bluuebunny/crossref_metadata_2025 huggingface dataset:
An eight‐case 1q21 region series: novel aberrations and clinical variability with new features
Authors: Ceylan A. C. , Sahin I. , Erdem H. B. , Kayhan G. , Simsek‐Kiper P. O. , Utine G. E. , Percin F. , Boduroglu K. , Alikasifoglu M.
Published: February 2019

Background

Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings.

Methods

Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1–6 in RBM8A.

Results

Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889‐kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12).

Conclusion

Although the deletion in case 5 did not include the thrombocytopenia‐absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia‐absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype–phenotype correlations for this region.
Age‐specific associations between oestradiol, cortico‐amygdalar structural covariance, and verbal and spatial skills
Authors: Nguyen Tuong‐Vi , Jones Sherri Lee , Gower Tricia , Lew Jimin , Albaugh Matthew D. , Botteron Kelly N. , Hudziak James J. , Fonov Vladimir S. , Louis Collins D. , Campbell Benjamin C. , Booij Linda , Herba Catherine M. , Monnier Patricia , Ducharme Simon , Waber Deborah , McCracken James T.
Published: February 2019

Oestradiol is known to play an important role in the developing human brain, although little is known about the entire network of potential regions that might be affected and how these effects may vary from childhood to early adulthood, which in turn can explain sexually differentiated behaviours. In the present study, we examined the relationships between oestradiol, cortico‐amygdalar structural covariance, and cognitive or behavioural measures typically showing sex differences (verbal/spatial skills, anxious‐depressed symptomatology) in 152 children and adolescents (aged 6‐22 years). Cortico‐amygdalar structural covariance shifted from positive to negative across the age range. Oestradiol was found to diminish the impact of age on cortico‐amygdalar covariance for the pre‐supplementary motor area/frontal eye field and retrosplenial cortex (across the age range), as well as for the posterior cingulate cortex (in older children). Moreover, the influence of oestradiol on age‐related cortico‐amygdalar networks was associated with higher word identification and spatial working memory (across the age range), as well as higher reading comprehension (in older children), although it did not impact anxious‐depressed symptoms. There were no significant sex effects on any of the above relationships. These findings confirm the importance of developmental timing on oestradiol‐related effects and hint at the non‐sexually dimorphic role of oestradiol‐related cortico‐amygdalar structural networks in aspects of cognition distinct from emotional processes.
Ghrelin‐mediated improvements in the metabolic phenotype in the R6/2 mouse model of Huntington's disease
Authors: Rudenko Olga , Springer Cecilie , Skov Louisa J. , Madsen Andreas N. , Hasholt Lis , Nørremølle Anne , Holst Birgitte
Published: February 2019

Huntington's disease (HD) is a heritable neurodegenerative disorder, characterised by metabolic disturbances, along with cognitive and psychiatric impairments. Targeting metabolic HD dysfunction via the maintenance of body weight and fat mass and restoration of peripheral energy metabolism can improve the progression of neurological symptoms. In this respect, we focused on the therapeutic potential of the orexigenic peptide hormone ghrelin, which plays an important role in promoting a positive energy balance. In the present study, we found a significant disruption of circadian metabolic regulation in a R6/2 mouse HD model in the late stage of disease. Daily circadian rhythms of activity, energy expenditure, respiratory exchange ratio and feeding were strongly attenuated in R6/2 mice. During the rest phase, R6/2 mice had a higher total activity, elevated energy expenditure and excessive water consumption compared to control mice. We also found that, in the late stage of disease, R6/2 mice had ghrelin axis deficiency as a result of low circulating ghrelin levels, in addition to down‐regulation of the ghrelin receptor and several key signalling molecules in the hypothalamus, as well as a reduced responsiveness to exogenous peripheral ghrelin. We demonstrated that, in pre‐symptomatic mice, responsiveness to ghrelin is preserved. Chronic ghrelin treatment efficiently increased lean body mass and decreased the energy expenditure and fat utilisation of R6/2 mice in the early stage of disease. In addition, ghrelin treatment was also effective in the normalisation of drinking behaviour and the rest activity of these mice. Ghrelin treatment could provide a novel therapeutic possibility for delaying disease progression; however, deficiency in ghrelin receptor expression could limit its therapeutic potential in the late stage of disease.
On Equilibrium When Contingent Capital Has a Market Trigger: A Correction to Sundaresan and Wang Journal of Finance (2015)
Authors: PENNACCHI GEORGE , TCHISTYI ALEXEI
Published: February 2019

This paper identifies an error in Sundaresan and Wang (2015, hereafter SW) that invalidates its Theorem 1. The paper develops a model of contingent capital (CC) with a stock price trigger that is consistent with SW's framework and yields closed‐form solutions for stock and CC prices. Yet, the model shows that unique stock price equilibria exist for a broader range of CC contractual terms than those required by SW. Specifically, when conversion terms benefit CC investors and penalize shareholders, a unique equilibrium can exist rather than the multiple equilibria stated in SW.
Financial Markets, the Real Economy, and Self‐Fulfilling Uncertainties
Authors: BENHABIB JESS , LIU XUEWEN , WANG PENGFEI
Published: February 2019

