465 research outputs found

    Field and chirality effects on electrochemical charge transfer rates: Spin dependent electrochemistry

    Get PDF
    This work examines whether electrochemical redox reactions are sensitive to the electron spin orientation by examining the effects of magnetic field and molecular chirality on the charge transfer process. The working electrode is either a ferromagnetic nickel film or a nickel film that is coated with an ultrathin (5\u201330 nm) gold overlayer. The electrode is coated with a self-assembled monolayer that immobilizes a redox couple containing chiral molecular units, either the redox active dye toluidine blue O with a chiral cysteine linking unit or cytochrome c. By varying the direction of magnetization of the nickel, toward or away from the adsorbed layer, we demonstrate that the electrochemical current depends on the orientation of the electrons\u2019 spin. In the case of cytochrome c, the spin selectivity of the reduction is extremely high, namely, the reduction occurs mainly with electrons having their spin-aligned antiparallel to their velocity

    Early versus Delayed Decompression for Traumatic Cervical Spinal Cord Injury: Results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS)

    Get PDF
    BACKGROUND:There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (<24 hours after injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI. METHODS:We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality. FINDINGS:A total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(± 5.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(± 29.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a ≥ 2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21). CONCLUSION:Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up

    Patient Complexity: More Than Comorbidity. The Vector Model of Complexity

    Get PDF
    BACKGROUND: The conceptualization of patient complexity is just beginning in clinical medicine. OBJECTIVES: This study aims (1) to propose a conceptual approach to complex patients; (2) to demonstrate how this approach promotes achieving congruence between patient and provider, a critical step in the development of maximally effective treatment plans; and (3) to examine availability of evidence to guide trade-off decisions and assess healthcare quality for complex patients. METHODS/RESULTS: The Vector Model of Complexity portrays interactions between biological, socioeconomic, cultural, environmental and behavioral forces as health determinants. These forces are not easily discerned but exert profound influences on processes and outcomes of care for chronic medical conditions. Achieving congruence between patient, physician, and healthcare system is essential for effective, patient-centered care; requires assessment of all axes of the Vector Model; and, frequently, requires trade-off decisions to develop a tailored treatment plan. Most evidence-based guidelines rarely provide guidance for trade-off decisions. Quality measures often exclude complex patients and are not designed explicitly to assess their overall healthcare. CONCLUSIONS/RECOMMENDATIONS: We urgently need to expand the evidence base to inform the care of complex patients of all kinds, especially for the clinical trade-off decisions that are central to tailoring care. We offer long- and short-term strategies to begin to incorporate complexity into quality measurement and performance profiling, guided by the Vector Model. Interdisciplinary research should lay the foundation for a deeper understanding of the multiple sources of patient complexity and their interactions, and how provision of healthcare should be harmonized with complexity to optimize health

    Comparison of three methods for detection of gametocytes in Melanesian children treated for uncomplicated malaria

    Get PDF
    Background: Gametocytes are the transmission stages of Plasmodium parasites, the causative agents of malaria. As their density in the human host is typically low, they are often undetected by conventional light microscopy. Furthermore, application of RNA-based molecular detection methods for gametocyte detection remains challenging in remote field settings. In the present study, a detailed comparison of three methods, namely light microscopy, magnetic fractionation and reverse transcriptase polymerase chain reaction for detection of Plasmodium falciparum and Plasmodium vivax gametocytes was conducted.Methods. Peripheral blood samples from 70 children aged 0.5 to five years with uncomplicated malaria who were treated with either artemether-lumefantrine or artemisinin-naphthoquine were collected from two health facilities on the north coast of Papua New Guinea. The samples were taken prior to treatment (day 0) and at pre-specified intervals during follow-up. Gametocytes were measured in each sample by three methods: i) light microscopy (LM), ii) quantitative magnetic fractionation (MF) and, iii) reverse transcriptase PCR (RTPCR). Data were analysed using censored linear regression and Bland and Altman techniques.Results: MF and RTPCR were similarly sensitive and specific, and both were superior to LM. Overall, there were approximately 20% gametocyte-positive samples by LM, whereas gametocyte positivity by MF and RTPCR were both more than two-fold this level. In the subset of samples collected prior to treatment, 29% of children were positive by LM, and 85% were gametocyte positive by MF and RTPCR, respectively.Conclusions: The present study represents the first direct comparison of standard LM, MF and RTPCR for gametocyte detection in field isolates. It provides strong evidence that MF is superior to LM and can be used to detect gametocytaemic patients under field conditions with similar sensitivity and specificity as RTPCR

