bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes
Authors: He Yan‐Ling , Haynes William , Meyers Charles D. , Amer Ahmed , Zhang Yiming , Mahling Ping , Mendonza Anisha E. , Ma Shenglin , Chutkow William , Bachman Eric
Published: February 2019

BACKGROUND

There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium‐glucose co‐transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity.

METHODS

Patients with obesity (BMI, 35‐50 kg/m2) were enrolled into a 12‐week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two‐part study, comprising a single‐dose cross‐over study (N = 12; 2.5 − 300 mg) and a 14‐day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE24) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP‐1, PYY3‐36, and GIP), insulin and glucagon.

RESULTS

Treatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC0‐4h) and suppressed insulin by 90% (P < 0.01; incremental AUC0‐4h). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24‐hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP‐1 by 54% (P < 0.001) and PYY3‐36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12‐week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%‐43% with licogliflozin vs 9%‐11% with placebo in the 12‐week study) were among the other gastrointestinal events reported.

CONCLUSION

Licogliflozin treatment (1‐84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes.
Normal values for tissue velocity and strain rate imaging parameters of left and right atrial myocardium in normal subjects
Authors: Safir‐Mardanloo Azam , Khorsand Askari Mani , Lotfi Tokaldany Masoumeh‐ , Ashrafi Mohammad Moein , Sadeghian Hakimeh
Published: February 2019

Objective

To determine normal values for tissue velocity imaging (TVI) and strain rate imaging (SRI) in the left atrium (LA) and right atrium (RA) in normal subjects.

Methods

A total of 63 healthy volunteers (50.8% male, age: 20–50 years) prospectively underwent TVI and SRI. The peak systolic velocity (TVs), strain (STs) and strain rate (SRs), peak early and late diastolic velocities (TVe and TVa), strain (STe and STa), and strain rate (SRe and SRa) were measured in the base and mid of the LA and RA walls and roofs.

Results

By TVI, TVs and TVe of LA walls decreased significantly from basal to mid‐level and from mid to the roof. Mean Tva of LA walls reduced significantly from basal to mid‐level and to the roof. By SRI, mean STs and STe of LA walls increased remarkably from basal to mid‐level and to the roof and also mean SRs, SRe and SRa increased significantly from basal to mid‐level and to the roof. For SRe, the changes were also significant from mid‐LA wall to the roof. Mean Tvs, Tve, and Tva of the RA walls reduced significantly from base to mid and then to the RA roof. RA systolic, early, and late diastolic ST and SR increased from base to mid and to the roof.

Conclusion

Peak systolic and diastolic velocities of the LA and RA decreased from the base to the mid and to the roof, while systolic and diastolic ST and SR increased from the base to the mid to the roof.
Peptidomic analysis of cartilage and subchondral bone in OA patients
Authors: Gatenholm Birgitta , Gobom Johan , Skillbäck Tobias , Blennow Kaj , Zetterberg Henrik , Brittberg Mats
Published: February 2019

Background

The objective of this study was to develop a method for directly analysing osteochondral samples straight out of the operating room without cell culturing, thereby enabling identification of potential peptide biomarkers to better understand the mechanisms involved in the development of osteoarthritis and pain.

Material and Methods

Osteochondral plugs from wounded and macroscopically nonwounded zones of the femur condyle were collected from six patients with manifest osteoarthritis (OA) undergoing total knee arthroplasty (TKA). The samples were demineralized and supernatant was collected and isotopically marked with Tandem Mass Tag (TMT) labelling and analysed using liquid chromatography coupled with tandem mass spectrometry LC‐MS/MS.

Results

Using peptidomics, 6292 endogenous peptides were identified. Five hundred sixty‐six peptides (8 identified endogenous peptides) differed significantly (P‐value 0.10) from wounded zones compared to nonwounded zones.

Conclusion

This pilot study shows promising results for enabling peptidomic analysis of cartilage and bone straight out of the operating room. With further refinement, peptidomics can potentially become a diagnostic tool for OA, and improve the knowledge of disease progression and genesis of pain.
Mechanistic, ecological, and evolutionary consequences of artificial light at night for insects: review and prospective
Authors: Desouhant Emmanuel , Gomes Elisa , Mondy Nathalie , Amat Isabelle
Published: February 2019

The alternation of light and dark periods on a daily or seasonal time scale is of utmost importance for the synchronization of physiological and behavioral processes in the environment. For the last 2 decades, artificial light at night (ALAN) has strongly increased worldwide, disrupting the photoperiod and its related physiological processes, and impacting the survival and reproduction of wild animals. ALAN is now considered as a major concern for biodiversity and human health. Here, we present why insects are relevant biological models to investigate the impact of ALAN. First the phenotypic responses to ALAN and their underpinning mechanisms are reviewed. The consequences for population dynamics, and the community composition and functioning are described in the second part. Because ALAN provides new and widespread selective pressure, we inventory evolutionary changes in response to this anthropogenic change. Finally, we identify promising future avenues, focusing on the necessity of understanding evolutionary processes that could help stakeholders consider darkness as a resource to preserve biodiversity as well as numerous ecosystem services in which insects are involved.
A review of the research literature on adult learning and employability
Authors: Midtsundstad Tove
Published: February 2019

