bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between concerns toward adverse reactions during pre‐approval drug reviews and the post‐approval addition of clinically significant adverse reactions to package inserts: A retrospective analysis of pre‐approval drug review reports and safety updates
Authors: Watanabe Ko , Murakami Masayasu , Masuyama Koichi , Ishiguro Chieko , Matsuda Tsutomu
Published: September 2018

Purpose

To determine if concerns toward adverse reactions (ARs) identified during the drug approval process are associated with their post‐approval addition to package inserts.

Methods

Pre‐approval concerns toward 24 target ARs were identified in the drug review reports and initial package inserts of 126 target drugs approved for use in Japan between April 2004 and March 2009. Each target drug was monitored for 5 years after approval for the addition of these ARs as clinically significant adverse reactions (CSARs) in the package inserts. Positive predictive values (PPVs) and negative predictive value (NPVs) were calculated. The odds ratios (ORs) and 95% confidence intervals (CIs) were also analyzed to test the association between pre‐approval concerns and post‐approval CSAR additions.

Results

Target ARs with pre‐approval concerns were added as CSARs in 88 of 406 AR‐drug pairs (PPV: 21.7%). In contrast, target ARs without pre‐approval concerns were added as CSARs in 93 of 2304 drugs (NPV: 96.0%). Hypoglycemia had the highest PPV (100%), whereas hepatitis and myocardial infarction had the lowest PPVs (0.0%). Abnormal hepatic function had the lowest NPV (85.4%), whereas myocardial infarction and convulsions had the highest NPVs (100%). Pre‐approval concerns showed a significantly positive association with post‐approval CSAR additions (OR: 6.57, 95% CI: 4.74, 9.11; P < 0.001).

Conclusions

The significant association between pre‐approval concerns and post‐approval CSAR additions indicates that Japan's drug regulatory agency has generally conducted rigorous examination of the safety information available in the submitted data packages during drug review for approval.
Branched peptides as bioactive molecules for drug design
Authors: Brunetti Jlenia , Falciani Chiara , Bracci Luisa , Pini Alessandro
Published: September 2018

Peptides are regarded as good candidates for new biotherapeutics in medicine. Several peptides have already completed clinical development, with more than 60 peptide‐based drugs already on the market, and a further 500 derivatives currently in developmental stages. Branched peptides are an emerging class of synthetic molecules being assessed for drug development. Here, we review possible clinical uses of branched peptides, considering major features such as stability, half‐life, toxicity, and efficacy compared to monomeric peptides, biodistribution, as well as modifications, encapsulation, and conjugation to improve delivery or bypass drug resistance. We focus in particular on the use of branched peptides in oncology and infectious diseases.
Protein engineering by chemical methods: Incorporation of nonnatural amino acids as a tool for studying protein folding, stability, and function
Authors: De Filippis Vincenzo , Pozzi Nicola , Acquasaliente Laura , Artusi Ilaria , Pontarollo Giulia , Peterle Daniele
Published: September 2018

Proteins are large complex biomolecules that act as the effectors of essentially all cell functions. Due to the intrinsic complexity of protein architecture at the microscopic level and the inadequacy of theoretical methods to predict protein reactivity (ie, folding, stability, and function), protein engineering has emerged as a valuable tool to investigate structure–stability–activity relationships in proteins and nowadays recombinant DNA technologies are the “gold standard” for site‐specifically manipulating a given protein chain. The usefulness of current mutagenesis techniques, however, is limited by the relatively poor chemical diversity of the 20 DNA‐coded amino acids, such that it is difficult to precisely assign the observed change of protein stability or function to the variation of a single physicochemical property at a protein site (ie, hydrophobicity, conformational propensity, polarizability, hydrogen bonding, etc). In this article, we report relevant examples from our laboratory showing that chemical methods, that is, enzyme‐catalyzed semisynthesis and stepwise solid‐phase synthesis, allow to conveniently incorporate non‐natural amino acids with “tailored” side chains into small proteins and thus effectively transfer the structure–activity relationship methodology, typical of the medicinal chemistry approach on small molecules, to the study of folding, stability, and molecular recognition in macromolecular protein systems.
CPProtectides: Rapid uptake of well‐folded β‐hairpin peptides with enhanced resistance to intracellular degradation
Authors: Safa Nora , Anderson Jeffery C. , Vaithiyanathan Manibarathi , Pettigrew Jacob H. , Pappas Gavin A. , Liu Dong , Gauthier Ted J. , Melvin Adam T.
Published: September 2018

