challenges ranging from insufficient buy-in by key stakeholders at state and local levels, to irregular and in some cases total non-provision of agreed midwife benefits that likely contributed to the program’s lack of impact. These challenges not only created a deep sense of dissatisfaction with the program but also had practical impacts on service delivery likely affecting households’ uptake of services. Conclusion: This paper highlights the challenge of effectively scaling up maternal and child health interventions. Our findings emphasize the critical importance of program design, particularly when programs are implemented at scale; the need to identify and involve key stakeholders during planning and implementation; the importance of clearly defining lines of authority and responsibility that align with existing structures; and the necessity for multi-faceted interventions that address multiple barriers at the same time.International Initiative for Impact Evaluatio

Computer-aided discovery of a metal-organic framework with superior oxygen uptake.

Current advances in materials science have resulted in the rapid emergence of thousands of functional adsorbent materials in recent years. This clearly creates multiple opportunities for their potential application, but it also creates the following challenge: how does one identify the most promising structures, among the thousands of possibilities, for a particular application? Here, we present a case of computer-aided material discovery, in which we complete the full cycle from computational screening of metal-organic framework materials for oxygen storage, to identification, synthesis and measurement of oxygen adsorption in the top-ranked structure. We introduce an interactive visualization concept to analyze over 1000 unique structure-property plots in five dimensions and delimit the relationships between structural properties and oxygen adsorption performance at different pressures for 2932 already-synthesized structures. We also report a world-record holding material for oxygen storage, UMCM-152, which delivers 22.5% more oxygen than the best known material to date, to the best of our knowledge

HDAC Inhibition by LBH589 Affects Phenotype and Function of Human Myeloid Dendritic Cells

LBH589 is a novel pan-HDAC inhibitor which has potent antitumor activity in multiple myeloma and other hematologic malignancies. However, its impact on immune system has not been defined. We here evaluated the effects of LBH589 on human myeloid dendritic cells (DCs) at clinically relevant concentrations. Exposure to LBH589 affected the surface molecule expression on immature and mature DCs, associated with DC maturation (CD83↓), antigen presentation (HLA-ABC↓), and T cell co-stimulation (CD40↓ and CD86↑). LBH589 decreased both protein and polysaccharide antigen uptake capacities by DCs. Importantly, LBH589 impaired DCs function to stimulate antigen-specific immune responses, resulting in the significant reduction of invariant NKT cell (CD1d-restricted) and T cell (MHC-restricted) activation in innate and adaptive immunity. LBH589 also significantly repressed the production of IL-6, IL-10, IL-12p70, IL-23 and TNF-α by TLR3 and TLR4-induced DCs activation, indicating an important role of HDAC activity in immune regulation and inflammation. RelB, a component of NF-κB signaling pathway, was the key component regulated by HDAC inhibition in DCs. Together, our preclinical study demonstrates that LBH589 significantly impairs phenotype and function of DCs, indicating a need for monitoring the immune status in patients receiving HDAC inhibitor therapy. It also provides a rationale to evaluate LBH589 activity for the treatment of inflammation

Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells

Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum (ER) chaperone that loads lipids onto apolipoprotein B, also regulates CD1d presentation of glycolipid antigens in the liver and intestine. We show MTP RNA and protein in antigen-presenting cells (APCs) by reverse transcription–polymerase chain reaction and by immunoblotting of mouse liver mononuclear cells and mouse and human B cell lines. Functional MTP, demonstrated by specific triglyceride transfer activity, is present in both mouse splenocytes and a CD1d-positive mouse NKT hybridoma. In a novel in vitro transfer assay, purified MTP directly transfers phospholipids, but not triglycerides, to recombinant CD1d. Chemical inhibition of MTP lipid transfer does not affect major histocompatibility complex class II presentation of ovalbumin, but considerably reduces CD1d-mediated presentation of α-galactosylceramide (α-galcer) and endogenous antigens in mouse splenic and bone marrow–derived dendritic cells (DCs), as well as in human APC lines and monocyte-derived DCs. Silencing MTP expression in the human monocyte line U937 affects CD1d function, as shown by diminished presentation of α-galcer. We propose that MTP acts upstream of the saposins and functions as an ER chaperone by loading endogenous lipids onto nascent CD1d. Furthermore, our studies suggest that a small molecule inhibitor could be used to modulate the activity of NKT cells