Because of rising life expectancy and declining birth rates, reducing early retirement and prolonging employees’ working lives have become major goals on social policy agendas. In this context, ensuring the adaptability and employability of the existing workforce has become an important issue. The aim of this article is to conduct a review of the most recent literature on employment outcomes of adult learning. The review covers literature published in English since 2010.
Ionome and elemental transport kinetics shaped by parallel evolution in threespine stickleback
Authors: Rudman Seth M. , Goos Jared M. , Burant Joseph B. , Brix Kevin V. , Gibbons Taylor C. , Brauner Colin J. , Jeyasingh Punidan D.
Published: February 2019

Evidence that organisms evolve rapidly enough to alter ecological dynamics necessitates investigation of the reciprocal links between ecology and evolution. Data that link genotype to phenotype to ecology are needed to understand both the process and ecological consequences of rapid evolution. Here, we quantified the suite of elements in individuals (i.e., ionome) and differences in the fluxes of key nutrients across populations of threespine stickleback. We find that allelic variation associated with freshwater adaptation that controls bony plating is associated with changes in the ionome and nutrient recycling. More broadly, we find that adaptation of marine stickleback to freshwater conditions shifts the ionomes of natural populations and populations raised in common gardens. In both cases ionomic divergence between populations was primarily driven by differences in trace elements rather than elements typically associated with bone. These findings demonstrate the utility of ecological stoichiometry and the importance of ionome‐wide data in understanding eco‐evolutionary dynamics.
Association of temperament with dental anxiety and behaviour of the preschool child during the initial dental visit
Authors: Jain Avani , Suprabha Baranya Shrikrishna , Shenoy Ramya , Rao Arathi
Published: February 2019

The aim of this study was to investigate whether there is an association between temperament characteristics of preschool children, dental anxiety, and their dental behaviour. A total of 100 children, aged 3–5 yr, who were attending their initial dental visit accompanied by a parent, were included in this cross‐sectional study. Dental anxiety of children was measured using the Facial Image Scale. The behaviour of children during the initial oral examination and oral prophylaxis was assessed using Frankl's behaviour rating scale. Temperament was assessed using Emotionality, Activity, Shyness Temperament Survey for Children (parental ratings). Statistically significant weak linear positive correlations were seen between the following: the percentage duration of definitely negative behaviour and shyness scores (rs = 0.28); anxiety level and emotionality scores (rs = 0.28); and anxiety level and shyness scores (rs = 0.26). Multinomial logistic regression analysis revealed that children with higher anxiety had higher odds of showing definitely negative behaviour, which decreased with increasing age of the child. Emotionality and shyness temperaments may be weakly associated with dental anxiety, and shyness may be weakly associated with the dental behaviour of the preschool child. Definitely negative dental behaviour is associated with dental anxiety and age of the child.
Carbonic anhydrases are involved in mitochondrial biogenesis and control the production of lactate by human Sertoli cells
Authors: Bernardino Raquel L. , Dias Tânia R. , Moreira Bruno P. , Cunha Mariana , Barros Alberto , Oliveira Elsa , Sousa Mário , Alves Marco G. , Oliveira Pedro F.
Published: February 2019

The process that allows cells to control their pH and bicarbonate levels is essential for ionic and metabolic equilibrium. Carbonic anhydrases (CAs) catalyse the conversion of CO2 to and H+ and are thus essential for this process. Herein, we inhibited CAs with acetazolamide – ACT and SLC‐0111 – to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells (hSCs), obtained from biopsies from men with conserved spermatogenesis. We were able to identify three isoforms of CAs, one mitochondrial isoform (CA VB) and two cell membrane‐bound isoforms (CA IX and CA XII) in hSCs. When assessing the expression of markers for mitochondrial biogenesis, we observed a decrease in HIF‐1α, SIRT1, PGC1α and NRF‐1 mRNAs after all CAs were inhibited, resulting in decreased mitochondrial DNA copy numbers. This was followed by an increased production of lactate and alanine in the same conditions. In addition, consumption of glucose was maintained after inhibition of all CAs in hSCs. These results indicate a reduced conversion of pyruvate to acetyl‐coA, possibly due to decreased mitochondrial function, caused by CA inhibition in hSCs. Inhibition of CAs also caused alterations in lipid metabolism, since we detected an increased expression of hormone‐sensitive lipase (HSL) in hSCs. Our results suggest that CAs are essential for mitochondrial biogenesis, glucose and lipid metabolism in hSCs. This is the first report showing that CAs play an essential role in hSC metabolic dynamics, being involved in mitochondrial biogenesis and controlling lactate production.
Lack of posterior occlusal support predicts the reduction in walking speed in 80‐year‐old Japanese adults: A 3‐year prospective cohort study with propensity score analysis by the SONIC Study Group
Authors: Hatta Kodai , Ikebe Kazunori , Mihara Yusuke , Gondo Yasuyuki , Kamide Kei , Masui Yukie , Sugimoto Ken , Matsuda Ken‐ichi , Fukutake Motoyoshi , Kabayama Mai , Shintani Ayumi , Ishizaki Tatsuro , Arai Yasumichi , Rakugi Hiromi , Maeda Yoshinobu
Published: February 2019

