bluuebunny/crossref_metadata_2025 huggingface dataset:
(R)‐Ketamine exerts antidepressant actions partly via conversion to (2R,6R)‐hydroxynorketamine, while causing adverse effects at sub‐anaesthetic doses
Authors: Zanos Panos , Highland Jaclyn N. , Liu Xin , Troppoli Timothy A. , Georgiou Polymnia , Lovett Jacqueline , Morris Patrick J. , Stewart Brent W. , Thomas Craig J. , Thompson Scott M. , Moaddel Ruin , Gould Todd D.
Published: April 2019

Background and Purpose

(R)‐Ketamine (arketamine) may have utility as a rapidly acting antidepressant. While (R)‐ketamine has lower potency than (R,S)‐ketamine to inhibit NMDA receptors in vitro, the extent to which (R)‐ketamine shares the NMDA receptor‐mediated adverse effects of (R,S)‐ketamine in vivo has not been fully characterised. Furthermore, (R)‐ketamine is metabolised to (2R,6R)‐hydroxynorketamine (HNK), which may contribute to its antidepressant‐relevant actions.

Experimental Approach

Using mice, we compared (R)‐ketamine with a deuterated form of the drug (6,6‐dideutero‐(R)‐ketamine, (R)‐d2‐ketamine), which hinders its metabolism to (2R,6R)‐HNK, in behavioural tests predicting antidepressant responses. We also examined the actions of intracerebroventricularly infused (2R,6R)‐HNK. Further, we quantified putative NMDA receptor inhibition‐mediated adverse effects of (R)‐ketamine.

Key Results

(R)‐d2‐Ketamine was identical to (R)‐ketamine in binding to and functionally inhibiting NMDA receptors but hindered (R)‐ketamine's metabolism to (2R,6R)‐HNK. (R)‐Ketamine exerted greater potency than (R)‐d2‐ketamine in several antidepressant‐sensitive behavioural measures, consistent with a role of (2R,6R)‐HNK in the actions of (R)‐ketamine. There were dose‐dependent sustained antidepressant‐relevant actions of (2R,6R)‐HNK following intracerebroventricular administration. (R)‐Ketamine exerted NMDA receptor inhibition‐mediated behaviours similar to (R,S)‐ketamine, including locomotor stimulation, conditioned‐place preference, prepulse inhibition deficits, and motor incoordination, with approximately half the potency of the racemic drug.

Conclusions and Implications

Metabolism of (R)‐ketamine to (2R,6R)‐HNK increases the potency of (R)‐ketamine to exert antidepressant‐relevant actions in mice. Adverse effects of (R)‐ketamine require higher doses than those necessary for antidepressant‐sensitive behavioural changes in mice. However, our data revealing that (R)‐ketamine's adverse effects are elicited at sub‐anaesthetic doses indicate a potential risk for sensory dissociation and abuse liability.
Anticosti foreland basin offshore of western Newfoundland: Concealed record of northern Appalachian orogen development
Authors: White Shawna E. , Waldron John W. F. , Harris Nicholas B.
Published: April 2019

The Anticosti Basin, largely hidden beneath the Gulf of St. Lawrence, includes foreland basin successions that record multiple tectonic events associated with the Ordovician to Devonian evolution of the northern Appalachian orogen. Due to the lack of well ties and minimal onshore exposure, geophysical data must be used in mapping the offshore stratigraphy. Outcropping geologic boundaries are tied to magnetic lineaments that parallel stratigraphy. These lineaments are correlated with reflections on seismic profiles in order to interpret the subsurface. Seismic isochron maps for successive basin development episodes display differences in geometry, implying that orogenic loading varied through time. The geometry and subsidence rates recorded by the Middle Ordovician Goose Tickle Group imply that it formed in a pro‐arc setting associated with loading during arc‐continent collision that was most intense in the northern Newfoundland Appalachians. The geometry and subsidence recorded by the overlying Long Point Group imply pro‐arc loading by Taconian allochthons in the Québec segment of the orogen. Diachronous subduction polarity reversal along the margin placed the Long Point Group in a combined retro‐arc and pro‐arc setting, comparable to that experienced by parts of the north Australian margin at the present day. The uppermost Silurian to Lower Devonian Clam Bank Formation and Lower Devonian Red Island Road Formation represent foreland basin successions associated with the later Salinian and Acadian orogenies. Their consistent thickness implies a broad, shallow basin, suggesting that the lithosphere was cooler and stronger than during earlier subsidence, and are consistent with a retro‐arc setting.
Longitudinal interrelationships between dental fear and dental attendance among adult Finns in 2000‐2011
Authors: Liinavuori Arja , Tolvanen Mimmi , Pohjola Vesa , Lahti Satu
Published: April 2019

Objectives

The aim of this longitudinal study was to investigate causal pathways among as well as interrelationships between changes in dental fear and dental attendance in a nationally representative sample of adult Finns aged 19 years or older in 2000, with 11 years of follow‐up.

