bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis, Dysbiosis and Expression of Inflammatory Cytokines are Sequential Events in the Development of 5‐Fluorouracil‐Induced Intestinal Mucositis in Mice
Authors: Hamouda Nahla , Sano Tatsushi , Oikawa Yosuke , Ozaki Toru , Shimakawa Masaki , Matsumoto Kenjiro , Amagase Kikuko , Higuchi Kazuhide , Kato Shinichi
Published: April 2017

The chemotherapeutic agent 5‐fluorouracil (5‐FU) causes intestinal mucositis with severe diarrhoea, but the pathogenesis is not fully understood. In this study, we investigated the pathogenic effects of 5‐FU in mice, focusing on apoptosis, enterobacteria and inflammatory cytokines. Repeated administration of 5‐FU caused severe intestinal mucositis on day 6, accompanied by diarrhoea and body‐weight loss. TNF‐α expression increased 1 day after exposure to the drug, and spiked a second time on day 4, at which point myeloperoxidase activity and IL‐1β expression also increased. Apoptotic cells were observed in intestinal crypts only on day 1. 5‐FU also induced dysbiosis, notably decreasing the abundance of intestinal Firmicutes while increasing the abundance of Bacteroidetes and Verrucomicrobia. Twice‐daily co‐administration of oral antibiotics significantly reduced the severity of intestinal mucositis and dysbiosis, and blocked the increase in myeloperoxidase activity and cytokine expression on day 6, without affecting apoptosis and TNF‐α up‐regulation on day 1. In cultured colonic epithelial cells, exposure to 5‐FU also up‐regulated TNF‐α expression. Collectively, the data suggest that crypt apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of intestinal mucositis after exposure to 5‐FU. In particular, 5‐FU appears to directly induce apoptosis via TNF‐α and to suppress intestinal cell proliferation, thereby resulting in degradation of the epithelial barrier, as well as in secondary inflammation mediated by inflammatory cytokines.
Doubly Robust Estimation of Generalized Partial Linear Models for Longitudinal Data with Dropouts
Authors: Lin Huiming , Fu Bo , Qin Guoyou , Zhu Zhongyi
Published: April 2017

We develop a doubly robust estimation of generalized partial linear models for longitudinal data with dropouts. Our method extends the highly efficient aggregate unbiased estimating function approach proposed in Qu et al. (2010) to a doubly robust one in the sense that under missing at random (MAR), our estimator is consistent when either the linear conditional mean condition is satisfied or a model for the dropout process is correctly specified. We begin with a generalized linear model for the marginal mean, and then move forward to a generalized partial linear model, allowing for nonparametric covariate effect by using the regression spline smoothing approximation. We establish the asymptotic theory for the proposed method and use simulation studies to compare its finite sample performance with that of Qu's method, the complete-case generalized estimating equation (GEE) and the inverse-probability weighted GEE. The proposed method is finally illustrated using data from a longitudinal cohort study.
Strengthening medical education in haematology and blood transfusion: postgraduate programmes in Tanzania
Authors: Makani Julie , Lyimo Magdalena , Magesa Pius , Roberts David J.
Published: April 2017

Haematology and blood transfusion, as a clinical and laboratory discipline, has a far‐reaching impact on healthcare both through direct patient care as well as provision of laboratory and transfusion services. Improvement of haematology and blood transfusion may therefore be significant in achieving advances in health in Africa. In 2005, Tanzania had one of the lowest distributions of doctors in the world, estimated at 2·3 doctors per 100 000 of population, with only one haematologist, a medical doctor with postgraduate medical education in haematology and blood transfusion. Here, we describe the establishment and impact of a postgraduate programme centred on Master of Medicine and Master of Science programmes to build the capacity of postgraduate training in haematology and blood transfusion. The programme was delivered through Muhimbili University of Health and Allied Sciences (MUHAS) with partnership from visiting medical and laboratory staff from the UK and complemented by short‐term visits of trainees from Tanzania to Haematology Departments in the UK. The programme had a significant impact on the development of human resources in haematology and blood transfusion, successfully training 17 specialists with a significant influence on delivery of health services and research. This experience shows how a self‐sustaining, specialist medical education programme can be developed at low cost within Lower and Middle Income Countries (LMICs) to rapidly enhance delivery of capacity to provide specialist services.
The role of Hippo/yes‐associated protein signalling in vascular remodelling associated with cardiovascular disease
Authors: He Jinlong , Bao Qiankun , Yan Meng , Liang Jing , Zhu Yi , Wang Chunjiong , Ai Ding
Published: April 2017

Vascular remodelling is a vital process of a wide range of cardiovascular diseases and represents the altered structure and arrangement of blood vessels. The Hippo pathway controls organ size by regulating cell survival, proliferation and apoptosis. Yes‐associated protein (YAP), a transcription coactivator, is a downstream effector of the Hippo pathway. There is growing evidence for the importance of the Hippo/YAP pathway in vascular‐remodelling and related cardiovascular diseases. The Hippo/YAP pathway alters extracellular matrix production or degradation and the growth, death and migration of vascular smooth muscle cells and endothelial cells, which contributes to vascular remodelling in cardiovascular diseases such as pulmonary hypertension, atherosclerosis, restenosis, aortic aneurysms and angiogenesis. In this review, we summarize and discuss recent findings about the roles and mechanisms of Hippo/YAP signalling in vascular remodelling and related conditions.

