Rationale, aims and objectives. Applying traditional industrial Quality Improvement (QI) methodologies to primary care is often inappropriate because primary care is best thought of as a network of highly interconnected agents in a complex adaptive system (CAS) that is particularly responsive to bottom-up rather than top-down management approaches. We report on a demonstration case study of improvements made in the Family Health Center (FHC) of the JPS Health Network in a refugee patient population that illustrate features of QI in a CAS framework as opposed to a traditional QI approach. Methods. We report on changes in health system utilization by new refugee patients of the FHC from 2016-2017 and summarize relevant theoretical understandings of quality management in complex adaptive systems. Results. Applying CAS principles in the FHC, utilization of the Emergency Department and Urgent Care by newly arrived refugee patients before their first clinic visit was reduced by more than half (total visits decreased from 31% to 14% of the refugee patients). Our review of the literature demonstrates that traditional top-down QI processes are most often unsuccessful in improving even a few single-disease metrics, and increases clinician burnout and penalizes clinicians who care for vulnerable patients. Improvement in a CAS occurs when front-line clinicians identify care gaps and are given the flexibility to learn and self-organize to enable new care processes to emerge, which are created from bottom-up leadership that utilize existing interdependencies made more sustainable as front-line clinicians use sensemaking to improve care processes. Conclusions and future directions. Recent reforms announced in primary care in Scotland, a few examples in the medical literature, and statements from some healthcare system leaders are examples of early adapters who are applying the principles of CAS to their QI efforts. Such initiatives and our example provide models for others to follow.

Pyrazolidines are very important compounds that widely exist in many natural products. Herein, we have employed high-level DFT calculations to systematically investigate the underlying mechanism of Cu(OTf)2 catalyzed [3+2] cycloaddition reactions that synthesis CF3­substituted pyrazolidines. About eight possible initial configurations of the [3+2] reaction is considered and all relevant reactants, transition states and products are optimized. Based on these structures, IRC paths and the wavefunction analysis, we concluded that the Cu(OTf)2 catalyzed [3+2] cycloaddition follow a concerted asynchronous mechanism. The C­N bond forms immediately after the formation of the C­C bond. Among all eight reaction paths, the energy barrier for the [3+2] reaction that lead to the CF3­substituted syn­pyrazolidine is the lowest one, ca. 3.2 kcal/mol, which might result in the diastereoselectivity that observed in experiment. We have also investigated the reaction processes that without Cu(OTf)2 molecule. The computational results indicate that the energy barriers that form the diastereoisomers are much closer and also larger than the Cu(OTf)2 catalyzed one. Therefore, Cu(OTf)2 catalyst plays an important role for the diastereoselectivity of the [3+2] cycloaddition reaction. Our present work not only gives the detail mechanism of the Cu(OTf)2 catalyzed [3+2] cycloaddition, but can also be helpful for the future designation of Cu(OTf)2 based cycloaddition processes.

Aims Clinical guidelines have made an impact on the quality of care but recently their drawbacks became more visible. In this article standards of care are introduced as a new and further step in de development of clinical guidelines in the Netherlands Methods An historical overview of guideline and care standard development and an example of the standard for depressive disorders are presented Results Standards of care describe in general terms from the perspective of the patient what good care is for people with a certain mental disorder during the entire care continuum, the patient journey. They describe for all parties in the mental health care system what is necessary in the care process. Generic standards describe healthcare components or healthcare topics that are relevant to multiple mental disorders More than 40 standards of care/generic standards have been developed. Conclusions Standards of care seem to be a solution for the problem of different and sometimes conflicting monodisciplinary guidelines, the limited scope of the monodisciplinary guidelines and the omission of clinical expertise and patients preferences in the clinical guidelines. However implementing the new set of comprehensive standards of care will be a challenge.