Methods

Data from the Health 2000 and 2011 Surveys (BRIF8901) in Finland were used. The Health 2000 survey used a stratified two‐stage cluster sampling design (N=9742). Of the participants in 2000, 7964 were eligible and invited to participate in 2011. Of the participants in 2011 (n=5806), 3,631 (63%) responded to both dental fear and attendance questions in both years. Both fear and attendance were assessed using single questions and dichotomized. The background variables included were age, gender and education. Path analysis and logistic regression models were used.

Results

Dental fear led to nonhabitual use of dental services rather than vice versa (−0.07 to 0.04 vs. 0.00). When confounders were considered, in both age groups (29‐39 years and 40+ years) an increase in fear predicted nonhabitual dental attendance. This association was stronger among the younger age group (OR = 4.91) than among those aged 40 years and older (OR = 2.88). Among the younger age group, improved dental fear decreased the risk of nonhabitual dental attendance (OR = 0.16), while among older age group, stable fear increased the risk of nonhabitual dental attendance (OR = 2.33).

Conclusions

Dental fear causes nonhabitual dental attendance, and decreasing dental fear increases habitual attendance. Oral health personnel should adapt measures to prevent and treat dental fear.
Impact of maternal adverse childhood experiences on child socioemotional function in rural Kenya: Mediating role of maternal mental health
Authors: Rieder Amber D. , Roth Sophia L. , Musyimi Christine , Ndetei David , Sassi Roberto B. , Mutiso Victoria , Hall Geoffrey B. , Gonzalez Andrea
Published: April 2019

Mothers in low‐ and middle‐income countries (LMIC) suffer heightened vulnerability for adverse childhood experiences (ACEs), which is exacerbated by the multitude of risk factors associated with poverty and may lead to increased risk of psychiatric disorder. The constellation of complex, co‐occurring biological, environmental, social, economic and psychological risk factors are in turn transmitted to her child, conferring vulnerability for adverse development. This study examines the association between maternal intra‐ and extra‐familial ACEs, maternal education and the mental health of her child, mediated by maternal mental health. Mother‐child dyads (n = 121) in Machakos, Kenya were examined cross‐sectionally using self‐report measures of ACEs, maternal mental health and child internalizing and externalizing mental health problems. The four models proposed to examine the relationship between intra‐ and extra‐familial maternal ACEs and child internalizing and externalizing problems demonstrated indirect pathways through maternal mental health. These effects were found to be conditional on levels of maternal education, which served as a protective factor at lower levels of maternal ACEs. These models demonstrate how the impact of ACEs persists across the lifespan resulting in a negative impact on maternal mental health and conferring further risk to subsequent generations. Elucidating the association between ACEs and subsequent intergenerational sequelae, especially in LMIC where risk is heightened, may improve targeted caregiver mental health programs for prevention and intervention.
Temporal variation of renal function in people with type 2 diabetes mellitus: A retrospective UK clinical practice research datalink cohort study
Authors: Spanopoulos Dionysis , Okhai Hajra , Zaccardi Francesco , Tebboth Abigail , Barrett Brendan , Busse Michael , Webb Joanne , Khunti Kamlesh
Published: April 2019

Aim

To characterize the longitudinal variability of estimated glomerular filtration rate (eGFR) in people with type 2 diabetes mellitus (T2DM), including variation between categories and individuals.

Methods

People with T2DM and sufficient recorded serum creatinine measurements were identified from the Clinical Practice Research Datalink (T2DM diagnosis from 1 January 2009 to 1 January 2011 with 5 years follow‐up); eGFR was calculated using the CKD‐EPI equation.

Results

In total, 7766 individuals were included; 32.8%, 50.2%, 12.4%, 4.0% and 0.6% were in glomerular filtration rate (GFR) categories G1, G2, G3a, G3b and G4, respectively. Overall, eGFR decreased by 0.44 mL/min/1.73 m2 per year; eGFR increased by 0.80 mL/min/1.73 m2 between index and year 1, then decreased by 0.75 mL/min/1.73 m2 annually up to year 5. Category G1 showed a steady decline in eGFR over time; G2, G3a and G3b showed an increase between index and year 1, followed by a decline. Category G4 showed a mean eGFR increase of 1.85 mL/min/1.73 m2 annually. People in categories G3‐G4 moved across a greater number of GFR categories than those in G1 and G2. Individual patients' eGFR showed a wide range of values (change from baseline at year 5 varied from −80 to +59 mL/min/1.73 m2).

Conclusion

Overall, eGFR declined over time, although there was considerable variation between GFR categories and individuals. This highlights the difficulty in prescribing many glucose‐lowering therapies, which require dose adjustment for renal function. The study also emphasizes the importance of regular monitoring of renal impairment in people with T2DM.
Temporal refinement of sensory‐evoked activity across layers in developing mouse barrel cortex
Authors: van der Bourg Alexander , Yang Jenq‐Wei , Stüttgen Maik C. , Reyes‐Puerta Vicente , Helmchen Fritjof , Luhmann Heiko J.
Published: April 2019

