Variable Capacities Research Articles

In silico design of a universal carrier protein: A potential solution to the variable immunogenicity observed in past vaccines against drugs of abuse

Abstract Vaccines against drugs of abuse (VADAs) show promise as a possible therapeutic for the alleviation of addiction due to their ability to modulate intake behavior via the altering of drug pharmacokinetics. In the past, however, these vaccines have failed to show clinical efficacy due to extensive variability in the magnitude of antibody response between individual vaccinees. Correspondingly, the future success of VADAs hinges directly on whether or not researchers can find ways to engineer more broadly effective vaccines. Differences in response must, to some extent, be the result of variable capacities for each individual’s immune system to process and/or present antigens. As such, we speculate that future VADAs will need to target the three key stages of vaccine processing, recognition, processing, and presentation, in order to achieve clinical effectiveness. Here, we describe a project aiming to engineer a broadly effective carrier protein based on this concept. Using haplotype frequency data provided by Be the Match, HLA-DQ and -DR haplotypes covering 99% of the population were selected for analysis. Next, the most common carrier proteins used in conjugate vaccine formulations were analyzed for MHC II epitope content using these haplotypes and NetMHCIIPan 3.2 prediction software. Finally, a modified version of the prediction output was used to excise the most likely MHC II epitopes. The highest-ranked epitopes were then stitched together using linkers designed with chemical conjugation sites and cathepsin cleavage sequences and subsequently tethered to cholera toxin subunit B. These results present the successful design of an in silico derived, broadly effective carrier protein to be used in future VADA formulations.

Leaf isoprene and monoterpene emission distribution across hyperdominant tree genera in the Amazon basin

Tropical forests are acknowledged to be the largest global source of isoprene (C5H8) and monoterpenes (C10H16) emissions, with current synthesis studies suggesting few tropical species emit isoprenoids (20–38%) and do so with highly variable emission capacities, including within the same genera. This apparent lack of a clear phylogenetic thread has created difficulties both in linking isoprenoid function with evolution and for the development of accurate biosphere-atmosphere models. Here, we present a systematic emission study of “hyperdominant” tree species in the Amazon Basin. Across 162 individuals, distributed among 25 botanical families and 113 species, isoprenoid emissions were widespread among both early and late successional species (isoprene: 61.9% of the species; monoterpenes: 15.0%; both isoprene and monoterpenes: 9.7%). The hyperdominant species (69) across the top five most abundant genera, which make up about 50% of all individuals in the Basin, had a similar abundance of isoprenoid emitters (isoprene: 63.8%; monoterpenes: 17.4%; both 11.6%). Among the abundant genera, only Pouteria had a low frequency of isoprene emitting species (15.8% of 19 species). In contrast, Protium, Licania, Inga, and Eschweilera were rich in isoprene emitting species (83.3% of 12 species, 61.1% of 18 species, 100% of 8 species, and 100% of 12 species, respectively). Light response curves of individuals in each of the five genera showed light-dependent, photosynthesis-linked emission rates of isoprene and monoterpenes. Importantly, in every genus, we observed species with light-dependent isoprene emissions together with monoterpenes including β-ocimene. These observations support the emerging view of the evolution of isoprene synthases from β-ocimene synthases. Our results have important implications for understanding isoprenoid function-evolution relationships and the development of more accurate Earth System Models.

Coexistence of nuclear and renewables in the V4 electricity system: Friends or enemies?

The paper examines the interactions between nuclear and variable renewable generation capacities (vRES) under various assumptions in the broader V4 region. Four exploratory scenarios are analysed with high and low penetration levels of vRES and nuclear applying electricity dispatch and unit commitment models. The assessment quantifies the impacts of the joint evolution of these technologies, measuring the effect on utilisation rates, wholesale prices, market values of vRES, energy not supplied (ENS) and the changing production and trading patterns in the projected 2035 electricity system. The results are indicative of a ‘double competition’ between (i) nuclear and vRES technologies within the merit order and (ii) between the NPPs in the region. If the ambitious V4 nuclear plans are indeed execute, NPPs will compete for limited export opportunities during times of high vRES production periods. Thus, coordination of long term energy policies within the V4 region is critical to manage nuclear and vRES developments and trade patterns with the aim of improving flexibility and security of supply to mitigate the negative economic impact on the electricity system.