We develop a model of informational interdependence between financial markets and the real economy, linking economic uncertainty to information production and aggregate economic activities in general equilibrium. The mutual learning between financial markets and the real economy creates a strategic complementarity in their information production, leading to self‐fulfilling surges in economic uncertainties. In a dynamic setting, our model characterizes self‐fulfilling uncertainty traps with two steady‐state equilibria and a two‐stage economic crisis in transitional dynamics.
Anxiety and the dynamic self as defined by the prospection and mental simulation of looming future threats
Authors: Riskind John H. , Calvete Esther
Published: February 2019

A more dynamic perspective of threats to the self may contribute to an enhanced understanding of the processes that develop and maintain anxiety and thus, potentially inform psychological interventions. This article presents the looming vulnerability model of anxiety, which stresses the threat or risk prospection and dynamic mental simulation of the course of threat. Individuals do not become anxious simply because they picture distant or static possible threats that represent threats to the self. Rather, their anxiety results from interpreting potential threats as dynamic, growing, and approaching. Following a review of a wide range of literature from clinical, personality, and social psychology, we present the looming vulnerability model and its underpinnings in evolution and examine its applications to cognitive vulnerability to anxiety and its therapeutic alleviation [Correction added on 6 August 2019, after first online publication: Abstract text has been corrected to ‘looming vulnerability model’ in two places.]. We also address the associations of the model to other self‐related concepts that are involved in anxiety.
Big Five personality domains and relationship satisfaction: Direct effects and correlated change over time
Authors: O’Meara Madison S. , South Susan C.
Published: February 2019

Objective

The Big Five Model (BFM) of personality domains is significantly related to romantic relationship outcomes, particularly marital satisfaction. Few studies to date, however, have examined the BFM domains and relationship outcomes longitudinally.

Method

We used latent growth curve modeling to estimate the initial levels (intercept) and the rate of change (slope) in the BFM domains and marital satisfaction and determine if change in one construct was associated with change in the other. All available data were retained from participants who remained married to the same individual, as well as early waves for participants who divorced or were widowed, in the Midlife in the United States study (N = 1,965). We expected negative associations between (a) intercepts of Neuroticism and relationship satisfaction and (b) the intercept/slope of Neuroticism with change in marital satisfaction. The other BFM domains were expected to have positive effects on change in satisfaction.

Results

The results suggested that change over time in Neuroticism and Conscientiousness is detrimental to satisfaction, while initial levels of Conscientiousness may predict declining marital satisfaction.

Conclusions

Changes in Neuroticism accompany parallel changes in relationship satisfaction in a large sample of married U.S. adults, suggesting an ongoing bidirectional influence between these constructs in enduring marriages.
Management of childhood obesity: An audit of clinical practice in secondary care
Authors: Dainty Gloria J , Reith David M , Taylor Barry J
Published: February 2019

Aim

Childhood obesity continues to be a major health issue for children world‐wide, with well‐recognised major health effects. This study evaluated the prevalence of obesity in children presenting to secondary care in Southern New Zealand, as well as their clinical management.

Methods

Obesity prevalence was determined by a review of data contained in the electronic anthropometry database in the region for the period 19 July 2010–16 July 2015. All clinical records were further examined using a standard data extraction form for 333 obese children regarding their clinical management.

Results

A total of 8551 individuals were identified in the database for review. The prevalence of overweight and obesity was higher than the average national rates but stable over the 5‐year period. Children of Maori and Pacific Island ethnicity, those most deprived and males were over‐represented in terms of obesity. Of the 333 obese children whose clinical management was examined, 45.0% received a diagnosis of obesity. Of those diagnosed, 24.7% had further investigations related to possible obesity complications, and 72.7% were given management plans. Older females were more likely to receive clinical intervention, while Maori and Pacific Island children were less likely.

Conclusions

Of the children seen in this secondary care setting, 40% are overweight or obese, and yet the rate of clinical intervention left room for improvement, suggesting a need for further staff education and clear guidelines. Maori and Pacific Island children have higher obesity burden but were less likely to receive clinical intervention. This may highlight a need for specific education regarding cultural practices.
Paediatric use of antibiotics in children with community acquired pneumonia: A survey from Da Nang, Vietnam
Authors: Nguyen Phuong TK , Tran Hoang T , Truong Huong TT , Nguyen Vu T , Graham Steve M , Marais Ben J
Published: February 2019

Aim

To characterise paediatricians' antibiotic‐prescribing behaviour when managing community acquired pneumonia.

Methods

We conducted a knowledge and attitudes survey of paediatric doctors practicing at a regional provincial hospital in central Vietnam over a 2‐week period (from 12 December 2017 to 29 December 2017).