Rhythmic whisking behavior in rodents fully develops during a critical period about 2 weeks after birth, in parallel with the maturation of other sensory modalities and the onset of exploratory locomotion. How whisker‐related sensory processing develops during this period in the primary somatosensory cortex (S1) remains poorly understood. Here, we characterized neuronal activity evoked by single‐ or dual‐whisker stimulation patterns in developing S1, before, during and after the occurrence of active whisking. Employing multi‐electrode recordings in all layers of barrel cortex in urethane‐anesthetized mice, we find layer‐specific changes in multi‐unit activity for principal and neighboring barrel columns. While whisker stimulation evoked similar early responses (0–50 ms post‐stimulus) across development, the late response (50–150 ms post‐stimulus) decreased in all layers with age. Furthermore, peak onset times and the duration of the late response decreased in all layers across age groups. Responses to paired‐pulse stimulation showed increases in spiking precision and in paired‐pulse ratios in all cortical layers during development. Sequential activation of two neighboring whiskers with varying stimulus intervals evoked distinct response profiles in the activated barrel columns, depending on the direction and temporal separation of the stimuli. In conclusion, our findings indicate that the temporal sharpening of sensory‐evoked activity coincides with the onset of active whisking.
Dangerous love? Predation risk does not affect female mate choice in blue‐black grassquits
Authors: de Moraes Pedro Z. , Diniz Pedro , Macedo Regina H.
Published: April 2019

Predation risk may be an important factor affecting female mate choice. Hypothetically, females could choose extravagantly ornamented males that survive in high predation risk environments. However, this decision could be different if choosing a conspicuous male under high predation risk is costly for females or results in reduced offspring survival. In such contexts, females could become indifferent to male quality or prefer inconspicuous males. We tested this idea using captive blue‐black grassquits (Volatinia jacarina, Linnaeus, 1766), a species in which males perform conspicuous leap displays coupled with songs during the breeding season, which presumably subjects females and offspring to higher predation risk. Females were placed in an arena with speakers on opposite sides emitting male courtship songs. One speaker emitted songs at a high rate (proxy for a conspicuous male) while the other speaker broadcast songs at a low rate (proxy for a less conspicuous male). While the female evaluated the two male songs, a third speaker emitted vocalizations characterizing three levels of risk: adult predator, nest predator, and no‐risk control. Females showed no preference for either male stimuli across the predation risk treatments. This lack of preference relative to frequency of male vocal displays suggests that leap‐song frequency is not used by females during mate choice. We suggest that in addition to its role in courtship, male grassquit displays also signal status to other males when competing for territories. Thus, we propose that predation risk does not directly influence blue‐black grassquit intersexual selection and that females in this species may exercise indirect mate choice, choosing social mates based on male ability to establish and defend a territory, and relying secondarily upon other aspects of male display attributes, such as its visual components.
Adaptive variation for growth and resistance to a novel pathogen along climatic gradients in a foundation tree
Authors: Ahrens Collin W. , Mazanec Richard A. , Paap Trudy , Ruthrof Katinka X. , Challis Anthea , Hardy Giles , Byrne Margaret , Tissue David T. , Rymer Paul D.
Published: April 2019

Natural ecosystems are under pressure from increasing abiotic and biotic stressors, including climate change and novel pathogens, which are putting species at risk of local extinction, and altering community structure, composition and function. Here, we aim to assess adaptive variation in growth and fungal disease resistance within a foundation tree, Corymbia calophylla to determine local adaptation, trait heritability and genetic constraints in adapting to future environments. Two experimental planting sites were established in regions of contrasting rainfall with seed families from 18 populations capturing a wide range of climate origins (~4,000 individuals at each site). Every individual was measured in 2015 and 2016 for growth (height, basal diameter) and disease resistance to a recently introduced leaf blight pathogen (Quambalaria pitereka). Narrow‐sense heritability was estimated along with trait covariation. Trait variation was regressed against climate‐of‐origin, and multivariate models were used to develop predictive maps of growth and disease resistance. Growth and blight resistance traits differed significantly among populations, and these differences were consistent between experimental sites and sampling years. Growth and blight resistance were heritable, and comparisons between trait differentiation (QST) and genetic differentiation (FST) revealed that population differences in height and blight resistance traits are due to divergent natural selection. Traits were significantly correlated with climate‐of‐origin, with cool and wet populations showing the highest levels of growth and blight resistance. These results provide evidence that plants have adaptive growth strategies and pathogen defence strategies. Indeed, the presence of standing genetic variation and trait heritability of growth and blight resistance provide capacity to respond to novel, external pressures. The integration of genetic variation into adaptive management strategies, such as assisted gene migration and seed sourcing, may be used to provide greater resilience for natural ecosystems to both biotic and abiotic stressors.
Developing a personal value analysis method of social media to support customer segmentation and business model innovation
Authors: Chen Tsung‐Yi , Cheng Hsiang‐An , Chen Yuh‐Min
Published: April 2019

