bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterosis from local drift load is likely insufficient to favor reversions to outcrossing
Authors: Harkness Alexander , Goldberg Emma E. , Brandvain Yaniv J
Published: March 2018

The evolutionary trajectory from cross-to self-fertilization is widely documented in nature, but results from several taxa also suggest that outcrossing may evolve in a formerly selfing population. Population genetic theory explains that selfing can evolve when its advantages overcome its immediate cost of inbreeding depression, but that this process will not run in reverse because a self-fertilizing population purges itself of inbreeding depression. That is, the primary short-term advantage of cross-fertilization over self-fertilization depends on the existence of deleterious alleles exposed upon inbreeding. Here, we explore whether outcrossing can evolve in selfing populations if allelic variation exists as divergence among populations. We consider two monomorphic populations of entirely self-fertilizing individuals, introduce a modifier allele that increases the rate of cross-fertilization, and investigate whether the heterosis among populations is sufficient for the modifier to invade and fix. We find that, despite an initial increase in the frequency of the outcrossing modifier, its fixation is possible only when populations harbor extremely large unique fixed genetic loads. These rare reversions to outcrossing become more likely as the load becomes more polygenic, or when the modifier appears on a rare background, such as by dispersal of an outcrossing genotype into a selfing population.
Recent upgrades of the neutron reflectometer D17 at ILL
Authors: Saerbeck Thomas , Cubitt Robert , Wildes Andrew , Manzin Giuliana , Andersen Ken H. , Gutfreund Philipp
Published: March 2018

The vertical sample-plane reflectometer D17 at the Institut Laue–Langevin in Grenoble, France, has undergone several major upgrades since its commissioning, which are summarized in this article. The three major improvements are (i) a new focusing guide, increasing the usable flux on the sample by a factor of 2.5; (ii) a new beam polarizer and new spin flippers, allowing for the use of polarized neutrons in time-of-flight mode; and (iii) a new detector with a particularly uniform response under homogeneous exposure, improved stability and state-of-the-art detector electronics. The combination of these factors has paved the road to new possibilities in fast kinetic measurements, magnetism and off-specular scattering. Examples and scientific references for the new capabilities are presented.
A novel multiobjective lognormal-beta differential evolution approach for the transformer design optimization
Authors: Tsili Marina , Amoiralis Eleftherios I. , Leite Jean Vianei , Moreno Sinvaldo R. , Coelho Leandro dos Santos
Published: March 2018

Purpose

Real-world applications in engineering and other fields usually involve simultaneous optimization of multiple objectives, which are generally non-commensurable and conflicting with each other. This paper aims to treat the transformer design optimization (TDO) as a multiobjective problem (MOP), to minimize the manufacturing cost and the total owing cost, taking into consideration design constraints.

Design/methodology/approach

To deal with this optimization problem, a new method is proposed that combines the unrestricted population-size evolutionary multiobjective optimization algorithm (UPS-EMOA) with differential evolution, also applying lognormal distribution for tuning the scale factor and the beta distribution to adjust the crossover rate (UPS-DELFBC). The proposed UPS-DELFBC is useful to maintain the adequate diversity in the population and avoid the premature convergence during the generational cycle. Numerical results using UPS-DELFBC applied to the transform design optimization of 160, 400 and 630 kVA are promising in terms of spacing and convergence criteria.

Findings

Numerical results using UPS-DELFBC applied to the transform design optimization of 160, 400 and 630 kVA are promising in terms of spacing and convergence criteria.

Originality/value

This paper develops a promising UPS-DELFBC approach to solve MOPs. The TDO problems for three different transformer specifications, with 160, 400 and 630 kVA, have been addressed in this paper. Optimization results show the potential and efficiency of the UPS-DELFBC to solve multiobjective TDO and to produce multiple Pareto solutions.
An improved binary bat flexible sampling algorithm for reliability-based design optimization of truss structures with discrete-continuous variables
Authors: Safaeian Hamzehkolaei Naser , Miri Mahmoud , Rashki Mohsen
Published: March 2018

Purpose

Reliability-based design optimizations (RBDOs) of engineering structures involve complex non-linear/non-differentiable performance functions, including both continuous and discrete variables. The gradient-based RBDO algorithms are less than satisfactory for these cases. The simulation-based approaches could also be computationally inefficient, especially when the double-loop strategy is used. This paper aims to present a pseudo-double loop flexible RBDO, which is efficient for solving problems, including both discrete/continuous variables.

Design/methodology/approach

The method is based on the hybrid improved binary bat algorithm (BBA) and weighed simulation method (WSM). According to this method, each BBA’s movement generates proper candidate solutions, and subsequently, WSM evaluates the reliability levels for design candidates to conduct swarm in a low-cost safe-region.