Results

Of 79 eligible paediatric doctors, 69 (87.3%) completed the questionnaire, of whom 65 (94.2%) thought that antibiotics were overused in Vietnam. Thirty‐eight doctors (55.1%) indicated that they routinely hospitalised children with pneumonia to provide intravenous antibiotics. Most doctors reported discharging children with non‐severe pneumonia after 5 days (76.9%) and those with severe pneumonia after 7–10 days (88.4%); older doctors generally continued intravenous antibiotics for longer. The two most important factors driving discharge decisions were clinical assessment (95.6%) and completion of the full course of intravenous antibiotics (80.0%). Antibiotic prescription was influenced by local guidelines (62.3%), drugs used before admission (50.0%) and the opinion of senior clinicians (37.7%). Most doctors believed antibiotic stewardship was necessary (98.6%) and that over‐the‐counter use of antibiotics should be restricted (97.1%).

Conclusions

Paediatricians recognised an urgent need for more effective regulation and antibiotic stewardship in Vietnam. Routinely completing a full course of intravenous antibiotics leads to unnecessary and prolonged hospitalisation.
Social Networks as a Factor in Volunteering Among Elderly Japanese with Lower Socioeconomic Status
Authors: Fukuzawa Ai , Katagiri Keiko , Harada Kazuhiro , Masumoto Kouhei , Chogahara Makoto , Kondo Narihiko , Okada Shuichi
Published: February 2019

We investigated the effect of social networks on volunteering, which is known to be beneficial for people and society, among elderly Japanese of lower socioeconomic status. Western studies have demonstrated that social networks boost volunteering among wealthy people because of the norm that they should help the less fortunate. However, wealthy East Asians do not share this norm. Therefore, socioeconomic variables and volunteering tend not to be significantly related in Japan. We hypothesized that social networks would be more important to volunteering among the Japanese elderly, especially among people of a lower socioeconomic status. A total of 768 respondents (319 men, 432 women, 17 sex unspecified; Mage = 73.99 years, SD = 7.40 years) completed the survey. The results indicated that social networks were positively related to volunteering only among people with lower financial status. This result suggests that social networks can increase opportunities and help less advantaged elderly people to reap the benefits of volunteering.
For an integrative theory of social behaviour: Theorising with and beyond rational choice theory
Authors: Rutar Tibor
Published: February 2019

Most sociologists are not content with merely relating macrosocial phenomena to preceding macrosocial causes in their causal explanations of social phenomena. Instead they are seeking to provide (non‐reductive) microfoundations with which they can corroborate and make understandable the connection between macrosocial phenomena. In order to do so a theory (or theories) of human action is required. One such theory, rational choice theory (RCT), has long been viewed with strong suspicion in sociology. I show such suspicion to be partially justified. RCT cannot be a general theory of social behaviour. Nonetheless, there are important insights in various versions of RCT that should not be discarded. In order to improve upon RCT and move toward a more unified or integrative theory of action social‐psychological research has to be taken note of. I demonstrate how dual‐process theories and the research on heuristics can help sociologists move beyond RCT without contradicting some of its more basic insights.
Detection of Bacillus anthracis in animal tissues using InBios active anthrax detect rapid test lateral flow immunoassay
Authors: Kolton C.B. , Marston C.K. , Stoddard R.A. , Cossaboom C. , Salzer J.S. , Kozel T.R. , Gates-Hollingsworth M.A. , Cleveland C.A. , Thompson A.T. , Dalton M.F. , Yabsley M.J. , Hoffmaster A.R.
Published: February 2019

The Active Anthrax Detect (AAD) Rapid Test lateral flow immunoassay is a point-of-care assay that was under investigational use for detecting Bacillus anthracis capsular polypeptide (polyglutamic acid) in human blood, serum and plasma. Small sample volumes, rapid results and no refrigeration required allow for easy use in either the field or laboratory. Although the test was developed for use in suspect cases of human inhalation anthrax, its features also make it a potentially powerful tool for testing suspect animal cases. We tested animal tissue samples that were confirmed or ruled out for B. anthracis. The AAD Rapid Tests were also deployed in the field, testing animal carcasses during an anthrax outbreak in hippopotami (Hippopotamus amphibius) and Cape buffalo (Syncerus caffer) in Namibia. Evaluation of all samples showed a specificity of 82% and sensitivity of 98%. However, when the assay was used on specimens from only fresh carcasses (dead for <24 h), the specificity increased to 96%. The AAD Rapid Test is a rapid and simple screening assay, but confirmatory testing needs to be done, especially when the age of the sample (days animal has been deceased) is unknown.

Significance and Impact of the Study

In countries where anthrax is endemic, many human outbreaks are often caused by epizootics. Earlier detection of infected animals may allow for identification of exposed people, early implementation of prevention and control methods, and ultimately lessen the number of people and animals affected. Detection of Bacillus anthracis in animal tissues using a simple, rapid and field-deployable method would allow for faster outbreak response. We evaluated a simple sample collection and processing method for use with the Active Anthrax Detect Rapid Test lateral flow immunoassay to screen dead animals for anthrax.
“The very ugly duckling” meetsMinecraft: identity work and interpretive competence
Authors: Wilson Sue , Rennie Jennifer
Published: February 2019