Objective

To investigate the association between posterior occlusal support by residual teeth and the reduction in walking speed in 80‐year‐old Japanese adults using propensity score matching.

Background data discussing the present status of the field

Previous studies have demonstrated an association between oral status and motor function; however, most of these studies had a cross‐sectional design.

Material and method

This study included 353 community‐dwelling Japanese people aged 79‐81 years. Low walking speed was defined as ≤0.8 m/s, and participants with a low walking speed at baseline were excluded. The participants were divided into two groups: with or without posterior occlusal support by residual teeth at baseline. Propensity score matching was used to reduce the effects of bias by matching participants with and without posterior occlusal support according to similar background factors at baseline. Conditional logistic regression was conducted to determine low walking speed at the 3‐year follow‐up, which included posterior occlusal support as an independent variable with matching data.

Results

Before matching for posterior occlusal support, significant differences existed between the groups in terms of sex, years of education, height, weight and grip strength. However, after matching, there was no significant difference between the groups in any characteristic. Logistic regression analysis showed that posterior occlusal support is a significant variable (odds ratio = 1.88; P = 0.04) associated with reduced walking speed.

Conclusion

Lack of posterior occlusal support at baseline independently predicted the incidence of reduced walking speed over 3 years.
Behavior changes by a buddy‐style intervention including physical training, and nutritional and social support
Authors: Winzer Eva , Dorner Thomas E , Grabovac Igor , Haider Sandra , Kapan Ali , Lackinger Christian , Schindler Karin
Published: February 2019

Aim

Previous research suggests that multicomponent interventions including physical training, and nutritional and social support are required to improve a person's behavior. As a pre‐specified secondary outcome, this analysis aimed to ascertain whether a “buddy‐style” intervention could produce physical activity and nutritional behavior changes in older adults.

Methods

A 12‐week, home‐based, randomized controlled trial was carried out with 80 older persons, who were randomly assigned to an intervention group (n = 39), including physical training and nutritional support, and a control group (n = 41). Trained non‐professional volunteers visited the participants at home twice a week. Physical activity and nutritional behavior were assessed through validated questionnaires.

Results

In total, 36 participants in the intervention group and 26 participants in the control group completed the final questionnaire. The intervention group showed significant improvements in physical activity behavior, such as light sport activity (β = 9.13, 95% CI 0.90–17.37 min/day; P = 0.030), muscle strength exercise (β = 68.18, 95% CI 46.45–89.91 min/week; P < 0.001) and overall activities (β = 0.69, 95% CI 0.21–1.18 h/day; P = 0.006), compared with the control group. Nutritional behavior improvements for the intervention group were observed in the consumption of legumes/nuts (β = 0.18, 95% CI 0.00–0.35 portions/day; P = 0.047) and fluids (β = 0.48, 95% CI 0.01–0.98 portions/day; P = 0.050), relative to controls.

Conclusions

A “buddy‐style” program in older adults living at home can produce effective physical activity changes and, to a lesser extent, changes in dietary behavior, and has the potential to be efficient and feasible. Geriatr Gerontol Int 2019; 19: 323–329.
Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting
Authors: Kruse‐Jarres Rebecca , Oldenburg Johannes , Santagostino Elena , Shima Midori , Kempton Christine L. , Kessler Craig M. , Lehle Michaela , Chebon Sammy , Selak Bienz Nives , Asikanius Elina , Mahlangu Johnny
Published: February 2019

Introduction

Prospectively collected real‐world data on bleeds, haemophilia treatment and safety in persons with haemophilia A (PwHA) without factor VIII (FVIII) inhibitors are limited. A global, non‐interventional study (NIS; NCT02476942) prospectively collected real‐world data in PwHA who were treated per local routine clinical practice.

Aim

Assess annualized bleeding rate (ABR), haemophilia treatment practices and adverse events (AEs) in adult/adolescent PwHA without inhibitors.

Methods

Eligible participants aged ≥12 years with severe HA without history of inhibitors prospectively collected bleeding and treatment information.