Linked Articles

This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc
Changes in Cenozoic depositional environment and sediment provenance in the Danube Basin
Authors: Kováč Michal , Rybár Samuel , Halásová Eva , Hudáčková Natália , Šarinová Katarína , Šujan Michal , Baranyi Victoria , Kováčová Marianna , Ruman Andrej , Klučiar Tomáš , Zlinská Adriena
Published: April 2017

The Danube Basin is situated between the Eastern Alps, Western Carpathians and Transdanubian mountain ranges and represents a classic petroleum prospection site. The basin fill is known from many 2D reflection seismic lines and deep wells with measured e‐logs which provided a good opportunity for theories about its evolution. New analyses of deep wells situated in the Danube Basin northeastern margin allowed us to refine stratigraphy and to interpret various depositional systems. This also allowed us to outline changes in provenance of sediment during the Cenozoic. The performed interpretation of the Palaeogene and Neogene depositional systems also confirmed the Oligocene–Early Miocene exhumation of the basin pre‐Neogene basement. Opening and development of the Middle to Late Miocene basin depocentres above the boundary between the Western Carpathians and Northern Pannonian domain was recognized. Our analysis contributed to a better understanding of the Hurbanovo–Diösjenő fault which acts as an inherited weakness zone along the boundary of two crustal fragments with different provenance. We document various basin types stacked one on another (retro‐arc, back‐arc and extensional hinterland basin). The analysis of sediment sources reveals intricate geodynamic processes during the Eastern Alpine–Western Carpathian orogenic system collision with European platform (formation ofALCAPAmicroplate) and its successive tectonics escape during the Pannonian Basin System origination.
Social facilitation is a better predictor of frog reproductive activity than environmental factors
Authors: Höbel Gerlinde
Published: April 2017

Anuran breeding activity is frequently linked to environmental factors, mainly temperature and rainfall. However, a key feature of anuran reproductive behavior—gathering in choruses and producing loud advertisement calls to attract females—generates a conspicuous social cue that may also facilitate reproductive behavior. Here, I examine the relative importance of environmental and social factors in explaining the intensity of reproductive activity in the Neotropical treefrog Hypsiboas rosenbergi. I show that social cues generally play an important role, but that there are sex differences: male behavior is associated with a combination of environmental and social factors, while female behavior is associated almost exclusively with social cues. I discuss the potential benefits of using social cues in regulating breeding activity, and suggest that conservation efforts may take advantage of the apparently widespread pattern of social facilitation in anuran reproductive ecology.
The Early Construction of Spatial Attention: Culture, Space, and Gesture in Parent–Child Interactions
Authors: McCrink Koleen , Caldera Christina , Shaki Samuel
Published: April 2017

American and Israeli toddler–caregiver dyads (mean age of toddler = 26 months) were presented with naturalistic tasks in which they must watch a short video (N = 97) or concoct a visual story together (N = 66). English‐speaking American caregivers were more likely to use left to right spatial structuring than right to left, especially for well‐ordered letters and numbers. Hebrew‐speaking Israeli parents were more likely than Americans to use right to left spatial structuring, especially for letters. When constructing a pictorial narrative for their children, Americans were more likely to place pictures from left to right than Israelis. These spatial structure biases exhibited by caregivers are a potential route for the development of spatial biases in early childhood, before children have developed automatic reading and writing habits.
Universality Without Uniformity: A Culturally Inclusive Approach to Sensitive Responsiveness in Infant Caregiving
Authors: Mesman Judi , Minter Tessa , Angnged Andrei , Cissé Ibrahima A. H. , Salali Gul Deniz , Migliano Andrea Bamberg
Published: April 2017

Do caregivers in non‐Western communities adapt their behaviors to the needs of infants? This question reflects one of the most long‐standing debates on the universality versus culture‐specificity of caregiver–infant interactions in general and sensitive responsiveness to infants in particular. In this article, an integration of both points of view is presented, based on the theoretical origins of the sensitive responsiveness construct combined with the ethnographic literature on caregivers and infants in different parts of the world. This integration advocates universality without uniformity, and calls for multidisciplinary collaborations to investigate the complexities and nuances of caregiver–infant interactions in different cultures. Salient issues are illustrated with observations of infants (ages 7–31 months) in Mali, the Republic of Congo, and the Philippines.
Accent, Language, and Race: 4–6‐Year‐Old Children's Inferences Differ by Speaker Cue
Authors: Weatherhead Drew , Friedman Ori , White Katherine S.
Published: April 2017

Three experiments examined 4‐ to 6‐year‐olds' use of potential cues to geographic background. In Experiment 1 (N = 72), 4‐ to 5‐year‐olds used a speaker's foreign accent to infer that they currently live far away, but 6‐year‐olds did not. In Experiment 2 (N = 72), children at all ages used accent to infer where a speaker was born. In both experiments, race played some role in children's geographic inferences. Finally, in Experiment 3 (N = 48), 6‐year‐olds used language to infer both where a speaker was born and where they currently live. These findings reveal critical differences across development in the ways that speaker characteristics are used as inferential cues to a speaker's geographic location and history.
Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects
Authors: Park So Young , Park Se Eun , Jung Sang Won , Jin Hyun Seok , Park Ie Byung , Ahn Song Vogue , Lee Sihoon
Published: April 2017

Objective

The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome.