    Neurobiology of rodent self-grooming and its value for translational neuroscience

    Get PDF
    Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders-including models of autism spectrum disorder and obsessive compulsive disorder-that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.National Institutes of Health (U.S.) (Grant NS025529)National Institutes of Health (U.S.) (Grant HD028341)National Institutes of Health (U.S.) (Grant MH060379

    Quality of life in patients treated with first-line antiretroviral therapy containing nevirapine or efavirenz in Uganda: A prospective non-randomized study

    Get PDF
    © 2015 Mwesigire et al. Background: The goal of antiretroviral therapy (ART) is to suppress viral replication, reduce morbidity and mortality, and improve quality of life (QoL). For resource-limited settings, the World Health Organization recommends a first-line regimen of two-nucleoside reverse-transcriptase inhibitors and one non-nucleoside transcriptase inhibitor (nevirapine (NVP) or efavirenz (EFV)). There are few data comparing the QoL impact of NVP versus EFV. This study assessed the change in QoL and factors associated with QoL among HIV patients receiving ART regimens based on EFV or NVP. Methods: We enrolled 640 people with HIV eligible for ART who received regimens including either NVP or EFV. QoL was assessed at baseline, three months and six months using Physical Health Summary (PHS) and Mental Health Summary (MHS) scores and the Global Person Generated Index (GPGI). Data were analyzed using generalized estimating equations, with ART regimen as the primary exposure, to identify associations between patient and disease factors and QoL. Results: QoL increased on ART. The mean QoL scores did not differ significantly for regimens based on NVP versus EFV during follow-up for MHS and GPGI regardless of CD4 stratum and for PHS among patients with a CD4 count >250 cells/μL. The PHS-adjusted β coefficients for ART regimens based on EFV versus NVP by CD4 count strata were as follows: -1.61 (95 % CI -2.74, -0.49) for CD4 count 250 cells/μL. The corresponding MHS-adjusted β coefficients were as follows: -0.39 (-1.40, 0.62) for CD4∈250 cells/μL. The GPGI-adjusted odds ratios for EFV versus NVP were 0.51 (0.25, 1.04) for CD4 count ∈250 cells/μL. QoL improved among patients on EFV over the 6-month follow-up period (MHS p

    A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission

    Get PDF
    Novel diagnostic tools, including PCR and high field gradient magnetic fractionation (HFGMF), have improved detection of asexual Plasmodium falciparum parasites and especially infectious gametocytes in human blood. These techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (LM).To determine how low-level gametocytemia may affect transmission in present large-scale efforts for P. falciparum control in endemic areas, we developed a refinement of the classical Ross-Macdonald model of malaria transmission by introducing multiple infective compartments to model the potential impact of highly prevalent, low gametocytaemic reservoirs in the population. Models were calibrated using field-based data and several numerical experiments were conducted to assess the effect of high and low gametocytemia on P. falciparum transmission and control. Special consideration was given to the impact of long-lasting insecticide-treated bed nets (LLIN), presently considered the most efficient way to prevent transmission, and particularly LLIN coverage similar to goals targeted by the Roll Back Malaria and Global Fund malaria control campaigns. Our analyses indicate that models which include only moderate-to-high gametocytemia (detectable by LM) predict finite eradication times after LLIN introduction. Models that include a low gametocytemia reservoir (requiring PCR or HFGMF detection) predict much more stable, persistent transmission. Our modeled outcomes result in significantly different estimates for the level and duration of control needed to achieve malaria elimination if submicroscopic gametocytes are included.It will be very important to complement current methods of surveillance with enhanced diagnostic techniques to detect asexual parasites and gametocytes to more accurately plan, monitor and guide malaria control programs aimed at eliminating malaria

    Syndromics: A Bioinformatics Approach for Neurotrauma Research

    Get PDF
    Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings
    corecore