Early stages of phase selection in MOF formation observed in molecular Monte Carlo simulations

Metal-organic frameworks (MOF) comprising metal nodes bridged by organic linkers show great promise because of their guest-specific gas sorption, separation, drug-delivery, and catalytic properties. The selection of metal node, organic linker, and synthesis conditions in principle offers engineered control over both structure and function. For MOFs to realise their potential and to become more than just promising materials, a degree of predictability in the synthesis and a better understanding of the self-assembly or initial growth processes is of paramount importance. Using cobalt succinate, a MOF that exhibits a variety of phases depending on synthesis temperature and ligand to metal ratio, as proof of concept, we present a molecular Monte Carlo approach that allows us to simulate the early stage of MOF assembly. We introduce a new Contact Cluster Monte Carlo (CCMC) algorithm which uses a system of overlapping "virtual sites" to represent the coordination environment of the cobalt and both metal-metal and metal-ligand associations. Our simulations capture the experimentally observed synthesis phase distinction in cobalt succinate at 348 K. To the best of our knowledge this is the first case in which the formation of different MOF phases as a function of composition is captured by unbiased molecular simulations. The CCMC algorithm is equally applicable to any system in which short-range attractive interactions are a dominant feature, including hydrogen-bonding networks, metal-ligand coordination networks, or the assembly of particles with "sticky" patches, such as colloidal systems or the formation of protein complexes.</p

Choosing an Evaluation Theory: A Supplement to Evaluation Roots (3rd Edition)

Background: Unlike scientific theories, evaluation theories are prescriptive: a set of actions and approaches that should be followed when conducting an evaluation. While evaluation theorists have offered a variety of writings describing their theories and approaches, few have offered a specific outline of what the theory looks like in practice. Thus, Alkin and Christie formulated a book to aid evaluators in how to apply theories in evaluations (Alkin &amp; Christie, forthcoming). This book culminates in a series of prototypes that outline each theory’s goals, appropriate contexts, prescriptions, and observable actions in application. Purpose: In order to aid evaluators in applying theories, this article seeks to provide a basis for comparison that can be used to help evaluators select which theory would be most appropriate in their practice. Setting: This comparison can be applied in any setting where evaluations fit the context prescribed by each of the theories. Intervention: Not applicable. Research Design: Not applicablre. Data Collection and Analysis: Not applicable. Findings: In order for theories to influence practice effectively, theories must be displayed in a way that allows for easy comparison. This comparison of three theory prototypes demonstrates that prototypes can be an effective way for selecting a prescriptive theory when conducting an evaluation. Keywords: prescriptive theories; practice; empowerment evaluation; learning centered model; developmental evaluatio

Using visualisation methods to analyse referral networks within community health care among patients aged 65 years and over

Community health care services are considered integral to overcoming future problems in health care. However, this sector faces its own challenges, such as how to organise services to provide coordinated care given: their physical distribution, patients using multiple services, increased patient use and differing patient needs. The aim of this work was to explore, analyse and understand patterns in community referrals for patients aged 65 years and over, and their use of multiple services through data visualisation. Working with a large community provider, these methods helped researchers and service managers to investigate questions that were otherwise difficult to answer from raw data. Each map focuses on a different characteristic of community referrals: patients reusing services, concurrent uses of different services and patterns of subsequent referrals. We apply these methods to routine patient data and discuss their implications in designing of a single point of access - a service for streamlining referrals

Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: A retrospective case-control study

Background Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormality that predicts bleeding is unclear, leading to varying transfusion therapy practices. Methods HIE infants treated with TH between 2008–2012 were included in this retrospective study. Initial, minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined as clinically significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24 hours, 2) transfusion of blood products for hemostasis, or 3) involvement of a critical organ system. Laboratory data between the bleeding group (BG) and non-bleeding group (NBG) were compared. Variables that differed significantly between groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses to determine cut-points to predict bleeding. Results Laboratory and bleeding data were collected from a total of 76 HIE infants with a mean (±SD) birthweight of 3.34 ± 0.67 kg and gestational age of 38.6 ± 1.9 wks. BG included 41 infants. Bleeding sites were intracranial (n = 13), gastrointestinal (n = 19), pulmonary (n = 18), hematuria (n = 11) or other (n = 1). There were no differences between BG and NBG in baseline characteristics (p \u3e 0.05). Both groups demonstrated INR and aPTT values beyond the acceptable reference ranges utilized for full tem newborns. BG had higher initial and max INR, initial aPTT, and lower min PLT and min Fib compared to NBG. ROC analyses revealed that platelet count \u3c130 \u3e× 109/L, fib level2 discriminated BG from NBG. Conclusions Laboratory evidence of coagulopathy is universal in HIE babies undergoing TH. Transfusion strategies to maintain PLT counts \u3e130 × 109/L, fib level \u3e1.5 g/L, and INRpopulation