Cell penetrating peptides (CPPs) have emerged as powerful tools for delivering bioactive cargoes, such as biosensors or drugs to intact cells. One limitation of CPPs is their rapid degradation by intracellular proteases. β‐hairpin “protectides” have previously been demonstrated to be long‐lived under cytosolic conditions due to their secondary structure. The goal of this work was to demonstrate that arginine‐rich β‐hairpin peptides function as both protectides and as CPPs. Peptides exhibiting a β‐hairpin motif were found to be rapidly internalized into cells with their uptake efficiency dependent on the number of arginine residues in the sequence. Cellular internalization of the β‐hairpin peptides was compared to unstructured, scrambled sequences and to commercially available, arginine‐rich CPPs. The unstructured peptides displayed greater uptake kinetics compared to the structured β‐hairpin sequences; however, intracellular stability studies revealed that the β‐hairpin peptides exhibited superior stability under cytosolic conditions with a 16‐fold increase in peptide half‐life. This study identifies a new class of long‐lived CPPs that can overcome the stability limitations of peptide‐based reporters or bioactive delivery mechanisms in intact cells.
The role of perceived dignity and control in the wish to hasten death among advanced cancer patients: A mediation model
Authors: Monforte‐Royo Cristina , Crespo Iris , Rodríguez‐Prat Andrea , Marimon Frederic , Porta‐Sales Josep , Balaguer Albert
Published: September 2018

Objective

The objective of the study is to test a model in which perceived loss of dignity and control are proposed, along with symptoms of depression and functional impairment, as risk factors for the wish to hasten death (WTHD) in advanced cancer patients.

Methods

This was a cross‐sectional study of 193 patients in an oncology unit. Outcome measures included perceived control, performance status, symptoms of depression, perceived dignity, and the WTHD. Structural equation modeling was performed.

Results

Structural equation modeling showed that perceived loss of control (−0.402) and functional impairment (−0.21) were risk factors for perceived loss of dignity. Loss of control (−0.385) and functional impairment (−0.283) were also risk factors for symptoms of depression. Perceived loss of dignity and symptoms of depression were the most proximal determinants of the WTHD, on which they had a direct, positive, and significant effect (0.246 and 0.209, respectively). Therefore, both symptoms of depression and perceived loss of dignity independently predicted the WTHD and mediated the effects of perceived loss of control and functional impairment on this wish.

Conclusions

The hypothesized model provides evidence for the impact of the four aforementioned factors on the WTHD. Our results suggest that personalized care plans which are able to enhance the sense of dignity and control among advanced cancer patients could help to reduce the likelihood or intensity of a WTHD.
Sesquiterpene lactones‐enriched fraction of Inula helenium L. induces apoptosis through inhibition of signal transducers and activators of transcription 3 signaling pathway in MDA‐MB‐231 breast cancer cells
Authors: Chun Jaemoo , Song Kwangho , Kim Yeong Shik
Published: September 2018