Regulating Medicines in a Globalized World With Increased Recognition and Reliance Among Regulators

Research and development of pharmaceuticals are now complex global endeavors, with drug companies operating worldwide using global supply chains. Pharmaceutical companies source their products from many countries, conduct trials in multiple sites, and market essential drugs and vaccines globally. Yet oversight of drug safety and effectiveness is primarily the responsibility of national regulators of variable capacities. National agencies often undertake product reviews without recognizing that similar reviews are occurring elsewhere, sometimes simultaneously. The result is duplication and redundancy, which benefits neither national nor global public health. Supported by the US Food and Drug Administration (FDA), the National Academies of Sciences, Engineering, and Medicine convened an expert committee to explore the benefits of mutual recognition and other reliance activities among regulators. Even well-resourced regulators (for example, the FDA, the European Medicines Agency, the Pharmaceutical and Medical Devices Agency Japan, and Health Canada) find it difficult to ensure the safety, efficacy, and quality of medicines in a globalized world. Regulatory failures cause harm to the population and undermine public trust in government. In 2008, following discovery of contaminated heparin originating from China, the Bush administration authorized the FDA to coordinate certain product manufacturing inspections with Australian and European regulators in China and India — setting the stage for “third country” inspections (ie, inspections conducted outside the jurisdiction of either regulator). Yet concerns about the quality of active pharmaceutical ingredients and finished pharmaceutical products persist. For example, in 2018, the FDA recalled generic medications used to treat hypertension and cardiovascular disease because of contamination.

A novel pinch-based method for process integration and optimization of Kalina cycle

Low-and-medium waste heat utilization is crucial for alleviating energy dilemma and carbon dioxide emissions in industrial plants. Although Organic Rankine Cycle (ORC) has made significant advances in waste heat recovery, other equally important thermodynamic ways to recover waste heat such as Kalina Cycle (KC) have not been fully explored. In this study, a novel pinch-based mathematical model is developed for process integration and optimization of Kalina Cycle. The model performs heat integration with variable heat capacities and enables the modifications of KC simultaneously, in a bid for generating maximum net power output without increasing the amount of hot utility. The proposed model allows for non-isothermal phase transition of working fluid and can be extended to handle multiple Kalina Cycles combined with process integration, thus enhancing waste heat recovery efficiency. The effectiveness of the proposed method is verified by a well-studied example from literature, in which the net power output is increased by 12.2% compared to the results using existing literature approaches. Furthermore, the developed model has been successfully applied to the post-combustion carbon capture process, where proper integration of process and Kalina Cycle leads to a 15.8% increase in net power output and a 4.13 percentage point decrease in the efficiency penalty.

A robust optimization model for affine/quadratic flow thinning: A traffic protection mechanism for networks with variable link capacity

AbstractFlow thinning (FT) is a traffic protection mechanism for communication networks with variable link capacities, for example wireless networks. With FT, end‐to‐end traffic demands use dedicated logical tunnels, for example MPLS tunnels, whose nominal capacity is subject to thinning in order to follow fluctuations in link capacities availability. Moreover, instantaneous traffic of each demand is throttled at its originating node accordingly to the current total capacity available on the demand's dedicated tunnels so that the network is always capable of carrying the admitted traffic. In this paper, we deal with efficient, implementable versions of FT, referred to as affine FT (AFT) and quadratic FT (QFT). By deriving appropriate link availability state and path generation algorithms, we show how real‐life network dimensioning problems for AFT/QFT can be efficiently treated using a proper characterization of the network link availability states. Results of a numerical study illustrate tractability of the cost minimization problems, and assess efficiency of AFT/QFT as compared with other protection mechanisms.