Results

Ninety‐four participants were enrolled (median [range] age, 34 [12‐76] years) and monitored for a median (range) of 29.8 (12.4‐47.7) weeks. In the episodic (n = 45) and prophylactic (n = 49) treatment groups, respectively, 872/1066 (81.8%) and 151/189 (79.9%), bleeds were treated; ABRs (95% confidence interval) were 36.1 (30.8‐42.3) and 5.0 (3.3‐7.5), respectively, for treated bleeds and 43.1 (36.5‐50.9) and 6.2 (4.2‐9.2), respectively, for all bleeds, and median (interquartile range) ABRs were 31.1 (19.8‐51.6) and 1.9 (0.0‐8.2), respectively, for treated bleeds and 35.3 (21.7‐62.9) and 2.7 (0.0‐9.4), respectively, for all bleeds. Half of the participants on FVIII prophylaxis had relatively high adherence to treatment, using 2.9 and 2.1 median doses/wk of standard and extended half‐life FVIII, respectively. Serious AEs included gastrointestinal polyp haemorrhage and haemarthrosis; the most common AE was viral upper respiratory tract infection.

Conclusion

PwHA without inhibitors continue to bleed on prophylaxis, consistent with the literature, and require treatment for breakthrough bleeds. This prospective NIS demonstrates the need for more efficacious haemostatic approaches.
Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac, endothelial function and arterial stiffness in ESRD (CERES) cohort
Authors: Ayer Amrita , Mills Claire , Donovan Catherine , Christenson Robert H. , Ganz Peter , Dubin Ruth F.
Published: February 2019

Introduction: Patients with end‐stage renal disease (ESRD) have reduced endothelial function, but whether macro‐ and microvascular endothelial function correlate with baseline risk factors and cardiovascular outcomes in this population is not well understood.

Methods: Among 146 participants of the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study, we evaluated macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation (FMD) and velocity time integral (VTI), respectively. We examined cross‐sectional correlations of baseline characteristics, inflammatory and cardiac markers with FMD and VTI. We followed participants for the composite outcome of cardiovascular hospitalization or all‐cause death over fourteen months. Cox survival analyses were adjusted for demographics, comorbidities, medications, systolic blood pressure, inflammation, high‐sensitivity troponin T (hs‐TnT), and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP).

Findings: Impaired VTI was associated with older age and Black race (P < 0.05), as well as female gender, atherosclerosis, and hemodialysis (as opposed to peritoneal dialysis) (P < 0.2). Myocardial injury, measured as hs‐TnT, inflammatory markers and NT‐proBNP correlated with impaired VTI. In unadjusted analyses, VTI was significantly associated with the composite outcome (HR per SD VTI 0.65 [95%CI 0.45, 0.95]), but FMD was not (HR per SD FMD 0.97 [95%CI 0.69, 1.4]). When VTI was calculated as the ratio of (hyperemic VTI‐baseline VTI)/baseline VTI, its association with the outcome persisted after multivariable adjustment.

Discussion: Microvascular function was associated with higher rates of cardiovascular hospitalizations and all‐cause mortality among individuals with ESRD on dialysis. Further research is needed to learn whether novel therapies that target microvascular endothelial function could improve outcomes in this high‐risk population.
Driving with cardiac devices in Australia. Does a review of recent evidence prompt a change in guidelines?
Authors: Lovibond Samuel W. , Odell Morris , Mariani Justin A.
Published: February 2019

Australian Driving Guidelines for patients with pacemakers and implanted cardioverter defibrillators are in line with many around the world, with some minor differences. Some aspects of these guidelines lack contemporary evidence in key decision‐making areas and make broad recommendations regarding groups with heterogeneous populations. In addition, more recent studies suggest lower rates of adverse events in some patients with these devices than previously thought. Through a systematic literature review, along with discussion of current guidelines, we combine new evidence with well established risk assessment tools to ask the following questions: (i) Given the heterogeneity of patient risk within the defibrillator population, should guidelines allow for further individualisation of risk and subsequent licensing restrictions?; and (ii) Could some patients with primary prevention automated cardioverter defibrillators be able to hold a commercial driving licence?
Artificial Intelligence and the Future of Work: Will Our Jobs be Taken by Machines?
Authors: Olhede Sofia , Wolfe Patrick J.
Published: February 2019

Sofia Olhede and Patrick Wolfe discuss the current state of data-driven automation and its implications for jobs
What can the Web Tell Us about Jobs and Gender?
Authors: Tarran Brian
Published: February 2019

A data science start-up is reading the web to see what it can learn about gender representation in the UK economy. Brian Tarran reports on some early findings
How do we know How Fast the Wind may Blow?
Authors: Winter Hugo , Brown Kate
Published: February 2019

Richard Leigh asks: How do weather forecasters calculate their estimates of average wind speeds and gusts?
Visualising theTitanicDisaster
Authors: Friendly Michael , Symanzik Jürgen , Onder Ortac
Published: February 2019