Design

This is a cross‐sectional study that included subjects in a medical health check‐up programme at a single institution.

Patients

The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 (FT4) and free T3 (FT3) levels within the institutional reference ranges.

Measurements

Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high‐density lipoprotein cholesterol, insulin and glucose were measured.

Results

There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women.

Conclusions

Thyrotropin levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH.
A prospective study on fetal posterior cranial fossa assessment for early detection of open spina bifida at 11–13 weeks
Authors: Kose Semir , Altunyurt Sabahattin , Keskinoglu Pembe
Published: April 2017

The objective of this study was to test three measurements: brain stem (BS), intracranial translucency (IT) and brain stem to occipital bone distance (BSOB), as well as one landmark: cisterna magna (CM) visibility, for early diagnosis of open spina bifida (OSB) in a low risk population. A prospective observational study was undertaken in a university hospital. A sample of 1479 women consented to participate between 20 September 2013 and 30 June 2015. Measurements were performed from the mid‐sagittal view, as is routinely used for nuchal thickness assessment. CM visibility was assessed qualitatively as the third anechoic band in the posterior cranial fossa (PCF). All pregnancies were screened with a combination of maternal serum alpha‐fetoprotein and second trimester anomaly scan and followed until delivery. Predictive values were calculated for each marker. We were able to diagnose two OSB cases and highly suspect one Dandy‐Walker malformation case at the first trimester scan by the observation of PCF. PCF characteristics of OSB cases were increased BS diameter, increased BS‐BSOB ratio and non‐visualization of the CM. All the markers demonstrated high sensitivity and specificity but CM visibility reached the highest positive predictive value. Due to relatively high false positive rates, PCF measurements could not reach a satisfactory performance to validate their clinical use as a single marker. CM visibility has the advantage of being a qualitative marker and reduces the need for sophisticated and time‐consuming measurements. Intracranial translucency and BS‐BSOB ratio measurements should be used when the CM visibility is absent or in doubt.
Survey on awareness of folic acid recognition and intake by female students
Authors: Matsuo Takuya , Kagohashi Yukiko , Senga Yasuko , Fukuda Hiromi , Shinozaki Keiko , Takemori Kumiko , Otani Hiroki , Kondo Atsuo
Published: April 2017

To reduce the risk of neural tube defects, studies have been conducted on female students of medical services, nutritional science, and nursery education that investigated the awareness of folic acid by using questionnaires. Many investigators have suggested the need to provide detailed information about the awareness of folic acid and knowledge about folic acid intake and neural tube defect risk reduction. The dietary habits of female students showed a positive correlation with their estimated folic acid intake, suggesting that improvements in dietary habits are associated with the consumption of folic acid. The importance of folic acid intake must be more aggressively promoted among female students. Thus, many learning opportunities should be provided for such students to help increase their folic acid intake.
Study of the Huntington's disease IT‐15 gene in different ethnic groups in Ecuador
Authors: Paz‐y‐Miño C. , Salazar‐Ruales C. , García‐Cárdenas J.M. , Cabrera‐Andrade A. , López‐Cortés A. , Pavón‐Realpe V.H. , Eras E. , Rodriguez P C , Domínguez Enríquez J.P. , Cusco Cuzco C.D. , Navarrete Socasi D.C. , Leone P.E.
Published: April 2017

This study aims to establish the current state of the IT‐15 (HTT) gene in different Ecuadorian ethnic groups and patients by determining CAG triplet repeats, compared with the ethnicity of individuals. A total of 412 individuals were studied using nested polymerase chain reaction and Sanger sequencing: 75 individuals were indigenous (Kichwas), 211 mestizos, and 65 Afro‐Ecuadorians. We included 31 patients who were clinically diagnosed with Huntington's disease (HD) and relatives of the affected patients (n = 30). Moreover, we correlated the presence of HD in Ecuadorian patients with 46 genetic ancestry‐informative insertion‐deletion polymorphic markers. We found that 77.20% had <28 CAG repetitions, 18.80% had mutable alleles, 2.27% had incomplete penetrance, and 1.70% reflected >39 repetitions. The average of CAG repetitions was 24 ± 3 for indigenous people; 28 ± 2 for mestizos; and 24 ± 3.2 repetitions for the Afro‐Ecuadorians. The ancestral component showed that the main ancestry corresponded to Native Americans (0.873) and European ascendants (0.145), Africans were less represented in the evaluated population (0.018). There was a significant difference between the number of CAG repeats in mestizos and indigenous people (P < .01), suggesting that the Ecuadorian mestizo population has a risk factor for the gene mutation.
Managerial control divergence and analysts’ information precision
Authors: Park KoEun , Tinaikar Surjit , Shin Yong‐Chul
Published: April 2017

Research Question/Issue

This study addresses how financial analysts’ information environment varies with the extent to which insiders’ voting rights diverge from their cash flow rights (i.e., control divergence) in the firm.

