bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods and Strategies for Reducing Seclusion and Restraint in Child and Adolescent Psychiatric Inpatient Care
Authors: Perers Charlotta , Bäckström Beata , Johansson Björn Axel , Rask Olof
Published: February 2021

Restraints and seclusions are restrictive interventions used in psychiatric inpatient units when there is an imminent risk of harm to the patient or others. Coercive measures are controversial and can lead to negative consequences, including negative emotions, re-traumatization, injuries, or death. The article summarizes the last 10 years of literature regarding methods and strategies used for reducing seclusions and restraints in child and adolescent psychiatric inpatient units, and reports on their outcomes. The literature was reviewed by searching PubMed and PsycInfo for English-language articles published between May 2010 and May 2020. Eighteen articles were found that described methods or strategies aimed at reducing restraint or seclusion utilization in child and adolescent psychiatric inpatient units. The following interventions were evaluated: Trauma-Informed Care (TIC), Six Core Strategies, Child and Family Centered Care (CFCC), Collaborative & Proactive Solutions (CPS), Strength-Based Care, Modified Positive Behavioral Interventions and Supports (M-PBIS), Behavioral Modification Program (BMP), Autism Spectrum Disorder Care Pathway (ASD-CP), Dialectical Behavior Therapy (DBT), sensory rooms, Mindfulness-Based Stress Reduction Training (MBSR) of staff, and Milieu Nurse-Client Shift Assignments. Most of the interventions reduced the use of seclusions and/or restraints. Two child-centered and trauma-informed initiatives eliminated the use of mechanical restraints. This review shows that the use of coercive measures can be reduced and should be prioritized. Successful implementation requires ongoing commitment on all levels of an organization and a willingness to learn. To facilitate comparisons, future models should evaluate different standardized parameters.
The symmetry problem for testimonial conservatism
Authors: Jope Matthew
Published: February 2021

A prima facie plausible and widely held view in epistemology is that the epistemic standards governing the acquisition of testimonial knowledge are stronger than the epistemic standards governing the acquisition of perceptual knowledge. Conservatives about testimony hold that we need prior justification to take speakers to be reliable but recognise that the corresponding claim about perception is practically a non-starter. The problem for conservatives is how to establish theoretically significant differences between testimony and perception that would support asymmetrical epistemic standards. In this paper I defend theoretical symmetry of testimony and perception on the grounds that there are no good reasons for taking these two belief forming methods to have significant theoretical differences. I identify the four central arguments in defence of asymmetry and show that in each case either they fail to establish the difference that they purport to establish or they establish a difference that is not theoretically significant.
Urban gardening as a means for fostering embodied urban human–food connection? A case study on urban vegetable gardens in Germany
Authors: Artmann Martina , Sartison Katharina , Ives Christopher D.
Published: February 2021

Urbanization is increasingly compromising residents’ connection to natural habitats and landscapes. With established relationships between human–nature connection (HNC) and pro-environmental behaviour and human well being, there are calls for effective interventions to strengthen HNC in urban settings. However, much of this research has operationalised HNC in narrow psychological terms. Based on an embodied framework of urban human–food connection (HFC) as a specific dimension of HNC, this article explores the role of active urban gardening in promoting different types of internal and external HFC and their link with pro-environmental food behaviour (PEFB). Based on a quantitative survey in Germany addressing vegetable gardeners in Munich (N = 254), a principal component analysis extracted four components of HFC comprising external body-related HFC (i.e. immediate urban garden-body activities: food harvesting and experiential food interaction) and internal mind-related HFC (i.e. immediate urban garden-mind activities including food discovery as well as food consciousness). These were found to be statistically related to one another. Furthermore, regression analysis revealed that food consciousness through concerns on food consumption and environmental impacts as well as food as part of life attitude as an internal HFC is the sole predictor of PEFB. The study suggests an embodied HFC model emphasizing the need for local body- and mind-based nature connections for fostering earth stewardship. Future research should explore the relationship between inner dimensions of nature connectedness and external behavioural change to enable transformations towards sustainability.
How does the position of firms in the supply chain affect their performance? An empirical study
Authors: Arora Siddharth , Brintrup Alexandra
Published: February 2021

The relationship between a firm and its supply chain has been well studied, however, the association between the position of firms in complex supply chain networks and their performance has not been adequately investigated. This is primarily due to insufficient availability of empirical data on large-scale networks. To addresses this gap in the literature, we investigate the relationship between embeddedness patterns of individual firms in a supply network and their performance using empirical data from the automotive industry. In this study, we devise three measures that characterize the embeddedness of individual firms in a supply network. These are namely: centrality, tier position, and triads. Our findings caution us that centrality impacts individual performance through a diminishing returns relationship. The second measure, tier position, allows us to investigate the concept of tiers in supply networks because we find that as networks emerge, the boundaries between tiers become unclear. Performance of suppliers degrade as they move away from the focal firm (i.e., Toyota). The final measure, triads, investigates the effect of buying and selling to firms that supply the same customer, portraying the level of competition and cooperation in a supplier’s network. We find that increased coopetition (i.e., cooperative competition) is a performance enhancer, however, excessive complexity resulting from being involved in both upstream and downstream coopetition results in diminishing performance. These original insights help understand the drivers of firm performance from a network perspective and provide a basis for further research.
Structural characterization and colour of Ni3−xCuxP2O8 (0 ≤ x ≤ 3) materials
Authors: Tena M. A. , Mendoza Rafael , Trobajo Camino , García José R. , García-Granda Santiago
Published: February 2021