Non-profit resource allocation and service scheduling with cross-subsidization and uncertain resource consumptions

We consider a mixture of for-profit and non-profit requests that share multiple resources at random consumption rates. The revenue from fulfilling for-profit requests is used to cross-subsidize the cost of non-profit operations, and we aim to maximize the number of completed non-profit service requests. We consider two problems that respectively optimize resource allocation and service schedules, and employ chance constraints to restrict the probability of undesired outcomes such as resource over-utilization and service delay. For the allocation model, we propose three approximations of the chance-constrained program, and derive their variants to allow variable resource capacities. For the scheduling model, we derive a mixed-integer linear programming reformulation and develop a two-phase algorithm that separately decides allocation decisions and the start time of each service request. We conduct numerical studies on randomly generated instances of non-profit surgery planning to demonstrate the computational results of different models, and the impact of varying parameters and cross-subsidization on non-profit operations.

Full-Annulus URANS Study on the Transportation of Combustion Inhomogeneity in a Four-Stage Cooled Turbine

AbstractThe inhomogeneity of temperature in a turbine is related to the nonuniform heat release and air injections in combustors, which is commonly measured by thermal couples at the turbine exit. Investigation of temperature inhomogeneity transportation in a multistage gas turbine should help in detecting and quantifying the over-temperature or flameout of combustors using turbine exhaust temperature. Here, the transportation of combustion inhomogeneity inside the four-stage turbine of a 300-MW gas turbine engine was numerically investigated. The computational domain included four turbine stages, consisting of more than 500 blades and vanes. Realistic components (N2, O2, CO2, and H2O) with variable heat capacities were considered for hot gas and cooling air. Coolants were added to the computational domain through more than 19,000 mass and momentum source terms. An unsteady Reynolds averaged Navier–Stokes computational fluid dynamics (URANS CFD) run with over-temperature/flameout at 6 selected combustors out of 24 was carried out. The temperature distributions at rotor–stator interfaces and the turbine outlet were quantified and characterized using Fourier transformations in the space domain. It is found that the transport process from the hot streaks/cold streaks at the inlet to the outlet is relatively stable. The cold and hot fluid is redistributed in time and space due to the stator and rotor blades, and in the region with a large parameter gradient at the inlet, a strong unsteady temperature field and a composition field appear. The distribution of the exhaust-gas composition has a stronger correlation with the inlet temperature distribution and is less susceptible to interactions.

Staphylococcus aureus ST398 Virulence Is Associated With Factors Carried on Prophage ϕSa3.

An increasing number of severe infections caused by Staphylococcus aureus ST398 strains has been observed. However, it has not been elucidated whether all ST398 strains are equally virulent. We collected 13 strains from China and Canada to test in a Caenorhabditis elegans infection model and compared their whole genome sequences (WGS) to explore potential insights into their virulence. All isolates belonged to ST398-methicillin-susceptible S. aureus (MSSA) with variant spa types (t034, t571, t1451, t1250). Pulsed field gel electrophoresis (PFGE) and WGS analyses showed that the 13 isolates clustered into 3 genomic types (Types A-C). WGS and prophage phylogenetic analyses also revealed that the strains could be divided into 3 phage groups (Groups 1–3), which correlated with high-, moderate-, and low-nematocidal activities, with mean killing rates of 94, 67, and 40%, respectively. Group 1 carried ϕSa3-Group 1 (ϕSa3-G1), Group 2 carried ϕSa3-G2, and Group 3 lacked ϕSa3. Interestingly, strain GD1706 (that genetically clustered within Type C) and strain GD487 (within Type B) both carried ϕSa3-G1 like phages and killed 92% of the nematodes, similar to the Type A strains carrying ϕSa3-G1. This study demonstrated that different ST398 sub-lineages possess variable virulence capacities, depending on the presence or absence, as well as the structure of the prophage ϕSa3 that carries virulence factors.IMPORTANCESince first being reported in the early 2000s, Staphylococcus aureus ST398 has not only become recognized as a frequent colonizing strain in economically important livestock animals, but has also proven to be a concern for infection in humans and, in particular, has been linked to higher rates of severe invasive human infections. We collected ST398 strains from China and Canada to test in a worm (Caenorhabditis elegans) infection model and compared their whole genome sequences to gain insight into pathogenesis. We have shown that different ST398 sub-strains differ in their virulence potential based on the presence or absence and structure of prophage ϕSa3, which carries important virulence factors. Our observations suggest that ST398 strains are relatively heterogeneous from a clinical perspective, and more studies are needed to differentiate between virulent and non-virulent ST398 strains to determine the true global spread of relevant sub-strains.