Research Findings/Insights

This study finds evidence that both analysts’ public and private information precisions are decreasing with insiders’ control divergence for a sample of US dual class share firms. Dual class share firms feature ownership structures that allow us to measure the control divergence between insiders’ voting rights and their cash flow rights. Furthermore, we document that these effects are more pronounced for firms with lower firm‐level uncertainty and for periods prior to the introduction of the SOX Act. Our results are robust to omitted variables, endogenous ownership, and any selection biases associated with dual class equity.

Theoretical/Academic Implications

Analysts’ skill and ability to formulate accurate forecasts are influenced by the quality of their information environment. We provide insights on how ownership mechanisms such as control divergence impact this ability by affecting their information environment. By using empirical proxies that precisely measure analysts’ information environment, we are able to better capture the adverse impact of control divergence on the public and private information that analysts convey in their forecasts.

Practitioner/Policy Implications

Policy makers are often concerned about issues that can constrain information processing by intermediaries such as analysts. Control divergence mechanisms can negatively impact analysts’ information processing by affecting their information environment and consequently their ability to effectively forecast earnings and stock prices. These have larger implications for social welfare and optimal capital allocation in the economy. Policy makers may therefore need to evolve better regulatory norms to negate some of the pernicious consequences of such ownership structures on information intermediation.
Sexualverhalten, STIs und HIV‐Übertragungsrisiken bei HIV‐positiven MSM – Ansätze für die ärztliche Präventionsarbeit
Authors: Esser Stefan , Krotzek Judith , Dirks Henrike , Scherbaum Norbert , Schadendorf Dirk
Published: April 2017

Hintergrund

Steigende Inzidenzen von HIV‐Infektionen und STIs (sexually transmitted infections) bei MSM (men having sex with men) seit 2001 in Deutschland erfordern neue Ansätze in der ärztlichen Präventionsarbeit. Diese Studie befasst sich mit geeigneten Parametern für gezielte ärztliche Angebote an HIV‐positive MSM mit hohem Risiko für die Übertragung von HIV und STIs.

Methodik und Patienten

In einem zweijährigen Beobachtungszeitraum wurden 233 HIV‐positive MSM in der HIV‐Ambulanz des Universitätsklinikums Essen zu ihrem Sexualverhalten, Suchtmittelkonsum und psychischem Befinden im vorhergehenden Jahr systematisch befragt. Die dokumentierten Labordaten und klinische Verläufe wurden von der Erstdiagnose der HIV‐Infektion bis zum Januar 2014 ausgewertet.

Ergebnisse

Drogengebrauch, Promiskuität, jüngeres Lebensalter und bekannte STIs in der Vorgeschichte waren bei HIV‐positiven MSM mit häufigerem ungeschützten Geschlechtsverkehr und einer höheren STI‐Inzidenz assoziiert. Zusätzliche HIV‐spezifische Parameter für ein erhöhtes HIV‐Transmissionsrisiko waren neben einer nachweisbaren HIViruslast unbehandelte HIV‐Infektionen, Therapieadhärenzprobleme, Wechsel der antiretroviralen Therapie in den letzten zwölf Monaten, bekannte HIV‐Multiresistenz und ein höherer CD4‐Zell‐Nadir. Obwohl die HIViruslast in der Routineversorgung quartalsweise bestimmt und anschließend vom Arzt mitgeteilt wird, schätzten nur 60 % der HIV‐positiven MSM ihr HIV‐Transmissionsrisiko korrekt ein.

Schlussfolgerungen

Aus Routineuntersuchungen ergeben sich bei HIV‐positiven MSM Profile, die auf ein Sexualverhalten mit hohem Risiko für die Übertragung von HIV und STIs hinweisen und Ansätze für die ärztliche Präventionsarbeit bieten.
Endoscopic drainage of pancreatic fluid collections: Long‐term outcomes in children
Authors: Nabi Zaheer , Lakhtakia Sundeep , Basha Jahangeer , Chavan Radhika , Gupta Rajesh , Ramchandani Mohan , Kalapala Rakesh , Pal Partha , Darisetty Santosh , Rao Guduru Venkat , Nageshwar Reddy D.
Published: April 2017

Background and Aim

Endoscopic drainage of pancreatic fluid collections (PFC) is the standard of care in adult patients. The literature is limited in children. In the present study, we aim to evaluate the safety and long‐term efficacy of endoscopic ultrasound (EUS)‐guided drainage of PFC in children.

Methods

Data of all children (<18 years) with PFC who underwent EUS‐guided drainage with plastic stents were analyzed retrospectively for technical feasibility, clinical efficacy and adverse events (AE).

Results

Thirty children (boys 22, girls 8) with PFC underwent EUS drainage (January 2013 to June 2016). Mean age of children was 13.07 ± 3.41 years (5–17 years). Majority of children had idiopathic pancreatitis (23), followed by trauma‐related (6) and gallstone‐related pancreatitis (1). Of 30 PFC, 13 (43.3%) and 17 (56.7%) were classified as pseudocyst and walled‐off necrosis, respectively. Median size of PFC was 95 mm (61–175). EUS drainage was successfully completed in 29 children (technical success 96.7%). Clinical success was achieved in 28/30 (93.3%) children. AE included perforation (2), major bleed (1), minor bleed (2), stent migration (4) and readmission as a result of hematemesis (1). Imaging revealed disconnected pancreatic duct in nine, ductal leak in two and stricture in one child. Cystogastric stents were left in situ in children with disconnected duct. At median follow up of 829 days (150–1230), two recurrences of PFC were noticed.