The structural characterization of Ni3−xCuxP2O8 (0.0 ≤ x ≤ 3.0) compositions was performed and the colour parameters of these materials measured. Solid solutions with Ni3P2O8, Ni2CuP2O8 and Cu3P2O8 structures were obtained and the compositional range in which they are formed was established. Structural distortion was detected in these solid solutions when x increases from the variation in the unit cell parameters and that of the interatomic distances. Solid solutions with Ni3P2O8 structure are stable at 1200 °C and may be used as ceramic pigments. Changes in the colour of these materials were related to the structural changes. Yellow materials are obtained from Ni3−xCuxP2O8 solid solutions with a Ni3P2O8 or Ni2CuP2O8 structure and a gradual change from yellow to brown is obtained with the introduction of Cu(II) in the Ni3P2O8 structure, 0.0 ≤ x ≤ 0.7 at 1200 °C.
Heat transfer and entropy generation analysis in a horizontal channel filled with a permeable medium in the presence of aligned magnetic field and temperature gradient heat source
Authors: Balamurugan K. S. , Udaya Bhaskara Varma N. , Ramaprasad J. L.
Published: February 2021

The current investigation is concerned with heat transfer and entropy generation analysis in a horizontal channel brimming with porous medium in the existence of aligned magnetic field, viscous and joules dissipation and temperature gradient heat source. The boundary conditions are treated as constant values for velocity and temperature at lower and upper walls. An explicit solution of governing equations has been attained in closed system. The repercussions of pertinent parameters on the fluid velocity, temperature, entropy generation and Bejan number are conferred and scrutinized through graphs in detail. Additionally the expressions for shear stress and the rate of heat transfer coefficients at the channel walls are derived and results obtained are physically interpreted through tables. From the conquered results, it is addressed that Brinkman number Br enhances boundary layer thickness. Entropy generation increases with intensifying values of $$M$$
M
, aligned angle ϕ, temperature gradient heat source parameter Q, characteristic temperature ration $$\omega$$
ω
and permeability parameter K. The shear stress is same at both the lower and upper walls.
Practical Smoothing
Authors: Eilers Paul H.C. , Marx Brian D.
Published: February 2021

This is a practical guide to P-splines, a simple, flexible and powerful tool for smoothing. P-splines combine regression on B-splines with simple, discrete, roughness penalties. They were introduced by the authors in 1996 and have been used in many diverse applications. The regression basis makes it straightforward to handle non-normal data, like in generalized linear models. The authors demonstrate optimal smoothing, using mixed model technology and Bayesian estimation, in addition to classical tools like cross-validation and AIC, covering theory and applications with code in R. Going far beyond simple smoothing, they also show how to use P-splines for regression on signals, varying-coefficient models, quantile and expectile smoothing, and composite links for grouped data. Penalties are the crucial elements of P-splines; with proper modifications they can handle periodic and circular data as well as shape constraints. Combining penalties with tensor products of B-splines extends these attractive properties to multiple dimensions. An appendix offers a systematic comparison to other smoothers.
Pragmatic Reconstruction in Jurisprudence: Features of a Realistic Legal Theory
Authors: Tamanaha Brian Z.
Published: February 2021

A century ago the pragmatists called for reconstruction in philosophy. Philosophy at the time was occupied with conceptual analysis, abstractions, a priori analysis, and the pursuit of necessary, universal truths. Pragmatists argued that philosophy instead should center on the pressing problems of the day, which requires theorists to pay attention to social complexity, variation, change, power, consequences, and other concrete aspects of social life. The parallels between philosophy then and jurisprudence today are striking, as I show, calling for a pragmatism-informed theory of law within contemporary jurisprudence. In the wake of H.L.A. Hart’s mid-century turn to conceptual analysis, “during the course of the twentieth century, the boundaries of jurisprudential inquiry were progressively narrowed.”1 Jurisprudence today is dominated by legal philosophers engaged in conceptual analysis built on intuitions, seeking to identify essential features and timeless truths about law. In the pursuit of these objectives, they detach law from its social and historical moorings, they ignore variation and change, they drastically reduce law to a singular phenomenon—like a coercive planning system for difficult moral problems2—and they deny that coercive force is a universal feature of law, among other ways in which they depart from the reality of law; a few prominent jurisprudents even proffer arguments that invoke aliens or societies of angels.
The Value of Vagueness: A Feminist Analysis
Authors: Chadha-Sridhar Ira
Published: February 2021