The sinking of the Titanic has inspired books, movies and documentaries. But it has also motivated data visualisation designers to tell the story of the tragedy in new ways. Michael Friendly, Jürgen Symanzik and Ortac Onder review the first graph of the disaster and some recent history
Turning Points: Fisher's Random Idea
Authors: Raper Simon
Published: February 2019

In this second article in our series on key moments in the history of statistics, Simon Raper invites us to a field in England, where R. A. Fisher urged scientists to stop trying to control nature and embrace randomness instead
Why Geography Matters
Authors: Johnston Ron , Jones Kelvyn , Manley David
Published: February 2019

Administrative data, analysed by geographical area, can tell us much about society. But the choice of geographical area frames how we see the world — and a poor choice of frame will present a misleading perspective. By Ron Johnston, Kelvyn Jones and David Manley
Gender Diversity in UK Public Appointments: A Personal Investigation
Authors: Bird Sheila M.
Published: February 2019

When Sheila M. Bird applied to sit on the board of the UK Statistics Authority, she was disappointed not to be selected for interview. But that disappointment soon sparked an investigation to find out more about the success rate of female applicants for UK public appointments
Graphical Interpretations of Data: East is East...
Authors: Reese R. Allan
Published: February 2019

R. Allan Reese looks at two graphs showing a statistical model for the number of hawks counted in autumn at a migration hotspot, related to local wind direction. Look for yourself and decide which way the wind is blowing
Characterization of LDH (phyllosilicate/carbonate) type compounds formed in the pozzolanic reaction of phyllosilicate‐rich industrial waste
Authors: Sánchez Isabel , Ramírez Mario , Casas Angulo Marina , Vigil de la Villa Raquel , García‐Giménez Rosario , Bomati Oscar , Zapardiel Antonio
Published: February 2019

Reutilization of industrial waste products as cement additives yields a number of secondary materials, yet their identification is not always trivial. Confirmation of the formation of a LDH‐type (phyllosilicate/carbonate) material is the main purpose of this study. Mineralogically, organic and inorganic compounds form some industrial wastes, among which the phyllosilicates are prominent. Crystalline and amorphous hydrated phases appeared during the pozzolanic reaction in a dehydroxylated phyllosilicate/lime system, whose controlled activation yielded dehydroxylated products with high pozzolanic properties. The LDH‐type (phyllosilicate/carbonate) material was one of the reaction products; this material could be considered as the superposition type 1:1 of tetrahedral layers of silicon and aluminum and octahedral layers of aluminum (dehydroxylated kaolinite), generating a positive charge in the interlaminar region compensated by carbonate anions with a basal spacing (001) measured by XRD at 7.57Å. Therefore, several techniques were used to determine whether they could be included in the structural group named Layered Double Hydroxides (LDHs), as they are, too, laminar layers of oxides and hydroxides with a positive laminar charge in the interlayer region compensated by the presence of anions with similar basal spacing. In this research, the effects of activation temperature and calcite proportion were analyzed on the hydrated phases formed after 28 days of pozzolanic reaction in a metakaolin (MK)/lime system. The MK was obtained from a mix of 1:1; 2:1 and 3:1 kaolinite:calcite mixture, thermally activated at 750°C for 2 hours, comparing it with kaolinite activated at 600°C for 2 hours. As the most LDH‐rich sample, the 1:1 LDH‐type (phyllosilicate/carbonate) phase was characterized using XRD, SEM‐EDX, HRTEM‐EDX, FTIR, NMR‐MAS, and Raman spectroscopy.
Role of oxygen‐vacancy in piezoelectric properties and fatigue behavior of (Bi0.5Na0.5)0.93Ba0.07Ti1+xO3 ceramics
Authors: Jia Xuanrui , Zhang Jingji , Wang Lejian , Wang Jiangying , Du Huiwei , Yao Yaxuan , Ren Lingling , Wen Fei , Zheng Peng
Published: February 2019

In this reported study, (Bi0.5Na0.5)0.93Ba0.07Ti1+xO3 (abbreviated as BNBT1+x) ceramics, containing Ti‐nonstoichiometry that ranged from a 2% deficiency to a 1% excess, were designed and systematically characterized. The results of the X‐ray diffraction Rietveld refinement and X‐ray photoelectron spectroscopy analysis of these materials revealed that the amount of Ti in the BNBT1+x ceramics significantly affected the degree of coexistent rhombohedral/tetragonal phases and also affected the content of singly/doubly charged oxygen‐vacancy (/) in the ceramics. After poling and 105 fatigue cycles, the variation in Raman resonance line‐width of the Ti–O bond in the BNBT1+x ceramics was found to be strongly dependent on the amount of Ti in the ceramic. The → transformation and clustering of the defects under electrical loading were considered to be a critical factor in electric field‐induced structural transition and fatigue properties of the material.
The effect of imprint on remanent piezoelectric properties and ferroelectric aging of PbZr0.52Ti0.48O3 thin films
Authors: Akkopru‐Akgun Betul , Zhu Wanlin , Lanagan Michael T. , Trolier‐McKinstry Susan
Published: February 2019