Picturebook discussions are commonplace literacy events in contemporary classrooms. The different experiences, backgrounds and ways of being that individual students draw upon during talk around texts prompt a broad range of ways to make, negotiate and share meanings. In addition to developing students' literacy skills such as oral language, vocabulary and comprehension, these discussions have been shown to be instrumental in developing students' interpretive competence which is important for achieving learning outcomes. In this article, we report a study that investigated how four diverse groups of 10‐ and 11‐year‐old students and teachers from two schools experienced such reading events. The study found that making sense of these books was more productive when students were given permission to switch identities and make connections to their out‐of‐school cyber and popular culture worlds. Using discourse analytic techniques, we uncover the identity work during a number of discussions around two different picturebooks and show how this enabled these learners to enter the academic space and demonstrate interpretive competence.
Becoming a teacher of early reading: charting the knowledge and practices of pre‐service and newly qualified teachers
Authors: Hendry Helen
Published: February 2019

Education policy in England requires student teachers to demonstrate effective teaching of early reading, including systematic synthetic phonics, in order to qualify to teach. Although there is a range of literature about initial teacher education, little is documented about how pre‐service or ‘student' teachers develop specific knowledge and practices for teaching early reading and how they apply these in their first term as newly qualified teachers (NQTs). This research used a primarily qualitative longitudinal, collective case study design involving seven lower primary (3–7 years) postgraduate certificate in education (PGCE) students enrolled at one university in the East Midlands of England. Semi‐structured interviews, classroom observations and documentary analysis with the students and their teacher mentors were used to gather data from entry onto the course to the participants' first term as qualified teachers. A thematic analysis was applied in conjunction with deductive observation codes developed from a previous study. Findings indicate a broad continuum of progression in student and newly qualified teacher knowledge and practice for teaching early reading which could be used to inform university organisation, mentoring and school participation. They highlight the influence of school cultures on the experiences of student and pre‐service teachers.
Transcriptional integration of the responses to iron availability in Arabidopsis by the bHLH factor ILR3
Authors: Tissot Nicolas , Robe Kevin , Gao Fei , Grant‐Grant Susana , Boucherez Jossia , Bellegarde Fanny , Maghiaoui Amel , Marcelin Romain , Izquierdo Esther , Benhamed Moussa , Martin Antoine , Vignols Florence , Roschzttardtz Hannetz , Gaymard Frédéric , Briat Jean‐François , Dubos Christian
Published: February 2019

Iron (Fe) homeostasis is crucial for all living organisms. In mammals, an integrated posttranscriptional mechanism couples the regulation of both Fe deficiency and Fe excess responses. Whether in plants an integrated control mechanism involving common players regulates responses both to deficiency and to excess is still to be determined.

In this study, molecular, genetic and biochemical approaches were used to investigate transcriptional responses to both Fe deficiency and excess.

A transcriptional activator of responses to Fe shortage in Arabidopsis, called bHLH105/ILR3, was found to also negatively regulate the expression of ferritin genes, which are markers of the plant's response to Fe excess. Further investigations revealed that ILR3 repressed the expression of several structural genes that function in the control of Fe homeostasis. ILR3 interacts directly with the promoter of its target genes, and repressive activity was conferred by its dimerisation with bHLH47/PYE. Last, this study highlighted that important facets of plant growth in response to Fe deficiency or excess rely on ILR3 activity.

Altogether, the data presented herein support that ILR3 is at the centre of the transcriptional regulatory network that controls Fe homeostasis in Arabidopsis, in which it acts as both transcriptional activator and repressor.
Gene expression profiling of Jagged1‐treated human periodontal ligament cells
Authors: Suwanwela Jaijam , Hansamuit Kanokporn , Manokawinchoke Jeeranan , Sa‐Ard‐Iam Noppadol , Mahanonda Rangsini , Pavasant Prasit , Osathanon Thanaphum
Published: February 2019

Objective

Jagged1 regulates several biological functions in human periodontal ligament cells (hPDLs). The present study aimed to evaluate mRNA expression profiling of Jagged1‐treated hPDLs using microarray technique.

Methods

Notch ligands, Jagged1, were indirectly immobilized on tissue culture surface. Subsequently, hPDLs were seeded on Jagged1 immobilized surface and maintained in growth medium for 48 hr. Total RNA was collected and processed. Gene expression profiling was examined using microarray technique. Real‐time polymerase chain reaction and immunofluorescence staining were employed to determine mRNA and protein expression levels, respectively. Cell proliferation and colony‐forming unit assay were performed. Cell cycle was evaluated using propidium iodide staining and flow cytometry analysis.

Results

The isolated cells demonstrated fibroblast‐like morphology and exhibited the co‐expression of CD44, CD90, and CD105 surface markers. After stimulated with Jagged1, the total of 411 genes was differentially expressed, consisting both coding and non‐coding genes. For coding genes, 165 and 160 coding genes were upregulated and downregulated, respectively. Pathway analysis revealed that the upregulated genes were mainly involved in cellular interactions, signal transduction, and collagen formation and degradation while the downregulated genes were in the events and phases in cell cycle. Jagged1 significantly decreased cell proliferation, reduced colony‐forming unit ability, and induced G0/G1 cell cycle arrest in hPDLs.