Judicial verdicts matter. Apart from deciding the fate of litigants, common law verdicts hold precedential value. They create and alter legal cultures. Considering their importance, it is crucial to ask: what do judicial verdicts turn on? Each verdict is certainly influenced by the case facts, evidence and argumentation presented before the court. However, verdicts are also importantly shaped by how we think about language.1 Questions about language—about the relationship between words and meaning—are central to legal philosophy.
The cognitive experience of engineering design: an examination of first-year student stress across principal activities of the engineering design process
Authors: Nolte Hannah , McComb Christopher
Published: February 2021

The engineering design process can produce stress that endures even after it has been completed. This may be particularly true for students who engage with the process as novices. However, it is not known how individual components of the design process induce stress in designers. This study explored the cognitive experience of introductory engineering design students during concept generation, concept selection and physical modelling to identify stress signatures for these three design activities. Data were collected for the design activities using pre- and post-task surveys. Each design activity produced distinct markers of cognitive experience and a unique stress signature that was stable across design activity themes. Rankings of perceived sources of stress also differed for each design activity. Students, however, did not perceive any physiological changes due to the stress of design for any of the design activities. Findings indicate that physical modelling was the most stressful for students, followed by concept generation and then concept selection. Additionally, recommendations for instructors of introductory engineering design courses were provided to help them apply the results of this study. Better understanding of the cognitive experience of students during design can support instructors as they learn to better teach design.
Entropy of killed-resurrected stationary Markov chains
Authors: Martínez Servet
Published: February 2021

We consider a strictly substochastic matrix or a stochastic matrix with absorbing states. By using quasi-stationary distributions we show that there is an associated canonical Markov chain that is built from the resurrected chain, the absorbing states, and the hitting times, together with a random walk on the absorbing states, which is necessary for achieving time stationarity. Based upon the 2-stringing representation of the resurrected chain, we supply a stationary representation of the killed and the absorbed chains. The entropies of these representations have a clear meaning when one identifies the probability measure of natural factors. The balance between the entropies of these representations and the entropy of the canonical chain serves to check the correctness of the whole construction.
PINDAR, OLYMPIAN 2.5–7, TEXT AND COMMENTARY—WITH EXCURSIONS TO ‘PERICTIONE’, EMPEDOCLES AND EURIPIDES’ HIPPOLYTUS
Authors: Silk M.S.
Published: February 2021

In 1998, I suggested a new text for a notably corrupt passage in Pindar's Isthmian 5. This article is in effect a sequel to that earlier discussion. In the 1998 article, I proposed, inter alia, that the modern vulgate text of I. 5.58, ἐλπίδων ἔκνισ’ ὄπιν, is indefensible and the product of scribal corruption in antiquity, and that chief among the indefensible products of corruption there is the supposed secular use of ὄπις, as if used to mean something like ‘zeal’. This (as I hope to have demonstrated) is a sense for which there is no good evidence in classical Greek, where ὄπις always has a delimited religious denotation, meaning either (a) ‘gods’ response’, ‘divine retribution’, or else (b) ‘religious awe’ or ‘reverence’ towards the gods, through fear of that response or that retribution. If we discount I. 5.58 itself (and likewise the focus of the present article, O. 2.6), all the pre-Hellenistic attestations can be straightforwardly listed under these headings: (a) Il. 16.388 θεῶν ὄπιν οὐκ ἀλέγοντες, Od. 14.88 ὄπιδος κρατερὸν δέος, Hes. Theog. 221–2 θεαὶ . . . | . . . ἀπὸ τῷ δώωσι κακὴν ὄπιν, Pind. P. 8.71–2 θεῶν δ’ ὄπιν | ἄφθονον αἰτέω, sim. Od. 20.215, 21.28, Hes. Op. 187, 251, 706, along with, seemingly, a fragmentary fifth-century Thessalian verse inscription, CEG 1.120.1 Hansen; (b) Hdt. 9.76.2 θεῶν ὄπιν ἔχοντας, 8.143.2. In addition, one other instance can be interpreted as either (a) or (b), or in effect both: Od. 14.82 (of the suitors) οὐκ ὄπιδα φρονέοντες . . . οὐδ’ ἐλεητύν. In all cases, though, ‘gods’ are specified, usually as a dependent genitive with ὄπις, or else separately but in the near context. Hellenistic and later occurrences of the word are few, and (as I argued in 1998) hints there of a secular reading can actually be taken to reflect misunderstandings based on, precisely, the early corruption in I. 5.
Fair Weather Neutron Bursts From Photonuclear Reactions by Extensive Air Shower Core Interactions in the Ground and Implications for Terrestrial Gamma‐ray Flash Signatures
Authors: Bowers Gregory S. , Shao Xuan‐Min , Blaine William , Dingus Brenda , Smith David M. , Chaffin Jeff , Ortberg John , Rassoul Hamid K. , Ho Cheng , Nellen Lukas , Fraija Nissim , Alvarez C. , Arteaga‐Velázquez J. C. , Baghmanyan V. , Belmont‐Moreno E. , Caballero‐Mora K. S. , Carramiñana A. , Casanova S. , De la Fuente E. , González M. M. , Hueyotl‐Zahuantitla F. , Martinez O. , Matthews J. A. , Moreno E. , Newbold M. , Pérez‐Pérez E. G. , Torres I.
Published: February 2021