There Is Treasure Everywhere: Reductive Plastid Evolution in Apicomplexa in Light of Their Close Relatives.

The phylum Apicomplexa (Alveolates) comprises a group of host-associated protists, predominately intracellular parasites, including devastating parasites like Plasmodium falciparum, the causative agent of malaria. One of the more fascinating characteristics of Apicomplexa is their highly reduced (and occasionally lost) remnant plastid, termed the apicoplast. Four core metabolic pathways are retained in the apicoplast: heme synthesis, iron–sulfur cluster synthesis, isoprenoid synthesis, and fatty acid synthesis. It has been suggested that one or more of these pathways are essential for plastid and plastid genome retention. The past decade has witnessed the discovery of several apicomplexan relatives, and next-generation sequencing efforts are revealing that they retain variable plastid metabolic capacities. These data are providing clues about the core genes and pathways of reduced plastids, while at the same time further confounding our view on the evolutionary history of the apicoplast. Here, we examine the evolutionary history of the apicoplast, explore plastid metabolism in Apicomplexa and their close relatives, and propose that the differences among reduced plastids result from a game of endosymbiotic roulette. Continued exploration of the Apicomplexa and their relatives is sure to provide new insights into the evolution of the apicoplast and apicomplexans as a whole.

Abstract GS3-05: Prospective optimization of estrogen receptor degradation yields ER ligands with variable capacities for ER transcriptional suppression

Abstract ER+ breast cancers can depend on ER signaling throughout disease progression, including after acquired resistance to existing endocrine agents, providing a rationale for further optimization and development of ER-targeting agents. Fulvestrant is unique amongst currently approved ER ligand therapeutics due to classification as a full ER antagonist, which is thought to be achieved through degradation of ER protein. However, the full clinical potential of fulvestrant is believed to be limited by poor bioavailability, spurring attempts to generate ligands capable of driving ER degradation but with improved drug-like properties. Here, we evaluate three ER ligand clinical candidates that recently emerged from prospective optimization of ER degradation – GDC-0810, AZD9496 and GDC-0927 - and show that they display distinct mechanistic features. GDC-0810 and AZD9496 are more limited in their ER degradation capacity relative to GDC-0927 and fulvestrant, display evidence of weak transcriptional activation of ER in breast cancer cells (i.e. partial agonist activity), and do not achieve the same degree of in vitro anti-proliferative activity as GDC-0927 and fulvestrant. In the HCI-013 (ER.Y537S) and HCI-011 (ER.WT) ER+ patient-derived xenograft models, GDC-0927 drives greater transcriptional suppression of ER, and greater anti-tumor activity relative to GDC-0810. We found that despite their full antagonist phenotype, GDC-0927 and fulvestrant promote association of ER with DNA, including at canonical ERE motifs, prior to ER degradation. Interestingly however, integration of ER ChIP-Seq and ATAC-Seq data revealed that ER complexed with fulvestrant or GDC-0927 fails to increase chromatin accessibility at DNA binding sites, in contrast to partial agonists which result in increased chromatin accessibility at ER binding sites. Thus, although ER contacts DNA when engaged with fulvestrant and GDC-0927, it is functionally inert. To further explore mechanistic features that might account for the differential activity of full antagonists and partial agonists that occurs prior to ER degradation, we used cell-based florescence recovery after photobleaching (FRAP) to measure the kinetics of ER diffusion within the nucleus. We demonstrate that while ER is generally highly mobile, including after engagement with GDC-0810 and AZD9496, GDC-0927 and fulvestrant immobilize intra-nuclear ER. A site saturating mutagenesis screen revealed a series of novel ER mutations that prevent ER immobilization by fulvestrant and GDC-0927. This class of “always mobile” ER variants promotes an antagonist-to-agonist transcriptional switch for fulvestrant and GDC-0927, and simultaneously prevents ER degradation by these molecules, implying that ER immobilization is a key functional determinant of robust transcriptional suppression. We thus propose that ER degradation is not a driver of full ER antagonism, but rather a downstream consequence of ER immobilization, occurring after a suppressive phenotype has been established at chromatin. We additionally argue that evaluating the transcriptional output of candidate ER therapeutics, both pre-clinically and clinically, will be critical for the identification of ER ligands with best-in-class potential. Citation Format: Metcalfe C, Zhou W, Guan J, Daemen A, Hafner M, Blake RA, Ingalla E, Young A, Oeh J, De Bruyn T, Ubhayakar S, Chen I, Giltnane JM, Li J, Wang X, Sampath D, Hager JH, Friedman LS. Prospective optimization of estrogen receptor degradation yields ER ligands with variable capacities for ER transcriptional suppression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-05.