Ferroelectric films suffer from both aging and degradation under high ac‐field drive conditions due to loss of polarization with time. In this study, the roles of defect chemistry and internal electric fields on the long‐term stability of the properties of piezoelectric films were explored. For this purpose, lead zirconate titanate (PZT) films with a Zr/Ti ratio of 52/48 doped with Mn‐ (PMZT) or Nb‐ (PNZT) were deposited on Pt coated Si substrates by the sol‐gel method. It was demonstrated that the magnitude of the internal field is much higher in PMZT films compared to PNZT films after poling in the temperature range of 25‐200°C under an electric field of −240 kV/cm. The development of the internal field is thermally activated, with activation energies from 0.5 ± 0.06 to 0.8 ± 0.1 eV in Mn doped films and from 0.8 ± 0.1 to 1.2 ± 0.2 eV in Nb doped films. The different activation energies for imprint suggests that the physical mechanism underlying the evolution of the internal field in PMZT and PNZT films differs; the enhanced internal field upon poling is attributed to (a) alignment of oxygen vacancy—acceptor ion defect dipoles (, ) in PMZT films, and (b) thermionic injection of electron charges and charge trapping in PNZT films. In either case, the internal field reduces back switching, enhances the remanent piezoelectric properties, and dramatically improves the aging behavior. PMZT films exhibited the greatest enhancement, with reduced high temperature (180°C) aging rates of 2%‐3%/decade due to improved stability of the poled state. In contrast, PNZT films showed significantly larger high temperature aging rates (15.5%/decade) in the piezoelectric coefficient, demonstrating that the fully poled state was not retained with time.
Orthostatic hypertension: From pathophysiology to clinical applications and therapeutic considerations
Authors: Magkas Nikolaos , Tsioufis Costas , Thomopoulos Costas , Dilaveris Polychronis , Georgiopoulos Georgios , Doumas Michael , Papadopoulos Dimitris , Tousoulis Dimitrios
Published: February 2019

Orthostatic hypertension (OHT), that is, sustained increase in blood pressure after standing, is an increasingly recognized cardiovascular disorder having been examined in much fewer studies compared with orthostatic hypotension (OH). However, in both OHT and OH, dysfunction of the autonomous nervous system is considered to be the primary pathophysiological disturbance, while significant associations with essential hypertension have been observed. Although in many studies OHT has been related to subclinical or clinical target organ damage, there is also evidence denying such an association. Because OHT is defined variably across different studies, the comparison of relevant outcomes is at least problematic. Since evidence about OHT treatment is exclusively based on limited non‐randomized studies, no specific recommendations have been developed. Therefore, both the prognostic role and the clinical significance of OHT remain largely undefined. The aim of the present review is to summarize the available evidence regarding the definition, diagnosis, pathophysiology, prognostic role and treatment of OHT and highlight potential clinical implications of this underestimated condition.
Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies
Authors: Chen Ruiling , Wang Gangyang , Zheng Ying , Hua Yingqi , Cai Zhengdong
Published: February 2019

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.
Weak premating isolation between Clitarchus stick insect species despite divergent male and female genital morphology
Authors: Langton‐Myers Shelley S. , Holwell Gregory I. , Buckley Thomas R.
Published: February 2019

Documenting natural hybrid systems builds our understanding of mate choice, reproductive isolation and speciation. The stick insect species Clitarchus hookeri and C. tepaki differ in their genital morphology and hybridize along a narrow peninsula in northern New Zealand. We utilize three lines of evidence to understand the role of premating isolation and species boundaries: (a) genetic differentiation using microsatellites and mitochondrial DNA; (b) variation in 3D surface topology of male claspers and 2D morphometrics of female opercular organs; and (c) behavioural reproductive isolation among parental and hybrid populations through mating crosses. The genetic data show introgression between the parental species and formation of a genetically variable hybrid swarm. Similarly, the male and female morphometric data show genital divergence between the parental species as well as increased variation within the hybrid populations. This genital divergence has not resulted in reproductive isolation between species, instead weak perimating isolation has enabled the formation of a hybrid swarm. Behavioural analysis demonstrates that the entire mating process influences the degree of reproductive isolation between species undergoing secondary contact. Mechanical isolation may appear strong, whereas perimating isolation is weak.
CPAP Adherence May Slow 1‐Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea
Authors: Richards Kathy C. , Gooneratne Nalaka , Dicicco Barry , Hanlon Alexandra , Moelter Stephen , Onen Fannie , Wang Yanyan , Sawyer Amy , Weaver Terri , Lozano Alicia , Carter Patricia , Johnson Jerry
Published: February 2019

Background/Objectives

Obstructive sleep apnea (OSA) has been linked to an increased risk for Alzheimer's disease (AD), but little prospective evidence exists on the effects of OSA treatment in preclinical AD. The objective was to determine if continuous positive airway pressure (CPAP) treatment adherence, controlling for baseline differences, predicts cognitive and everyday function after 1 year in older adults with mild cognitive impairment (MCI) and to determine effect sizes for a larger trial.