We report on anomalously long duration (2 ms) count rate bursts following the impact of cosmic ray showers near a 7.62 cm x⊘7.62 cm LaBr3 scintillation detector at the High Altitude Water Cherenkov array in Mexico, previously described by Stenkin et al. (2001), and termed “neutron bursts.” The largest burst produced 198 counts within 2 ms in our LaBr3 detector. We simulate the neutron burst albedo flux (that is, secondary emissions from an extensive air shower core impacting the ground), and show that (1) the characteristic spectra and count rates are well explained by neutron absorption in the ground and (2) any cosmic ray secondary that produces neutrons, either through hadron inelastic collisions, or photoneutron production by gamma‐rays, produces the same characteristic spectra. This implies that other natural phenomena that produce downward beams of gamma‐rays, like Terrestrial gamma ray flashes, should produce a similar “neutron burst” signature from the photoneutron reactions occurring in the soil.
Spatiotemporal Variations in Surface Heat Loss Imply a Heterogeneous Mantle Cooling History
Authors: Karlsen Krister S. , Conrad Clinton P. , Domeier Mathew , Trønnes Reidar G.
Published: February 2021

Earth's heat budget is strongly influenced by spatial and temporal variations in surface heat flow caused by plate tectonic cycles. Here, we use a novel set of paleo‐seafloor age grids extending back to the mid‐Paleozoic to infer spatiotemporal variations in surface heat loss. The time‐averaged oceanic heat flow is 36.6 TW, or ∼25% greater than at present‐day. Our thermal budget for the mantle indicates that 149 K/Gyr of cooling occurred over this period, consistent with geochemical estimates of mantle cooling for the past 1 Gyr. Our analysis also suggests sustained rapid cooling of the Pacific mantle hemisphere, which may have cooled ∼50 K more than its African counterpart since 400 Ma. The extra heat released from the Pacific mantle may have been trapped there by the earlier long‐lived supercontinent Rodinia (∼1.1–0.7 Ga), and the Pacific mantle may still be hotter than the African mantle today.
Post‐Earthquake Fold Growth Imaged in the Qaidam Basin, China, With Interferometric Synthetic Aperture Radar
Authors: Daout Simon , Parsons Barry , Walker Richard
Published: February 2021

Questions regarding the development of folds and their interactions with the seismic faults within thrust systems remain unanswered. However, estimating fault slip and earthquake hazards using surface observations and kinematic models of folding requires an understanding of how the shortening is accommodated during the different phases of the earthquake cycle. Here, we construct 16‐years of interferometric synthetic aperture radar time series across the North Qaidam thrust system (NE Tibet), where three Mw 6.3 earthquakes occurred along basement faults underlying shortened folded sediments. The analysis reveals spatio‐temporal changes of post‐earthquake surface displacement rates and patterns, which continue more than 10 years after the seismic events. The decomposition of the Sentinel‐1 ascending and descending line of sight velocities into vertical and shortening post‐earthquake components indicates that long‐term transient uplift and shortening is in agreement with the deformation that might be expected from kinematic models of folding. Long‐term uplift coincides spatially with young anticlines observed in the geomorphology, with steep gradients in the forelimbs, gentle gradients in the back‐limbs, an absence of subsidence in the footwalls, and higher gradients along interpreted bedding planes. Long‐term shortening is also different from the surface displacements expected for typical time‐varying creep on a narrow dislocation interface and shows rates higher than the average convergence across the whole region. These findings provide evidence for anelastic fold buckling during the post‐earthquake phase and highlight the contribution of distributed aseismic deformation to the growth of topography.
Author Correction: Long-ranged Cu-based order with $$d_{z^2}$$ orbital character at a YBa2Cu3O7/manganite interface
Authors: Gaina Roxana , Nicholson Christopher W. , Rumo Maxime , Sarkar Subhrangsu , Khmaladze Jarji , Paris Eugenio , Tseng Yi , Zhang Wenliang , Asmara Teguh C. , McNally Daniel , Piamonteze Cinthia , Weschke Eugen , Schmitt Thorsten , Monney Claude , Bernhard Christian
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41535-021-00323-8
Superior predatory ability and abundance predicts potential ecological impact towards early-stage anurans by invasive ‘Killer Shrimp’ (Dikerogammarus villosus)
Authors: Warren Daniel A. , Bradbeer Stephanie J. , Dunn Alison M.
Published: February 2021

