bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized, Phase 3, Multicenter, Open‐Label Study
Authors: Akizawa Tadao , Otsuka Tetsuro , Reusch Michael , Ueno Mai
Published: June 2019

Roxadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor developed to treat anemia in chronic kidney disease (CKD) patients. This Phase 3, randomized, open‐label, 24‐week study investigated the efficacy and safety of roxadustat in Japanese CKD patients with anemia on peritoneal dialysis (PD) who were previously treated or not treated with erythropoiesis stimulating agents (ESAs). Patients not previously receiving ESA (ESA‐Naïve group) were randomized to roxadustat at a starting dose of 50 or 70 mg three times weekly; patients previously receiving ESA (ESA‐Converted group) switched from ESA to roxadustat 70 or 100 mg three times weekly depending on the prior ESA dose. Outcomes included maintenance rate of average hemoglobin (Hb) level within 10–12 g/dL at weeks 18–24, cumulative response rate at end of treatment (Hb thresholds, 10.0 g/dL or 10.5 g/dL; Hb increase, ≥1.0 g/dL), and average Hb levels at weeks 18–24. Safety was assessed by occurrence of treatment‐emergent adverse events (TEAEs). Fifty‐six patients were enrolled (ESA‐Naïve, n = 13; ESA‐Converted, n = 43). Maintenance rates (weeks 18–24) were 92.3% (95% CI: 64.0–99.8; ESA‐Naïve) and 74.4% (95% CI: 58.8–86.5; ESA‐Converted). Cumulative response rate was 100.0% in the ESA‐Naïve group. Average Hb levels (weeks 18–24) were 11.05 g/dL (95% CI: 10.67–11.42; ESA‐Naïve) and 10.93 g/dL (95% CI: 10.73–11.13; ESA‐Converted). Common TEAEs included nasopharyngitis and back pain. Roxadustat was well tolerated and effective in maintaining target Hb levels in CKD patients on PD who were previously treated or not treated with ESA.
Effect of alcohol on the sense of agency in healthy humans
Authors: De Pirro Silvana , Lush Peter , Parkinson Jim , Duka Theodora , Critchley Hugo D. , Badiani Aldo
Published: June 2019

Even at low to moderate doses, ingestion of the widely used recreational drug alcohol (ethanol) can impact cognitive and emotional processing. Recent studies show that the sense of agency (SoA; ie, the subjective experience of voluntary control over actions) can be modulated by specific pharmacological manipulations. The SoA, as quantified by the intentional binding (IB) paradigm, is enhanced by direct or indirect dopaminergic agonists in patients with Parkinson's disease and by ketamine (an N‐methyl‐D‐aspartate (NMDA) receptor antagonist) in healthy individuals. These findings implicate dopaminergic and glutamatergic neurotransmission in mechanisms underlying SoA. Alcohol has a complex set of actions, including disinhibition of dopaminergic neurotransmission and allosteric antagonism at NMDA receptors. Here, we tested the hypothesis that low to moderate doses of alcohol would enhance SoA, and impact impulsivity and subjective emotional state. We conducted two experiments in 59 healthy male and female social drinkers, who ingested either a placebo “vehicle,” or one of two doses of ethanol: 0.4 and 0.6 g/kg. In both experiments, we observed increased SoA/IB at both doses of alcohol exposure, relative to the placebo condition. We found no correlation between the effects of alcohol on IB and on impulsivity or subjective emotional state. Our findings might have implications for social and legal responsibility related to alcohol use, particularly in states prior to overt intoxication. Further studies are necessary to investigate the effects of alcohol and other addictive substances on the SoA.
The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC‐2) to predict the requirement for early postoperative tracheal re‐intubation: a hospital registry study
Authors: Lukannek C. , Shaefi S. , Platzbecker K. , Raub D. , Santer P. , Nabel S. , Lecamwasam H.S. , Houle T.T. , Eikermann M.
Published: June 2019

Postoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non‐cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re‐intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re‐intubated. In addition to five pre‐operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra‐operative predictors: early post‐tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung‐protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82–0.85] vs. 0.76 [95%CI 0.75–0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re‐intubation.
A systematic review of cannabidiol dosing in clinical populations
Authors: Millar S.A. , Stone N.L. , Bellman Z.D. , Yates A.S. , England T.J. , O'Sullivan S.E.
Published: June 2019

Aims

Cannabidiol (CBD) is a cannabis‐derived medicinal product with potential application in a wide‐variety of contexts; however, its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts.

Methods

Publications involving administration of CBD alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov.

Results

A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. Twenty‐three studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 and 50 mg/kg/d. Plasma concentrations were not provided in any publication. CBD was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of CBD on reducing seizure frequency or severity (average 15 mg/kg/d within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n = 6–62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/kg/d) were used in these studies.

Conclusion

This review highlights that CBD has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.
Simultaneous phenotyping of CYP2E1 and CYP3A using oral chlorzoxazone and midazolam microdoses
Authors: Hohmann Nicolas , Blank Antje , Burhenne Jürgen , Suzuki Yosuke , Mikus Gerd , Haefeli Walter E.
Published: June 2019

Aims

Chlorzoxazone is the paradigm marker substrate for CYP2E1 phenotyping in vivo. Because at the commonly used milligram doses (250–750 mg) chlorzoxazone acts as an inhibitor of the CYP3A4/5 marker substrate midazolam, previous attempts failed to combine both drugs in a common phenotyping cocktail. Microdosing chlorzoxazone could circumvent this problem.