Turbulence driven by outflow-blown cavities in the molecular cloud of NGC 1333

Outflows from young stellar objects have been identified as a possible source of turbulence in molecular clouds. To investigate the relationship between outflows, cloud dynamics and turbulence, we compare the kinematics of the molecular gas associated with NGC 1333, traced in 13CO(1-0), with the distribution of young stellar objects (YSOs) within. We find a velocity dispersion of ~ 1-1.6 km/s in 13CO that does not significantly vary across the cloud, and is uncorrelated with the number of nearby young stellar outflows identified from optical and submillimeter observations. However, from velocity channel maps we identify about 20 cavities or depressions in the 13CO intensity of scales > 0.1-0.2 pc and velocity widths 1-3 km/s. The cavities exhibit limb brightened rims in both individual velocity channel maps and position velocity diagrams, suggesting that they are slowly expanding. We interpret these cavities to be remnants of past YSO outflow activity: If these cavities are presently empty, they would fill in on time scales of a million years. This can exceed the lifetime of a YSO outflow phase, or the transit time of the central star through the cavity, explaining the the absence of any clear correlation between the cavities and YSO outflows. We find that the momentum and energy deposition associated with the expansion of the cavities is sufficient to power the turbulence in the cloud. In this way we conclude that the cavities are an important intermediary step between the conversion of YSO outflow energy and momentum into cloud turbulent motions.Comment: Accepted for publication in ApJ. Check out http://astro.pas.rochester.edu/~aquillen/coolpics.html for channel map and PosVel movies of N133

Dopamine D2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse

Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio-behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D2-receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed, protein expression levels of dopamine D2-receptor were higher in knockout mice compared with wild-type. However, the binding of dopamine D2-receptor agonist was compromised in the same fractions of knockout mice. Coupling efficiency of dopamine D2-receptors to G-proteins was also significantly reduced in knockout mice, supporting the compromised agonist binding. Furthermore, pre-synaptic dopamine release in knockout striatal sections was less responsive than control sections to dopamine D2-receptor ligands. Behaviorally, the locomotor activity of knockout mice was less responsive to the inhibitory effect of quinpirole than wild-type mice. Involvement of specific methionine residue oxidation in the dopamine D2-receptor third intracellular loop is suggested by in vitro studies. We conclude that ablation of methionine sulfoxide reductase can affect dopamine signaling through altering dopamine D2-receptor physiology and may be related to symptoms associated with neurological disorders and diseases

Estimated Ultraviolet Radiation Doses in Wetlands in Six National Parks

Ultraviolet-B radiation (UV-B, 280–320-nm wavelengths) doses were estimated for 1024 wetlands in six national parks: Acadia (Acadia), Glacier (Glacier), Great Smoky Mountains (Smoky), Olympic (Olympic), Rocky Mountain (Rocky), and Sequoia/ Kings Canyon (Sequoia). Estimates were made using ground-based UV-B data (Brewer spectrophotometers), solar radiation models, GIS tools, field characterization of vegetative features, and quantification of DOC concentration and spectral absorbance. UV-B dose estimates were made for the summer solstice, at a depth of 1 cm in each wetland. The mean dose across all wetlands and parks was 19.3 W-h m-2 (range of 3.4–32.1 W-h m-2). The mean dose was lowest in Acadia (13.7 W-h m-2) and highest in Rocky (24.4 W-h m-2). Doses were significantly different among all parks. These wetland doses correspond to UV-B flux of 125.0 µW cm-2 (range 21.4–194.7 µW cm)2) based on a day length, averaged among all parks, of 15.5 h. Dissolved organic carbon (DOC), a key determinant of water-column UV-B flux, ranged from 0.6 (analytical detection limit) to 36.7 mg C L-1 over all wetlands and parks, and reduced potential maximal UV-B doses at 1-cm depth by 1%–87 %. DOC concentration, as well as its effect on dose, was lowest in Sequoia and highest in Acadia (DOC was equivalent in Acadia, Glacier, and Rocky). Landscape reduction of potential maximal UV-B doses ranged from zero to 77% and was lowest in Sequoia. These regional differences in UV-B wetland dose illustrate the importance of considering all aspects of exposure in evaluating the potential impact of UV-B on aquatic organisms

Enhanced protein-energy provision via the enteral route in critically ill patients: a single center feasibility trial of the PEP uP protocol

INTRODUCTION: The purpose of this pilot study is to assess the feasibility, acceptability, and safety of a new feeding protocol designed to enhance the delivery of enteral nutrition (EN). METHODS: In a prospective before and after study, we evaluated a new protocol compared to our standard feeding protocol. Innovative elements of the new protocol included setting daily volume based goals instead of hourly rate targets, initiating motility agents and protein supplements on Day 1, liberalizing the gastric residual volume threshold, and the option to use trophic feeds. Bedside nurses filled out questionnaires to assess the acceptability of the new approach and we assessed patients' nutritional and clinical outcomes. RESULTS: We enrolled 20 mechanically ventilated patients who stayed in the Intensive Care Unit for more than three days in the before group and 30 such patients in the after group. On a scale where 1 = totally unacceptable and 10 = totally acceptable, 30 nurses rated the new protocol as 7.1 (range 1 to 10) and no incidents compromising patient safety were observed. In the before group, on average, patients received 58.8% of their energy and 61.2% of their protein requirements by EN compared to 67.9% and 73.6% in the after group (P = 0.33 and 0.13). When the subgroup of patients prescribed to receive full volume feeds in the after group were evaluated (n = 18), they received 83.2% and 89.4% of their energy and protein requirements by EN respectively (P = 0.02 for energy and 0.002 for protein compared to the before group). The rates of vomiting, regurgitation, aspiration, and pneumonia were similar between the two groups. CONCLUSIONS: This new feeding protocol seems to be safe and acceptable to critical care nurses. The adoption of this protocol may be associated with enhanced delivery of EN but further trials are warranted to evaluate its effect on nutritional and clinical endpoints. TRIAL REGISTRATION: ClinicalTrials.gov NCT0110234

New best1 mutations in autosomal recessive bestrophinopathy

PURPOSE: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. METHODS: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. RESULTS: Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected. CONCLUSION: Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy-associated dominant mutations