Invasive alien species negatively impact upon biodiversity and generate significant economic costs worldwide. Globally, amphibians have suffered considerable losses, with a key driver being predation by large invasive invertebrate and vertebrate predators. However, there is no research regarding the potential ecological impact of small invertebrate invaders. The invasive freshwater amphipodDikerogammarus villosuscan act as a top predator capable of displacing native amphipods and preying heavily upon a range of native species. Listed as one of Europe’s top 100 worst invaders,D. villosushas significantly restructured freshwater communities across western Europe and is expected to invade North America in the near future. Here we explore the ecological impact of invasiveD. villosusupon UK native and invasive amphibians (Rana temporariaandXenopus laevisrespectively) using the “Relative Impact Potential” (RIP) metric. By combining estimations ofper capitaeffects (i.e. functional response; FR) and relative field abundances, we apply the RIP metric to quantify the potential ecological impact of invasiveD. villosusupon embryonic and larval amphibian prey, compared to the native amphipodGammarus pulex. Both native and invasive amphipods consumed early-stage amphibians and exhibited potentially destabilising Type II FRs. However, larger body size in invasiveD. villosustranslated into a superior FR through significantly lower handling times and subsequently higher maximum feeding rates—up to seven times greater than nativeG. pulex. Higher invader abundance also drove elevated RIP scores for invasiveD. villosus, with potential impact scores predicted up to 15.4 times greater than nativeG. pulex. Overall,D. villosusis predicted to have a greater predatory impact upon amphibian populations thanG. pulex, due primarily to its larger body size and superior field abundance, potentially reducing amphibian recruitment within invaded regions.
The interaction on hypertension between family history and diabetes and other risk factors
Authors: Li An-le , Peng Qian , Shao Yue-qin , Fang Xiang , Zhang Yi-ying
Published: February 2021

To explore the individual effect and interaction of diabetes and family history and other risk factors on hypertension in Han in Shanghai China. The method of case–control study with l:l matched pairs was used, 342 cases of hypertension and 342 controls were selected and investigate their exposed factors with face-to-face. The method of epidemiology research was used to explore the individual effect and interaction of diabetes and family history and other risk factors on hypertension. The individual effect of family history (OR = 4.103, 95%CI 2.660–6.330), diabetes (OR = 4.219, 95%CI 2.926–6.083), personal taste (OR = 1.256, 95%CI 1.091–1.593), drinking behavior (OR = 1.391, 95%CI 1.010–1.914) and smoking behavior (OR = 1.057, 95%CI 1.00–1.117) were significant (p < 0.05). But individual effect of sex, education, occupation, work/life pressure, environmental noise, sleeping time and sports habit were not significant (p > 0.05). The OR of interaction between FH and DM to hypertension was 16.537 (95%CI 10.070–21.157), between FH and drinking behavior was 4.0 (95%CI 2.461–6.502), FH and sport habit was 7.668 (95%CI 3.598–16.344), FH and personal taste was 6.521 (95%CI 3.858–11.024), FH and smoking behavior was 5.526 (95%CI 3.404–8.972), FH and work/life pressure was 4.087 (95%CI 2.144–7.788). The SI of FH and DM was 2.27, RERI was 8.68, AP was 52.48% and PAP was 55.86%. FH and DM, personal taste, smoking behavior had positive interaction on hypertension, but FH and sport habits, drinking behavior, work/life pressure had reverse interaction on hypertension. FH and diabetes were very important risk factors with significant effect for hypertension. FH and diabetes, personal taste, smoking behavior had positive interaction on hypertension, but FH and sport habits, drinking behavior, work/life pressure had reverse interaction on hypertension.
Flow velocity quantification by exploiting the principles of the Doppler effect and magnetic particle imaging
Authors: Pantke Dennis , Mueller Florian , Reinartz Sebastian , Kiessling Fabian , Schulz Volkmar
Published: February 2021

Changes in blood flow velocity play a crucial role during pathogenesis and progression of cardiovascular diseases. Imaging techniques capable of assessing flow velocities are clinically applied but are often not accurate, quantitative, and reliable enough to assess fine changes indicating the early onset of diseases and their conversion into a symptomatic stage. Magnetic particle imaging (MPI) promises to overcome these limitations. Existing MPI-based techniques perform velocity estimation on the reconstructed images, which restricts the measurable velocity range. Therefore, we developed a novel velocity quantification method by adapting the Doppler principle to MPI. Our method exploits the velocity-dependent frequency shift caused by a tracer motion-induced modulation of the emitted signal. The fundamental theory of our method is deduced and validated by simulations and measurements of moving phantoms. Overall, our method enables robust velocity quantification within milliseconds, with high accuracy, no radiation risk, no depth-dependency, and extended range compared to existing MPI-based velocity quantification techniques, highlighting the potential of our method as future medical application.
A matched irrigation and obturation strategy for root canal therapy
Authors: Fernandes Zancan Rafaela , Hadis Mohammed , Burgess David , Zhang Zhenyu Jason , Di Maio Alessandro , Tomson Phillip , Hungaro Duarte Marco Antonio , Camilleri Josette
Published: February 2021

