Advancing the Transition to a High Performance Rural Health System

There are growing concerns about the current and future state of rural health. Despite decades of policy efforts to stabilize rural health systems through a range of policies and loan and grant programs, accelerating rural hospital closures combined with rapid changes in private and public payment strategies have created widespread concern that these solutions are inadequate for addressing current rural health challenges. The rural health system of today is the product of legacy policies and programs that often do not “fit” current local needs. Misaligned incentives undermine high-value and efficient care delivery. While there are limitations related to scalability in rural health system development, rural communities do have enormous potential to achieve the objectives of a high performance rural health system. This brief (and a companion paper at http://www.rupri.org/areas-of-work/health-policy/) discusses strategies and options for creating a pathway to a transformed, high performing rural health system

Ischemia monitoring in off-pump coronary artery bypass surgery using intravascular near-infrared spectroscopy

BACKGROUND: In off-pump coronary artery bypass surgery, manipulations on the beating heart can lead to transient interruptions of myocardial oxygen supply, which can generate an accumulation of oxygen-dependent metabolites in coronary venous blood. The objective of this study was to evaluate the reliability of intravascular near-infrared spectroscopy as a monitoring method to detect possible ischemic events in off-pump coronary artery bypass procedures. METHODS: In 15 elective patients undergoing off-pump myocardial revascularization, intravascular near-infrared spectroscopic analysis of coronary venous blood was performed. NIR signals were transferred through a fiberoptic catheter for signal emission and collection. For data analysis and processing, a miniature spectrophotometer with multivariate statistical package was used. Signal acquisition and analysis were performed before and after revascularization. Spectroscopic data were compared with hemodynamic parameters, electrocardiogram, transesophageal echocardiography and laboratory findings. RESULTS: A conversion to extracorporeal circulation was not necessary. The mean number of grafts per patient was 3.1 ± 0.6. An intraoperative myocardial ischemia was not evident, as indicated by electrocardiogram and transesophageal echocardiography. Continuous spectroscopic analysis showed reproducible absorption spectra of coronary sinus blood. Due to uneventful intraoperative courses, clear ischemia-related changes could be detected in none of the patients. CONCLUSION: Our initial results show that intravascular near-infrared spectroscopy can reliably be used for an online intraoperative ischemia monitoring in off-pump coronary artery bypass surgery. However, the method has to be further evaluated and standardized to determine the role of spectroscopy in off-pump coronary artery bypass surgery

Pursuing High Performance in Rural Health Care

Rural Futures Lab Foundation Papers are intended to present current thinking on the economic drivers and opportunities that will shape the future of rural America. They provide the foundation upon which it will be possible to answer the question that drives the Lab’s work—What has to happen today in order to achieve positive rural outcomes tomorrow

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria

<p>Abstract</p> <p>Background</p> <p>Several non-governmental organisations (NGOs) are promoting the use of <it>Artemisia annua </it>teas as a home-based treatment for malaria in situations where conventional treatments are not available. There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.</p> <p>Method</p> <p>A questionnaire about the cultivation of <it>A. annua</it>, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda. Some of the respondents were then selected purposively for more in-depth semi-structured interviews.</p> <p>Results</p> <p>Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought. Overall about 3,000 cases of presumed malaria had been treated with <it>A. annua </it>teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy. The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey. Two miscarriages were reported in pregnant patients. Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using <it>A. annua </it>tea to treat illnesses other than malaria.</p> <p>Conclusions</p> <p>Local cultivation and preparation of <it>A. annua </it>are feasible where growing conditions are appropriate. Few adverse events were reported even in children and pregnant women. Where ACT is in short supply, it would make sense to save it for young children, while using <it>A. annua </it>infusions to treat older patients who are at lower risk. An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.</p

The use of happiness research for public policy

Research on happiness tends to follow a "benevolent dictator" approach where politicians pursue people's happiness. This paper takes an antithetic approach based on the insights of public choice theory. First, we inquire how the results of happiness research may be used to improve the choice of institutions. Second, we show that the policy approach matters for the choice of research questions and the kind of knowledge happiness research aims to provide. Third, we emphasize that there is no shortcut to an optimal policy maximizing some happiness indicator or social welfare function since governments have an incentive to manipulate this indicator