Conclusion

Jagged1 regulates various biological pathways in hPDLs. This gene expression profiling could help to understand the mechanisms potentially involved in the Notch signaling regulation in periodontal homeostasis.
Rehabilitation needs and activity limitations of adults with a visual impairment entering a low vision rehabilitation service in England
Authors: Macnaughton Jane , Latham Keziah , Vianya‐Estopa Marta
Published: February 2019

Purpose

To evaluate outcome measures of the Participation and Activity Inventory (PAI) in a sample of adults with acquired visual impairment entering vision rehabilitation. Both Priority Scores, indicating level of rehabilitative need, and Person Measures, indicating goal difficulty, were considered.

Methods

Participants were newly registered adults with visual impairment within Leicestershire, United Kingdom. The importance and difficulty of 48 goals of the PAI were assessed, as were demographic factors, clinical visual function (visual acuity, contrast sensitivity, reading function) and psychosocial function (adjustment to visual loss, depression, anxiety and fear of falling). Priority scores were calculated as the product of importance and difficulty of each goal. All questionnaires were Rasch analysed, and person and item measures of perceived difficulty with goals were derived.

Results

Sixty people (mean age ± S.D. = 75.8 ± 13.8 years) took part. PAI goals with greatest rehabilitative need were reading (6.82 ± 2.91), mobility outdoors (6.55 ± 3.92), mobility indoors within an unfamiliar environment (5.52 ± 3.93) and writing (5.27 ± 3.02). Greater rehabilitative need was associated with younger age (β = −0.46, p < 0.001), and with higher depressive symptomatology (β = 0.35, p < 0.01; model R2 34%). Goals with greatest difficulty were mending clothing (−1.95 ± 0.35 logits) and hobbies and crafts (−1.32 ± 0.23 logits). Greater difficulty was associated with higher depressive symptomatology (β = 0.39, p < 0.001), lower visual acuity (β = 0.42, p < 0.001) and lower adjustment of visual loss (β = 0.31, p < 0.01; model R2 53%).

Conclusions

Key rehabilitation needs for adults at entry to services require both optical and non‐optical interventions. As rehabilitative need was not associated with the level of visual impairment, eyecare professionals should not wait until the end of medical treatment before referral for support. Similarly, rehabilitative need was associated with younger age, indicating the importance to refer younger people with sight loss at an early stage. The use of structured assessment, such as the PAI, ensures goals that have an impact upon quality of life are specifically identified. Depression screening on entry to rehabilitation is relevant as it predicts both perceived difficulty and rehabilitative need.
Adolescent psychopathy, heart rate, and skin conductance
Authors: MacDougall Emily A.M. , Salekin Randall T. , Gillen Christopher T.A.
Published: February 2019

Researchers have advocated for a greater focus on measuring neurobiological underpinnings of serious psychological conditions such as psychopathy. This has become particularly important to investigate early in the life span, when intervention efforts for psychopathy‐related behavior like conduct disorder (CD) are more successful. Given that psychopathy is a complex syndrome, it is also important to investigate physiological processes at a dimensional level. Using a sample of 56 adolescent male offenders (Mage = 15.92; SD = 1.31), this study explored the relationship between the Psychopathy Checklist–Youth Version (Forth, Kosson, & Hare, 2003), heart rate (HR), and skin conductance (SC). A white noise countdown task was used to measure autonomic activity across a baseline, anticipatory (prenoise), and reactivity (postnoise) period. Findings revealed no significant associations between psychopathy and HR activity across the time intervals. However, results revealed a positive association between grandiose‐manipulative traits and SC activity and a negative association between callous‐unemotional traits and SC activity. The results indicate that autonomic processes may contribute to distinct psychopathic traits in different ways, implicating slightly differential brain functioning. The findings suggest that, in order to better understand and treat youth with CD, future research should continue to examine the biological correlates of psychopathy at the broader construct level but perhaps especially at the component level.
U.K. hemophilia treaters’ knowledge of risk assessment for prolonged bleeding associated with dental procedures
Authors: Rahman Aza , Nizarali Najla , Dougall Alison , Daly Blánaid
Published: February 2019

Introduction

Optimal delivery of dental care for adults with congenital bleeding disorders (CBD) requires close collaboration between hemophilia treaters and dentists.

Aim

To explore U.K. hemophilia treaters’ knowledge of dental procedures and associated hemostatic management in adults with CBD.

Method

Staff (N = 180) from N = 60 hemophilia facilities in the United Kingdom were invited to participate in a questionnaire‐based study using a web‐based tool. The questionnaire assessed participants’ knowledge, adherence and appropriateness of application of U.K. guidance on hemostatic management of common dental procedures.

Results

The response rate was 23% of treaters (n = 41) from 62% (n = 32) hemophilia facilities. Individual participants (87%; n = 34) reported they adhered to guidelines, though knowledge of guidance was poor with only 36% (n = 15) applying guidance appropriately in 3 common dental scenarios. There was a tendency for participants to assign the use of systemic hemostatic measures independent of the agreed bleeding risk associated with the proposed dental procedure.