In root canal therapy, irrigating solutions are employed to eliminate the bacterial load and also prepare dentin for sealer interaction. The aim of this research was to assess how irrigating solutions employed on their own or in sequence affected the tooth structure. The best way to prepare the tooth for obturation using hydraulic calcium silicate cement (HCSC) sealers and gutta-percha, thus guiding clinicians on a matched irrigation-obturation strategy for optimized root canal treatment was investigated. The effect of irrigating solutions on dentine was investigated by assessing changes in dentin microhardness, ultrastructure and mineral content, organic/inorganic matter, surface roughness and Young’s modulus. The interaction of four root canal sealers with the dentin was analysed by assessing the changes in microhardness of the dentin after sealer placement and also the sealer to dentin interface by scanning electron and confocal laser microscopy. The irrigating solutions damaged the dentin irreversibly both when used on their own and in combination. The best sequence involved sodium hypochlorite followed by chelator and a final rinse with sodium hypochlorite and obturation using HCSC sealers that enabled the restoration of dentin properties. The HCSC sealers did not rely on chelator irrigating solutions for a good material adaptation to dentin.
Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor
Authors: Ranieri Marianna , Di Mise Annarita , Centrone Mariangela , D’Agostino Mariagrazia , Tingskov Stine Julie , Venneri Maria , Pellegrino Tommaso , Difonzo Graziana , Caponio Francesco , Norregaard Rikke , Valenti Giovanna , Tamma Grazia
Published: February 2021

Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. It has been shown that certain phytocompounds are beneficial to human health. Here, the effects of the Olive Leaf Extract (OLE) have been evaluated using in vitro and in vivo models. Confocal studies showed that OLE prevents the vasopressin induced AQP2 translocation to the plasma membrane in MCD4 cells and rat kidneys. Incubation with OLE decreases the AVP-dependent increase of the osmotic water permeability coefficient (Pf). To elucidate the possible effectors of OLE, intracellular calcium was evaluated. OLE increases the intracellular calcium through the activation of the Calcium Sensing Receptor (CaSR). NPS2143, a selective CaSR inhibitor, abolished the inhibitory effect of OLE on AVP-dependent water permeability. In vivo experiments revealed that treatment with OLE increases the expression of the CaSR mRNA and decreases AQP2 mRNA paralleled by an increase of the AQP2-targeting miRNA-137. Together, these findings suggest that OLE antagonizes vasopressin action through stimulation of the CaSR indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption.
Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
Authors: Park Jong-Ho , Lim Shinn-Won , Myung Woojae , Park Inho , Jang Hyeok-Jae , Kim Seonwoo , Lee Min-Soo , Chang Hun Soo , Yum DongHo , Suh Yeon-Lim , Kim Jong-Won , Kim Doh Kwan
Published: February 2021

Achieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic studies do not provide robust evidence to aid pharmacogenetic decision-making in clinical settings. Thus, the objective of this study was to perform whole-genome sequencing (WGS) using genomic DNA to identify genetic variants associated with the treatment outcomes of selective serotonin reuptake inhibitors (SSRIs). We performed WGS on 100 patients with MDD who were treated with escitalopram (discovery set: 36 remitted and 64 non-remitted). The findings were applied to an additional 553 patients with MDD who were treated with SSRIs (replication set: 185 remitted and 368 non-remitted). A novel loss-of-function variant (rs3213755) in keratin-associated protein 1–1 (KRTAP1-1) was identified in this study. This rs3213755 variant was significantly associated with remission following antidepressant treatment (p = 0.0184, OR 3.09, 95% confidence interval [CI] 1.22–7.80 in the discovery set; p = 0.00269, OR 1.75, 95% CI 1.22–2.53 in the replication set). Moreover, the expression level of KRTAP1-1 in surgically resected human temporal lobe samples was significantly associated with the rs3213755 genotype. WGS studies on a larger sample size in various ethnic groups are needed to investigate genetic markers useful in the pharmacogenetic prediction of remission following antidepressant treatment.
Explainable AI reveals changes in skin microbiome composition linked to phenotypic differences
Authors: Carrieri Anna Paola , Haiminen Niina , Maudsley-Barton Sean , Gardiner Laura-Jayne , Murphy Barry , Mayes Andrew E. , Paterson Sarah , Grimshaw Sally , Winn Martyn , Shand Cameron , Hadjidoukas Panagiotis , Rowe Will P. M. , Hawkins Stacy , MacGuire-Flanagan Ashley , Tazzioli Jane , Kenny John G. , Parida Laxmi , Hoptroff Michael , Pyzer-Knapp Edward O.
Published: February 2021