Companies need to find out about the personal values of customers and identify customer segments before developing effective business models (BMs) or marketing strategies. Therefore, understanding the personal values of customers is critical in BM design. Traditional personal value evaluation methods are laborious and time‐consuming. In recent years, social media have become an important platform for people to share ideas and express views, making the presence of a huge amount of opinions on platforms that can cater for the demand of data for personal value analysis of customers. This study took Facebook and Instagram as the targets and developed a novel personal value forecasting method to help enterprises obtain the various personal values of customer segments automatically at a lower cost. This study adopted Schwartz's value theory as the value model and proposed a consistency model and a relativity model for weighted calculations, so as to determine the feature of a value tag. Finally, the feature selection algorithm and classification algorithm were used for judging values. In the evaluation phase of this study, 61 participants were recruited to test the proposed method. The proposed method could assist enterprises in better understanding personal value information.
Head mouse control system for people with disabilities
Authors: Abiyev Rahib H. , Arslan Murat
Published: April 2019

In this paper, a human–machine interface for disabled people with spinal cord injuries is proposed. The designed human–machine interface is an assistive system that uses head movements and blinking for mouse control. In the proposed system, by moving one's head, the user moves the mouse pointer to the required coordinates and then blinks to send commands. The considered head mouse control is based on image processing including facial recognition, in particular, the recognition of the eyes, mouth, and nose. The proposed recognition system is based on the convolutional neural network, which uses the low‐quality images that are captured by a computer's camera. The convolutional neural network (CNN) includes convolutional layers, a pooling layer, and a fully connected network. The CNN transforms the head movements to the actual coordinates of the mouse. The designed system allows people with disabilities to control a mouse pointer with head movements and to control mouse buttons with blinks. The results of the experiments demonstrate that this system is robust and accurate. This invention allows people with disabilities to freely control mouse cursors and mouse buttons without wearing any equipment.
MicroRNA‐520c‐3p functions as a novel tumor suppressor in lung adenocarcinoma
Authors: Li Xiaofeng , Fu Qiang , Li Hui , Zhu Lei , Chen Wei , Ruan Tonglei , Xu Wengui , Yu Xiaozhou
Published: April 2019

Lung cancer is a malignancy with one of the highest incidence rates, and it is the leading cause of cancer‐related death. To gain further insights into the underlying mechanisms of tumor growth and metastasis, we investigated the role and expression of microRNAs in lung adenocarcinoma (LUAD). We discovered a significantly lower expression level of microRNA‐520c‐3p (miR‐520c‐3p) in LUAD tissues than in nontumor tissues. miR‐520c‐3p is known to regulate multiple biological functions and cellular behaviors. In this study, we show that AKT1 and AKT2 are key direct targets of miR‐520c‐3p, which are required for its biological roles in LUAD. Mechanistically, downregulation of miR‐520c‐3p in LUAD is due to DNA methylation of the miR‐520c‐3p promoter region. Conversely, the activity of the transcription factor Yin Yang 1 (YY1) results in the upregulation of miR‐520c‐3p. Taken together, our results reveal methylation/YY1/miR‐520c‐3p/AKT1/AKT2 as a molecular axis with a potent biological function and highlight miR‐520c‐3p as a novel potent tumor suppressor in LUAD.
Effect of family characteristics on periodontal diseases in children and adolescents—A systematic review
Authors: Tadakamadla Santosh K. , Tadakamadla Jyothi , Kroon Jeroen , Lalloo Ratilal , Johnson Newell W.
Published: April 2019

Aim

To synthesize the literature on the influence of family/parents characteristics on periodontal diseases in children and adolescents.

Methods

An electronic search for relevant literature published between 2007 and 2017 was undertaken in PubMed, Embase, Cinahl and Cochrane databases; the search was updated in April 2018. Two reviewers independently reviewed the abstracts of these; of which, 43 articles were reviewed in full.

Results

Of the 746 retrieved titles, 649 remained after removing duplicates. Thirty articles met the inclusion criteria, and 13 were excluded. Also, two were included from the updated search. Data from the reviewed articles indicate that all three indicators of parent's socioeconomic status (income, education and occupation) are significantly associated with periodontal diseases in children. Better periodontal status was observed in children of parents with higher SES than those whose parents were of lower SES. Although the association between parent's smoking practices, level of periodontal diseases and children's periodontal status was explored only in few studies, findings indicate that children exposed to passive smoking and having parents with periodontal diseases are more likely to present with periodontal diseases as well.

Conclusions

Most of the studies considered socioeconomic factors and had not attempted to explore the impact of parental psychosocial variables on periodontal diseases in children. The literature indicates that these variables significantly influence health practices, including oral hygiene practices, which could ultimately affect periodontal health. More studies are required to explore the association of these variables with periodontal outcomes in children.
Variation in syntactic complexity: Introduction
Authors: Kuiken Folkert , Vedder Ineke , Housen Alex , De Clercq Bastien
Published: April 2019

This special issue, focusing on different types of variation in syntactic complexity, offers a critical discussion of the role of variation in syntactic complexity research in SLA. Special attention is paid to inter‐learner variation (i.e., individual developmental trajectories of acquiring syntactic complexity) and to interactions with related constructs, for instance between syntax and morphology, and between syntactic and lexical complexity. The overarching focus of the different contributions is to investigate the possible variation of (syntactic) complexity according to various external factors, such as levels of linguistic proficiency (developmental variation), variation in task modality (i.e., oral, written), task types and genres, and variation in source and target languages (cross‐linguistic variation
Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives
Authors: Berquist Sean W , Yim Kendrick , Ryan Stephen T , Patel Sunil H , Eldefrawy Ahmed , Cotta Brittney H , Bradshaw Aaron W , Meagher Margaret F , Bindayi Ahmet , McKay Rana R , Autorino Riccardo , Staehler Michael , Derweesh Ithaar H
Published: April 2019

Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high‐risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron‐sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double‐blind placebo‐controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.
Pilot feasibility study of the Walking Away from Diabetes programme for adults with intellectual disabilities in two further education colleges: Process evaluation findings
Authors: Maine Andrew , Brown Michael J. , Dickson Adele , Truesdale Maria
Published: April 2019

Background

People with intellectual disabilities remain at high risk of developing type 2 diabetes (T2D) due to lifestyle‐associated risk factors. Educational programmes have been adapted for people with intellectual disabilities targeting ongoing T2D self‐management. However, there are no adapted programmes which aim to prevent T2D through reducing risk factors. The present study initiates addressing this gap.

Methods

Further education (FE) colleges in Scotland were recruited for feasibility study using the Walking Away (WA) from Diabetes programme. Process evaluation assessed recruitment, retention, baseline physical activity levels, and acceptability and accessibility using focus groups.

Results

Ninety six percent of invited students agreed to participate. WA was positively received, and some short‐term impact was described. Suggestions for further adaptations regarding materials, delivery and content were provided, including delivery embedded within FE college curriculum.

Conclusions

Recruitment, retention and acceptability provide rationale for further research on T2D prevention in FE colleges.
Social movement in stages: a reply to Shultziner and Goldberg
Authors: Elliott‐Maksymowicz Katarzyna
Published: April 2019

This paper is a reply to Doron Shultziner and Sarah Goldberg's article The Stages of Mass Mobilization: Separate Phenomena and Distinct Causal Mechanisms. The article recognizes the theoretical contribution of the study, in particular the re‐introduction of the largely neglected stage approach in social movement studies. It then raises two major concerns related to how the authors narrow their approach to single episodes of mass mobilization and how definitively they distinguish movement stages.
Rice sulfoquinovosyltransferase SQD2.1 mediates flavonoid glycosylation and enhances tolerance to osmotic stress
Authors: Zhan Xinqiao , Shen Qingwen , Chen Jie , Yang Pei , Wang Xuemin , Hong Yueyun
Published: April 2019

Sulfoquinovosyltransferase 2 (SQD2) catalyses the final step in the sulfoquinovosyldiacylglycerol (SQDG) biosynthetic pathway. It is involved in the phosphate starvation response. Here, we show that rice SQD2.1 has dual activities catalysing SQDG synthesis and flavonoid glycosylation. SQD2.1 null mutants (sqd2.1) in rice had decreased levels of glycosidic flavonoids, particularly apigenin 7‐O‐glucoside (A7G), whereas these metabolites were increased in rice plants overexpressing SQD2.1. The sqd2.1 mutants and SQD2.1 overexpressing lines showed reduced and enhanced, respectively, tolerance to salinity and drought. Treating the sqd2.1 mutants with A7G decreased oxidative damage and restored stress tolerance to the wild‐type levels. These findings demonstrate that SQD2.1 has a novel function in the glycosylation of flavonoids that is required for osmotic stress tolerance in rice. The novel activity of SQD2.1 in the production of glycosidic flavonoids improves scavenging of reactive oxygen species and protects against excessive oxidation.
Extending the metatheoretical framework of social/political influence to leadership: Political skill effects on situational appraisals, responses, and evaluations by others
Authors: Frieder Rachel E. , Ferris Gerald R. , Perrewé Pamela L. , Wihler Andreas , Brooks C. Darren
Published: April 2019

Building off and extending the metatheoretical framework of political skill, we examined the cognitive and behavioral mechanisms through which the intrapsychic effects of political skill inform its interpersonal effects, and how these interpersonal effects ultimately are transmitted into desirable outcomes. Specifically, we argue that politically skilled leaders demonstrate better situational appraisals (i.e., understanding), and thus, more appropriate situational responses (e.g., consideration and initiating structure behaviors); the demonstration of appropriate situational responses is argued to positively affect subordinates’ evaluations of their leaders (i.e., instrumentality) and subordinates’ concomitant attitudes (e.g., job satisfaction) and behaviors (e.g., performance). Results provided mixed support for the hypothesized relationships. Specifically, leader understanding mediated the relationship between political skill and consideration but not the relationship between political skill and structuring behaviors. Moreover, consideration was positively related to subordinates’ group‐level instrumentality perceptions, whereas initiating structure was not. Finally, subordinates’ individual (within‐level) perceptions of leader instrumentality were positively related to job satisfaction and performance. The implications of these findings as they relate to theory and practice are discussed along with this investigation's strengths, limitations, and directions for future research.
Leveraging Administrative Data to Better Serve Children and Families
Authors: Fischer Robert L. , Richter Francisca García‐Cobián , Anthony Elizabeth , Lalich Nina , Coulton Claudia
Published: April 2019