Reef predators are partly sustained by oceanic production sources, but the pathways through which this occurs remain poorly understood. Studies exploring reef-pelagic linkages have used bulk stable isotopes, yet these have limited power to discriminate between major source types. We used δ13C values of essential amino acids (δ13CEAA), which can better resolve different modes of carbon acquisition, to trace the origin of the carbon sources sustaining reef predator biomass in the Maldives. White muscle tissue was sampled from four key fishery target groupers and eight primary consumer species (representing six energy pathways). Primary consumer δ13CEAA values separated into four distinct clusters: 1) algae/detritus, 2) coral, 3) reef plankton, and 4) pelagic plankton. Bayesian stable isotope mixing models identified pelagic plankton as primarily sustaining all four groupers across the atoll, indicating that oceanic nutrients are available throughout and that these reefs may be more resilient to bleaching-induced loss of live coral.

The supply of ecosystem services (ES) is critical to sustaining human livelihoods, and understanding their driving mechanisms and impacts can contribute to sustainable ecological management. This paper aims to reveal the spatiotemporal changes and dynamics of ES in China from 1992 to 2015.SC (Soil conservation), WY (Water yield), NPP (Net primary productivity) and FS (Food supply) are selected for evaluation. The ability of ES to provide is increasing; the area where ES synergy is more dominant accounts for about half of the total land area, and ecological restoration here has a very high added value; in addition, we do not think that we cannot blindly pursue forest coverage during the ecological restoration The specific case is that afforestation activities in the Loess Plateau and Continental basin have exacerbated water shortages. It is the practical significance of this paper to clarify and reverse the regional ES trade-off relationship to achieve sustainable development.

Pathogen persistence in host communities is influenced by a hierarchy of heterogeneities from individual host to landscape-level attributes, but isolating the relative contributions of these heterogeneities is challenging. We developed theory to partition the influence of host species, habitat patches, and landscape connectivity on pathogen persistence within host-pathogen metacommunities. We used the framework to quantify the contributions of host species composition and habitat patch identity on the persistence of an amphibian pathogen across the landscape. By sampling over 11,000 hosts of six amphibian species, we found that a single host species could maintain the pathogen in 91% of the metacommunities we observed. Moreover, this dominant maintenance species contributed, on average, twice as much to landscape-level pathogen persistence compared to the most influential source patch in a metacommunity. Our analysis demonstrates substantial inequality in how species and patches contribute to pathogen persistence, with important implications for targeted disease management.

Cell adhesion on 3D-scaffolds is a challenging task to succeed high cell densities and even cell distribution. We aimed to design a static 3D-cell Culture Device which limits cell loss, facilitates circulation of fluids and can be used with any scaffold. 3D printing technology was used for both scaffold and device fabrication. Apart from testing the device, the purpose of this study was to assess and compare static and dynamic methods and their effects on parameters such as cell seeding efficiency, cell distribution and cell proliferation in different culture conditions. Human adipose tissue was harvested and cultured in 3D-printed polycaprolactone scaffolds. Half the scaffolds were dry and the rest of them were prewetted. Micro-CT scans were performed and projection images were reconstructed into cross section images. We created 3D images to visualize cell distribution and orientation inside the scaffolds. The group of prewetted scaffols was the most favorable to cell attachement. The 3D-cell Culture Device (3D-CD) enhanced cell seeding efficiency in static culture, with almost no cell loss. We suggest that the most favorable outcome can be produced with static seeding in the device for 24 hours, followed by proliferation either in the same device or with dynamic culture.

We present, for the first time the S0 → S1 (S01) and S0 → S2 (S02) transition densities for fulvene, using the 3-D next generation QTAIM constructed using the preferred direction of electronic charge density accumulation. There is a symmetrization of the position of the bond critical point (BCP) of the torsional C2-C6 BCP along the bond-path associated with the presence of a conical intersection (CI) between the ground and first excited state (S1). The corresponding transition density S0 → S1 (S01) displays hindered BCP motion that is associated with a large rearrangement of the total electronic charge density, made apparent by the form of a 3-D bond-path. The reaction pathway for the second excited state does not have an associated CI to an adjacent state along this path, or symmetrization of the BCP position for the S0 → S2 (S02) transition density, or hindered motion, or a large deviation in the 3-D bond-path. We hypothesize that the symmetrization of the position of the torsional C2-C6 BCP along a bond-path for an excited state pathway is associated with a CI, where the transition density BCP is hindered and as a consequence the electron density undergoes a large rearrangement, made apparent by the form of the 3-D bond-path.