Findings

The accuracy of the proposed enhanced BBA and also the hybrid WSM-BBA are examined for ten benchmark deterministic optimizations and also four RBDO problems of truss structures, respectively. The solved examples reveal computational efficiency and superiority of the method to conventional RBDO approaches for solving complex problems including discrete variables.

Originality/value

Unlike other RBDO approaches, the proposed method is such organized that only one simulation run suffices during the optimization process. The flexibility future of the proposed RBDO framework enables a designer to present multi-level design solutions for different arrangements of the problem by using the results of the only one simulation for WSM, which is very helpful to decrease computational burden of the RBDO. In addition, a new suitable transfer function that enhanced convergence rate and search ability of the original BBA is introduced.
A multi-objective robust optimization approach for engineering design under interval uncertainty
Authors: Zhou Qi , Shao Xinyu , Jiang Ping , Xie Tingli , Hu Jiexiang , Shu Leshi , Cao Longchao , Gao Zhongmei
Published: March 2018

Purpose

Engineering system design and optimization problems are usually multi-objective and constrained and have uncertainties in the inputs. These uncertainties might significantly degrade the overall performance of engineering systems and change the feasibility of the obtained solutions. This paper aims to propose a multi-objective robust optimization approach based on Kriging metamodel (K-MORO) to obtain the robust Pareto set under the interval uncertainty.

Design/methodology/approach

In K-MORO, the nested optimization structure is reduced into a single loop optimization structure to ease the computational burden. Considering the interpolation uncertainty from the Kriging metamodel may affect the robustness of the Pareto optima, an objective switching and sequential updating strategy is introduced in K-MORO to determine (1) whether the robust analysis or the Kriging metamodel should be used to evaluate the robustness of design alternatives, and (2) which design alternatives are selected to improve the prediction accuracy of the Kriging metamodel during the robust optimization process.

Findings

Five numerical and engineering cases are used to demonstrate the applicability of the proposed approach. The results illustrate that K-MORO is able to obtain robust Pareto frontier, while significantly reducing computational cost.

Practical implications

The proposed approach exhibits great capability for practical engineering design optimization problems that are multi-objective and constrained and have uncertainties.

Originality/value

A K-MORO approach is proposed, which can obtain the robust Pareto set under the interval uncertainty and ease the computational burden of the robust optimization process.
Uncertainties evaluation of coordinate transformation parameters in the large-scale measurement for aircraft assembly
Authors: Deng Zhengping , Li Shuanggao , Huang Xiang
Published: March 2018

Purpose

For the measurement of large-scale components in aircraft assembly, the evaluation of coordinate transformation parameters between the coordinate frames of individual measurement systems to the assembly frame is an essential task, which is usually completed by registration of the enhanced reference system (ERS) points. This paper aims to propose an analytical method to evaluate the uncertainties of transformation parameters considering both the measurement error and the deployment error of ERS points.

Design/methodology/approach

For each measuring station, the measured coordinates of ERS points are first roughly registered to the assembly coordinate system using the singular value decomposition method. Then, a linear transformation model considering the measurement error and deployment error of ERS points is developed, and the analytical solution of transformation parameters’ uncertainties is derived. Moreover, the covariance matrix of each ERS points in the transformation evaluation is calculated based on a new uncertainty ellipsoid model and variance-covariance propagation law.

Findings

For the transformation of both single and multiple measuring stations, the derived uncertainties of transformation parameters by the proposed analytical method are identical to that obtained by the state-of-the-art iterative method, but the solution process is simpler, and the computation expenses are much less.

Originality/value

The proposed uncertainty evaluation method would be useful for in-site measurement and optimization of the configuration of ERS points in the design of fixture and large assembly field. It could also be applied to other registration applications with errors on both sides of registration points.
Effect of the vapour concentration decrease on the solder joints temperature in a vacuum vapour phase soldering system
Authors: Illés Balázs , Skwarek Agata , Géczy Attila , Jakab László , Bušek David , Dušek Karel
Published: March 2018

Purpose

The vacuum vapour phase soldering method was investigated by numerical simulations. The purpose of this study was to examine the temperature changes of the solder joints during the vapour suctioning process. A low pressure is used to enhance the outgassing of the trapped gas within the solder joints, which otherwise could form voids. However, the system loses heat near the suction pipe during the suctioning process, and it can result in preliminary solidification of the solder joints before the gas could escape.

Design/methodology/approach

A three-dimensional numerical flow model based on the Reynolds averaged Navier–Stokes equations with the standard k-e turbulence method was developed. The effect of the vapour suctioning on the convective heat transfer mechanism was described by the model. Temperature change of the solder joints was studied at the mostly used substrate and component combinations, as well as at different system settings.