Method

We enrolled 12 healthy volunteers in a trial investigating the dose–exposure relationship of single ascending chlorzoxazone oral doses over a 10,000‐fold range (0.05–500 mg) and assessed the effect of 0.1 and 500 mg of chlorzoxazone on oral midazolam pharmacokinetics (0.003 mg).

Results

Chlorzoxazone area under the concentration–time curve was dose‐linear in the dose range between 0.05 and 5 mg. A nonlinear increase occurred with doses ≥50 mg, probably due to saturated presystemic metabolic elimination. While midazolam area under the concentration–time curve increased 2‐fold when coadministered with 500 mg of chlorzoxazone, there was no pharmacokinetic interaction between chlorzoxazone and midazolam microdoses.

Conclusion

The chlorzoxazone microdose did not interact with the CYP3A marker substrate midazolam, enabling the simultaneous administration in a phenotyping cocktail. This microdose assay is now ready to be further validated and tested as a phenotyping procedure assessing the impact of induction and inhibition of CYP2E1 on chlorzoxazone microdose pharmacokinetics.
Do we have a right to an unmanipulated genome? The human genome as the common heritage of mankind
Authors: Primc Nadia
Published: June 2019

The human genome is commonly regarded as a ‘natural’ connection between all human beings, as it has been handed down to us by our predecessors. As such, it is believed to represent common heritage of humanity, e.g. a resource of outstanding value that should be the object of special protection and international concern. Some critics argue that germline manipulation would disrupt this natural heritage and that we have a duty to preserve the integrity of the human germline. However, a closer look reveals that the concept of common heritage of humanity does not necessarily imply the impermissibility of germline manipulation. If it is restricted to the prevention of severe diseases, germline manipulation does not represent a threat to the unity and identity of the human species, even though this would create a new form of relationship between human beings, namely that between a designer and a genetically designed person.
The role of values in scientific theory selection and why it matters to medical education
Authors: Ellis Rebecca D.
Published: June 2019

In this paper, I argue that the role of values in theory selection is an important issue within medical education. I review the underdetermination argument, which is the idea within philosophy of science that the data serving as evidence for theories are by themselves not sufficient to support a theory to the exclusion of alternatives. There are always various explanations compatible with the data, and we ultimately appeal to certain values as our grounds for choosing one theory over another. I explore some of the ways contemporary feminist philosophers have chosen to grapple with the problem of underdetermination and proposed solutions to systematize how values might be incorporated into theory choice, drawing primarily from the work of Helen Longino and Elizabeth Anderson. I conclude by discussing how value‐laden inquiry should be incorporated within medical education to promote reflection towards medicine’s normative underpinnings.
Anxiety among women experiencing medically complicated pregnancy: A systematic review and meta‐analysis
Authors: Abrar Ambar , Fairbrother Nichole , Smith André P. , Skoll Amanda , Albert Arianne Y. K.
Published: June 2019

Background

Symptoms of anxiety are common among pregnant and postpartum women, and 15%‐20% of pregnancies are affected by medical complications. Despite this, little is known about the relationship of medical complications in pregnancy and women's experience of anxiety. The purpose of this research was to conduct a systematic review and meta‐analysis of differences in anxiety symptom severity among women experiencing a medically complicated versus a medically uncomplicated pregnancy.

Methods

This work was guided by the PRISMA reporting process. Electronic databases MEDLINE and PsycINFO were searched to identify studies that met the inclusion criteria. An adaptation of the Newcastle‐Ottawa Quality Assessment Scale for case‐control studies was used to perform a quality assessment review. A random‐effects meta‐analysis was used to calculate the estimated average standardized mean differences.

Results

Based on the five studies which met our inclusion criteria, findings provide evidence of higher levels of anxiety symptoms among pregnant women experiencing a medically complicated versus a medically uncomplicated pregnancy. Despite considerable heterogeneity, all mean difference estimates are in the direction of greater anxiety in the high‐risk groups.

Conclusions

Women experiencing a medically complex pregnancy report higher levels of anxiety symptoms compared to women experiencing a medically uncomplicated pregnancy.
The immune response‐related mutational signatures and driver genes in non‐small‐cell lung cancer
Authors: Chen Hao , Chong Wei , Teng Changcai , Yao Yueliang , Wang Xin , Li Xue
Published: June 2019