Microbial decomposition of soil organic matter is a key component of the global carbon cycle. As Earth’s climate changes, the response of microbes and microbial enzymes to rising temperatures will largely determine the soil carbon feedback to atmospheric CO2. While increasing attention focuses on physiological and ecological mechanisms of microbial responses, the role of evolutionary adaptation remains little studied. To address this gap, we developed an ecosystem-evolutionary model of a soil microbe-enzyme system under warming. Constraining the model with observations from five contrasting sites reveals evolutionary aggravation of soil carbon loss to be the most likely outcome; however, temperature-dependent increases in mortality could cause an evolutionary buffering effect instead. We generally predict a strong latitudinal pattern, from small evolutionary effects at low latitude to large evolutionary effects at high latitudes. Accounting for microbial evolutionary adaptation will likely be critical for improving projections of Earth system responses to climate change.

Clinical use of pancreatic beta islets for regenerative medicine applications requires mass production of functional cells. Current technologies are insufficient for large-scale production in a cost-efficient manner. Here, we evaluate advantages of a porous cellulose scaffold and demonstrate scale-up to a wicking-matrix bioreactor as a platform for culture of human endocrine cells. Scaffold modifications were evaluated in a multi-well platform to find the optimum surface condition for pancreatic cell expansion followed by bioreactor culture to confirm suitability. Preceding scale-up, cell morphology, viability and proliferation of primary pancreatic cells were evaluated. Two optimal surface modifications were chosen and evaluated further for insulin secretion, cell morphology and viable cell density for human induced pluripotent stem cell-derived pancreatic cells at different stages of differentiation. Scale-up was accomplished with uncoated, amine-modified cellulose in a miniature bioreactor, and insulin secretion and cell metabolic profiles were determined for 13 days. We achieved 10-fold cell expansion in the bioreactor along with a significant increase in insulin secretion compared with cultures on tissue-culture plastic. Our findings define a new method for expansion of pancreatic cells on wicking-matrix cellulose platform to advance cell therapy biomanufacturing for diabetes.

Human tissue kallikreins (KLKs) constitute a family of 15 serine proteases scattered in various tissues of the human body. They are implicated in several pathological disorders and physiological events, such as cancer, the formation of blood clot, and skin desquamation, among others, and therefore, it is believed that specific inhibitors of these enzymes may represent new therapeutic targets. KLK7 is an unusual serine protease that presents both trypsin-like and chymotrypsin-like specificity and seems to be upregulated in pathologies related to skin desquamation processes such as atopic dermatitis, psoriasis and Netherton syndrome, suggesting that this enzyme is a potential target for new therapeutic procedures. Thus, in this work, we describe the generation of recombinant IgG-like human antibodies (scFv-Fc) with high affinity for KLK7, which can be useful for detecting and neutralizing the activity of this enzyme in tissues where it appears to be upregulated. In addition, we have developed and characterized a poloxamer-based drug delivery system to encapsulate the anti-KLK7 antibodies considering the biopharmaceutical parameters of the antibodies.

Calcium carbonate (CaCO3) is an inorganic compound which is widely used in industry, chemistry, construction, ocean acidification and biomineralization due to its rich constituent on earth and excellent performance, in which calcium carbonate hydrates are important systems. In Z.Y. Zou et al’s work (Science, 2019, 363, 396–400), they found a novel calcium carbonate hemihydrate phase, but the structure stability, optical and mechanical properties has not been studied. In this work, the stability, electronic, optical, and mechanical properties of novel calcium carbonate hydrates were investigated by using the first-principles calculations within density functional theory (DFT). CaCO3·xH2O (x=1/2, 1 and 6) are determined dynamically stable phases by phonon spectrum, but the Gibbs energy of reaction of CaCO3·1/2H2O is higher than other calcium carbonate hydrates. That’s why the CaCO3·1/2H2O is hard to synthesize in the experiments. In addition, the optical and mechanical properties of CaCO3·xH2O (x=1/2, 1 and 6) are expounded in detail. It shows that the CaCO3·1/2H2O has the largest bulk modulus, shear modulus, Young’s modulus with the values 60.51, 36.56 and 91.28 GPa with respect to other two calcium carbonate hydrates investigated in this paper. This work will provide guidance for experiments and its applications, such as biomineralization, geology, and industrial processes.