Rapid Optical Fluctuations in the Black Hole Binary, V4641 Sgr

We report on unprecedented short-term variations detected in the optical flux from the black hole binary system, V4641 Sgr. Amplitudes of the optical fluctuations were larger at longer time scales, and surprisingly reached ~60% around a period of ~10 min. The power spectra of fluctuations are characterized by a power law. It is the first case in black hole binaries that the optical emission was revealed to show short-term and large-amplitude variations given by such a power spectrum. The optical emission from black hole binaries is generally dominated by the emission from the outer portion of an accretion disc. The rapid optical fluctuations however indicate that the emission from an inner accretion region significantly contributes to the optical flux. In this case, cyclo-synchrotron emission associated with various scales of magnetic flares is the most promising mechanism for the violently variable optical emission.Comment: 5 pages, 2 figures, accepted for publication in PAS

Use of Complementary and Alternative Medicine Among Patients With Arthritis

Introduction: Previous studies suggest that people with arthritis have high rates of using complementary and alternative medicine (CAM) approaches for managing their arthritis, in addition to conventional treatments such as prescription medications. However, little is known about the use of CAM by diagnosis, or which forms of CAM are most frequently used by people with arthritis. This study was designed to provide detailed information about use of CAM for symptoms associated with arthritis in patients followed in primary care and specialty clinics in North Carolina. Methods: Using a cross-sectional design, we drew our sample from primary care (n = 1,077) and specialist (n = 1,063) physician offices. Summary statistics were used to calculate differences within and between diagnostic groups, practice settings, and other characteristics. Logistic regression models clustered at the site level were used to determine the effect of patient characteristics on ever and current use of 9 CAM categories and an overall category of "any use." Results: Most of the participants followed by specialists (90.5%) and a slightly smaller percentage of those in the primary care sample (82.8%) had tried at least 1 complementary therapy for arthritis symptoms. Participants with fibromyalgia used complementary therapies more often than those with rheumatoid arthritis, osteoarthritis, or chronic joint symptoms. More than 50% of patients in both samples used over-the-counter topical pain relievers, more than 25% used meditation or drew on religious or spiritual beliefs, and more than 19% used a chiropractor. Women and participants with higher levels of education were more likely to report current use of alternative therapies. Conclusion: Most arthritis patients in both primary care and specialty settings have used CAM for their arthritis symptoms. Health care providers (especially musculoskeletal specialists) should discuss these therapies with all arthritis patients

Resource Allocation in a National Dental Service Using Program Budgeting Marginal Analysis

Introduction: In any health system, choices must be made about the allocation of resources (budget), which are often scarce. Economics has defined frameworks to aid resource allocation, and program budgeting marginal analysis (PBMA) is one such framework. In principle, patient and public values can be incorporated into these frameworks, using techniques such as willingness to pay (WTP). However, this has not been done before, and few formal resource allocation processes have been undertaken in dentistry. This study aimed to undertake a PBMA with embedded WTP values in a national dental setting. Methods: The PBMA process was undertaken by a panel of participant-researchers representing commissioners, dentists, dental public health staff, and academics. The panel reviewed current allocations and generated a set of weighted criteria to evaluate services against. Services to be considered for removal and investment were determined by the panel and wider discussion and then scored against the criteria. Values from a nationally representative WTP survey of the public contributed to the scores for interventions. Final decisions on removal and investment were taken after panel discussion using individual anonymous electronic voting. Results: The PBMA process resulted in recommendations to invest in new program components to improve access to general dentists, care home dentistry, and extra support for dental public health input into local government decisions. Disinvestments were recommended in orthodontics and to remove routine scaling and polishing of teeth. Discussion: The PBMA process was successful in raising awareness of resource allocation issues. Implementation of findings will depend on the ability of decision makers to find ways of operationalizing the decisions. The process illustrates practical aspects of the process that future dental PBMAs could learn from. Knowledge Transfer Statement: This study illustrates a framework for resource allocation in dental health services and will aid decision makers in implementing their own resource allocation systems