Immune checkpoint blockade (ICB) therapy has achieved remarkable clinical benefit in non‐small‐cell lung cancer (NSCLC), but our understanding of biomarkers that predict the response to ICB remain obscure. Here we integrated somatic mutational profile and clinicopathologic information from 113 NSCLC patients treated by ICB (CTLA‐4/PD‐1). High tumor mutation burden (TMB) and neoantigen burden were identified significantly associated with improved efficacy in NSCLC immunotherapy. Furthermore, we identified apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like (APOBEC) mutational signature was markedly associated with responding of ICB therapy (log‐rank test, P = .001; odds ratio (OR), 0.18 [95% CI, 0.06‐0.50], P < .001). The association with progression‐free survival remained statistically significant after controlling for age, sex, histological type, smoking, PD‐L1 expression, hypermutation, smoking signature and mismatch repair (MMR) (HR, 0.30 [95% CI, 0.12‐0.75], P = .010). Combined high TMB with APOBEC signature preferably predict immunotherapy responders in NSCLC cohort. The CIBERSORT algorithm revealed that high APOBEC mutational activity samples were associated with increased infiltration of CD4 memory activated T cells, CD8+ T cells and natural killer (NK) cells, but reduced infiltration of regulatory T cells. Besides, individual genes mutation of IFNGR1 or VTCN1 were only found in responders; however, the PTEN mutation was only found in non‐responders (Fisher's exact test, all P < .05). These findings may be applicable for guiding immunotherapy for patients with NSCLC.
Effect of hyperinsulinaemia and insulin resistance on endocrine, metabolic and fertility outcomes in women with polycystic ovary syndrome undergoing ovulation induction
Authors: Zhang Duojia , Yang Xinming , Li Jian , Yu Jiarui , Wu Xiaoke
Published: June 2019

Objective

The aim of this study was to evaluate the effects of hyperinsulinaemia and insulin resistance (IR) on reproductive and metabolic disorders and fertility in women with polycystic ovary syndrome (PCOS).

Design, Setting, Participants and Measurements

This was a multicenter, randomized controlled trial involving a total of 1000 women diagnosed with PCOS according to the modified Rotterdam criteria at 21 sites (27 hospitals). We evaluated the effects of serum insulin levels and HOMA‐IR on parameters and outcomes. The main outcome measures were anthropometric, biometric and ultrasound parameters at baseline and the clinical outcomes of ovulation, conception, pregnancy, live birth and pregnancy loss.

Results

The relevant analysis between hyperinsulinaemia and IR and clinical characteristics showed that weight, waist and hip circumference, BMI, waist‐to‐hip ratio, acanthosis nigricans score and menstrual period were significantly correlated with fasting insulin (FIN) and HOMA‐IR. There was no significant correlation between the hirsutism score or acne score with FIN or HOMA‐IR. The relevant analysis between hyperinsulinaemia and IR and circulating sex steroids and gonadotrophins showed that FAI was significantly correlated with FIN and HOMA‐IR (r = 0.240, P < 0.001 and r = 0.191, P < 0.001, respectively). Free testosterone was significantly correlated with FIN after adjusting for the influence of age. LH and LH/FSH were not related to FIN or HOMA‐IR after statistical correction for differences in BMI. The relevant analysis between hyperinsulinaemia and IR and metabolic profile showed that FIN and HOMA‐IR were positively associated with fasting glucose, cholesterol, triglycerides, low‐density lipoprotein, Apo B, and the incidence of metabolic syndrome and were negatively associated with high‐density lipoprotein. The predictive analysis between hyperinsulinaemia and IR with fertility showed that the levels of FIN and HOMA‐IR were related to the fertility outcome (ovulation, pregnancy, conception or live birth) in patients with PCOS. After adjustments for age, total testosterone and free testosterone, increasing serum insulin levels and HOMA‐IR were significantly associated with decreased cycle ovulation, conception, pregnancy and live birth rates.

Conclusions

Hyperinsulinaemia and IR are associated with reproductive and metabolic disorders and can predict the fertility outcomes in PCOS patients.
14‐3‐3ζ targeting induced senescence in Hep‐2 laryngeal cancer cell through deneddylation of Cullin1 in the Skp1‐Cullin‐F‐box protein complex
Authors: Seo Sung Bin , Baek Ji‐Ye , Lim Ji‐Hee , Jin Xuyan , Lee Mun‐Yong , Lee Jeong‐Hwa
Published: June 2019

Objectives

Despite of the aberrant expression of 14‐3‐3ζ in head and neck squamous cell carcinoma (HNSCC), little is known about the role of 14‐3‐3ζ in the regulation of senescence in HNSCC. This study was performed to investigate whether 14‐3‐3ζ is implicated in senescence evasion of Hep‐2 laryngeal cancer cells.

Methods

The expression of 14‐3‐3ζ was suppressed using RNA interference strategy. Senescence induction was determined by senescence‐associated β‐galactosidase staining and the numbers of promyelocytic leukaemia nuclear body. Real‐time PCR, western blotting and immunohistochemistry were applied for the expression of corresponding proteins. Xenograft experiment was performed to show in vivo effect of 14‐3‐3ζ silencing on tumour growth.

Results

14‐3‐3ζ silencing significantly induced senescence phenotypes via 27 accumulations. Subsequently, we demonstrated that p27 accumulation is linked to inactivation of SCFSkp2 complex activity, probably due to the deneddylation of cullin‐1 (Cul‐1) as follows. (a) Neddylated Cul‐1 is decreased by 14‐3‐3ζ silencing. (b) Blocking neddylation using MLN4924 reproduces senescence phenotypes. (c) Knockdown of CSN5, which functions as a deneddylase, was shown to restore the senescence phenotypes induced by 14‐3‐3ζ depletion. Finally, we demonstrated that 14‐3‐3ζ depletion effectively hindered the proliferation of Hep‐2 cells implanted into nude mice.