In this work, the potential relation between magnetic response properties (isotropic shielding (σiso) and total atomic magnetizabilities, Χ(Ω)) with QTAIM atomic charges of boron and nitrogen atoms in (4,4), (5,3) and (7,0) single-walled boron nitride nanotubes (SWBNNTs) are investigated at DFT B3LYP/ 6-31G(d) level of theory using periodic boundary condition (PBC) approach. The results show that a liner correlation exists between atomic charges of B and N in (4,4) and (5,3) BNNTs and the isotropic shielding. The results show a solid correlation between chemical shielding and total-atomic magnetizabilities, Χ(Ω) in (4,4) BNNT with the lowest conductivity.

On the example of forty ion pairs, the study demonstrates how the core-level binding energy values can be calculated and used to plot theoretical spectra at a low computational cost using density functional theory methods. Three approaches for obtaining the binding energy values are based on delta Kohn–Sham (ΔKS) calculations, 1s Kohn–Sham orbital energies, and atomic charges. The ΔKS results show a good agreement between the available experimental X-ray photoelectron data. 1s Kohn–Sham orbital energies and atomic charges also correlate with the ΔKS results.

The Irtysh River is the main water resource of eastern Kazakhstan and its upper basin is severely affected by spring floods each year, primarily as a result of snowmelt. Knowledge of the large scale processes that influence the timing of these snow-induced floods is currently lacking, but critical for the management of water resources in the area. In this study, we evaluated the variability in winter-spring snow cover in five major sub-basins of the Upper Irtysh basin between 2000 and 2017 as a possible explanatory factor of spring flood events, assessing the time of peak snow cover depletion rate and snow cover disappearance from the MODIS MOD10A2 dataset. We found that on average, peak snow cover retreat occurs between 22 March and 14 April depending on the basin, with large inter-annual variations but no clear trend over the observation period. In contrast, the annual peak snow cover depletion rate displays a weak increasing trend over the study period and exceeded 5900 km2 day-1 in 2017. The timing of snow disappearance in spring shows significant correlations of up to 0.82 for the largest basin with winter indices of the Arctic Oscillation over the region. The primary driver is the impact of the large scale pressure anomalies upon the mean spring (MAM) air temperatures and resultant timing of snow cover disappearance, particularly at elevations 500-2000 m above sea level. This suggests a lagged effect of this atmospheric circulation pattern in spring snow cover retreat. The winter Arctic Oscillation index could therefore be incorporated into long-term runoff forecasts for the Irtysh. Our approach is easily transferable to other similar catchments, and could support flood management strategies in Kazakhstan and other countries.

Manually collected snow data are often considered as ground truth for many applications such as climatological or hydrological studies. However, there are many sources of uncertainty that are not quantified in detail. For the determination of water equivalent of snow cover (SWE), different snow core samplers and scales are used, but they are all based on the same measurement principle. We conducted two field campaigns with 9 samplers commonly used in observational measurements and research in Europe and northern America to better quantify uncertainties when measuring depth, density and SWE with core samplers. During the first campaign, as a first approach to distinguish snow variability measured at the plot and at the point scale, repeated measurements were taken along two 20 m long snow pits. The results revealed a much higher variability of SWE at the plot scale (resulting from both natural variability and instrumental bias) compared to repeated measurements at the same spot (resulting mostly from error induced by observers or very small scale variability of snow depth). The exceptionally homogeneous snowpack found in the second campaign permitted to almost neglect the natural variability of the snowpack properties and focus on the separation between instrumental bias and error induced by observers. Under such measurement conditions, the uncertainty in bulk snow density estimation is about 5% for an individual instrument and is close to 10% among different instruments. Results confirmed that instrumental bias exceeded both the natural variability and the error induced by observers, even in the case when observers were not familiar with a given snow core sampler.

