A QM-CAMD approach to solvent design for optimal reaction rates

The choice of solvent in which to carry out liquid-phase organic reactions often has a large impact on reaction rates and selectivity and is thus a key decision in process design. A systematic methodology for solvent design that does not require any experimental data on the effect of solvents on reaction kinetics is presented. It combines quantum mechanical computations for the reaction rate constant in various solvents with a computer-aided molecular design (CAMD) formulation. A surrogate model is used to derive an integrated design formulation that combines kinetics and other considerations such as phase equilibria, as predicted by group contribution methods. The derivation of the mixed-integer nonlinear formulation is presented step-by-step. In the application of the methodology to a classic SN2 reaction, the Menschutkin reaction, the reaction rate is used as the key performance objective. The results highlight the tradeoffs between different chemical and physical properties such as reaction rate constant, solvent density and solid reactant solubility and lead to the identification of several promising solvents to enhance reaction performance

A participatory action research approach to strengthening health managers’ capacity at district level in Eastern Uganda

BACKGROUND: Many approaches to improving health managers’ capacity in poor countries, particularly those pursued by external agencies, employ non-participatory approaches and often seek to circumvent (rather than strengthen) weak public management structures. This limits opportunities for strengthening local health managers’ capacity, improving resource utilisation and enhancing service delivery. This study explored the contribution of a participatory action research approach to strengthening health managers’ capacity in Eastern Uganda. METHODS: This was a qualitative study that used open-ended key informant interviews, combined with review of meeting minutes and observations to collect data. Both inductive and deductive thematic analysis was undertaken. The Competing Values Framework of organisational management functions guided the deductive process of analysis and the interpretation of the findings. The framework builds on four earlier models of management and regards them as complementary rather than conflicting, and identifies four managers’ capacities (collaborate, create, compete and control) by categorising them along two axes, one contrasting flexibility versus control and the other internal versus external organisational focus. RESULTS: The findings indicate that the participatory action research approach enhanced health managers’ capacity to collaborate with others, be creative, attain goals and review progress. The enablers included expanded interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability. Tension and conflict across different management functions was apparent; for example, while there was a need to collaborate, maintaining control over processes was also needed. These tensions meant that managers needed to learn to simultaneously draw upon and use different capacities as reflected by the Competing Values Framework in order to maximise their effectiveness. CONCLUSIONS: Improved health manager capacity is essential if sustained improvements in health outcomes in lowincome countries are to be attained. The expansion of interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability were the key means by which participatory action research strengthened health managers’ capacity. The participatory approach to implementation therefore created opportunities to strengthen health managers’ capacity

A specialized rehabilitation approach improves mobility in children with osteogenesis imperfecta

Objective: Osteogenesis imperfecta (OI) is a rare disease leading to recurrent fractures, hyperlaxicity of ligaments, short stature and muscular weakness. Physiotherapy is one important treatment approach. The objective of our analysis was to evaluate the effect of a new physiotherapy approach including side alternating whole body vibration on motor function in children with OI. Methods: In a retrospective analysis data of 53 children were analyzed. The 12 months approach included 6 months of side alternating whole body vibration training, concomitant physiotherapy, resistance training, treadmill training and 6 months follow up. Primary outcome parameter was the Gross Motor Function Measure after 12 months (M12). Results: 53 children (male: 32; age (mean +/- SEM): 9.1 +/- 0.61, range 2.54-24.81 years) participated in the treatment approach. A significant increase of motor function (GMFM-66 score 55.47 +/- 2.45 to 58.67 +/- 2.83; p= 0.001) and walking distance (47.04 m +/- 6.52 to 63.36 +/- 8.25 m (p< 0.01) between M0 and M12 was seen. Total body without head bone mineral density increased significantly at M12 (p= 0.0189). Conclusions: In the cohort of OI children which participated in the specialized treatment approach improvements of motor function were observed. Therefore this program should be considered as additional therapeutic approach for children with severe OI

Los Alamos National Laboratory Report LA-1304

A tentative nickel-plutonium constitutional diagram was based on data obtained by thermal analysis, metallography, and x-ray-diffraction techniques. The systema is a complex one with the following important features. Nickel is soluble in epsilon plutonium, extending the epsilon field to 4.3 at.% nickel at 465 deg C. Nickel and plutonium form six intermetallic compounds, PuNi, EnNi/sub 2/, PuNi/sub 3/, PuNi/sub 4/, PuNi/sub 5/, and PuNi/sub 9/. The compound PuNi/ sub 5/ forms congruently from the melt at approximately l300 deg C, whereas the other compounds form peritectoidally. The extended epsilon field terminates in a eutectoid reaction at 415 deg C and l.5 at.% nickel. Epsilon plutonium and the compound PuNi form a eutectic system at 465 deg C with a eutectic composition of l2.5 at,% nickel. Nickel and the compound PuNi/sub 9/ form a eutectic system at l2l0 deg C with a eutectic composition of 92 at.% nickel. Plutonium forms a limited solid solution with nickel