Alterations in the human microbiome have been observed in a variety of conditions such as asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiome’s role in human health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the collection of leg skin microbiome samples from two healthy cohorts of women with the application of anexplainable artificial intelligence (EAI)approach that provides accurate predictions of phenotypes with explanations. The explanations are expressed in terms of variations in the relative abundance of key microbes that drive the predictions. We predict skin hydration, subject's age, pre/post-menopausal status and smoking status from the leg skin microbiome. The changes in microbial composition linked to skin hydration can accelerate the development of personalized treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal/gut microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any condition from microbiome samples and has the potential to accelerate the development of microbiome-based personalized therapeutics and non-invasive diagnostics.
SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection
Authors: McGovern Kathryn E. , Nance J. Philip , David Clément N. , Harrison Reed E. S. , Noor Shahani , Worth Danielle , Landrith Tyler A. , Obenaus Andre , Carson Monica J. , Morikis Dimitrios , Wilson Emma H.
Published: February 2021

Central nervous system (CNS) injury and infection can result in profound tissue remodeling in the brain, the mechanism and purpose of which is poorly understood. Infection with the protozoan parasiteToxoplasma gondiicauses chronic infection and inflammation in the brain parenchyma. Control of parasite replication requires the continuous presence of IFNγ-producing T cells to keepT. gondiiin its slowly replicating cyst form. During infection, a network of extracellular matrix fibers, revealed using multiphoton microscopy, forms in the brain. The origin and composition of these structures are unknown but the fibers have been observed to act as a substrate for migrating T cells. In this study, we show a critical regulator of extracellular matrix (ECM) remodeling, Secreted Protein, Acidic, Rich in Cysteine (SPARC), is upregulated in the brain during the early phases of infection in the frontal cortex. In the absence of SPARC, a reduced and disordered fibrous network, increased parasite burden, and reduced antigen-specific T cell entry into the brain points to a role for SPARC in T cell recruitment to and migration within the brain. We also report SPARC can directly bind to CCR7 ligands CCL19 and CCL21 but not CXCL10, and enhance migration toward a chemokine gradient. Measurement of T cell behavior points to tissue remodeling being important for access of immune cells to the brain and facilitating cellular locomotion. Together, these data identify SPARC as an important regulatory component of immune cell trafficking and access to the inflamed CNS.
Small area variation in child undernutrition across 640 districts and 543 parliamentary constituencies in India
Authors: Rajpal Sunil , Kim Julie , Joe William , Kim Rockli , Subramanian S. V.
Published: February 2021

In India, districts serve as central policy unit for program development, administration and implementation. The one-size-fits-all approach based on average prevalence estimates at the district level fails to capture the substantial small area variation. In addition to district average, heterogeneity within districts should be considered in policy design. The objective of this study was to quantify the extent of small area variation in child stunting, underweight and wasting across 36 states/Union Territories (UTs), 640 districts (and 543 PCs), and villages/blocks in India. We utilized the 4th round of Indian National Family Health Survey (NFHS-4) conducted in 2015–2016. The study population included 225,002 children aged 0–59 months whose height and weight information were available. Stunting was defined as height-for-age z-score below 2 SD from the World Health Organization child growth reference standards. Similarly, underweight and wasting were each defined as weight-for-age < -2 SD and weight-for-height < -2 SD from the age- and sex-specific medians. We adopted a four-level logistic regression model to partition the total variation in stunting, underweight and wasting. We computed precision-weighted prevalence of child anthropometric failures across districts and PCs as well as within-district/PC variation using standard deviation (SD) measures. For stunting, 56.4% (var: 0.237; SE: 0.008) of the total variation was attributed to villages/blocks, followed by 25.8% (var: 0.109; SE: 0.030) to states/UTs, and 17.7% (Var: 0.074; SE: 0.006) to districts. For underweight and wasting, villages/blocks accounted for 38.4% (var: 0.224; SE: 0.007) and 50% (var: 0.285; SE: 0.009), respectively, of the total contextual variance in India. Similar findings were shown in multilevel models incorporating PC as a geographical unit instead of districts. We found high positive correlations between mean prevalence and SD for stunting (r = 0.780, p < 0.001), underweight (r = 0.860, p < 0.001), and wasting (r = 0.857, p < 0.001) across all districts in India. A similar pattern of correlation was found for PCs. Within-district and within-PC variation are the primary source of variation for child malnutrition in India. Our results suggest the importance of considering heterogeneity within districts and PCs when planning and administering child nutrition policies.
Capital-income breeding in wild boar: a comparison between two sexes
Authors: Brogi Rudy , Chirichella Roberta , Brivio Francesca , Merli Enrico , Bottero Elisa , Apollonio Marco
Published: February 2021