The challenge of complex social issues drives the need for data systems that can connect information across multiple service delivery systems. Integrated data systems provide significant value for needs assessment, program planning, policy decision making, and collective impact evaluation across a range of social issues. This case study describes a mature county‐based integrated data system. The case study has three aims: (1) to highlight the value of integrated data systems to research, (2) to outline common challenges that such initiatives face, and (3) to present several ongoing considerations for the field that could inform policy recommendations to facilitate the use of integrated data. The authors present examples from the experience of developing this integrated data system, including involvement in the design and evaluation of the first county‐level social impact bond. The case study highlights the benefits and limitations of integrated data use in research and the potential to advance evidence‐based social decision making.
Description of the novel KIR3DL3*063 allele identified in a Southern Chinese Han individual
Authors: Deng Zhi‐hui , Zhang Guobin , Cai Siqi
Published: April 2019

The novel KIR3DL3*063 allele differs from the closest allele KIR3DL3*04802 by a single missense mutation.
Evaluation of unsatisfactory student performance
Authors: Pratt Maria
Published: April 2019

Background

The ‘failure to fail’ phenomenon has been reported in studies involving preceptors and students in nursing and in other practice professions, but it has yet to be the subject of exploration among clinical nursing instructors. Research has revealed that assigning a failing grade in a practice profession is not always a straightforward task; however, passing students who are incompetent in their nursing practice could have a deleterious impact on the quality and delivery of patient care.

Methods

The author interviewed eight clinical instructors who had failed unsatisfactory students to gain an in‐depth understanding of each instructor's experience in evaluating these students. Gadamer's hermeneutic principles were used to interpret the interview texts and dialogue with the participants through the hermeneutic circle of understanding, use of the researcher's prior experience and openness to new understanding.

Findings

The experiences of the clinical instructors in this study suggest that they have struggled with their emotions, particularly when they were novices, during the multiple personal, professional and organisational challenges that they have encountered within their teaching roles and responsibilities.

Discussion

The difficulties and challenges highlighted in this study may offer insight for academic stakeholders in nursing schools on how to mitigate these issues through developing an onboarding orientation and mentorship programme that will support faculty member development in the evaluation of unsatisfactory student performance.
Genetic interactions reveal the antagonistic roles of FT/TSF and TFL1 in the determination of inflorescence meristem identity in Arabidopsis
Authors: Lee Chunghee , Kim Soo‐Jin , Jin Suhyun , Susila Hendry , Youn Geummin , Nasim Zeeshan , Alavilli Hemasundar , Chung Kyung‐Sook , Yoo Seong Jeon , Ahn Ji Hoon
Published: April 2019

During the transition to the reproductive phase, the shoot apical meristem switches from the developmental program that generates vegetative organs to instead produce flowers. In this study, we examined the genetic interactions of FLOWERING LOCUS T (FT)/TWIN SISTER OF FT (TSF) and TERMINAL FLOWER 1 (TFL1) in the determination of inflorescence meristem identity in Arabidopsis thaliana. The ft‐10 tsf‐1 mutants produced a compact inflorescence surrounded by serrated leaves (hyper‐vegetative shoot) at the early bolting stage, as did plants overexpressing TFL1. Plants overexpressing FT or TSF (or both FT and TFL1) generated a terminal flower, as did tfl1‐20 mutants. The terminal flower formed in tfl1‐20 mutants converted to a hyper‐vegetative shoot in ft‐10 tsf‐1 mutants. Grafting ft‐10 tsf‐1 or ft‐10 tsf‐1 tfl1‐20 mutant scions to 35S::FT rootstock plants produced a normal inflorescence and a terminal flower in the scion plants, respectively, although both scions showed similar early flowering. Misexpression of FT in the vasculature and in the shoot apex in wild‐type plants generated a normal inflorescence and a terminal flower, respectively. By contrast, in ft‐10 tsf‐1 mutants the vasculature‐specific misexpression of FT converted the hyper‐vegetative shoot to a normal inflorescence, and in the ft‐10 tsf‐1 tfl1‐20 mutants converted the shoot to a terminal flower. TFL1 levels did not affect the inflorescence morphology caused by FT/TSF overexpression at the early bolting stage. Taking these results together, we proposed that FT/TSF and TFL1 play antagonistic roles in the determination of inflorescence meristem identity, and that FT/TSF are more important than TFL1 in this process.
Prehospital whole blood resuscitation prevents coagulopathy and improves acid–base status at hospital arrival in a nonhuman primate hemorrhagic shock model
Authors: Sheppard Forest R. , Mitchell Thomas A. , Cap Andrew P. , Schaub Leasha J. , Macko Antoni R. , Glaser Jacob J.
Published: April 2019

BACKGROUND

Hemorrhage remains the primary cause of preventable death in civilian and military trauma. The Committee on Tactical Combat Casualty Care recommends prehospital (PH) resuscitation with whole blood (WB). However, 6% hetastarch in lactated electrolyte (HEX) and crystalloids are more commonly available and used for PH resuscitation in military and civilian environments, respectively. The mechanistic benefits of PH WB resuscitation have not been well studied and remain to be elucidated.