Lattice Boltzmann advection-diffusion model for conjugate heat transfer in heterogeneous media

Abstract Many practical flow configurations involve energy transfer in fluids, or in solids and fluids with different thermo-physical properties. The classical advection-diffusion lattice Boltzmann (LB) solver admits some errors when dealing with such configurations. Given that the macroscopic equation recovered by this model is only valid in the limit of incompressible flows with constant heat capacities, one would, for example, observe inconsistent fluxes at the interface of a fluid and solid with different densities or specific heat capacities. This inconsistency being second-order in space, it will have non-negligible effects on the final results. In this work, a modified equilibrium distribution function (EDF) is proposed to overcome these issues. The proposed scheme recovers the correct partial differential equation (PDE) describing energy transfer, as shown by a multi-scale Chapman–Enskog analysis. The performance of the model is checked through a variety of test-cases, involving conjugate heat transfer and variable specific heat capacities in both steady and unsteady configurations. In all cases the obtained results are in excellent agreement with reference data.

Future developments and advances in disinfectants and application modes for use in departments, military units and medical facilities in a climate of the Arctic and Extreme North

There were performed test and development review concerning disinfection procedures in a climate of the Arctic and Extreme North, an assessment of their sophistication, and determination of possible ways to enhancement of efficiency. It was found that long-term low temperatures, geographical distance and hard-to-reach territories, weak natural self-regeneration mechanism of biocenosis, development of human hypersensitivity to infectious agents, congestion of personnel at camping and operation places define the urgency of creation of modern chemical and technical disinfectants which are effective in the north. The basic requirements to these disinfectants were formulated. Thus, process chemical solutions should not become frozen over a period that biocide effect takes; disinfectants to use in human presence should meet the operational criteria for sealable inhabited objects. Engineering tools should be equipped with productive snowmelters, heat-insulated rooms, all-terrain running gear, liquid fuel -powered cauldrons, heaters, electric power station. Promising directions of new disinfectants advancing and development were determined. It’s necessary to study infectious and parasitic morbidity in the Arctic and Extreme North, the causes and conditions governing its structure and dynamics, specificity of epidemic process. The establishment of special climate chambers with variable capacities for materials and goods disinfection mode development, including the use of engineering tools; it is essential to choose or develop the study methods of arctic climatic factors influence on test microorganisms, operating procedure behavior of disinfection, worked objects’ properties. The studies of microbial contamination specifics seemed perspective, both in the environment and within inhabited objects, under long-term exposure of low temperatures; the search of biocidic technologies and factors for making disinfectants, modes and methods of application; substantiation of disinfection procedures tactics. Instructional and methodological base preparing will allow to perform perspective studies and disinfection procedures in a climate of the Arctic and Extreme North in accordance with contemporary requirements.