Conclusions

EUS‐guided drainage using plastic stents is safe and effective in children with PFC. Cystogastric plastic stents can be left safely long term. However, more studies with larger sample sizes are required.
Evidence for increasing physical activity in children with physical disabilities: a systematic review
Authors: Bloemen Manon , Van Wely Leontien , Mollema Jurgen , Dallmeijer Annet , de Groot Janke
Published: April 2017

Aim

To summarize the best evidence of interventions for increasing physical activity in children with physical disabilities.

Method

A systematic review was conducted using an electronic search executed in Academic Search Elite, Academic Search Premier, CINAHL, Embase, MEDLINE, PEDro, PsychINFO, and SPORTDiscus up to February 2016. The selection of articles was performed independently by two researchers according to predetermined eligibility criteria. Data extraction, methodological quality, and levels of evidence were independently assessed by two researchers using a data‐collection form from the Cochrane Collaboration and according to the guidelines of the American Academy for Cerebral Palsy and Developmental Medicine.

Results

Seven studies were included. Five randomized controlled trials ranged from strong level I to weak level II studies, and two pre–post design studies were classified as level IV. There is level I evidence for no effect of physical training on objectively measured physical activity, conflicting level II evidence for interventions with a behavioural component on the increase of objectively measured physical activity directly after the intervention, and level II evidence for no effect during follow‐up. Results are limited to children with cerebral palsy as no other diagnoses were included.

Interpretation

Increasing physical activity in children with physical disabilities is very complex and demands further development and research.
The Trunk Control Measurement Scale: reliability and discriminative validity in children and young people with neuromotor disorders
Authors: Marsico Petra , Mitteregger Elena , Balzer Julia , van Hedel Hubertus J A
Published: April 2017

Aim

This study investigated the intra‐ and interrater reliability of the Trunk Control Measurement Scale (TCMS) German version, with its subscores, in children with neuromotor disorders. Further, the discriminative validity of the TCMS was assessed by comparing the TCMS scores with the Functional Independence Measure for children.

Method

Bland–Altman analyses and intraclass correlation coefficients were applied to investigate reliability. The discriminative ability of the TCMS was evaluated with receiver operating characteristics.

Results

Ninety children (mean age 11y 5mo; range 5y–18y 11mo) participated for the reliability, and 50 for the discriminative validity study. The reliability proved to be excellent (intrarater: bias=0.57 points, 95% confidence interval [CI] −3.71 to 4.85; interrater: bias=−0.31 points, 95% CI −5.77 to 5.10). A change in the TCMS total score of six points (10%) can be considered a true change. The TCMS subscores appeared to be clinically relevant because children with less than around 80% of the static balance score, less than 55% of the dynamic reaching score, or less than around 35% of the selective movement control score needed support for daily life activities.

Interpretation

The TCMS is a reliable and clinically relevant assessment for children aged 5 years and older with different neurological impairments.
Associations of mortality and cardiovascular disease risks with diabetes and albuminuria in urban Indigenous Australians: the DRUID follow‐up study
Authors: Barr E. L. M. , Cunningham J. , Tatipata S. , Dunbar T. , Kangaharan N. , Guthridge S. , Li S. Q. , Condon J. R. , Shaw J. E. , O'Dea K. , Maple‐Brown L. J.
Published: April 2017

Aim

To assess the relationships of diabetes and albuminuria with all‐cause mortality and cardiovascular disease outcomes in a population without prior cardiovascular disease using data from the Darwin Region Urban Indigenous Diabetes (DRUID) study.

Methods

We conducted a prospective cohort study of 706 participants (aged 15–81 years, 68% women) without prior cardiovascular disease who underwent a 75‐g oral glucose tolerance test. Deaths and fatal or non‐fatal cardiovascular disease were determined over 7 years, and hazard ratios with 95% CIs and population attributable risks were estimated for baseline glycaemia and albuminuria.

Results

Compared with normoglycaemia and after adjustment for age, sex, hypertension, dyslipidaemia and smoking, known diabetes was associated with an adjusted hazard ratio of 4.8 (95% CI 1.5–14.7) for all‐cause mortality and 5.6 (95% CI 2.1–15.2) for cardiovascular disease. Compared with normoalbuminuria, the respective adjusted risks for macroalbuminuria were 10.9 (95% CI 3.7–32.1) and 3.9 (95% CI 1.4–10.8). The Adjusted all‐cause mortality and cardiovascular disease estimated population attributable risks for diabetes were 27% and 32%, and for albuminuria they were 32% and 21%, respectively.