Detection of a Parkinson's Disease-Specific MicroRNA Signature in Nasal and Oral Swabs

BackgroundBiomaterials from oral and nasal swabs provide, in theory, a potential resource for biomarker development. However, their diagnostic value has not yet been investigated in the context of Parkinson's disease (PD) and associated conditions. ObjectiveWe have previously identified a PD-specific microRNA (miRNA) signature in gut biopsies. In this work, we aimed to investigate the expression of miRNAs in routine buccal (oral) and nasal swabs obtained from cases with idiopathic PD and isolated rapid eye movement sleep behavior disorder (iRBD), a prodromal symptom that often precedes & alpha;-synucleinopathies. We aimed to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression. MethodsHealthy control cases (n = 28), cases with PD (n = 29), and cases with iRBD (n = 8) were prospectively recruited to undergo routine buccal and nasal swabs. Total RNA was extracted from the swab material, and the expression of a predefined set of miRNAs was quantified by quantitative real-time polymerase chain reaction. ResultsStatistical analysis revealed a significantly increased expression of hsa-miR-1260a in cases who had PD. Interestingly, hsa-miR-1260a expression levels correlated with diseases severity, as well as olfactory function, in the PD and iRBD cohorts. Mechanistically, hsa-miR-1260a segregated to Golgi-associated cellular processes with a potential role in mucosal plasma cells. Predicted hsa-miR-1260a target gene expression was reduced in iRBD and PD groups. ConclusionsOur work demonstrates oral and nasal swabs as a valuable biomarker pool in PD and associated neurodegenerative conditions. & COPY;2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Effects of age, parity, and pregnancy abnormalities on foal birth weight and uterine blood flow in the mare

Color Doppler sonography has become routine for the evaluation of high-risk pregnancies in human medicine. Previous studies documenting uterine blood flow parameters in the pregnant mare have found a decrease in peripheral blood flow resistance in the first pregnancy weeks and an increase in uterine blood flow, especially in the last trimester of pregnancy. However, these studies involved only a small number of mares. No naturally occurring pregnancy abnormalities occurred that would allow blood flow changes to be retrospectively examined and analyzed. The objective of the present study was to monitor the diameter of the uterine artery, uterine blood flow, and the combined thickness of the uterus and placenta (CTUP) throughout gestation in a large number of pregnant mares of different age and parity. In the present study, 51 warmblood mares were examined by ultrasonography on Days 16 and 30, at monthly intervals until Day 300, and then every 10 days from Day 300 until parturition. After localization of the uterine artery ipsilateral and contralateral to the conceptus, the diameter of each artery, the uterine blood flow (pulsatility index [PI], blood flow volume [BFV], and the presence of early diastolic notch), and the CTUP were measured and correlated to placental and foal birth weight after delivery. Furthermore, the effect of age (3–7 years [n = 16], 8–11 years [n = 17], 12–16 years [n = 18]) and parity (0–2 foals [n = 22], 3–4 foals [n = 15], 5–8 foals [n = 14]) on these parameters were analyzed. The diameter of the uterine artery increased more than threefold in the ipsilateral artery (0.40 ± 0.07–1.33 ± 0.08 cm) and 2.7-fold in the contralateral artery (0.39 ± 0.07–1.07 ± 0.08 cm [P 52.6 kg) had a 1.38-fold higher BFV in the last 2 months (P < 0.05) compared with lighter foals. Pulsatility index decreased 2-fold until completion of placentation at around Day 150 and continued to decline until Day 240 where it then stayed constant and at a low level until delivery. Age predominantly influenced PI, whereas the diameter of the uterine arteries, which is correlated to BFV (r ipsilateral = 0.919, P < 0.0001 and r contralateral = 0.909, P < 0.000), was strongly affected by parity. Four mares spontaneously aborted (Days 200, 208, 213, and 246) and four mares spontaneously developed placentitis that was diagnosed by the presence of an increased CTUP and/or placental pathology after delivery. Although not statistically relevant, the aborting mares showed a slightly increased total BFV, but no differences in PI were seen compared with mares without abnormalities of pregnancy. Mares that developed placentitis had a late (Days 150–210) disappearance of the early diastolic notch and an increased PI in the first half of pregnancy. In conclusion, the study documented differences in uterine artery diameter and blood flow in a large number of pregnant mares. Furthermore, this is the first known report to document uteroplacental blood flow changes associated with naturally occurring placentitis and abortion in mares