Design

Quasi‐experimental pilot clinical trial with CPAP adherence defined as CPAP use 4 hours or more per night over 1 year.

Setting

Sleep and geriatric clinics and community.

Participants

Older adults, aged 55 to 89 years, with an apnea‐hypopnea index of 10 or higher participated: (1) MCI, OSA, and CPAP adherent (MCI +CPAP), n = 29; and (2) MCI, OSA, CPAP nonadherent (MCI −CPAP), n = 25.

Intervention

CPAP.

Measurements

The primary cognitive outcome was memory (Hopkins Verbal Learning Test‐Revised), and the secondary cognitive outcome was psychomotor/cognitive processing speed (Digit Symbol subtest from the Wechsler Adult Intelligence Scale Substitution Test). Secondary function and progression measures were the Everyday Cognition, Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change Scale, and Clinical Dementia Rating.

Results

Statistically significant improvements in psychomotor/cognitive processing speed in the MCI +CPAP group vs the MCI −CPAP group were observed at 1 year after adjustment for age, race, and marital status (parameter estimate = 1.68; standard error = 0.47; 95% confidence interval = 0.73‐2.62), with a 6‐month effect size (ES) of 0.46 and a 1‐year ES of 1.25. There were small to moderate ESs for memory (ES 0.20, 6 mo), attention (ES 0.25, 1 y), daytime sleepiness (ES 0.33, 6 mo and ES 0.22, 1 y), and everyday function (ES 0.50, 6 mo) favoring the MCI +CPAP group vs the MCI −CPAP group.

Conclusion

Controlling for baseline differences, 1 year of CPAP adherence in MCI +OSA significantly improved cognition, compared with a nonadherent control group, and may slow the trajectory of cognitive decline.

Trial Registration Number

Memories; NCT01482351; https://clinicaltrials.gov/ct2/show/NCT01482351?cond=MCI+and+OSA&rank=1 J Am Geriatr Soc 67:558–564, 2019.
Access to Care for Older Adults: An Insurmountable Flight of Stairs?
Authors: Dawson Catherine M.P. , Cooney Leo M.
Published: February 2019

Inability to climb stairs safely can lead older adults to miss desired medical appointments. To facilitate adequate access to routine medical care for older adults, affordable transportation assistance up and down stairs should be available. J Am Geriatr Soc 67:663–664, 2019.
CD4CD8 Double Positive T cell responses during Mycobacterium tuberculosis infection in cynomolgus macaques
Authors: Diedrich Collin Richard , Gideon Hannah Priyadarshini , Rutledge Tara , Baranowski Tonilynn Marie , Maiello Pauline , Myers Amy J. , Lin Philana Ling
Published: February 2019

Background

Tuberculosis (TB) kills millions of people every year. CD4 and CD8 T cells are critical in the immune response against TB. T cells expressing both CD4 and CD8 (CD4CD8 T cells) are functionally active and have not been examined in the context of TB.

Methods

We examine peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage cells (BAL) and lung granulomas from 28 cynomolgus macaques during Mycobacterium tuberculosis (Mtb) infection.

Results

CD4CD8 T cells increase in frequency during early Mtb infection in PBMC and BAL from pre‐infection. Peripheral, airway, and lung granuloma CD4CD8 T cells have distinct patterns and greater cytokine production than CD4 or CD8 T cells.

Conclusion

Our data suggest that CD4CD8 T cells transient the blood and airways early during infection to reach the granulomas where they are involved directly in the host response to Mtb.
Sustainability via Active Garden Education: Translating Policy to Practice in Early Care and Education
Authors: Lee Rebecca E. , Soltero Erica G. , Ledoux Tracey A. , Sahnoune Iman , Saavadra Fiorella , Mama Scherezade K. , McNeill Lorna H.
Published: February 2019

BACKGROUND

We describe the development of sustainability via active garden education (SAGE), an early care and education (ECE) garden‐based curriculum developed from a 5‐year community partnership to link national health policy guidelines with ECE accreditation standards.

METHODS

National health guidelines and ECE accreditation standards were reviewed, and community advisory board members, ECE staff, and parents provided feedback and support throughout the development of the curriculum. The SAGE curriculum components were guided by the Ecologic Model of Physical Activity and Social Cognitive Theory. Strengths‐weaknesses‐opportunities‐threat analyses were used to refine and revise the curriculum to overcome challenges to implementation.