Conclusion and recommendations

While hemophilia treaters were aware of current guidelines, their knowledge of the guidelines and ability to risk assess dental procedures was poor. There was a tendency to overprescribe systemic hemostatic measures for dental procedures. Education initiatives to aid decision making are needed.
Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study
Authors: Hollyer Ian , Varias Francesca , Ho Bing , Ison Michael G.
Published: February 2019

Background

Recurrent urinary tract infections (UTI) are an important cause of morbidity and mortality in renal transplant recipients (RTR).

Methods

In this retrospective study we gathered clinical data from patients prescribed methenamine hippurate to prevent recurrent UTI pre‐ and post‐intervention. Thirty‐eight RTR ≥18 years old at Northwestern Memorial Hospital from 2006‐2017 were included in the final analysis.

Results

The median and range for follow‐up days were 365 (299‐365) pre‐ vs 314 (105‐365) post‐methenamine. Total UTI frequency (9.16 vs 5.01/1000 patient follow‐up days), days of antibiotic therapy to treat UTI (215 vs 132/1000 patient follow‐up days), and hospitalization due to UTI (2.64 vs 1.07/1000 patient follow‐up days) decreased while patients took methenamine. Escherichia coli and Klebsiella pneumoniae were the most commonly identified cause of UTI both pre‐ and post‐intervention. Drug resistant bacteria (ESBL‐producing or VRE) affected 3 patients pre‐ and recurred in 1 of those patients plus 3 new patients post‐methenamine. Methenamine had few adverse side effects for patients. One patient had nausea and 1 was intolerant.

Conclusion

We found that methenamine is well tolerated and is useful in reducing UTI, antibiotic prescriptions, and hospitalization in RTR with recurrent UTI. Larger prospective studies are needed to confirm these findings.
Red cell transfusion in cardiac surgery: what is the right balance?
Authors: Shehata Nadine , Mazer C. David
Published: February 2019

KEY IDEAS

Patients undergoing cardiac surgery are considered at increased risk of anemia‐induced tissue hypoxia and transfusion‐associated adverse events.

Large recent randomized controlled trials addressing lowering the hemoglobin concentration for red cell transfusion (restrictive strategies) for these patients demonstrated slightly inconsistent results.

Combining all randomized trials of restrictive strategies for red cell transfusion in cardiac surgery demonstrated that restrictive transfusion strategies are not inferior to liberal strategies.
Effect of immediate postoperative intracameral tissue plasminogen activator (tPA) on anterior chamber fibrin formation in dogs undergoing phacoemulsification
Authors: Mancuso Laura A. , Nadelstein Brad , Berdoulay Andrew , Spatola Ronald A.
Published: February 2019

Objective

To evaluate the postoperative effect of intracameral tPA (alteplase; Activase®, Genentech, San Francisco, CA), administered at immediate conclusion of phacoemulsification, on anterior chamber fibrin formation in dogs.

Procedures

Forty‐one dogs (82 eyes) undergoing bilateral phacoemulsification received 25 μg/0.1 mL intracameral tPA in one eye and 0.1 mL unmedicated aqueous vehicle in the contralateral eye immediately after corneal incision closure. Intraocular pressure (IOP) was measured, and severity of anterior chamber fibrin formation, aqueous flare, pigment precipitates on the intraocular lens (IOL) implant, posterior capsular opacification (PCO), and corneal edema were graded at approximately 1 week, 2‐3 weeks, 4‐6 weeks, 8‐12 weeks, and greater than 3 months postoperatively.

Results

Anterior chamber fibrin developed postoperatively in 68.3% of dogs (28/41) and 50% of eyes (41/82). In tPA‐treated eyes, 53.7% (22/41) developed fibrin compared to 46.3% of control eyes (19/41). Some degree of postoperative ocular hypertension (POH) occurred in 53.7% of dogs (22/41) and 36.5% of eyes (30/82). In tPA‐treated eyes, 34.1% (14/41) experienced POH compared to 39% of control eyes (16/41). Additional intracameral tPA injection was later required in 29.3% of both tPA‐treated (12/41) and control eyes (12/41).

Conclusions

Administration of intracameral tPA at immediate conclusion of canine phacoemulsification had no clinically observable effect on anterior chamber fibrin incidence at any time point. tPA‐treated eyes showed no prophylaxis against POH or secondary glaucoma compared to control eyes and received late postoperative tPA injections at the same frequency as control eyes.
Quantitative, noninvasive assessment of intra‐ and extraocular perfusion by contrast‐enhanced ultrasonography and its clinical applicability in healthy dogs
Authors: Blohm Klaas‐Ole , Hittmair Katharina M. , Tichy Alexander , Nell Barbara
Published: February 2019

Objective

To assess quantitative perfusion of intra‐ and extraocular regions of interest (ROIs) in conscious, healthy dogs utilizing contrast‐enhanced ultrasonography (CEUS); to compare varying enhancement with the first and second bolus injection and in the right and left eye; and to determine the most appropriate examination time.

Procedures

Gray scale ultrasonography and contrast harmonic imaging using sulfur hexafluoride were performed randomly assigned in both eyes in 10 university‐owned beagles. Perfusion parameters including slope time, time to peak (TTP), peak intensity (PI), and area under the curve (AUC) were measured at individually drawn ROIs (retrobulbar cone = ROI 1, choroid‐retina complex = ROI 2, medial = ROI 3, and lateral anterior uvea = ROI 4).