Timing matters: survey timing during extended heat stress can influence perceptions of coral susceptibility to bleaching

The frequency and duration of episodic ocean warming events are increasing, threatening the integrity of coral reefs globally. Interspecific differences in susceptibility to heat stress result from variable capacities of corals to resist bleaching or to persist in a bleached state. During shorter bleaching events, stress responses occur rapidly and the “window” for detecting bleaching is tightly constrained. However, during longer bleaching events, we argue that the timing of surveys can radically influence results, which need to be interpreted with care. For example, although “heat-resistant” corals may survive prolonged bleaching events, they have a greater chance of being recorded as having bleached because they can persist for longer in a bleached state. This could lead to erroneous conclusions about their vulnerability to heat stress compared with taxa that bleach and die rapidly. Therefore, as bleaching events lengthen, it is vital to consider not only temperature at the time of sampling, but also the accumulation of heat stress over the entire warming event. We present a simplified conceptual framework and an example from the Central Pacific to emphasize the importance of survey timing to perceived susceptibility of coral taxa to bleaching.

Moist Adiabats with Multiple Condensing Species: A New Theory with Application to Giant-Planet Atmospheres

AbstractA new formula is derived for calculating the moist adiabatic temperature profile of an atmosphere consisting of ideal gases with multiple condensing species. This expression unifies various formulas published in the literature and can be generalized to account for chemical reactions. Unlike previous methods, it converges to machine precision independent of mesh size. It accounts for any ratio of condensable vapors to dry gas, from zero to infinity, and for variable heat capacities as a function of temperature. Because the derivation is generic, the new formula is not only applicable to planetary atmospheres in the solar system but also to hot Jupiters and brown dwarfs in which a variety of alkali metals, silicates, and exotic materials condense. It is demonstrated that even though the vapors are ideal gases, they interact in their effects on the moist adiabatic lapse rate. Finally, the authors apply the new thermodynamic model to study the effects of downdrafts on the distribution of minor constituents and the thermal profile in the Galileo probe hot spot. The authors find that the Galileo probe measurements can be interpreted as a strong downdraft that displaces an air parcel from the 1-bar to the 4-bar level (1 bar = 100 000 Pa).

Tuning the hydrophobic cores of self-immolative polyglyoxylate assemblies

Amphiphilic block copolymers containing different self-immolative polyglyoxylates were synthesized and self-assembled to provide drug carriers with variable celecoxib loading capacities and release rates, as well as different in vitro toxicities.

Optimal selection of modular products in reconfigurable manufacturing systems using analytic hierarchy process

Reconfigurable manufacturing systems (RMS) are considered as a major resource of providing variable production capacities and capabilities by different manufacturing companies. To fulfil the market requirement variety of a modular product, manufactured in a reconfigurable manufacturing system, a methodology for optimal selection of modular products in reconfigurable manufacturing systems using analytic hierarchy process (AHP) is proposed. The analytic hierarchy process is a theory of measurement through pair-wise comparisons and relies on the decisions of experts to obtain priority scales. The comparisons are made using a scale of absolute judgments that shows how much better one component is than another with respect to a given attribute. AHP is also helpful in taking decision when both qualitative and quantitative attributes are in a system. A case study is given to understand the applicability of the proposed methodology on a given system.

Different Mixed Astrocyte Populations Derived from Embryonic Stem Cells Have Variable Neuronal Growth Support Capacities.

Central nervous system injury often leads to functional impairment due, in part, to the formation of an inhibitory glial scar following injury that contributes to poor regeneration. Astrocytes are the major cellular components of the glial scar, which has led to the belief that they are primarily inhibitory following injury. Recent work has challenged this by demonstrating that some astrocytes are required for spinal cord regeneration and astrocytic roles in recovery depend on their phenotype. In this work, two mixed populations containing primarily either fibrous or protoplasmic astrocytes were derived from mouse embryonic stem cells (mESCs). Motoneuron and V2a interneuron growth on live cultures, freeze-lysed cultures, or decellularized extracellular matrix (ECM) from astrocytes were assessed. Both neuronal populations were found to extend significantly longer neurites on protoplasmic-derived substrates than fibrous-derived substrates. Interestingly, neurons extended longer neurites on protoplasmic-derived ECM than fibrous-derived ECM. ECM proteins were compared with in vivo astrocyte expression profiles, and it was found that the ESC-derived ECMs were enriched for astrocyte-specific proteins. Further characterization revealed that protoplasmic ECM had significantly higher levels of axon growth promoting proteins, while fibrous ECM had significantly higher levels of proteins that inhibit axon growth. Supporting this observation, knockdown of spondin-1 improved neurite growth on fibrous ECM, while laminin α5 and γ1 knockdown decreased neurite growth on protoplasmic ECM. These methods allow for scalable production of specific astrocyte subtype-containing populations with different neuronal growth support capacities, and can be used for further studies of the functional importance of astrocyte heterogeneity.