Findings

In the function of the substrate thickness and the component size, the solder joints can lose large amount of heat during the void reduction process, which leads to preliminary solidification before the entrapped gas voids could be removed.

Research limitations/implications

The results provide setting information of vacuum vapour phase technology for appropriate and optimal applications.

Originality/value

The relationship between low pressure generation and convective heat transfer mechanism during vacuum vapour phase soldering has not been studied yet. The possible negative effects of the vapour suctioning process on the solder joint temperature are unknown.
Public Sector Discount Rates: A Comparison of Alternative Approaches
Authors: Creedy John , Passi Hemant
Published: March 2018

This article describes alternative approaches to the public sector discount rate and explains the assumptions involved. Time‐varying rates are also considered. The social opportunity cost of capital (SOC) is the rate of return that could be earned on the ‘next best alternative’. The social rate of time preference (SRTP) is the rate of return required in order to divert resources to a public investment. Only in an ‘ideal’ market are these two rates brought into alignment in equilibrium. Essentially the discount rate reflects how the government values the future when making decisions on behalf of society: value judgements are unavoidable.
Choosing the Social Discount Rate for Australia
Authors: Abelson Peter , Dalton Tim
Published: March 2018

This article argues that in cost–benefit analysis government should adopt the opportunity cost of capital as represented by the alternative project rate of return as the social discount rate rather than the private or social time discount rate or a weighted cost of funds rate that reflects estimated proportions of investment and consumption foregone. The appropriate metric for the alternative project rate of return is average market return allowing for non‐diversifiable risk but not for diversifiable project risk. The article concludes that the appropriate social discount rate for Australia, for all sectors and states and territories, is approximately 6.5 per cent.
Macroeconomic Policies in a Low Interest Rate Environment: Back to Keynes?
Authors: Castelnuovo Efrem , Lim Guay , Pellegrino Giovanni
Published: March 2018

This article discusses macroeconomic policies in a low interest rate environment, the central theme of the 2017 edition of the Melbourne Institute Macroeconomic Policy Meeting. After reviewing possible causes of the decline in interest rates observed since the 1990s, we present and discuss some of the challenges that monetary and fiscal policy face in a ‘new normal’ environment characterised by a real natural interest rate close to zero. Proposals by leading researchers on how to operate in such an environment are presented and discussed. We conclude by outlining some research questions that are highly relevant from a policy perspective.
Fatal Chest Injury Caused by Windblown Beach Umbrella
Authors: Harris Allyse B. , Gunther Wendy M. , Fantaskey Amy P. , Weinstein Lawrence B.
Published: March 2018

We present the case of a windblown beach umbrella inflicting fatal penetrating blunt force to the chest of a 55‐year‐old female beachgoer. A postmortem examination and detailed case history review were performed which revealed left ventricular trauma, determined to be the cause of death. Using recorded wind speeds from the date of the incident and the weight of the umbrella, we were able to calculate the pressure with which the umbrella struck the victim to be 16,000 PSI. Witness reports, medical records, scene details, and examination of a rental beach umbrella allowed the forensic pathologist to conclude that the object causing this woman's death was a windblown beach umbrella.
Development of Latent Fingermarks on Nonporous and Semiporous Substrates Using Photoluminescent Eu(Phen)2 Complex Intercalated Clay Hybrids with Enhanced Adhesion
Authors: Kim Aran , Ryu Seung‐Jin , Lee Jihye , Jung Hyun
Published: March 2018

In forensic science, developing latent fingermarks using powders is a critical, general method to identify individuals. Photoluminescent Eu(Phen)2 complex intercalated clay hybrids have been used to improve the visualization of fingermarks on nonporous (glass and polymer film) and semiporous (euro and dollar banknotes) substrates. An ion exchange reaction has been successfully used to intercalate Eu(Phen)2 complex ions into the interlayer spacing of two different Na+‐clays, Na+‐montmorillonite and Na+‐hectorite, with different primary particle sizes. To change the surface properties of the obtained hybrid to be more lipophilic, the hydroxyl groups at the edge of the hectorite hybrid were modified with hexadecyltrimethoxysilane via silylation. We investigated the correlation of the size and surface properties of the hybrids with their adhesion to fingermark residues. Fingermarks were successfully visualized using hybrids under UV illumination. In particular, ridge details on semiporous substrates can be more clearly seen using hybrids with smaller primary particles and greater lipophilicity.
The Effects of Storage and Additives on Postmortem HbA1c Measurements
Authors: Fournier Jeffrey E. , Northrup Victoria , Canales Donaldo D. , Moore Christa , Shea Jennifer L.
Published: March 2018