RESULTS

Twelve 1‐hour, developmentally appropriate, modularized lessons were created using the garden as a metaphor for human development. Lessons featured songs, simple games, pretend play, modeling, and garden activities. Parents were engaged via weekly newsletters with information about activities in the classroom, strategies to improve health habits at home, and free community resources.

CONCLUSION

SAGE partnered scientific theory and rigor with community ingenuity and innovation to create a clear translation of policy guidelines to easily implementable practice in a fun and engaging manner.
Comprehensive coronary plaque assessment in patients with obstructive sleep apnea
Authors: Bikov Andras , Kolossváry Márton , Jermendy Adam L. , Drobni Zsofia D. , Tarnoki Adam D. , Tarnoki David L. , Forgó Bianka , Kovacs Daniel T. , Losonczy Gyorgy , Kunos Laszlo , Voros Szilard , Merkely Bela , Maurovich‐Horvat Pal
Published: February 2019

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non‐calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty‐one adult subjects (59 ± 9 years, 15 men) underwent a 256‐slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty‐two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea‐hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.
ECEIM consensus statement on equine metabolic syndrome
Authors: Durham Andy E. , Frank Nicholas , McGowan Cathy M. , Menzies‐Gow Nicola J. , Roelfsema Ellen , Vervuert Ingrid , Feige Karsten , Fey Kerstin
Published: February 2019

Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long‐term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.
Theory, a lost character? As presented in general practice education research papers
Authors: Brown James , Bearman Margaret , Kirby Catherine , Molloy Elizabeth , Colville Deborah , Nestel Debra
Published: February 2019

Objectives

The use of theory in research is reflected in its presence in research writing. Theory is often an ineffective presence in medical education research papers. To progress the effective use of theory in medical education, we need to understand how theory is presented in research papers. This study aims to elicit how theory is being written into general practice (GP) vocational education research papers in order to elucidate how theory might be more effectively used. This has relevance for the field of GP and for medical education more broadly.

Methods

This is a scoping review of the presentation of theory in GP vocational education research published between 2013 and 2017. An interpretive approach is taken. We frame research papers as a form of narrative and draw on the theories of Aristotle's poetics and Campbell's monomyth. We seek parallels between the roles of theory in a research story and theories of characterisation.

Results

A total of 23 papers were selected. Theories of ‘reflective learning’, ‘communities of practice’ and ‘adult learning’ were most used. Six tasks were assigned to theory: to align with a position; to identify a research problem; to serve as a vehicle for an idea; to provide a methodological tool; to interpret findings, and to represent an object of examination. The prominence of theory in the papers ranged from cameo to major roles. Depending on the way theory was used and the audience, theory had different impacts. There were parallels between the tasks assigned to theory and the roles of four of Campbell's archetypal characters. Campbell's typology offers guidance on how theory can be used in research paper ‘stories’.

Conclusions

Theory can be meaningfully present in the story of a research paper if it is assigned a role in a deliberate way and this is articulated. Attention to the character development of theory and its positioning in the research story is important.
Multiple‐role mentoring: mentors’ conceptualisations, enactments and role conflicts
Authors: Meeuwissen Stephanie N E , Stalmeijer Renée E , Govaerts Marjan
Published: February 2019

Introduction

Outcome‐based approaches to education and the inherent emphasis on programmatic assessment in particular, require models of mentoring in which mentors fulfil dual roles: coach and assessor. Fulfilling multiple roles could result in role confusion or even role conflicts, both of which may affect mentoring processes and outcomes. In this study, we explored how mentors conceptualise and enact their role in a multiple‐role mentoring system and to what extent they experience role conflicts.

Methods

We conducted a constructivist grounded theory study at one undergraduate medical school. A purposive sample of 12 physician‐mentors active in a programmatic assessment system was interviewed. Data analysis followed stages of open, axial and selective coding through which themes were constructed.

Results

Three predominant mentoring approaches were constructed: (i) empowering (a reflective and holistic approach to student development); (ii) checking (an observant approach to check whether formal requirements are met), and (iii) directing (an authoritative approach to guide students’ professional development). Each approach encompassed a corresponding type of mentor‐mentee relationship: (i) partnership; (ii) instrumental, and (iii) faculty‐centred. Furthermore, mentors’ strategies, focus, agency provided to students and perception of the assessment system characterised mentoring approaches and relationships. Role conflicts were mainly experienced by mentors with a directing mentoring approach. They used various coping mechanisms, including deviation from assessment guidelines.

Conclusions

In multiple‐role mentoring in the context of programmatic assessment, mentors adopted certain predominant mentoring approaches, which were characterised by different strategies for mentoring and resulted in different mentor–mentee relationships. Multiple‐role mentoring does not necessarily result in role conflict. Mentors who do experience role conflict seem to favour the directing approach, which is most at odds with key principles of competency‐based education and programmatic assessment. These findings build upon existing mentoring literature and offer practical suggestions for faculty development regarding approaches to mentoring in programmatic assessment systems.