The onset of acute illness may be accompanied by a profound sense of disorientation for patients. Addressing this vulnerability is a key part of a physician’s purview, yet well-intended efforts to do so may be impeded by myriad competing tasks in clinical practice. Resolving this dilemma goes beyond appealing to altruism, as its limitless demands may lead to physician burnout, disillusionment, and a narrowed focus on the biomedical aspects of care in the interest of self-preservation. The authors propose an ethic of hospitality that may better guide physicians in attending to the comprehensive needs of patients that have entered “the kingdom of the sick”. Using philosophical methods, the authors explore what compels people to present to emergent medical attention and why altruism may not offer physicians a sustainable way to address the vulnerabilities that occur in such situations. They then present the concept of hospitality from a Derridean perspective and use it to interpret a narrative case of an on-call paediatrician caring for an infant with bronchiolitis to demonstrate how this approach may be practically implemented in the acute care hospital context. Hospitality allows physicians to acknowledge that clinical presentations that are routine in their world may be disorienting and frightening to patients experiencing them acutely. Further, it recognizes that the vulnerability that accompanies acute illness may be compounded by the unfamiliarity of the hospital environment in which patients have sought support. While it is unlikely that anything physicians do will make the hospital a place where patients and caregivers will desire to be, hospitality may focus their efforts upon making it less unwelcoming. Specifically, it offers an orientation that supports patients in navigating the disorienting and unfamiliar terrains of acute illness, the hospital setting in which help is sought, and engagement with the health care system writ large.

L’inquinamento delle acque è un argomento di estrema sensibilità per il sistema odierno. C’è un netto collegamento tra  il trattamento delle acque reflue e le relative emissioni odorigene. Un aspetto molto importante riguarda negli impianti di trattamento, la presenza di alcuni elementi chimici, di sostanze organiche, componenti batteriche e così via.  Perciò con lo sviluppo delle tecnologie degli ultimi anni sono stati eseguiti degli studi che hanno utilizzato i risultati ottenuti al fine di trattare le acque reflue nel modo migliore, mitigandone gli impatti e consentendo la più possibile minimizzazione degli odori. Questa attenzione porta ad un miglioramento dell’ambiente stesso e consente di viverlo in modo piacevole.

This is draft #2 

1. IntroductionBiology literally means “the study of life”. Life Sciences attempts to untie the living things mysteries from the working of protein ‘machines’, to the growth of organism from a single cell to the majesty and intricacy of whole ecosystem. Questions about life sciences are as diverse and fascinating as life itself like; how a single cell knows to build up complex organism? How interpretation of genetic information takes place?How the properties of organism are affected due to gene mutation? How ecosystem changes due to climate?What can human genetic variation tell us about the history of human evolution and migration? Evolution is the change in heritable traits of biological populations over successive generations. Evolutionary processes give rise to diversity at every biological organization level. All life on earth shares a common ancestor known as the last universal ancestor. In the mid-19th century, Charles Darwin formulated the scientific theory of evolution by natural selection, while in the early 20th century the modern evolutionary synthesis integrated classical genetics with Darwin’s theory of evolution by natural selection through the discipline of population genetics. Evolution is a cornerstone of modern science, accepted as one of the most reliably established of all facts and theories of science, based on evidence not just from the biological sciences but also from anthropology, psychology, astrophysics, chemistry, geology, physics, mathematics, and other scientific disciplines, as well as behavioral and social sciences.

Transference and countertransference phenomena are present in every physician–patient interaction. The aim of this text is to present the concepts of transference and countertransference found in daily non-psychiatric clinical practice and some possible interventions addressing these phenomena that could improve the clinician´s work with his or her patients. To render understandable the concepts of transference and countertransference, first the basic psychological concepts from which they emerge will be presented. Modern medicine has been losing its humane aspects and the quality of the physician-patient relationship. Recognition of the phenomena of transference and countertransference could be used to face this dehumanization crisis.

