Icosahedral (A5) Family Symmetry and the Golden Ratio Prediction for Solar Neutrino Mixing

We investigate the possibility of using icosahedral symmetry as a family symmetry group in the lepton sector. The rotational icosahedral group, which is isomorphic to A5, the alternating group of five elements, provides a natural context in which to explore (among other possibilities) the intriguing hypothesis that the solar neutrino mixing angle is governed by the golden ratio. We present a basic toolbox for model-building using icosahedral symmetry, including explicit representation matrices and tensor product rules. As a simple application, we construct a minimal model at tree level in which the solar angle is related to the golden ratio, the atmospheric angle is maximal, and the reactor angle vanishes to leading order. The approach provides a rich setting in which to investigate the flavor puzzle of the Standard Model.Comment: 22 pages, version to be published in Phys. Rev.

Human monoclonal antibodies to Plasmodium falciparum circumsporozoite protein for transient passive protection of malaria travelers to endemic areas

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment. The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite development into a blood-stage infection that causes malaria morbidity and mortality. Antibodies isolated from individuals who have received the RTS,S vaccine have been shown to prevent infection of hepatocytes, suggesting that CSP antibodies could be used prophylactically. However, phase III trial results of the vaccine have shown underwhelming efficacy in children. Growing resistance to transient protection strategies for travelers and low efficacy in vaccine trials suggest there is a need for a new treatment strategy. The generation of CSP specific human monoclonal antibodies (mAbs) would be useful as prevention especially for individuals that are temporarily exposed to Malaria in endemic regions such as travelers or military personnel. Isolation and production of therapeutic mAbs traditionally utilizes a handful of techniques including antibody engineering, phage display or hybridoma generation from transgenic mice. We have sorted antigen-specific memory B-cells from the peripheral blood of children naturally infected with malaria to isolate CSP-specific memory B-cells. These cells were individually sorted and PCR was performed to amplify antibody variable regions of the B-cell’s antibody mRNA. Samples that produced heavy and light chain antibody sequence were cloned and transiently expressed. We plan to characterize these mAbs for binding and neutralization of CSP to identify functional therapeutic mAbs

Do people with Parkinson’s disease look at task relevant stimuli when walking? An exploration of eye movements

Eye movements are impaired by Parkinson's disease (PD) although limited research has explored if PD affects the relevance of visual fixations when walking. Visual fixations may provide crucial contextual information for safe navigation and important insights into fall risk. This study aimed to: investigate visual fixations made while walking under a range of conditions in PD; identify their task relevance; and explore their relationship with clinical features. Thirty-eight people with mild-moderate PD and forty age-matched control participants completed a straight walk with (i) no additional stimuli and (ii) with additional stimuli (visual cues or a high contrast obstacle), whilst wearing a mobile eye-tracker. Fixations were extracted and classified by location and relevance. PD participants made proportionally fewer task-relevant fixations (floor, walls and additional stimuli ahead), caused by significantly more task-irrelevant fixations (floor, walls and ceiling away from waking path) during normal walking (p = 0.014). These group differences were not apparent with visual cues (p = 0.359). During obstacle crossing trials, PD made significantly more task-relevant fixations than controls (p = 0.007). Reduced bilateral visual acuity was associated with fewer fixations in PD. Our findings suggest that people with PD visually explore complex environments less efficiently likely owing to underlying PD pathology. Visual exploration improved with the addition of salient stimuli (for example visual cues or an obstacle) and thus developing and optimising visual interventions could prove critical to improving locomotor safety and reducing falls risk in home environments

Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction

BACKGROUND: Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin angiotensin system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic minipump in mice. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). OBJECTIVES: To evaluate effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post infarction. METHODS: C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular (LV) pressure-volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation–contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff perfused whole heart model. RESULTS: Gene delivery of Ang-(1-9) significantly reduced sudden cardiac death post-MI. Pressure–volume measurements revealed complete restoration of end systolic pressure, ejection fraction, end systolic volume and the end diastolic pressure–volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and increasing contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. CONCLUSIONS: Our novel findings show that Ang-(1-9) gene therapy preserves LV systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) has a direct effect on cardiomyocyte 3 calcium handling through a protein kinase A-dependent mechanism. These data highlight Ang-(1-9) gene therapy as a potential new strategy in the context of MI

Supporting weight management services during the COVID-19 pandemic: Phase I insights

Societal changes required to manage the coronavirus (COVID-19) pandemic may have inadvertently promoted weight gain, due to the adverse impact on socio-economics, psychological health, and the resulting metabolic impact of elevated stress, emotional eating and physical inactivity. Evidence on the impact of COVID-19 has rapidly accumulated, to demonstrate that people living with obesity are at higher risk of severe illness from COVID-19 infection. It is therefore important to understand what is happening in terms of weight management practice to develop local and national thinking. This project will explore the impact of the COVID-19 upon the provision of tier 2 and 3 weight management services (WMS) in England during the lockdown period (phase I; March-June 2020); and determine what needs to happen in the future (phase II; September-November 2020). This report documents findings from phase I

Antiparkinson Drug Adherence and Its Association with Health Care Utilization and Economic Outcomes in a Medicare Part D Population

AbstractObjectivesWe examine the associations of adherence to antiparkinson drugs (APDs) with health care utilization and economic outcomes among patients with Parkinson’s disease (PD).MethodsBy using 2006–2007 Medicare administrative data, we examined 7583 beneficiaries with PD who filled two or more APD prescriptions during 19 months (June 1, 2006, to December 31, 2007) in the Part D program. Two adherence measures— duration of therapy (DOT) and medication possession ratio (MPR)—were assessed. Negative binomial and gamma generalized linear models were used to estimate the rate ratios (RRs) of all-cause health care utilization and expenditures, respectively, conditional upon adherence, adjusting for survival risk, sample selection, and health-seeking behavior.ResultsApproximately one-fourth of patients with PD had low adherence (MPR < 0.80, 28.7%) or had a short DOT (≤400 days, 23.9%). Increasing adherence to APD therapy was associated with decreased health care utilization and expenditures. For example, compared with patients with low adherence, those with high adherence (MPR = 0.90–1.00) had significantly lower rates of hospitalization (RR = 0.86), emergency room visits (RR = 0.91), skilled nursing facility episodes (RR = 0.67), home health agency episodes (RR = 0.83), physician visits (RR = 0.93), as well as lower total health care expenditures (−$2242), measured over 19 months. Similarly, lower total expenditure (−$6308) was observed in patients with a long DOT versus those with a short DOT.ConclusionsIn this nationally representative sample, higher adherence to APDs and longer duration of use of APDs were associated with lower all-cause health care utilization and total health care expenditures. Our findings suggest the need for improving medication-taking behaviors among patients with PD to reduce the use of and expenditures for medical resources