HbA1c is used in forensic toxicology to identify undiagnosed diabetes mellitus (DM) and those with poor glycemic control prior to death. HbA1c is typically measured in whole blood collected in tubes containing ethylenediaminetetraacetic acid (EDTA). The effect of other additives, including sodium fluoride (NaF), is unclear. Furthermore, the assessment of short‐ and long‐term stability of HbA1c has produced conflicting results. In this study, we collected paired postmortem blood samples in EDTA and NaF tubes (n = 142) to assess their comparability for HbA1c measurement. Stability was assessed by measuring HbA1c at baseline, 2, 3, and 4 weeks postcollection (stored at 4°C) and at 2, 4, 6, and 12 months postcollection (stored at −20°C). We found no significant difference in HbA1c between the two preservatives at any of the time points indicating NaF is a suitable preservative for HbA1c measurement. We also determined that DM status, postmortem interval, and decomposition had no effect on stability.
DOES IT WORK FOR YOU?
Authors: PARKE MICHAEL
Published: March 2018

What makes us happy in the workplace is different for all of us, Michael Parke argues – so the trick is to enjoy the process of finding out what's right for you
READ YOURSELF HAPPY
Authors: CABLE DAN
Published: March 2018

Dan Cable's top ten books to help you get more out of life
MEASURING HAPPINESS
Authors: GWYTHER MATTHEW
Published: March 2018

Wealth and wellbeing: does being better off make us more cheerful?
CLIMATE: CHANGE
Authors: SCOTT ANDREW
Published: March 2018

New technologies will disrupt our lives – but they always have and humanity has always coped, argues Andrew Scott
MAKING BIG DATA DELIVER
Authors: SAVVA NICOS , STRAUB GABRIEL
Published: March 2018

Investment in data science can reap great rewards – but if it doesn't yield what you want, ask where you're going wrong, say Nicos Savva and Gabriel Straub
ACCOUNTING FOR TAKEOVERS
Authors: ALESZCZYK ALEKSANDER A , DE GEORGE EMMANUEL T , ERTAN AYTEKIN , VASVARI FLORIN
Published: March 2018

When a company changes hands, its finances appear to undergo an instant and dramatic change. Why? Aleksander A Aleszczyk, Emmanuel T De George, Aytekin Ertan and Florin Vasvari believe they have the answer
Clinical correlates of augmentation/combination treatment strategies in major depressive disorder
Authors: Dold M. , Bartova L. , Mendlewicz J. , Souery D. , Serretti A. , Porcelli S. , Zohar J. , Montgomery S. , Kasper S.
Published: March 2018

Objective

This multicenter, multinational, cross‐sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD).

Method

Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses.

Results

60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in‐patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive‐compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses.

Conclusion

Our findings suggest a clear association between augmentation/combination strategies and treatment‐resistant/difficult‐to‐treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities.
Combining biological and socio‐political criteria to set spatial conservation priorities for the endangered African wild dog
Authors: Kuiper T. , Dickman A. J. , Hinks A. E. , Sillero‐Zubiri C. , Macdonald E. A. , Macdonald D. W.
Published: March 2018

The effectiveness of biodiversity conservation projects is influenced by socio‐political context, a reality overlooked by traditional prioritization schemes that use only measures of biological value and threat when deciding where to invest limited conservation resources. We combined ecological and socio‐political criteria to illuminate options for prioritizing investment in African wild dog Lycaon pictus conservation among countries and subpopulations. Countries and subpopulations were assigned scores for conservation priority (based on their wild dog populations) and conservation likelihood (based on their governance quality and other indicators of the likelihood of effective conservation action for wild dogs). Seven of the 19 wild dog countries scored above the median value for both priority and likelihood and supported 74% of the total wild dog population. Investment in these ‘higher priority, higher likelihood’ countries may offer the greatest returns on conservation investment. The intention of this study is not, however, to be prescriptive, nor to suggest abandoning disadvantaged countries, but to provide a tool for understanding and managing trade‐offs between where conservation is most needed for wild dogs and where it is most feasible. The prioritization framework presented in this paper may easily and profitably be applied to other taxa, extending the scope of our results.
Energy‐milk price transmission at the product brand level
Authors: Li Xun , Lopez Rigoberto , Yang Shuai
Published: March 2018