Novel thio-kaolinite nanohybrid materials and their application as heavy metal adsorbents in wastewater

A new clay nanohybrid adsorbent material was obtained by grafting the compound 3,6-dithia-1,8-octanediol (HO(CH2)2S(CH2)2S(CH2)2OH) onto the internal aluminol surfaces of both the urea- and dimethylsulfoxide (DMSO) precursors of two kaolinite clay minerals: the Source clay KGa-1b and a Portuguese clay sample collected from the Clays of Taveiro formation. All samples were characterised by X-ray diffraction and solid-state 13C cross-polarisation nuclear magnetic resonance (CP-MAS NMR) spectroscopy. Initial materials and final products were also characterised by thermal gravimetric analysis (TGA) and Fourier-Transform infrared (FTIR) spectroscopy. The results describe nanohybrid materials that are resistant to hydrolysis and exhibit different grafting fashions.The potential application of these materials as a heavy metal adsorbents was tested in ZnCl2 solutions as well as in zinc-spiked raw wastewater. The first assessment of the zinc adsorption capacity of the Source clay KGa-1b was made. Zinc concentrations were analysed concomitant with other metal species by inductively coupled plasma mass spectrometry (ICP-MS), demonstrating variable adsorption capacities of the different clay samples, and a consistently greater zinc removal in the wastewater system compared to simple zinc solutions. Measured concentrations of concomitantly analysed metals reveal a potentially worrying release of certain heavy metal species from some of the clay samples as a result of zinc adsorption.

Nurse practitioners as primary care providers with their own patient panels and organizational structures: A cross-sectional study

BackgroundHealth care systems globally are facing challenges of meeting the growing demand for primary care services due to a shortage of primary care physicians. Policy makers and administrators are searching for solutions to increase the primary care capacity. The effective utilization of nurse practitioners (NPs) has been proposed as a solution. However, organizations utilize NPs in variable capacities. In some settings, NPs serve as primary care providers delivering ongoing continuous care to their patients, referred to as patient panels, whereas in other settings they deliver episodic care. Little is known about why organizations deploy NPs differently. ObjectivesInvestigate the NP role in care delivery—primary care providers with the own patient panels or delivering episodic care—within their organizations and understand how work environments affect their role. DesignA cross-sectional survey design was used to collect data from primary care NPs. SettingsThe study was conducted in one state in the United States (Massachusetts). Data from 163 primary care organizations was obtained, which employed between one to 12 NPs. Participants807 NPs recruited from the Massachusetts Provider Database received mail surveys; 314 completed and returned the survey, yielding a response rate of 40%. MethodsThe survey contained measures of NP role in care delivery and work environment. NP role was measured by an item asking NPs to report if they deliver ongoing continuous care to their patient panel or if they do not have patient panel. The work environment was measured with the Nurse Practitioner Primary Care Organizational Climate Questionnaire (NP-PCOCQ). The multilevel Cox regression models investigated the influence of organization-level work environment on NP role in care delivery. ResultsAbout 45% of NPs served as primary care providers with their own patient panel. Organization-level Independent Practice and Support subscale, an NP-PCOCQ subscale, had a significant positive effect on NP role (risk ratio=2.33; 95% CI: 1.06-5.13); with a one unit increase on this subscale, the incidence of the NPs serving as primary care providers with their own patient panel doubled. ConclusionsNPs can help meet the increasing demand for primary care by taking responsibilities as primary care providers, and organizations can assign NPs their own patient panels. Supporting NP independent practice within organizations promotes NP role as primary care providers. Policy and organizational change focused on promoting NP work environments so NPs can practice as primary care providers can be an effective strategy to increase the primary care capacity.