Conclusion

14‐3‐3ζ negatively regulates senescence in Hep‐2 cells, suggesting that 14‐3‐3ζ targeting may serve to suppress the expansion of laryngeal cancer via induction of senescence through the Cul‐1/SCFSkp2/p27 axis.
Long‐term effects of repeated botulinum neurotoxin A, bimanual training, and splinting in young children with cerebral palsy
Authors: Lidman Git R M , Nachemson Ann K , Peny‐Dahlstrand Marie B , Himmelmann Kate M E
Published: June 2019

Aim

To investigate long‐term development of hand function after repeated botulinum neurotoxin A (BoNT‐A) and occupational therapy at a young age.

Method

Twenty children with unilateral spastic cerebral palsy (CP) (14 males, six females; median inclusion age 3y 1mo, range 1y 11mo–4y 3mo) participated in this longitudinal study. Ten children received occupational therapy after a randomized controlled trial and 10 repeated BoNT‐A plus occupational therapy during 1‐year. The Assisting Hand Assessment (AHA) and active supination, assessed the following 3 years. The assessments were compared with data from a reference group to investigate development over time.

Results

The improvement in AHA (7.5 AHA units) after BoNT‐A plus occupational therapy was maintained at final follow‐up. The occupational therapy group, unchanged after 1‐year, improved by 5 AHA units (96% confidence interval [CI] 2–10), thus there was no difference between the groups. Median active supination increased in comparison with the reference group. In the BoNT‐A/occupational therapy group, 9 out of 10 (97.85% CI 45 115) children improved in active supination. In the occupational therapy group, 7 out of 10 (97.85% CI –2 to 68) children improved in active supination. No correlation between active supination and AHA was found.

Interpretation

Bimanual performance achieved after BoNT‐A plus occupational therapy was maintained, while it increased by follow‐up in the occupational therapy group, suggesting that combined intervention gave earlier access to bimanual skills. Active supination was unrelated to AHA.

What this paper adds

Children whose bimanual performance improved after botulinum neurotoxin A and/or occupational therapy, maintained skills or progressed during follow‐up.

Bimanual performance increased with age, similar to a quality‐register reference group.

Increased active supination after intervention improved at follow‐up but was not related to bimanual performance.
Residual herbicide treatments reduce Andropogon gayanus (Gamba Grass) recruitment for mine site restoration in northern Australia
Authors: Luck Linda , Bellairs Sean M. , Rossiter‐Rachor Natalie A.
Published: June 2019

Weed invasion is a major threat to Australian tropical savannas, and controlling weeds is essential for successful re‐establishment of native species on disturbed sites. Gamba Grass (Andropogon gayanus) is an African grass which has invaded large areas of tropical savanna across northern Australia. Current management strategies in northern Australia focus on fire and glyphosate to effectively control mature plants; however, re‐establishment of infestations from the soil seed bank remains a major challenge to eradication efforts. This study focused on the effects of soil seed bank treatments on Gamba Grass recruitment on a mine site in northern Australia. Adult Gamba Grass plants within test plots were killed with glyphosate to exclude resource competition. Chemical, physical and biological treatments were then applied, and the treatment effects on subsequent Gamba Grass seedling emergence and survival quantified. Seedling emergence was significantly reduced by three of the four residual herbicide treatments tested. The most effective herbicide treatments, dalapon and sulfometuron, reduced emergence by 90% compared to the standard glyphosate treatment alone. This equated to a reduction in Gamba Grass seedling emergence from 1 seedling/m2 to 1 seedling 10 m−2, a major improvement for Gamba Grass management. These residual herbicide treatments significantly reduced the population density of Gamba Grass for at least 5 months after emergence. The physical and biological treatments did not have a significant effect on seedling emergence. This significant reduction in Gamba Grass seedling emergence and survival can substantially improve Gamba Grass management. Reducing re‐colonisation from the soil seed bank using residual herbicides provides a valuable management tool for land managers, integrating readily with established strategies for controlling the mature plants.
Comparative and international education research in a post‐truth era
Authors: Suspitsyna Tatiana
Published: June 2019

The paper offers a postcolonial critique of comparative and international education (CIE) research in the United States (US) by tracing the Euro‐centrism of its agendas, methodologies and publications to their colonial entanglements in the past and examining the current predicament of CIE in the context of the rising nationalist and anti‐science discourses in the US. Viewed through the prism of actor‐network theory, CIE represents a circulatory network of scholars and students, methods and surveys, national and supranational funding agencies and the public opinion that shapes education policymaking. As they seek to garner public support, create new allies among politicians and donors and infuse their network with international knowledge and scholars, CIE researchers revisit the ontological and epistemological assumptions of their field, address the dominance of Western perspectives in CIE in the context of the White House rhetoric of hostility toward non‐Western nations and justify the veracity of their science to policymakers.
Kaposi sarcoma in Southern Finland (2006–2018)
Authors: Kluger Nicolas , Blomqvist Carl , Kivelä Pia
Published: June 2019

Background

Kaposi sarcoma (KS) age‐standardized incidence rate is below 0.3 per 100,000 in Nordic countries. Data on KS in Finland have been sparse.