STUDY DESIGN AND METHODS

The aim of this study was to evaluate the differences in simulated PH WB and HEX resuscitation, specifically with regards to coagulation, physiologic, and metabolic outcomes to better elucidate the mechanistic benefits of WB. In a randomized study, the physiologic, coagulation, and metabolic responses to simulated PH WB (n = 12) or HEX (n = 12) were evaluated in a nonhuman primate model of severe polytraumatic hemorrhagic shock.

RESULTS

Notable findings included 1) equivalence of shock reversal between simulated PH WB and HEX treatment groups as determined by hemodynamics and base deficit and 2) prevention of coagulopathy at simulated hospital arrival with initial WB resuscitation as determined by viscoelastic and plasmatic coagulation assays.

CONCLUSION

The major benefit of WB, as compared to HEX, in simulated PH resuscitation appears to be prevention of coagulopathy at hospital arrival. Both fluids effectively reversed shock in this model, implying that efficacious provision preload (cardiac output support and hence oxygen delivery) and coagulation proteins (prevention of coagulopathy) are mechanisms underlying WB's effectiveness in early resuscitation of hemorrhagic shock.
The Effect of Oxidation on the Mechanical Response of Isolated Elastin and Aorta
Authors: Mythravaruni P. , Ravindran Parag
Published: April 2019

Oxidation of aorta by hydroxyl radicals produces structural changes in arterial proteins like elastin and collagen. This in turn results in change in the mechanical response of aorta. In this paper, a thermodynamically consistent constitutive model is developed within the framework of mixture theory, to describe the changes in aorta and isolated elastin with oxidation. The model is then studied under uniaxial extension using experimental data from literature.
VVER 1000 Severe Accident Analyses Using MELCOR Code
Authors: Ruščák Marek , Mazzini Guido , Kynčl Milos , Savanyuk Sevastyan , Hrehor Miroslav , Musa Alis , Flores y Flores Alain
Published: April 2019

This work describes the computer model development of the water–water energetic reactor (VVER) 1000 nuclear power plant (NPP) in the methods for estimation of leakages and consequences of releases (MELCOR) 1.8.6 code and its subsequent use for the accident scenarios analysis leading to the core melting. The baseline accident scenario was a stress test case—the station blackout (SBO, the complete loss of alternating current electric power in a nuclear power plant). In addition to this, four other scenarios were analyzed in which the SBO was combined with other technological failures—the loss of steam generator feedwater system and small, medium, and large break coolant accidents (LOCA). The results provided detailed information on the time course of accident scenarios, their temperature and pressure parameters, hydrogen production, and the mass inventory released from the molten corium and debris into the containment of the NPP.
The Effect of Material and Geometrical Uncertainty on the Homogenized Properties of Graphene Sheet-Reinforced Composites
Authors: Savvas Dimitrios , Stefanou George
Published: April 2019

This paper focuses on the computational homogenization of graphene sheet-reinforced composites with randomly dispersed inclusions and uncertainty in the constituent materials. Material uncertainty of the matrix and of the graphene inclusions are considered separately and their relative effect on the homogenized properties is assessed. The uncertainty in the inclusion material is due to structural defects of the graphene lattice and is taken into account using random variables for each component of the elasticity matrix. Moreover, Monte Carlo simulation is used to extract the statistical characteristics of the homogenized properties of the composite material. The results lead to useful conclusions regarding the effect of material and geometrical uncertainty on the macroscopic properties of graphene sheet-reinforced composites.
Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder
Authors: Etkin Amit , Maron-Katz Adi , Wu Wei , Fonzo Gregory A. , Huemer Julia , Vértes Petra E. , Patenaude Brian , Richiardi Jonas , Goodkind Madeleine S. , Keller Corey J. , Ramos-Cejudo Jaime , Zaiko Yevgeniya V. , Peng Kathy K. , Shpigel Emmanuel , Longwell Parker , Toll Russ T. , Thompson Allison , Zack Sanno , Gonzalez Bryan , Edelstein Raleigh , Chen Jingyun , Akingbade Irene , Weiss Elizabeth , Hart Roland , Mann Silas , Durkin Kathleen , Baete Steven H. , Boada Fernando E. , Genfi Afia , Autea Jillian , Newman Jennifer , Oathes Desmond J. , Lindley Steven E. , Abu-Amara Duna , Arnow Bruce A. , Crossley Nicolas , Hallmayer Joachim , Fossati Silvia , Rothbaum Barbara O. , Marmar Charles R. , Bullmore Edward T. , O’Hara Ruth
Published: April 2019

A subgroup of patients with post-traumatic stress disorder, characterized by a particular brain and behavioral signature, showed a poor treatment outcome.
Proteomic Analysis of the Pseudomonas aeruginosa Iron Starvation Response Reveals PrrF Small Regulatory RNA-Dependent Iron Regulation of Twitching Motility, Amino Acid Metabolism, and Zinc Homeostasis Proteins
Authors: Nelson Cassandra E. , Huang Weiliang , Brewer Luke K. , Nguyen Angela T. , Kane Maureen A. , Wilks Angela , Oglesby-Sherrouse Amanda G.
Published: April 2019