Conclusions

In our study population, the burden of mortality and cardiovascular disease was largely driven by diabetes and albuminuria. This finding on the influence of diabetes and albuminuria is consistent with reports in other high‐risk Indigenous populations and should be better reflected in risk scores and intervention programmes.
Long‐term prognostic value of peak exercise echocardiogram in patients hospitalized with acute chest pain
Authors: Merchan Ortega German , Bonaque Gonzalez Juan Carlos , Sanchez Espino Alejandro Dionisio , Aguado Martin Maria Jose , Navarro Garcia Francisco , Ruiz Lopez Fuensanta , Ramos Perales Francisco , Zamorano Gomez Jose Luis
Published: April 2017

Introduction

Peak exercise echocardiogram (EEcho) has shown reasonable sensitivity and specificity in detecting significant coronary artery disease (CAD). The objective was to evaluate the prognostic value of EEcho in patients hospitalized for acute chest pain (CP) and its additional prognostic information regarding exercise electrocardiogram test (EECG).

Methods

Prospective observational study performed between May 2011 and September 2013, including 250 patients consecutively admitted for acute CP with normal cardiac biomarkers and nondiagnostic electrocardiogram. All patients were prospectively followed for 1 year, and major adverse cardiovascular events (MACE) were recorded: cardiac death, nonfatal myocardial infarction (MI), or angina with coronary revascularization.

Results

EEcho was positive in 16%. Patients with positive EEcho had a higher incidence of hypertension and higher TIMI risk score, showing significant CAD in 66%. We observed contradictory results (EECG‐EEcho) in 20%. Patients with positive EEcho and negative EECG had significant CAD in the 66%, and patients undergoing coronary angiography with negative EEcho and positive EECG did not show significant coronary artery disease. Only positive EEcho (P<.001, HR 0.169; 95% CI, 0.088–0.250) and atrial fibrillation (P<.025, HR 0.125; 95% CI, 0.016–0.233) were independently associated with MACE during follow‐up. In patients with negative EEcho, the presence of MACE was 2%.

Conclusions

EEcho in patients hospitalized for acute chest pain presents good ability to diagnose acute coronary syndrome, while providing additional information when combined with an EECG in up to 20% of cases. Moreover, a negative EEcho in this cohort seems to provide prognostic information beyond the acute event to predict long‐term MACE.
Comparative effects of the restriction method in two large observational studies of body mass index and mortality among adults
Authors: Flegal Katherine M. , Graubard Barry I. , Yi Sang‐Wook
Published: April 2017

Background

A method applied in some large studies of weight and mortality is to begin with a well‐defined analytic cohort and use successive restrictions to control for methodologic bias and arrive at final analytic results.

Materials and methods

Two observational studies of body mass index and mortality allow a comparative assessment of these restrictions in very large data sets. One was a meta‐analysis of individual participant data with a sample size of 8 million. The second was a study of a South Korean cohort with a sample size of 12 million. Both presented results for participants without pre‐existing disease before and after restricting the sample to never‐smokers and deleting the first 5 years of follow‐up.

Results

Initial results from both studies were generally similar, with hazard ratios (HRs) below 1 for overweight and above 1 for underweight and obesity. The meta‐analysis showed higher HRs for overweight and obesity after the restrictions, including a change in the direction of the HR for overweight from 0·99 (95% CI: 0·98–1·01) to 1·11 (95% CI: 1·10, 1·11). The South Korean data showed little effect of the restrictions and the HR for overweight changed from 0·85 (95% CI: 0·84–0·86) to 0·91 (95% CI: 0·90, 0·91). The summary effect size for overweight was 0·90 (95% CI: 0·89–0·91) before restrictions and 1·02 (95% CI: 1·02, 1·03) after restrictions.

Conclusions

The effect of the restrictions is not consistent across studies, weakening the argument that analyses without such restrictions lack validity.
Phylloplane bacteria increase the negative impact of food limitation on insect fitness
Authors: OLSON GRANT L. , MYERS JUDITH H. , HEMERIK LIA , CORY JENNY S.
Published: April 2017

1. When populations of herbivorous insects increase in density, they can alter the quantity or quality of their food. The impacts of diet‐related stressors on insect fitness have been investigated singly, but not simultaneously.

2. Foliage quantity and quality of red alder, Alnus rubra, were manipulated together with the presence of non‐entomopathogenic phylloplane bacteria to investigate their impacts, singly and in combination, on survival, pupal mass, growth rate, fecundity and egg quality of a cyclic forest insect, the western tent caterpillar, Malacosoma californicum pluviale.

3. Food limitation (half food) had strong negative impacts on all life‐history traits. When the larvae were fed continuously, however, neither ingesting phylloplane bacteria nor eating leaves from damaged branches (induced foliage) affected survival. In the half‐food treatment, ingesting bacteria further increased mortality, while feeding on induced foliage improved survival.

4. Growth rate and pupal mass of both sexes were reduced for larvae with food limitation compared with continuously fed insects and this was exacerbated when the larvae also ate bacteria‐treated leaves. A combination of bacteria and induced foliage also reduced larval growth rate by 5% in the full‐food treatment.