Organisms differ in the strategy adopted to fuel reproduction by using resources either previously acquired and stored in body reserves (capital breeding) or, conversely, acquired during their reproductive activity (income breeding). The choice of one or the other strategy is related to several internal and external factors which are counteractive in wild boar. Based on a large dataset of culled wild boar, we investigated individual body weight variability throughout the period of 1st September–31st January, which included the main part of the mating season, among different sex and age classes to determine their position along the capital-income breeding continuum. Though food resources were abundant during the rut, adult males lost body weight suggesting they adopted a predominantly capital breeding strategy, likely owing to the high intra-sexual competition entailed by the peculiar mating system of the species. On the contrary, subadult males seemed to behave as income breeders, likely enhancing the reproductive flexibility of wild boar populations. During the rut, females stored reserves, thus suggesting that they substantially relied on them to cover future reproductive costs.
Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
Authors: Lassé Moritz , Pilbrow Anna P. , Kleffmann Torsten , Andersson Överström Elin , von Zychlinski Anne , Frampton Christopher M. A. , Poppe Katrina K. , Troughton Richard W. , Lewis Lynley K. , Prickett Timothy C. R. , Pemberton Christopher J. , Richards Arthur M. , Cameron Vicky A.
Published: February 2021

To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A “Discovery cohort” of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS). Associations with cardiovascular events were tested using Cox regression, adjusted for the New Zealand Cardiovascular Risk Score. Concentrations of leading protein candidates were subsequently measured with ELISAs in a larger (n = 151) independent subset. In the Discovery cohort, 76 plasma proteins were robustly quantified by DIA-MS, with 8 independently associated with cardiovascular events. These included (HR = hazard ratio [95% confidence interval] above vs below median): fibrinogen alpha chain (HR = 1.84 [1.19–2.84]); alpha-2-HS-glycoprotein (also called fetuin A) (HR = 1.86 [1.19–2.93]); clusterin isoform 2 (HR = 1.59 [1.06–2.38]); fibrinogen beta chain (HR = 1.55 [1.04–2.30]); hemoglobin subunit beta (HR = 1.49 [1.04–2.15]); complement component C9 (HR = 1.62 [1.01–2.59]), fibronectin isoform 3 (HR = 0.60 [0.37–0.99]); and lipopolysaccharide-binding protein (HR = 1.58 [1.00–2.49]). The proteins for which DIA-MS and ELISA data were correlated, fibrinogen and hemoglobin, were analyzed in an Extended cohort, with broader inclusion criteria and longer time to events, in which these two proteins were not associated with incident cardiovascular events. We have identified eight candidate proteins that may independently predict cardiovascular events occurring within three years in asymptomatic, low-to-moderate risk individuals, although these appear not to predict events beyond three years.
High optical enhancement in Au/Ag alloys and porous Au using Surface-Enhanced Raman spectroscopy technique
Authors: Awada C. , Dab C. , Grimaldi M. G. , Alshoaibi A. , Ruffino F.
Published: February 2021

We report high optical enhancement in Ag/Au alloys and porous gold nanostructures using Surface Enhanced Raman Spectroscopy (SERS) technique. Scanning electron microscopy investigation shows the formation of Ag/Au alloys particles during irradiation of Ag–Au bilayer deposited on FTO (SnO2:F) substrate by laser fluency equal to 0.5 J/cm2 or 1.0 J/cm2 with 12 ns laser pulse duration. The dealloying process of these Au–Ag alloy particles leads to the formation of Au nanoporous particles. The obtained nanostructures were studied with SERS and revealed a promising enhancement factor in porous Au nanostructure and tunability of localized surface plasmon resonance. The highly dense strong hot spots and large specific area in porous structure of gold nanostructures is the origin of the highly enhancement factor observed experimentally and theoretically. A very good agreement between simulation and experimental results was found confirming the potential of Au/Ag alloys and particularly porous gold nanostructure in SERS application.
Environmental impact of the cultivation of energy willow in Poland
Authors: Kowalczyk Zbigniew , Kwaśniewski Dariusz
Published: February 2021

The purpose of the work is to analyze the structure of the environmental impact of energy willow cultivation (Salix spp.) on plantations of various sizes, divided per materials and processes. The research covered 15 willow plantations, ranging from 0.31 ha to 12 ha, located in southern Poland. It was found, among others, that the so-called processes, i.e. the use of technical means of production, dominate the structure of the environmental impact (EI) related to the cultivation of energy willow, and that the cultivation of energy willow on larger plantations has a much lower environmental impact compared to cultivation on smaller plantations. Also, in the case of the environmental impact of processes, the largest environmental impact was recorded in the human health category, which is mainly associated with the consumption of fuel, i.e. diesel. It was determined, e.g., that the cultivation of energetic willow on larger plantations is characterized by a much lower environmental impact (as per the cultivation area), at approx. 108 Pt, compared to the cultivation on smaller plantations, where the value of the environmental impact is 168 Pt. A decisively dominant position in the structure of the environmental impact (EI), related to the cultivation of energy willow, is held by the so-called processes, i.e. the use of technical means of production. Their share in the total environmental impact decreases from 148.5 Pt in the group of the smallest plantations to 77.9 Pt in the group of the largest plantations.