Methods

A retrospective review of all the patients with KS cases managed in the Helsinki University Central Hospital between 2006 and 2018.

Results

Forty patients (median age at diagnosis 45 years, 38 males) were included. About 2.5 new cases were diagnosed per year (incidence 0.16 /100,000). The different subtypes of KS were: human immunodeficiency virus (HIV) (65%), classical KS (30%), and immunodepression (5%). Patients with HIV were significantly younger, more likely to have cutaneous lesions of the face, the trunk, and mucosal lesions, and KS within lymph nodes and inner organs. KS was diagnosed at the same time as HIV in 77% of cases, 28% with CD4‐cell level above 300 cells/mm3. Among the patients with classical KS (n = 12), 75% were of Finnish origin, 41% had a second primary malignancy diagnosed, and 25% had noninsulin dependent diabetes mellitus. Among HIV patients, 27% had another AIDS‐related illness, 7% of the patients developed lymphoproliferative disorders, and 7% a hemophagocytic syndrome. Patients with HIV were always treated with antiviral therapy, with pegylated liposomal doxorubicin in 57% of the cases. Local radiotherapy was the main treatment for other KS types. None of the 5 deaths during follow‐up was related to KS.

Conclusions

Classical KS (KS‐CLA) occurs among native Finns, frequently with other present malignancies. Screening of HIV and other malignancies is warranted in new cases of KS.
Current understanding of bioaccessibility and bioavailability of food‐derived bioactive peptides
Authors: Mine Yoshinori , Matsui Toshiro
Published: June 2019

This Editorial should have been published in Special Issue 54:6 (‘Bio‐accessibility and bio‐availability of food derived bioactive peptides’) but, due to a production error, was published in issue 54:7 instead. The publisher apologizes for this error and the inconvenience caused.
Uranium brannerite with Tb(III)/Dy(III) ions: Phase formation, structures, and crystallizations in glass
Authors: Zhang Yingjie , Wei Tao , Zhang Zhaoming , Kong Linggen , Dayal Pranesh , Gregg Daniel J.
Published: June 2019

Uranium brannerite phases with terbium(III) or dysprosium(III) ions have been investigated. The precursors with molar ratio of 0.5:0.5:2 (Ln: U: Ti with Ln = Tb or Dy) were prepared and calcined at 750°C in argon. Sintering the pelletized samples in argon at 1200°C led to the formation of pyrochlore phases with TiO2 rutile and U‐rich oxides while sintering in air led to the formation of brannerite phases with the nominal composition close to Ln0.5U0.5Ti2O6 together with trace amounts of TiO2 rutile and LnUO4. Incorporating an excess of TiO2 (20 wt%) and sintering at higher temperature (1300°C) resulted in no obvious change to the phase equilibrium. As designed, pentavalent uranium has been proven to be dominant in these brannerite phases with diffuse reflectance spectroscopy. The relationships between the cell parameters and the ionic radii of the A‐site cations have been explored and rationalized from the structure point of view for a range of titanate brannerite phases (ATi2O6). In addition, the crystallization of Ln0.5U0.5Ti2O6 brannerite in glass has been achieved via heat treatment at 1200°C and confirmed with X‐ray diffraction, scanning electron microscopy‐energy dispersive spectroscopy and transmission electron microscopy–selected area electron diffraction.
Thermal activation effects in crack propagation and reliability of fused silica
Authors: Cook Robert F.
Published: June 2019

The thermal activation energy u1 characterizing changes in crack velocity with temperature for fused silica in water is determined. The determination is based on a new analysis that incorporates the familiar Arrhenius term for thermally activated processes and a term characterizing the departure of the propagating crack system from fracture equilibrium. In determining u1 from experimental data, the Arrhenius term and the nonequilibrium term are of approximately equal magnitude. The analysis is applied to an extensive compilation of crack velocity measurements in fused silica to arrive at an estimate of u1 = (69 ± 11) kJ mol−1, where the value represents the multi‐laboratory mean ± variability. This value is greater than that assumed in some earlier works and characterizes a typical within‐laboratory increase in crack velocity of a factor of approximately 102 in fused silica between freezing and boiling water conditions and a decrease of a factor of 103 in component time to failure for the same change in conditions. The multi‐laboratory variation in velocity at fixed temperature is comparable to the within‐laboratory maximum increase, perhaps obscuring temperature effects.
A rapid review of educational preparedness of advanced clinical practitioners
Authors: Dover Nicola , Lee Geraldine A. , Raleigh Mary , Baker Edward J. , Starodub Roksolana , Bench Suzanne , Garry Brendan
Published: June 2019

Aim

The aim of this study was to synthesize available data on current educational provision related to preparation for the advanced clinical practice role.

Design

A mixed methods rapid review of the literature.

Data Sources

A search of Ovid Medline and Ovid EMBASE for English language papers published 2006–2018 resulted in 38 publications, which met the criteria for inclusion.

Review Methods

Using Tricco's seven‐stage process, following an identification of relevant papers and data extraction, a data‐based convergent synthesis was used to convert quantitative papers into qualitative data prior to completing a narrative synthesis.