5. Fecundity (eggs per egg mass) was 2.7 times greater in full‐food than in food‐limited treatments but neither phylloplane bacteria nor plant induction had an effect. Insects fed induced foliage produced smaller eggs. Overall, there was no evidence of a three‐way interaction between the three stressors, although there were negative synergistic effects, primarily between food limitation and the ingestion of phylloplane bacteria.
Elevationally biased avian predation as a contributor to the spatial distribution of geometrid moth outbreaks in sub‐arctic mountain birch forest
Authors: PEPI ADAM A. , VINDSTAD OLE PETTER L. , EK MALIN , JEPSEN JANE U.
Published: April 2017

1. Population dynamics and interactions that vary over a species' range are of particular importance in the context of latitudinal clines in biological diversity. Winter moth (Operophtera brumata) and autumnal moth (Epirrita autumnata) are two species of eruptive geometrids that vary widely in outbreak tendency over their range, which generally increases from south to north and with elevation.

2. The predation pressure on geometrid larvae and pupae over an elevational gradient was tested. The effects of background larval density and bird occupancy of monitoring nest boxes on predation rates were also tested. Predation on larvae was tested through exclusion treatments at 20 replicate stations over four elevations at one site, while pupae were set out to measure predation at two elevations at three sites.

3. Larval densities were reduced by bird predation at three lower elevations, but not at the highest elevation, and predation rates were 1.9 times higher at the lowest elevation than at the highest elevation. The rate of predation on larvae was not related to background larval density or nest box occupancy, although there were more eggs and chicks at the lowest elevation. There were no consistent differences in predation on pupae by elevation.

4. These results suggest that elevational variation in avian predation pressure on larvae may help to drive elevational differences in outbreak tendency, and that birds may play a more important role in geometrid population dynamics than the focus on invertebrate and soil predators of previous work would suggest.
Medial temporal lobe atrophy as a predictor of poor cognitive outcomes in general paresis
Authors: Chen Ben , Shi Haishan , Hou Le , Zhong Xiaomei , Wang Yanhua , Wu Zhangying , Peng Qi , Zheng Dong , Zhang Yuefen , Tan Yan , Fang Ziyan , Chen Xinru , Luo Xinni , Liu Sha , Yuping Ning
Published: April 2017

Background

The effect of penicillin therapy on clinical outcomes vary among patients with general paresis (GP). We sought to explore biomarkers that might serve as predictors of clinical outcomes in GP and identify patients requiring early intervention.

Methods

Thirty‐five inpatients with GP were recruited. Each GP patient underwent comprehensive neuropsychological, neuroimaging and laboratory assessments before receiving penicillin therapy, and returned for follow‐up evaluations after 6 months. The visual rating of medial temporal lobe atrophy (MTA) and the Fazekas scale was used to analyze the neuroimaging abnormalities.

Results

MTA scores were correlated with the pre‐treatment cognitive scores and change in Mini Mental State Examination scores. GP patients with a Clinical Dementia Rating Scale (CDR) ≤1 or MTA scores ≤2 achieved significant improvement in neuropsychological test scores, as compared with patients with CDR >1 or MTA scores >2. Fazekas scale scores correlated with the pre‐treatment attention scores. Significant improvements in cognitive test scores were observed in GP patients with normalization of serum rapid plasma regain (RPR) titers, but not those without normalization of RPR titers.

Conclusions

Severe MTA may serve as a predictor of poor cognitive outcome and an indicator of severe cognitive impairment in GP patients. Thus, early interventions for improving cognitive function may be considered for GP patients with severe MTA. White matter hyperintensities may associated with attention impairment. Serum RPR titer may serve as a sensitive indicator of therapeutic effect in GP.
A core‐transient framework for trait‐based community ecology: an example from a tropical tree seedling community
Authors: Umaña Maria Natalia , Zhang Caicai , Cao Min , Lin Luxiang , Swenson Nathan G.
Published: April 2017

Trait‐based studies in community ecology have generally focused on the community as a unit where all species occur due to stochasticity, determinism or some mixture of the two. However, the processes governing population dynamics may vary greatly among species. We propose a core‐transient framework for trait‐based community studies where a core group of species has a strong link to the local environment while transient species have weaker responses to the environment. Consistent with the expectations of the framework, we found that common species exhibit clear linkages between performance and their environment and traits while rare species tend to have weaker or non‐significant relationships. Ultimately, trait‐based ecology should move beyond applying a set of processes to a community as a whole and towards quantifying inter‐specific variation in the drivers of population dynamics that ultimately scale up to determine community structure.
Remission in epilepsy: How long is enough?
Authors: Sillanpää Matti , Schmidt Dieter , Saarinen Maiju M. , Shinnar Shlomo
Published: April 2017

Objective

The International League Against Epilepsy (ILAE) has proposed to expand the definition of remission to 10 years seizure‐free with the last 5 years off antiepileptic drugs (AEDs). We examined if a 10‐year remission is needed to predict the lowest recurrence risk.

Methods

The population‐based study cohort consisted of 148 patients with new‐onset childhood epilepsy living in the catchment area of Turku University Hospital. They were prospectively followed for 44 years (median). Patients in first remission were prospectively followed for the duration of remission or possible relapse at 2 years in remission with the last year without antiepileptic drugs (AEDs), at 5 years in remission with the last 2 years without AEDs, and at 10 years with the last 5 years without AEDs. For comparison of the proportions of relapsed patients within each remission category exact Clopper Pearson 95% confidence intervals were used.