Results

Time‐intensity curve parameters revealed no significant differences in eyes examined by the first or second bolus injection (P > 0.05) or in the right or left eye (P > 0.05). Pooled data from all eyes were analyzed. Peak intensity of ROI 2 was significantly higher compared to all other ROIs (P < 0.001). Area under the curve at ROI 2 was significantly higher compared to all other ROIs (P < 0.05), and AUC at ROI 1 was significantly higher than at ROI 4 (P < 0.05). No significant differences in TTP were observed between different ROIs (P > 0.05). Ratios relative to different ROI sizes showed fastest enhancement in the retrobulbar cone and most intense perfusion in the anterior uveal regions. The first minute after contrast injection provided the highest diagnostic value.

Conclusion

Quantitative perfusion in nondiseased canine eyes revealed consistent parameters. Application of standardized CEUS protocols may be a promising diagnostic tool to differentiate ocular lesions.
Using Shock Control Bumps to Improve Transonic Fan/Compressor Blade Performance
Authors: John Alistair , Qin Ning , Shahpar Shahrokh
Published: February 2019

Shock control bumps can help to delay and weaken shocks, reducing loss generation and shock-induced separation and delaying stall inception for transonic turbomachinery components. The use of shock control bumps on turbomachinery blades is investigated here for the first time using 3D analysis. The aerodynamic optimization of a modern research fan blade and a highly loaded compressor blade is carried out using shock control bumps to improve their performance. Both the efficiency and stall margin of transonic fan and compressor blades may be increased through the addition of shock control bumps to the geometry. It is shown how shock-induced separation can be delayed and reduced for both cases. A significant efficiency improvement is shown for the compressor blade across its characteristic, and the stall margin of the fan blade is increased by designing bumps that reduce shock-induced separation near to stall. Adjoint surface sensitivities are used to highlight the critical regions of the blade geometries, and it is shown how adding bumps in these regions improves blade performance. Finally, the performance of the optimized geometries at conditions away from where they are designed is analyzed in detail.
Comprehensive Geometric Description of Manufacturing Scatter of High-Pressure Turbine Nozzle Guide Vanes for Probabilistic CFD Analysis
Authors: Voigt Paul , Högner Lars , Fiedler Barbara , Voigt Matthias , Mailach Ronald , Meyer Marcus , Nasuf Alkin
Published: February 2019

The increasing demands on jet engines require progressive thermodynamic process parameters, which typically lead to higher aerothermal loadings and accordingly to designs with high complexity. State-of-the-art high-pressure turbine (HPT) nozzle guide vane (NGV) design involves vane profiles with three-dimensional features including a high amount of film cooling and profiled endwalls (PEWs). Typically, the specific mass flow, also called capacity, which governs the engine's operation, is set by the HPT NGV. Hence, geometric variations due to manufacturing scatter of the HPT NGV's passage can affect relevant aerodynamic quantities and the entire engine behavior. Within the traditional deterministic design approach, the influences of those geometric variations are covered by conservative assumptions and engineering experience. This paper addresses the consideration of variability due to the manufacturing of HPT NGVs through probabilistic CFD investigations. To establish a statistical database, 80 HPT NGVs are digitized with a high precision optical 3D scanning system to record the outer geometry. The vane profiles are parametrized by a section-based approach. For this purpose, traditional profile theory is combined with a novel method that enables the description of NGV profile variability taking the particular leading edge (LE) shape into account. Furthermore, the geometric variability of PEWs is incorporated by means of principle component analysis (PCA). On this basis, a probabilistic system assessment including a sensitivity analysis in terms of capacity and total pressure loss coefficient is realized. Sampling-based methods are applied to conduct a variety of 3D CFD simulations for a typical population of profile and endwall geometries. This probabilistic investigation using realistic input parameter distributions and correlations contributes to a robust NGV design in terms of relevant aerodynamic quantities.
Elastic Wave Propagation in Open-Cell Foams
Authors: Bayat Alireza , Gaitanaros Stavros
Published: February 2019

This work examines elastic wave propagation phenomena in open-cell foams with the use of the Bloch wave method and finite element analysis. Random foam topologies are generated with the Surface Evolver and subsequently meshed with Timoshenko beam elements, creating open-cell foam models. Convergence studies on band diagrams of different domain sizes indicate that a representative volume element (RVE) consists of at least 83 cells. Wave directionality and energy flow features are investigated by extracting phase and group velocity plots. Explicit dynamic simulations are performed on finite size domains of the considered foam structure to validate the RVE results. The effect of topological disorder is studied in detail, and excellent agreement is found between the wave behavior of the random foam and that of both the regular and perturbed Kelvin foams in the low-frequency regime. In higher modes and frequencies, however, as the wavelengths become smaller, disorder has a significant effect and the deviation between regular and random foam increases significantly.
Doravirine and the Potential for CYP3A-Mediated Drug-Drug Interactions
Authors: Khalilieh Sauzanne G. , Yee Ka Lai , Sanchez Rosa I. , Fan Li , Anderson Matt S. , Sura Monali , Laethem Tine , Rasmussen Scott , van Bortel Luc , van Lancker Griet , Iwamoto Marian
Published: February 2019