Results

The four themes identified from data synthesis were consolidation; theory to practice gap; competency and mentoring. A lack of preparedness for new advanced clinical practitioners completing an educational programme was noted with a need identified for a clinically focussed consolidation period to enable practitioners to develop their skills under supervision in the clinical environment.

Conclusion

As the needs for different models of health care evolve with the expansion of advanced practice, appropriate education and clinical supervision are important aspects in the delivery of programmes that allow individuals to be competent and confident practitioners providing safe and effective health care.

Impact

There is a paucity of papers on educational preparedness of advanced clinical practitioners. Our findings demonstrate a lack of preparedness and the need for a clinically focussed consolidation period with good role models and mentors following completion of a Master's programme. Employers and higher education institutions need to ensure a protected period of time is available for newly qualified advanced clinical practitioners to allow consolidation of clinical practice.
Depression as a mediator of quality of life in patients with neuropathic pain: A cross‐sectional study
Authors: Lu Yue , Li Jing , Liu Yu
Published: June 2019

Aims

To explore whether pain intensity has an indirect effect on quality of life through mediation of depression in patients with neuropathic pain (NeP).

Design

An observational, questionnaire‐based, cross‐sectional study.

Methods

A convenience sample of patients suffering from NeP were enrolled from June 2015 ‐ May 2016. Three questionnaires were used to collect data of pain intensity, Quality of life and depression. Andrew Hayes' PROCESS macro modelling tool for the SPSS software, based on the mediation Bootstrap confidence interval method, was used to analyse the mediation effect.

Results

Both pain intensity and depression correlated negatively with the quality of life of patients. The indirect effect of pain intensity on the quality of life through depression was negative.

Conclusions

Increased pain intensity and depression were associated with a decreased quality of life in patients suffering from NeP and pain intensity had an indirect effect on the quality of life of patients through depression.

Impact

A low quality of life and depression are commonly seen in patients with NeP. However, little is known about the relationship between pain, quality of life and depression. Both pain intensity and depression had some negative effect on quality of life in patients with NeP. Pain intensity had an indirect effect on quality of life through a mediation effect of depression in patients with NeP. When caring for patients with NeP, nurses should assess depression routinely and try to alleviate it.
Psychometric validation of the Multidimensional Nursing Generations Questionnaire (MNGQ)
Authors: Stevanin Simone , Mikkonen Santtu , Bressan Valentina , Vehviläinen‐Julkunen Katri , Kvist Tarja
Published: June 2019

Aims

To perform a psychometric test of the factor structure of the Multidimensional Nursing Generation Questionnaire, an instrument developed to measure nursing generational characteristics in the workplace and investigate the relations among its factors and background variables.

Background

Nurses today include members of the Baby Boomer and X and Y generations, whose characteristics in the work environment have not been studied thoroughly.

Design

Instrument and construct cross‐sectional study for psychometric testing/validation.

Methods

Questionnaire components and constructs were tested using confirmatory factor analysis (CFA), structural equation modelling and Cronbach's alpha. For this purpose, a survey was conducted in November 2016 on a sample of Finnish and Italian nurses working in public hospitals (N = 3,218).

Results

Eight hundred twenty‐two nurses completed the questionnaire, where CFA identified 48 items and six factors with acceptable internal consistency (Cronbach's alpha range: 0.73–0.88): (a) Conflicts between generations; (b) Patient safety view; (c) Relationships issues between generations; (d) Working as a multigenerational team; (e) Orientation to change; and (f) Work propensity and availability. Various relations were identified among the background variables and factors that related largely to generational belonging, educational level and country.

Conclusion

The final version of the questionnaire demonstrates a more robust factor structure than did the preliminary. Further tests should be conducted on nurses in different countries/cultures and work environments.

Impact

The complete validation of the Multidimensional Nursing Generation Questionnaire will provide research evidence useful to create an inclusive work environment for each generation.
A web‐based tailored nursing intervention (TAVIE en m@rche) aimed at increasing walking after an acute coronary syndrome: Multicentre randomized trial
Authors: Kayser John William , Cossette Sylvie , Côté José , Tanguay Jean‐Francois , Tremblay Jean‐Francois , Diodati Jean Gino , Bourbonnais Anne , Purden Margaret , Juneau Martin , Terrier Julien , Dupuis Jocelyn , Maheu‐Cadotte Marc‐André , Fontaine Guillaume , Cournoyer Daniel
Published: June 2019

Aim

Evaluate a web‐based tailored nursing intervention, TAVIE en m@rche, on increasing daily steps after an acute coronary syndrome.

Design

Parallel two‐group multicentre randomized trial.

Methods

An experimental group receiving TAVIE en m@rche, was compared to  a control group receiving hyperlinks to public websites. Acute coronary syndrome patients who were insufficiently active were recruited from three coronary care units. Daily steps at 12 weeks were the primary outcome. Secondary outcomes included self‐reported walking and moderate to vigorous physical activity (MVPA). Exploratory outcomes were angina frequency, emergency department visits, hospitalizations and secondary prevention programme attendance.

Results

Primary data were analysed for 39 participants. No significant effects were found. At 12 weeks 275.9 more daily steps and 1,464.3 more energy expenditure in MVPA were found in the experimental group relative to the control. No effects were found for angina frequency, emergency department visits, hospitalizations and secondary prevention programme attendance.