We investigate the ability of mechanical and electronic density functional theory (DFT)-based embedding approaches to describe the solvent effects on nuclear magnetic resonance (NMR) shielding constants of the ⁹⁵Mo nucleus in the molybdate ion in aqueous solution. From the description obtained from calculations with two- and four-component relativistic Hamiltonians, we find that for such systems spin-orbit coupling effects are clearly important for absolute shielding values, but for relative quantities a scalar relativistic treatment provides a sufficient estimation of the solvent effects. We find that the electronic contributions to the solvent effects are relatively modest yet decisive to provide a more accurate magnetic response of the system, when compared to reference supermolecular calculations. We analyze the errors in the embedding calculations by statistical methods as well as through a real-space representation of NMR shielding densities, which are shown to provide a clear picture of the physical processes at play.

Josiane Ap. Gomes Figueiredo. Professora titular e Coordenadora do Programa de Residência Pedagógica no Curso de Ciências Biológicas da Universidade Estadual do Paraná /UNESPAR - Campus de Paranaguá.  Pesquisadora na Formação de Professores e Práticas Pedagógicas no Ensino de Ciências e Biologia, josiane.figueiredo@unespar.edu.br  Roberta Ravaglio Gagno. Professora titular e Coordenadora Institucional do Programa Residência Pedagógica da Universidade Estadual do Paraná - UNESPAR - Campus Curitiba 1. Pesquisadora sobre a Formação de Professores e em Políticas e Gestão de Ensino,  roberta.ravaglio@unespar.edu.br Resumo: A fim de formar professores reflexivos e preparados para atender as exigências de sua atividade profissional almeja-se um aprendizado participativo, correlacionando o conhecimento prático e teórico. O primeiro contato com a docência pode ser realizado por meio do estágio curricular e atualmente através de programas pertencentes à Política Nacional de Formação de Professores do Ministério da Educação como o Programa Institucional de Bolsa de Iniciação à Docência (Pibid) e o de Residência Pedagógica (RP). É importante analisar como foi concretizada a aproximação entre Universidade e Escola na formação de licenciandos do RP desenvolvido no Curso de Licenciatura de Ciências Biológicas da UNESPAR, Campus Paranaguá. Neste contexto, o objetivo deste trabalho é descrever reflexões sobre a qualidade de ensino, o engajamento de futuros docentes, o feedback dos alunos, os obstáculos dos acadêmicos e a ações que podem tomadas para uma educação de qualidade. Todas as reflexões e apontamentos tratam de um trabalho coletivo no qual os componentes foram elencados nas reuniões realizadas semanalmente e foram sendo paulatinamente discutidos e refletidos entre preceptores, residentes e coordenação. Buscou-se identificar os principais componentes norteadores entre a Universidade e a Escola favorecendo espaços híbridos de formação e aproximação entre a teoria e a prática. Percebe-se que quando tem-se o discurso de educação de qualidade a mesma requer um projeto pedagógico bem estruturado, infraestrutura adequada, metodologias inovadoras, tecnologias de ensino, docentes capacitados e alunos motivados pois mesmo diante de tantas ferramentas inovadoras no campo da educação e em ascendência hoje, o professor e o aluno de graduação que participa dos programas mencionados acima e, ou desenvolve o estágio curricular nas escolas ainda encontram muitas dificuldades em sala de aula, principalmente no que diz respeito à motivação dos alunos para a aprendizagem.  Palavras-chave: Professor, Educação, Ensino-aprendizagem.

Fine root traits are critical to the plant's capacity and efficiency to uptake water and nutrients. Although plant diversity is decreasing, our understanding of its effects on fine root traits remains elusive. By synthesizing 103 studies, we found that the effects of plant mixtures were highly dependent on species richness in mixtures, stand age, and soil depth. The positive mixture effects on root biomass increased with species richness, soil depth, and mean annual temperature. Plant mixture effects on root length density shifted from negative to positive, from young to older stands, topsoil to deep soils, and warm to cold climates. The mixture effects on specific root length shifted from positive to negative, from two to higher number species mixtures and topsoil to deep soils, and then negative to positive with increasing stand age. Our results demonstrate the profound plasticity of root traits in response to productivity dynamics in plant mixtures.