Iron is central for growth and metabolism of almost all microbial pathogens, and as such, this element is sequestered by the host innate immune system to restrict microbial growth. Here, we used label-free proteomics to investigate the
Pseudomonas aeruginosa
iron starvation response, revealing a broad landscape of metabolic and metal homeostasis changes that have not previously been described. We further provide evidence that many of these processes, including twitching motility, are regulated through the iron-responsive PrrF small regulatory RNAs. As such, this study demonstrates the power of proteomics for defining stress responses of microbial pathogens.
Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function
Authors: Nguyen Hanh T. , Alsahafi Nirmin , Finzi Andrés , Sodroski Joseph G.
Published: April 2019

The human immunodeficiency virus type 1 (HIV-1) envelope proteins (Envs) bind receptors on the host cell and change shape to allow the virus to enter the cell. Most virus-inhibiting antibodies and drugs recognize a particular shape of Env called state 1. Disulfide bonds formed by cysteine residues have been introduced into soluble forms of the flexible envelope proteins in an attempt to lock them into state 1 for use in vaccines and as research tools. We evaluated the effect of these cysteine substitutions on the ability of the membrane Env to support virus entry and on susceptibility to inhibition by antibodies and small molecules. We found that the conformation of the envelope proteins with the cysteine substitutions differed from that of the unmodified membrane envelope proteins. Awareness of these effects can assist efforts to create stable HIV-1 Env complexes that more closely resemble the state 1 conformation.
Complete Genome Sequence for
Asinibacterium
sp. Strain OR53 and Draft Genome Sequence for
Asinibacterium
sp. Strain OR43, Two Bacteria Tolerant to Uranium
Authors: Brzoska Ryann M. , Huntemann Marcel , Clum Alicia , Chen Amy , Kyrpides Nikos , Palaniappan Krishnaveni , Ivanova Natalia , Mikhailova Natalia , Ovchinnikova Galina , Varghese Neha , Mukherjee Supratim , Reddy T. B. K. , Daum Chris , Shapiro Nicole , Woyke Tanja , Bollmann Annette
Published: April 2019

Asinibacterium
sp. strains OR43 and OR53 belong to the phylum
Bacteroidetes
and were isolated from subsurface sediments in Oak Ridge, TN. Both strains grow at elevated levels of heavy metals. Here, we present the closed genome sequence of
Asinibacterium
sp. strain OR53 and the draft genome sequence of
Asinibacterium
sp. strain OR43.
Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study
Authors: Sacchetti Marta , Lambiase Alessandro , Schmidl Doreen , Schmetterer Leopold , Ferrari Mauro , Mantelli Flavio , Allegretti Marcello , Garhoefer Gerhard
Published: April 2019

Background

Dry eye disease (DED) affects more than 14% of the elderly population causing decrease of quality of life, high costs and vision impairment. Current treatments for DED aim at lubricating and controlling inflammation of the ocular surface. Development of novel therapies targeting different pathogenic mechanisms is sought-after. The aim of this study is to evaluate safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops in patients with DED.

Methods

Forty consecutive patients with moderate to severe DED were included in a phase IIa, prospective, open label, multiple-dose, clinical trial to receive rhNGF eye drops at 20 µg/mL (Group 1: G1) or at 4 µg/mL (Group 2: G2) concentrations, two times a day in both eyes for 28 days (NCT02101281). The primary outcomes measures were treatment-emerged adverse events (AE), Symptoms Assessment in Dry Eye (SANDE) scale, ocular surface staining and Schirmer test.

Results

Of 40 included patients, 39 completed the trial. Both tested rhNGF eye drop concentrations were safe and well tolerated. Twenty-nine patients experienced at least one AE (14 in G1 and 15 in G2), of which 11 had at least 1 related AE (8 in G1 and 3 in G2). Both frequency and severity of DED symptoms and ocular surface damage showed significant improvement in both groups, while tear function improved only in G1.

Conclusions

The data of this study indicate that rhNGF eye drops in both doses is safe and effective in improving symptoms and signs of DED. Randomised clinical trials are ongoing to confirm the therapeutic benefit of rhNGF in DED.

Trial registration number

NCT02101281.
Could this be measles?
Authors: O’Donnell Shaun , Davies Ffion , Vardhan Madhur , Nee Patrick
Published: April 2019

Infection with the measles virus causes an unpleasant disease with many potentially serious complications. It is predominantly a childhood illness but can affect any age. Measles is extraordinarily contagious, but immunisation with measles containing vaccine provides comprehensive protection. An international programme of universal immunisation from the mid-1980s has been very effective; measles was declared eliminated in the USA nearly two decades ago and became a rarity in other countries with high rates of vaccine uptake. Until recently, this was a forgotten disease in high-income countries, but paediatricians, emergency and primary care physicians worldwide are now encountering measles with increased frequency. Attributed to international travel and pockets of vaccine hesitancy locally, new outbreaks of measles have been recorded in many regions thought to have been free of the disease. Because it was previously so uncommon, measles presents a diagnostic challenge and an unrecognised case may cause infection to spread among communities. The present article presents a case of confirmed measles infection and discusses the epidemiology, clinical features, investigation, management and prevention of measles.