Conclusion

The lack of effect on our primary result may be explained by the intervention goal that was mismatched to the needs of our mostly sufficiently active sample at randomization, resulting in no meaningful change in daily steps. Although the non‐significantly greater increase in self‐reported MVPA may represent gains in health among the participants that accessed TAVIE en m@rche, this result should be interpreted with caution.

Impact

From 40%‐60% of acute coronary syndrome patients self‐report insufficient levels of physical activity. No effect was found on the primary outcome of daily steps. Although not significant, a greater increase in MVPA was found at 12 weeks. The primary outcome can be explained by most of the sample having attained the physical activity recommendation at randomization. Caution in interpreting the non‐significant increase in MVPA is warranted due to attrition bias and statistical uncertainty. Future directions may consider the timing of randomization in relation to meeting the needs of insufficiently active acute coronary syndrome patients.
Development and cross‐validation of a new instrument to measure nurse’s positive energy of retention: A methodological study
Authors: Wu Chia‐Chen , Lin Chiu‐Chu , Chang Shu‐Chen , Chou Hsiu‐Ling , Jone Kuen‐Yung , Lin Huey‐Shyan
Published: June 2019

Aim

The aim of this study was to develop and psychometrically test a new instrument for measuring nurse’s positive energy of retention (NPER).

Background

The shortage of professional nurses is an unresolved global issue. Few studies explored the issue of the retention of nurses in terms of a positive psychological viewpoint.

Design

Methodological study.

Methods

Data collection was from June 2016–August 2017. Nurses (N = 947) recruited from northern, central and southern Taiwan covering different levels of hospitals were divided into three samples, which were used for explaratory factor analysis (EFA), confirmatory factor analysis (CFA) and cross‐validation respectively.

Results

EFA resulted in a three‐factor solution: proactive and persevering characteristics, nursing professional identity and passion accounting for 61.8% of total variance. The proposed three‐factor model was confirmed by CFA. Cross‐validation provided further evidence for the construct validity of the NPER instrument with 24 items. Cronbach's alpha coefficient of three subscales of the instrument were 0.95, 0.89, and 0.92 separately and 0.96 for the total scale.

Conclusion

Psychometric properties indicate that the newly formulated NPER instrument is a valid and reliable assessment tool to recruit nurses who are more likely to remain in nursing.

Impact

The study addressed the personal intrinsic factors, which are very important for nurses’ retention. The NPER instrument consisted of three subscales is a reliable and psychometrically valid new instrument. Managers could apply the NPER instrument to recruit nurses possessing the attributes of positive energy of retention. Furthermore, researchers could use the rigorous process provided in the study to establish a new instrument.
The association of obstructive sleep apnea and left ventricular hypertrophy in obese and overweight children with history of elevated blood pressure
Authors: Hanlon Colleen E. , Binka Edem , Garofano Jeffrey S. , Sterni Laura M. , Brady Tammy M.
Published: June 2019

Obesity is a potent cardiovascular disease (CVD) risk factor and is associated with left ventricular hypertrophy (LVH). Obstructive sleep apnea (OSA) is common among individuals with obesity and is also associated with CVD risk. The authors sought to determine the association of OSA, a modifiable CVD risk factor, with LVH among overweight/obese youth with elevated blood pressure (EBP). This was a cross‐sectional analysis of the baseline visit of 61 consecutive overweight/obese children with history of EBP who were evaluated in a pediatric obesity hypertension clinic. OSA was defined via sleep study or validated questionnaire. Children with and without OSA were compared using Fisher's exact tests, Student's t tests, and Wilcoxon rank sum test. Multivariable logistic regression evaluated the association between OSA and LVH. In this cohort, 71.7% of the children had LVH. Children with OSA were more likely to have LVH (85.7% vs 59.4%, P = 0.047). OSA was associated with 4.11 times greater odds of LVH (95% CI 1.15, 14.65; P = 0.030), remaining significant after adjustment for age, sex, race, and BMI z‐score (after adjustment for hypertension, P = 0.051). A severe obstructive apnea‐hypopnea index (AHI >10) was associated with 14 times greater odds of LVH (95% CI 1.14, 172.64, P = 0.039). OSA was significantly associated with LVH among overweight/obese youth with EBP, even after adjustment for age, sex, race, and BMI z‐score. Those with the most severe OSA (AHI >10) had the greatest risk for LVH. Future studies exploring the impact of OSA treatment on CVD risk in children are needed.
Hepatic functional and pathological changes of type 1 diabetic mice in growing and maturation time
Authors: Jiang Saizhi , Tang Xiaoqiang , Wang Kai , Liang Yaqing , Qian Yan , Lu Chaosheng , Cai Lu
Published: June 2019