This article estimates the pass‐through rates between diesel fuel and retail milk prices at the product brand level. Using a random coefficient logit demand model and taking the direct and indirect impacts of energy prices, this research identifies changes in pass‐through rates before and after the great recession in 2008. Empirical results show that diesel prices significantly impacted the retail prices of milk products and are an important determinant of food price inflation. Pass‐through rates are estimated to range from 0.16 to approximately 0.60 through 2008 with an average of 0.22 for the whole period. Statistical tests indicate that pass‐through rates before June 2008 were significantly higher than after June 2008 when they dropped significantly to 0.04 to 0.17. Interestingly, private label brands have the lowest pass‐through rates, implying that compared to manufacturer brands, private label prices are more insulated from diesel price shocks.
Pleiotropic roles of melatonin in endometriosis, recurrent spontaneous abortion, and polycystic ovary syndrome
Authors: Yang Hui‐Li , Zhou Wen‐Jie , Gu Chun‐Jie , Meng Yu‐Han , Shao Jun , Li Da‐Jin , Li Ming‐Qing
Published: March 2018

Melatonin is a neurohormone synthesized from the aromatic amino acid tryptophan mainly by the pineal gland of mammals. Melatonin acts as a broad‐spectrum antioxidant, powerful free radical scavenger, anti‐inflammatory agent, anticarcinogenic factor, sleep inducer and regulator of the circadian rhythm, and potential immunoregulator. Melatonin and reproductive system are interrelated under both physiological and pathological conditions. Oxidative stress, inflammation, and immune dysregulation are associated with the pathogenesis of the female reproductive system which causes endometriosis (EMS), recurrent spontaneous abortion (RSA), and polycystic ovary syndrome (PCOS). Accumulating studies have indicated that melatonin plays pleiotropic and essential roles in these obstetrical and gynecological disorders and would be a candidate therapeutic drug to regulate inflammation and immune function and protect special cells or organs. Here, we systematically review the pleiotropic roles of melatonin in EMS, RSA, and PCOS to explore its pathological implications and treatment potential.
Carvedilol for reducing portal pressure in primary prophylaxis of variceal bleeding: a dose‐response study
Authors: Schwarzer R. , Kivaranovic D. , Paternostro R. , Mandorfer M. , Reiberger T. , Trauner M. , Peck‐Radosavljevic M. , Ferlitsch A.
Published: March 2018

Background

Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension.

Aims

To assess the rates of HVPG response to different doses of carvedilol.

Methods

Consecutive patients with cirrhosis undergoing HVPG‐guided carvedilol therapy for primary prophylaxis of variceal bleeding between 08/2010 and 05/2015 were retrospectively included. After baseline HVPG measurement, carvedilol 6.25 mg/d was administered and HVPG response (HVPG‐decrease ≥20% or to ≤12 mm Hg) was assessed after 3‐4 weeks. In case of nonresponse, carvedilol dose was increased to 12.5 mg/d and a third HVPG‐measurement was performed after 3‐4 weeks. We also assessed HVPG‐response rates according to the Baveno VI consensus (HVPG decrease ≥10% or to ≤12 mm Hg) and changes in systolic arterial pressure (SAP).

Results

Seventy‐two patients (Child A, 37%; B, 35%; C, 28%) were included. 28 (39%) patients achieved a HVPG‐decrease ≥ 20% with carvedilol 6.25 mg/d and another 10 (14%) with carvedilol 12.5 mg/d. Forty (56%) patients had a HVPG decrease ≥10% with carvedilol 6.25 mg/d and 24 (33%) with carvedilol 12.5 mg/d. Thus, in total, a HVPG‐response of ≥20% and ≥10% and was achieved in 38 (53%) and 55 (76%) and of patients respectively. Notably, 6 patients (n = 4 with ascites) did not tolerate an increase to 12.5 mg/d due to hypotension/bradycardia. However, none of the other patients had a SAP < 90 mm Hg at the final HVPG measurement.

Conclusion

Carvedilol 12.5 mg/d was more effective than 6.25 mg/d in decreasing HVPG in primary prophylaxis. A total of 76% of patients achieved a HVPG‐response of ≥ 10% to carvedilol 12.5 mg/d, however, arterial hypotension might occur, especially in patients with ascites.
Predictors of failure to detect early hepatocellular carcinoma in patients with chronic hepatitis B who received regular surveillance
Authors: Chon Y. E. , Jung K. S. , Kim M.‐J. , Choi J.‐Y. , An C. , Park J. Y. , Ahn S. H. , Kim B. K. , Kim S. U. , Park H. , Hwang S. K. , Rim K. S. , Han K.‐H. , Kim D. Y.
Published: March 2018

Background

A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance.

Aims

To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance.

Methods

CHB patients with well‐preserved liver function, who underwent ultrasonography and alpha‐foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C.