Results

The magnitude of the relapse rate estimates off AEDs did not significantly improve when remission increased from 2 years (2YR) to 5 years (5YR) and further to 10 years (10YR). However, 10YR was a more sensitive measure of no relapse than 2YR. Among patients with remission on or off AEDs, the ability to predict lower relapse rate increased markedly from 2 to 5 years, and again from 5 to 10 years. The risk of relapse was virtually the same estimated after 2YR off AEDs as after 10YR on or off AEDs, except for patients with generalized epilepsy whose 2YR off AEDs was a weaker predictor than 10YR on or off AEDs.

Significance

Given the modest differences in relapse rates between the 5 years seizure‐free with last 2 years off medications definition and the 10 years seizure‐free with last 5 years off medications, and the adverse impact of not being considered in remission, we propose that a return to the 5‐year definition may be warranted.
Contextualized behavior patterns for change reasoning in Ambient Assisted Living: A formal model
Authors: Lago Paula , Jiménez‐Guarín Claudia , Roncancio Claudia
Published: April 2017

Ambient Assisted Living, smart environments and technology used for elder care, increases independent living time and cuts long‐term care costs. An important requirement for these systems is detecting and informing about abnormal behavior in users' routines. Still, routines may change when certain context conditions hold, which does not mean these changes should concern caregivers. However, changes due to context conditions are not often considered in current proposals. In this paper, we formalize the main concepts related to activities in Ambient Assisted Living, and we introduce contextualized behavior patterns, a long‐term behavior model that considers variability due to context. We adopt a semantic similarity that allows to better detect behavior changes and to understand what makes an observation of daily living different from expected patterns. The results of the experience with three public data sets are promising.
Intergenerational Equity: Treatment of Infrastructure in New Zealand Local Government Financial Planning
Authors: Barnes Kevin , Lord Beverley
Published: April 2017

This paper examines how local government authorities plan and financially provide for infrastructure while considering the needs of current and future communities. In New Zealand the Local Government Act 2002 provides a mandate for local authority planning through the requirement to publish Long Term Council Community Plans (LTCCPs). Our content analysis of the LTCCPs, annual plans and annual reports of five New Zealand local authorities reveals that these local authorities make conscious decisions about infrastructure that reflect concern for matters of intergenerational equity. They do so despite problems in relation to valuation, depreciation, deferred maintenance and financing of infrastructure assets.
Folding of proteins with a flavodoxin‐like architecture
Authors: Houwman Joseline A. , van Mierlo Carlo P. M.
Published: April 2017

The flavodoxin‐like fold is a protein architecture that can be traced back to the universal ancestor of the three kingdoms of life. Many proteins share this α‐β parallel topology and hence it is highly relevant to illuminate how they fold. Here, we review experiments and simulations concerning the folding of flavodoxins and CheY‐like proteins, which share the flavodoxin‐like fold. These polypeptides tend to temporarily misfold during unassisted folding to their functionally active forms. This susceptibility to frustration is caused by the more rapid formation of an α‐helix compared to a β‐sheet, particularly when a parallel β‐sheet is involved. As a result, flavodoxin‐like proteins form intermediates that are off‐pathway to native protein and several of these species are molten globules (MGs). Experiments suggest that the off‐pathway species are of helical nature and that flavodoxin‐like proteins have a nonconserved transition state that determines the rate of productive folding. Folding of flavodoxin from Azotobacter vinelandii has been investigated extensively, enabling a schematic construction of its folding energy landscape. It is the only flavodoxin‐like protein of which cotranslational folding has been probed. New insights that emphasize differences between in vivo and in vitro folding energy landscapes are emerging: the ribosome modulates MG formation in nascent apoflavodoxin and forces this polypeptide toward the native state.
A Generalized Earnings‐Based Stock Valuation Model with Learning
Authors: Jacoby Gady , Paseka Alexander , Wang Yan
Published: April 2017

We present a stock valuation model in an incomplete‐information environment in which the unobservable mean of earnings growth rate (MEGR) is learned and price is updated continuously. We calibrate our model to a market portfolio to empirically evaluate its performance. Of the 8.84% total risk premium we estimate, the earnings growth premium is 4.57%, the short‐rate risk contributes 3.38%, and the learning‐induced risk premium on the unknown MEGR is 0.89% (a nontrivial 10% of the total risk premium). This result highlights the significant learning effect on valuation, implying an additional risk premium in an incomplete‐information environment.
Do Capital Structure Adjustments by Takeover Targets Influence Acquisition Gains?
Authors: Jandik Tomas , Lallemand Justin
Published: April 2017

We link debt issuances by target companies around takeover announcements to enhanced target bargaining power in negotiations with bidders over merger synergy gains in completed takeovers. Announcements of debt issuances by targets—especially new bank loans—are associated with more positive target equity returns relative to those made by nontargets, particularly for debt issuances immediately surrounding the takeover announcement. At least some of these gains to targets come at the expense of bidder shareholders, as bidder equity abnormal returns at target debt issuance are negative. We further show that targets issuing debt are primarily those with relatively low acquisition abnormal returns, consistent with initially poor target bargaining power. Subsequent debt issuances by targets increase the likelihood of positive adjustments to acquisition premiums offered by acquirers.