To detect the changes in the liver function in both male and female OVE26 mice from young to adults for better understanding of type 1 diabetes‐induced hepatic changes, OVE26 mice and wild‐type FVB mice were raised in the same environment without any intervention, and then killed at 4, 12, 24 and 36 weeks for examining liver's general properties, including pathogenic and molecular changes. The influence of diabetes on the bodyweight of male and female mice was different. Both male and female OVE26 mice did not obtain serious liver injury or non‐alcoholic fatty liver disease, manifested by mild elevation of plasma alanine transaminase, and less liver lipid content along with significantly suppressed lipid synthesis. Uncontrolled diabetes also did not cause hepatic glycogen accumulation in OVE26 mice after 4 weeks. Oxidative stress test showed no change in lipid peroxidation, but increased protein oxidation. Changed endoplasmic reticulum stress and apoptosis along with increased antioxidant capacity was observed in OVE26 mice. In conclusion, uncontrolled type 1 diabetes did not cause hepatic lipid deposition most likely because of reduced lipids synthesis in response to insulin deficiency. Enhanced antioxidant capacity might not only prevent the occurrence of severe acute liver injury but also the self‐renewal, leading to liver dysfunction.
Comparison of drying methods on drying efficiency and physicochemical quality of okra (Abelmoschus esculentus) cultivated in China
Authors: Wang Hua , Zhao Qingsheng , Zhao Bing
Published: June 2019

Okra (Abelmoschus esculentus) is difficult to preserve after harvest. If not properly dried, because of its high moisture content, which will reduce the product value of okra and the value of nutrition. In this study, the effects of vacuum freeze‐drying (VFD), ultrasonic pretreatment assisted vacuum drying (UPVD), and ultrasonic combined vacuum drying (UCVD) are compared and analyzed in terms of the drying characteristics effects and the physicochemical qualities of okra were studied. Compared with the drying curve and drying rate curve of okra dried by VFD, the drying time of okra dried by UCVD and UPVD was significantly reduced by 53.3% and 20.0%, respectively, and the total energy consumption of okra dried by UCVD and UPVD was saved by 21.8% and18.9%, respectively. The samples of UCVD had a higher b (yellowness), which keeps the original green color of Okra. The shrinkage ratio of samples dried by UPVD and UCVD had a significant difference (p < .05), and was 27.0% and 26.1%, respectively higher than that of samples dried by VFD. The rehydration curve of VFD sample was higher than that of other samples at 25°C, and was the same as that of UCVD samples for 12 min at 100°C. The total phenolic content of okra sample dried by UCVD was 7.7 ± 0.14 mg/g, higher than others samples. Since polyphenols have good antioxidant activity, the ABTS radical‐scavenging ability of UCVD samples was slightly higher than the other two samples, and the FRAP value of UCVD samples was significantly (p < .05) higher than the other two samples. SEM images of UCVD samples further confirmed the channeling effect caused by ultrasonic irradiation, which also confirmed the reliability of the above data in structure. Considering cost‐effectiveness, practicability and scale‐up, UCVD is a promising technology in the production of dried Okra.

Practical application

Ultrasonic combined vacuum drying (UCVD) is a novel technology for the food industry to reduce the energy consumption and improve food quality. Okra drying with UCVD can be successfully described by the Logarithmic model. The UCVD can significantly shorten the drying time and reduce the energy consumption of vegetables compared to the vacuum freeze drying. The products dried by UCVD retain various functional components of raw materials. Because of potential health, economic, and ecological benefits for the society, the UCVD is a promising technology in the production of Okra.
Capnography monitoring of non‐anesthesiologist provided sedation during percutaneous endoscopic gastrostomy placement: A prospective, controlled, randomized trial
Authors: Peveling‐Oberhag Jan , Michael Florian , Tal Andrea , Welsch Christoph , Vermehren Johannes , Farnik Harald , Grammatikos Georgios , Lange Christian , Walter Dirk , Blumenstein Irina , Filmann Natalie , Herrmann Eva , Albert Jörg , Zeuzem Stefan , Bojunga Jörg , Friedrich‐Rust Mireen
Published: June 2019

Background and Aim

A number of studies were able to show a reduction of hypoxemia episodes during procedural sedation through the use of capnography (CA). The present study investigates the number of episodes of hypoxemia during percutaneous endoscopic gastrostomy (PEG) placement with propofol sedation comparing standard monitoring (SM) versus SM with additional CA surveillance.

Methods

In this single center randomized controlled trial, 150 patients were prospectively randomized 1:1 in either the SM group or the CA group after stratification for ASA class, PEG method (push or pull method), presence of head and neck tumor, and tracheostomy. CA analysis was performed for all patients but was blinded for the endoscopic team in the SM group.

Results

In the SM group, 57% episodes of hypoxemia (SpO2 < 90% for > 15 s) and 41% episodes of severe hypoxemia (SpO2 < 85% for > 15 s) were observed in comparison with 28% and 20% in the CA group, respectively. Odds ratios for hypoxemia and severe hypoxemia were 0.29 (confidence interval 0.15–0.57; P = 0.0005) and 0.35 (confidence interval 0.17–0.73; P = 0.008) in favor of the CA group. On average, CA was able to detect imminent mild and severe hypoxemia 83 and 99 s before standard monitoring. Standard monitoring represented an independent risk factor for hypoxemia and severe hypoxemia.

Conclusions

Respiratory complications of sedation during PEG placement are frequent events. CA is able to detect imminent hypoxemia at an early time point. This allows an early intervention and consecutively the avoidance of mild and severe hypoxemia. Therefore, CA monitoring can be recommended particularly during PEG insertion procedures.