An all order identity between ABJM and N=4 SYM four-point amplitudes

We derive an exact algebraic identity between the two-loop four-point amplitude in ABJM theory and the corresponding one-loop amplitude in N=4 SYM theory. This identity generalizes previous partial results to an exact relation valid at all orders in the IR regulator. Moreover, it allows to conjecture an exact iterative expression for the complete three dimensional amplitude in terms of the BDS ansatz for the four dimensional one, indicating that the strict relation between the two amplitudes experimented at two loops might propagate to all orders. In particular, an almost complete expression for the ABJM amplitude at four loops is derived.Comment: 1+24 page

A Randomized Placebo-Controlled Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Synthetic Peptides in Healthy Adult Volunteers

BACKGROUND AND OBJECTIVES: Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides. The specific objective was to demonstrate the safety and immunogenicity of two virosome-formulated P. falciparum protein derived synthetic peptide antigens given in two different doses alone or in combination. METHODOLOGY/PRINCIPAL FINDINGS: The design was a single blind, randomized, placebo controlled, dose-escalating study involving 46 healthy Caucasian volunteers aged 18-45 years. Five groups of 8 subjects received virosomal formulations containing 10 microg or 50 microg of AMA 49-CPE, an apical membrane antigen-1 (AMA-1) derived synthetic phospatidylethanolamine (PE)-peptide conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP) derived synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 6 subjects received unmodified virosomes. Virosomal formulations of the antigens (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, respectively) or unmodified virosomes were injected i. m. on days 0, 60 and 180. In terms of safety, no serious or severe adverse events (AEs) related to the vaccine were observed. 11/46 study participants reported 16 vaccine related local AEs. Of these 16 events, all being pain, 4 occurred after the 1(st), 7 after the 2(nd) and 5 after the 3(rd) vaccination. 6 systemic AEs probably related to the study vaccine were reported after the 1(st) injection, 10 after the 2(nd) and 6 after the 3(rd). Generally, no difference in the distribution of the systemic AEs between either the doses applied (10 respectively 50 microg) or the synthetic antigen vaccines (PEV301 and PEV302) used for immunization was found. In terms of immunogenicity, both PEV301 and PEV302 elicited already after two injections a synthetic peptide-specific antibody response in all volunteers immunized with the appropriate dose. In the case of PEV301 the 50 microg antigen dose was associated with a higher mean antibody titer and seroconversion rate than the 10 microg dose. In contrast, for PEV302 mean titer and seroconversion rate were higher with the lower dose. Combined delivery of PEV301 and PEV302 did not interfere with the development of an antibody response to either of the two antigens. No relevant antibody responses against the two malaria antigens were observed in the control group receiving unmodified virosomes. CONCLUSIONS: The present study demonstrates that three immunizations with the virosomal malaria vaccine components PEV301 or/and PEV302 (containing 10 microg or 50 microg of antigen) are safe and well tolerated. At appropriate antigen doses seroconversion rates of 100% were achieved. Two injections may be sufficient for eliciting an appropriate immune response, at least in individuals with pre-existing anti-malarial immunity. These results justify further development of a final multi-stage virosomal vaccine formulation incorporating additional malaria antigens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400101

Syntactic learning by mere exposure - An ERP study in adult learners

<p>Abstract</p> <p>Background</p> <p>Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation.</p> <p>Results</p> <p>The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect.</p> <p>Conclusion</p> <p>The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers.</p

No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts

OBJECTIVE: To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with >500 CD4+ cells/μL. DESIGN: Randomized trial. METHODS: The START parent study randomized participants to commence immediate versus deferred ART until CD4+ <350 cells/μL. The START Neurology substudy used 8 neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. RESULTS: 592 participants had a median age of 34 years; median baseline CD4+ count of 629 cells/μL; the mean follow-up was 3.4 years. ART was used for 94% and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI: -0.062 to 0.027, p = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (p < 0.001 for increase from baseline). CONCLUSIONS: We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4+ cell counts above 500 cells/μL