Results

Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389‐6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307‐11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341‐8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066‐59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613‐14.297; P = 0.005) as predictors of detection failure.

Conclusions

In CHB patients undergoing regular surveillance with ultrasonography and alpha‐foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure.
Use of attention‐deficit/hyperactivity disorder medication among older adults in Denmark
Authors: Ormhøj Stina Schultz , Pottegård Anton , Gasse Christiane , Rasmussen Lotte
Published: March 2018

Aims

Knowledge on the use of attention‐deficit/hyperactivity disorder (ADHD) medication among older adults is limited. We hypothesized that ADHD medication is used off‐label in adults aged ≥50 years as part of palliative care in e.g. cancer patients. The aim of this study was to describe the use of ADHD medication among adults aged ≥50 years in Denmark.

Methods

Using the Danish health registries, we identified new users ≥50 years of ADHD medication during 2000–2012. We estimated the annual incidence of ADHD medication use and ADHD diagnoses. We described new users of ADHD medication according to co‐medication, comorbidities and assessed the 1‐year cumulative mortality rate. A posthoc analysis allowed us to include new users until 2015.

Results

We identified 6690 new users of ADHD medication from 2000 to 2012. From 2000 to 2015 we observed an increase in the incidence of ADHD medication use from 12.5 to 30.3 per 100 000 person‐years. However, the incidence rate decreased from 2010 to 2015. Throughout the study period, the incidence rate of ADHD diagnoses was low (overall prevalence among new users ≤2%). Opioids were the most frequent comedication used (used by 54%), while cancer was the most frequent diagnosis preceding treatment (prevalence of 52%). The 1‐year cumulative mortality was 50%, primarily driven by patients with a preceding cancer diagnosis.

Conclusion

There was an increase in the incidence of ADHD medication use in adults aged ≥50 years from 2000–2010 and a decreasing incidence from 2010–2015. Our results suggest that ADHD medication is used off‐label in older adults as part of palliative care.
A MODEL OF INFLATION TRANSMISSION IN AN EXCHANGE RATE TARGET ZONE
Authors: Chua Kevin C.
Published: March 2018

I incorporate an exchange rate target zone with intramarginal interventions in a small open economy model. Using the method of undetermined coefficients, I solve for the price level and the nominal exchange rate to determine how price shocks from the large economy affect the small open economy. The results show that the behaviour of inflation transmission within the band differs from the behavior of inflation transmission at the edge of the band of the target zone. Foreign shocks can affect local prices in both cases but the central bank can respond through market interventions within the band while it cannot do so at the edge. Near the edge of the band, a central bank has to intervene to stop the exchange rate from breaching the band. My model predicts that if the interventions are robust, then the exchange rate is mean reverting and an exchange rate target zone can insulate an economy from foreign price shocks. Based on the model, central bank interventions contribute to long‐run price stability in a target zone regime. Finally, I empirically test the model using unit root and cointegration tests, and present some policy implications.
Seismic geomorphology and origin of diagenetic geobodies in the Upper Cretaceous Chalk of the North Sea Basin (Danish Central Graben)
Authors: Smit F. W. H. , van Buchem F. S. P. , Holst J. C. , Lüthje M. , Anderskouv K. , Thibault N. , Buijs G. J. A. , Welch M. J. , Stemmerik L.
Published: March 2018

Kilometre‐scale geobodies of diagenetic origin have been documented for the first time in a high‐resolution 3D seismic survey of the Upper Cretaceous chalks of the Danish Central Graben, North Sea Basin. Based on detailed geochemical, petrographic and petrophysical analyses, it is demonstrated that the geobodies are of an open‐system diagenetic origin caused by ascending basin fluids guided by faults and stratigraphic heterogeneities. Increased amounts of porosity‐occluding cementation, contact cement and/or high‐density/high‐velocity minerals caused an impedance contrast that can be mapped in seismic data, and represent a hitherto unrecognized, third type of heterogeneity in the chalk deposits in addition to the well‐known sedimentological and structural features. The distribution of the diagenetic geobodies is controlled by porosity/permeability contrasts of stratigraphic origin, such as hardgrounds associated with formation tops, and the feeder fault systems. One of these, the Top Campanian Unconformity at the top of the Gorm Formation, is particularly effective and created a basin‐wide barrier separating low‐porosity chalk below from high‐porosity chalk above (a Regional Porosity Marker, RPM). It is in particular in this upper high‐porosity unit (Tor and Ekofisk Formations) that the diagenetic geobodies occur, delineated by “Stratigraphy Cross‐cutting Reflectors” (SCRs) of which eight different types have been distinguished. The geobodies have been interpreted as the result of: (i) escaping pore fluids due to top seal failure, followed by local mechanical compaction of high‐porous chalks, paired with (ii) ascension of basinal diagenetic fluids along fault systems that locally triggered cementation of calcite and dolomite within the chalk, causing increased contact cements and/or reducing porosity. The migration pathway of the fluids is marked by the SCRs, which are the outlines of high‐density bodies of chalk nested in highly porous chalks. This study, thus, provides new insights into the 3D relationship between fault systems, fluid migration and diagenesis in chalks and has important applications for basin modelling and reservoir characterization.
Effects of sumatriptan nasal spray (Imigran) on human nasal mucosa
Authors: Cheng L‐H. , Wu P‐C. , Lin Y‐Y. , Chu Y‐H. , Wang H‐W.
Published: March 2018