Identifying and understanding potential drug-drug interactions (DDIs) are vital for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This article discusses DDIs between doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), and cytochrome P450 3A (CYP3A) substrates and drugs that modulate CYP3A activity.
An Integrative Database of β-Lactamase Enzymes: Sequences, Structures, Functions, and Phylogenetic Trees
Authors: Keshri Vivek , Diene Seydina M. , Estienne Adrien , Dardaillon Justine , Chabrol Olivier , Tichit Laurent , Rolain Jean-Marc , Raoult Didier , Pontarotti Pierre
Published: February 2019

β-Lactamase enzymes have attracted substential medical attention from researchers and clinicians because of their clinical, ecological, and evolutionary interest. Here, we present a comprehensive online database of β-lactamase enzymes.
The Prophages of
Citrobacter rodentium
Represent a Conserved Family of Horizontally Acquired Mobile Genetic Elements Associated with Enteric Evolution towards Pathogenicity
Authors: Magaziner Samuel J. , Zeng Ziyue , Chen Bihe , Salmond George P. C.
Published: February 2019

Bacteriophages are obligate intracellular parasites of bacteria. Some bacteriophages can confer novel bacterial phenotypes, including pathogenicity, through horizontal gene transfer (HGT). The pathogenic bacterium
Citrobacter rodentium
infects mice using mechanisms similar to those employed by human gastrointestinal pathogens, making it an important model organism. Here, we examined the 10 prophages of
C. rodentium
, investigating their roles in its evolution toward virulence. We characterized ΦNP and ΦSM, two endogenous active temperate bacteriophages likely important for HGT. We showed that the 10 prophages encode predicted virulence factors and are conserved within other intestinal pathogens. Phylogenetic analysis suggested that they represent a conserved family of horizontally acquired enteric-bacterium-associated pathogenic determinants. Consequently, similar analysis of prophage elements in other pathogens might further understanding of their evolution and pathology.
Global Lysine Acetylation in
Escherichia coli
Results from Growth Conditions That Favor Acetate Fermentation
Authors: Schilling Birgit , Basisty Nathan , Christensen David G. , Sorensen Dylan , Orr James S. , Wolfe Alan J. , Rao Christopher V.
Published: February 2019

Bacteria alter their metabolism in response to nutrient availability, growth conditions, and environmental stresses using a number of different mechanisms. One is lysine acetylation, a posttranslational modification known to target many metabolic enzymes. However, little is known about this regulatory mode. We investigated the factors inducing changes in lysine acetylation by comparing growth on glucose and xylose. We found that the specific sugar used for growth did not alter the pattern of acetylation; rather, the amount of sugar did, with more sugar causing more acetylation. These results imply that lysine acetylation is a global regulatory mechanism that is responsive not to the specific carbon source
per se
but rather to the accumulation of downstream metabolites.
Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
Authors: Windmann Sonja , Otto Lucas , Hrycak Camilla Patrizia , Malyshkina Anna , Bongard Nadine , David Paul , Gunzer Matthias , Dittmer Ulf , Bayer Wibke
Published: February 2019

Human immunodeficiency virus is notorious for its ability to avoid clearance by therapeutic interventions, which is partly attributed to the establishment of reservoirs in latently infected cells and cells that reside in immunologically privileged B cell follicles. In the work presented here, we show that cells of the B cell follicle are equally infected by a simple mouse gammaretrovirus. Using fluorescently labeled Friend retrovirus, we found that B cells and T cells in the B cell follicle, while not carrying the bulk of the virus load, were indeed infected by Friend virus in the early acute phase of the infection and persisted in the chronic infection. Our results suggest that infection of follicular cells may be a shared property of lymphotropic viruses and propose the FV infection of mice as a useful model to study strategies for follicular reservoir elimination.
Endopeptidase Regulation as a Novel Function of the Zur-Dependent Zinc Starvation Response
Authors: Murphy Shannon G. , Alvarez Laura , Adams Myfanwy C. , Liu Shuning , Chappie Joshua S. , Cava Felipe , Dörr Tobias
Published: February 2019

Bacteria encode a variety of adaptations that enable them to survive during zinc starvation, a condition which is encountered both in natural environments and inside the human host. In
Vibrio cholerae
, the causative agent of the diarrheal disease cholera, we have identified a novel member of this zinc starvation response, a cell wall hydrolase that retains function and is conditionally essential for cell growth in low-zinc environments. Other Gram-negative bacteria contain homologs that appear to be under similar regulatory control. These findings are significant because they represent, to our knowledge, the first evidence that zinc homeostasis influences cell wall turnover. Anti-infective therapies commonly target the bacterial cell wall; therefore, an improved understanding of how the cell wall adapts to host-induced zinc starvation could lead to new antibiotic development. Such therapeutic interventions are required to combat the rising threat of drug-resistant infections.