Toward the clinical application of time-domain fluorescence lifetime imaging

High-speed (video-rate) fluorescence lifetime imaging (FLIM) through a flexible endoscope is reported based on gated optical image intensifier technology. The optimization and potential application of FLIM to tissue autofluorescence for clinical applications are discussed. (c) 2005 Society of Photo-Optical Instrumentation Engineers

Countdown to 2015 country case studies: What have we learned about processes and progress towards MDGs 4 and 5?

BACKGROUND: Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. METHODS: Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing). RESULTS: The majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30-40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns - which require higher-level health workers, more infrastructure, and increased community engagement - showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. CONCLUSIONS: These Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements in RMNCH. Interventions with major global investments achieved higher levels of coverage, reduced equity gaps and improvements in associated health outcomes. Given many competing priorities for the Sustainable Development Goals era, it is essential to maintain attention to the unfinished RMNCH agenda, particularly health systems improvements for maternal and neonatal outcomes where progress has been slower, and to invest in data collection for monitoring progress and for rigorous analyses of how progress is achieved in different contexts

Stability and Reversible Oxidation of Sub-Nanometric Cu5 Metal Clusters: Integrated Experimental Study and Theoretical Modeling**

Sub-nanometer metal clusters have special physical and chemical properties, significantly different from those of nanoparticles. However, there is a major concern about their thermal stability and susceptibility to oxidation. In situ X-ray Absorption spectroscopy and Near Ambient Pressure X-ray Photoelectron spectroscopy results reveal that supported Cu5 clusters are resistant to irreversible oxidation at least up to 773 K, even in the presence of 0.15 mbar of oxygen. These experimental findings can be formally described by a theoretical model which combines dispersion-corrected DFT and first principles thermochemistry revealing that most of the adsorbed O2 molecules are transformed into superoxo and peroxo species by an interplay of collective charge transfer within the network of Cu atoms and large amplitude “breathing” motions. A chemical phase diagram for Cu oxidation states of the Cu5-oxygen system is presented, clearly different from the already known bulk and nano-structured chemistry of Cu

Real-time time-domain fluorescence lifetime imaging including single-shot acquisition with a segmented optical image intensifier

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How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

National health policy-makers’ views on the clarity and utility of Countdown to 2015 country profiles and reports: findings from two exploratory qualitative studies

Background: The use of sets of indicators to assess progress has become commonplace in the global health arena. Exploratory research has suggested that indicators used for global monitoring purposes can play a role in national policy-making, however, the mechanisms through which this occurs are poorly understood. This article reports findings from two qualitative studies that aimed to explore national policy-makers’ interpretation and use of indicators from country profiles and reports developed by Countdown to 2015. Methods: An initial study aimed at exploring comprehension of Countdown data was conducted at the 2010 joint Women Deliver/Countdown conference. A second study was conducted at the 64th World Health Assembly in 2011, specifically targeting national policy-makers. Semi-structured interviews were carried out with 29 and 22 participants, respectively, at each event. Participants were asked about their understanding of specific graphs and indicators used or proposed for use in Countdown country profiles, and their perception of how such data can inform national policy-making. Responses were categorised using a framework analysis. Results: Respondents in both studies acknowledged the importance of the profiles for tracking progress on key health indicators in and across countries, noting that they could be used to highlight changes in coverage, possible directions for future policy, for lobbying finance ministers to increase resources for health, and to stimulate competition between neighbouring or socioeconomically similar countries. However, some respondents raised questions about discrepancies between global estimates and data produced by national governments, and some struggled to understand the profile graphs shown in the absence of explanatory text. Some respondents reported that use of Countdown data in national policy-making was constrained by limited awareness of the initiative, insufficient detail in the country profiles to inform policy, and the absence of indicators felt to be more appropriate to their own country contexts. Conclusions: The two studies emphasise the need for country consultations to ensure that national policy-makers understand how to interpret and use tools like the Countdown profile for planning purposes. They make clear the value of qualitative research for refining tools used to promote accountability, and the need for country level Countdown-like processes

Non-operative management of posterior tibialis tendon dysfunction: design of a randomized clinical trial [NCT00279630]

BACKGROUND: Posterior tibialis tendon dysfunction (PTTD) is a common cause of foot pain and dysfunction in adults. Clinical observations strongly suggest that the condition is progressive. There are currently no controlled studies evaluating the effectiveness of exercise, orthoses, or orthoses and exercise on Stage I or IIA PTTD. Our study will explore the effectiveness of an eccentric versus concentric strengthening intervention to results obtained with the use of orthoses alone. Findings from this study will guide the development of more efficacious PTTD intervention programs and contribute to enhanced function and quality of life in persons with posterior tibialis tendon dysfunction. METHODS/DESIGN: This paper presents the rationale and design for a randomized clinical trial evaluating the effectiveness of a treatment regime for the non-operative management of Stage I or IIA PTTD. DISCUSSION: We have presented the rationale and design for an RCT evaluating the effectiveness of a treatment regimen for the non-operative management of Stage I or IIA PTTD. The results of this trial will be presented as soon as they are available

Synthesis of a square-planar rhodium alkylidene N-heterocyclic carbene complex and its reactivity toward alkenes

The first rhodium alkylidene square-planar complex stabilized by an N-heterocyclic carbene ligand, RhCl(-CHPh)(IPr)PPh3 (2; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-carbene), has been prepared by reaction of RhCl(IPr)(PPh3)2 (1) with phenyldiazomethane and its dynamic behavior in solution studied. Treatment of 2 with alkenes results in the formation of the ¿2-olefin complexes RhCl(¿2-CH2-CHR)(IPr)PPh3 (3, R = H; 4, R = Ph; 5, R = OEt) and new olefins arising from the coupling of the alkylidene with the alkenes, likely via a metallacyclobutane intermediate

Leishmania Mitochondrial Peroxiredoxin Plays a Crucial Peroxidase-Unrelated Role during Infection: Insight into Its Novel Chaperone Activity

Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report the functional relevance of one of such enzymes, the mitochondrial 2-Cys peroxiredoxin (mTXNPx), was investigated along the Leishmania infantum life cycle. mTXNPx null mutants (mtxnpx−) produced by a gene replacement strategy, while indistinguishable from wild type promastigotes, were found unable to thrive in a murine model of infection. Unexpectedly, however, the avirulent phenotype of mtxnpx− was not due to lack of the peroxidase activity of mTXNPx as these behaved like controls when exposed to oxidants added exogenously or generated by macrophages during phagocytosis ex vivo. In line with this, mtxnpx− were also avirulent when inoculated into murine hosts unable to mount an effective oxidative phagocyte response (B6.p47phox−/− and B6.RAG2−/− IFN-γ−/− mice). Definitive conclusion that the peroxidase activity of mTXNPx is not required for parasite survival in mice was obtained by showing that a peroxidase-inactive version of this protein was competent in rescuing the non-infective phenotype of mtxnpx−. A novel function is thus proposed for mTXNPx, that of a molecular chaperone, which may explain the impaired infectivity of the null mutants. This premise is based on the observation that the enzyme is able to suppress the thermal aggregation of citrate synthase in vitro. Also, mtxnpx− were more sensitive than controls to a temperature shift from 25°C to 37°C, a phenotype reminiscent of organisms lacking specific chaperone genes. Collectively, the findings reported here change the paradigm which regards all trypanosomatid 2-Cys peroxiredoxins as peroxide-eliminating devices. Moreover, they demonstrate, for the first time, that these 2-Cys peroxiredoxins can be determinant for pathogenicity independently of their peroxidase activity