Objectives

Sumatriptan (Imigran) is a potent and highly selective 5‐HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran on human nasal mucosa have rarely been well explored, to verify the effect of Imigran, which act on human nasal mucosa directly in vitro.

Design and participants

We examined the effectiveness of Imigran on human nasal mucosa by testing: (i) effect on human nasal mucosa resting tension; (ii) effect on contraction caused by 10−6 mol/L methoxamine as a sympathetic mimetic; and (iii) effect of the drugs on electrically induced on human nasal mucosa contractions.

Results

The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose‐dependent manner. Addition of Imigran at doses of 10−4 mol/L elicited a significant relaxation response to 10−6 mol/L methoxamine‐induced contraction. Imigran could not inhibit electrical field stimulation‐induced spike contraction. It also had a minimal effect on the basal tension of nasal mucosa as the concentration increased.

Conclusions

The study indicated that high concentrations of Imigran had a significant spasmolytic effect by antagonising α‐adreoceptors and nasal obstruction could not be released in the patient combined with acute migraine and stuffy nose by concomitant α‐adrenergic agonist nasal spray plus Imigran nasal spray.
Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence
Authors: Xu E.‐S. , Yang M.‐H. , Liu C.‐Y. , Liu K.‐W. , Yang T.‐T. , Chou T.‐Y. , Hwang T.‐Z. , Hsu C.‐T.
Published: March 2018

Objectives

Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis.

Methods

CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method.

Results

CK13 was predominately expressed in non‐cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan‐Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10‐year follow‐up.

Conclusion

Our findings provide the first evidence that CK17 under‐expression might be a potential predictor of nodal metastasis and adverse prognosis.
Does otitis media in early childhood affect later behavioural development? Results from the Western Australian Pregnancy Cohort (Raine) Study
Authors: Da Costa C. , Eikelboom R.H. , Jacques A. , Swanepoel D.W. , Whitehouse A.J.O. , Jamieson S.E. , Brennan‐Jones C.G.
Published: March 2018

Objectives

To examine the relationship between early life episodes of otitis media and later behavioural development with adjustment for confounders.

Design

Longitudinal cohort study.

Setting

The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women from King Edward Memorial Hospital (KEMH) in Perth, Western Australia, between 1989 and 1991.

Participants

Data from the children born were collected at both the Year 3 and Year 5 follow‐up. At Year 3, n = 611 were diagnosed with recurrent otitis media through parent‐report and clinical examination. At Year 5, n = 299 were considered exposed to otitis media based upon tympanometry results.

Main outcome measures

Performance in the Child Behaviour Checklist (CBCL), a questionnaire completed by the primary caregiver at Year 10.

Results

Significant associations were found between recurrent otitis media at Year 3 and internalising behaviours (P = .011), and the somatic (P = .011), withdrawn (P = .014), attention (P = .003) and thought problems domains (P = .021), and the totalCBCLscore (P = .010). A significant association was also found between exposure to otitis media at Year 5 and externalising behaviours (P = .026).

Conclusions

A modest association was seen between recurrent otitis media at Year 3 and exposure to otitis media at Year 5 and a number of behaviour domains at Year 10.
Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart
Authors: Basu Ananda , Pieber Thomas R. , Hansen Ann K. , Sach‐Friedl Stefanie , Erichsen Lars , Basu Rita , Haahr Hanne
Published: March 2018

Aim

To investigate the mechanisms behind the lower postprandial glucose (PPG) concentrations achieved with fast‐acting insulin aspart (faster aspart) than with insulin aspart (IAsp).

Materials and methods

In a randomized, double‐blind, crossover trial, 41 people with type 1 diabetes received identical subcutaneous single faster aspart and IAsp doses (individualized for each participant), together with a standardized mixed meal (including 75 g carbohydrate labelled with [1‐13C] glucose). PPG turnover was determined by the triple‐tracer meal method using continuous, variable [6‐3H] glucose and [6,6‐2H2] glucose infusion.

Results

Insulin exposure within the first hour was 32% greater with faster aspart than with IAsp (treatment ratio faster aspart/IAsp 1.32 [95% confidence interval {CI} 1.18;1.48]; P < .001), leading to a 0.59‐mmol/L non‐significantly smaller PPG increment at 1 hour (ΔPG1h; treatment difference faster aspart–IAsp −0.59 mmol/L [95% CI –1.19; 0.01]; P = .055). The trend towards reduced ΔPG1h with faster aspart was attributable to 12% greater suppression of endogenous glucose production (EGP; treatment ratio 1.12 [95% CI 1.01; 1.25]; P = .040) and 23% higher glucose disappearance (1.23 [95% CI 1.05; 1.45]; P = .012) with faster aspart than with IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster aspart than for IAsp (1.36 [95% CI 1.01;1.88]; P = .042).

Conclusions

The trend towards improved PPG control with faster aspart vs IAsp in this study was attributable to both greater early suppression of EGP and stimulation of glucose disappearance.
Glucose‐lowering effects and mechanisms of the bile acid‐sequestering resin sevelamer
Authors: Brønden Andreas , Mikkelsen Kristian , Sonne David P. , Hansen Morten , Våben Christoffer , Gabe Maria N. , Rosenkilde Mette , Tremaroli Valentina , Wu Hao , Bäckhed Fredrik , Rehfeld Jens F. , Holst Jens J. , Vilsbøll Tina , Knop Filip K.
Published: March 2018

Aims

Sevelamer, a non‐absorbable amine‐based resin used for treatment of hyperphosphataemia, has been demonstrated to have a marked bile acid‐binding potential alongside beneficial effects on lipid and glucose metabolism. The aim of this study was to investigate the glucose‐lowering effect and mechanism(s) of sevelamer in patients with type 2 diabetes.

Materials and Methods

In this double‐blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n = 20) or placebo (n = 10). Participants were subjected to standardized 4‐hour liquid meal tests at baseline and after 7 days of treatment. The main outcome measure was plasma glucagon‐like peptide‐1 excursions as measured by area under the curve. In addition, blood was sampled for measurements of glucose, lipids, glucose‐dependent insulinotropic polypeptide, C‐peptide, glucagon, fibroblast growth factor‐19, cholecystokinin and bile acids. Assessments of gastric emptying, resting energy expenditure and gut microbiota composition were performed.

Results

Sevelamer elicited a significant placebo‐corrected reduction in plasma glucose with concomitant reduced fibroblast growth factor‐19 concentrations, increased de novo synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon‐like peptide‐1‐mediated effects on insulin, glucagon or gastric emptying were evident, which points to a limited contribution of this incretin hormone to the glucose‐lowering effect of sevelamer. Furthermore, no sevelamer‐mediated effects on gut microbiota composition or resting energy expenditure were observed.

Conclusions

Sevelamer reduced plasma glucose concentrations in patients with type 2 diabetes by mechanisms that seemed to involve decreased intestinal and hepatic bile acid‐mediated farnesoid X receptor activation.
Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials
Authors: Henry Robert R. , Müller‐Wieland Dirk , Taub Pam R. , Bujas‐Bobanovic Maja , Louie Michael J. , Letierce Alexia , Ginsberg Henry N.
Published: March 2018

Aims

This analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.

Materials and Methods

Data from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo‐controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe‐controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL‐C.

Results

LDL‐C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non‐MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non‐MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non‐high‐density lipoprotein cholesterol (non‐HDL‐C), lipoprotein(a) and HDL‐C. Overall, the percentage change at Week 24 in LDL‐C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection‐site reactions occurred more frequently in alirocumab vs control groups.

Conclusions

Across study pools, alirocumab‐associated reductions in LDL‐C, apolipoprotein B, and non‐HDL‐C were significant vs control, and did not vary by MetS status.
International bimetallism and silver absorption in Singapore, 1840–73
Authors: Kobayashi Atsushi
Published: March 2018

This study reveals the mechanism underlying the silver trade in Singapore during the third quarter of the nineteenth century by analysing banking business and bullion arbitrage. After 1849, the California Gold Rush induced gold depreciation and silver appreciation in Singapore's bullion market, and arbitrage profits for silver imports from Britain emerged. At the same time, the expansion of banking business by eastern exchange banks enhanced the connectivity of Singapore's exchange market with London, and enabled bullion arbitrage between the two distant cities. As a result, there was an influx of silver from Britain. In addition, Dutch silver, which was exported to Java by the Netherlands after 1854, flowed into Singapore due to the unfavourable exchange policy of the Dutch government.