Inula helenium L., commonly known as Elecampane, has been extensively used for many countries in the folk medicine. Its root is a rich source of sesquiterpene lactones, which possess various pharmacological activities. To develop the phytomedicine including sesquiterpene lactones, we prepared hexane fraction from I. helenium (HFIH) and examined the inhibitory effect of HFIH on signal transducers and activators of transcription 3 (STAT3) activation in human breast cancer MDA‐MB‐231 cells. Additionally, detailed chemical investigation was done to pinpoint the most active sesquiterpene lactones responsible for its anticancer activity. HFIH selectively suppressed STAT3 phosphorylation at tyrosine 705, not affecting its upstream kinases. HFIH downregulated the expression of STAT3 target genes including cyclin D1, c‐myc, and bcl‐2 and induced caspase‐mediated apoptosis. Moreover, sesquiterpene lactones of HFIH clearly suppressed STAT3 activation. The in vivo results further supported that HFIH inhibits the growth of human breast xenograft tumors. Our results suggest that HFIH possesses potential anticancer activity, which is mainly mediated through STAT3 signaling pathway. These findings provide the potential of HFIH as a promising phytomedicine for the treatment and prevention of triple‐negative breast cancer.
Implications of the variation in biological 18O natural abundance in body water to inform use of Bayesian methods for modelling total energy expenditure when using doubly labelled water
Authors: Singh Priya A. , Orford Elise R. , Donkers Kevin , Bluck Leslie J.C. , Venables Michelle C.
Published: September 2018

Rationale

Variation in 18O natural abundance can lead to errors in the calculation of total energy expenditure (TEE) when using the doubly labelled water (DLW) method. The use of Bayesian statistics allows a distribution to be assigned to 18O natural abundance, thus allowing a best‐fit value to be used in the calculation. The aim of this study was to calculate within‐subject variation in 18O natural abundance and apply this to our original working model for TEE calculation.

Methods

Urine samples from a cohort of 99 women, dosed with 50 g of 20% 2H2O, undertaking a 14‐day breast milk intake protocol, were analysed for 18O. The within‐subject variance was calculated and applied to a Bayesian model for the calculation of TEE in a separate cohort of 36 women. This cohort of 36 women had taken part in a DLW study and had been dosed with 80 mg/kg body weight 2H2O and 150 mg/kg body weight H218O.

Results

The average change in the δ18O value from the 99 women was 1.14‰ (0.77) [0.99, 1.29], with the average within‐subject 18O natural abundance variance being 0.13‰2 (0.25) [0.08, 0.18]. There were no significant differences in TEE (9745 (1414), 9804 (1460) and 9789 (1455) kJ/day, non‐Bayesian, Bluck Bayesian and modified Bayesian models, respectively) between methods.

Conclusions

Our findings demonstrate that using a reduced natural variation in 18O as calculated from a population does not impact significantly on the calculation of TEE in our model. It may therefore be more conservative to allow a larger variance to account for individual extremes.
Effects of splitter plate on reducing local scour around bridge pier
Authors: Wu Peng , Balachandar Ram , Ramamurthy Amruthur
Published: September 2018

Local scour around bridge piers has been shown to be the most common reason for bridge failures. The use of splitter plates to modify the flow field around the pier has the potential to reduce the maximum scour depth. To test the effect of the splitter plate, the present study was conducted by using plates of various lengths (1 ≤ L/D ≤ 2). Here, D is the diameter of the pier, and L is the length of the splitter plate. The splitter plate was located both in the front and at the rear of the pier. The results show that for a constant splitter plate height, the plate with a length of 1.33D located in front of the pier has the greatest impact in reducing maximum scour. Results also showed that with increasing height of the splitter plate located in front of the pier, the maximum scour depth as well as the scoured area decreased correspondingly. In the range of test variables used in this study, the back splitter plate located with or without a gap between the pier and the plate showed limited impact on reducing the maximum scour around the pier. However, a significant change of dune height was observed in the back of the pier.
Judgment post‐stratification in finite mixture modeling: An example in estimating the prevalence of osteoporosis
Authors: Omidvar Sedigheh , Jafari Jozani Mohammad , Nematollahi Nader
Published: September 2018

Judgment post‐stratification is used to supplement observations taken from finite mixture models with additional easy to obtain rank information and incorporate it in the estimation of model parameters. To do this, sampled units are post‐stratified on ranks by randomly selecting comparison sets for each unit from the underlying population and assigning ranks to them using available auxiliary information or judgment ranking. This results in a set of independent order statistics from the underlying model, where the number of units in each rank class is random. We consider cases where one or more rankers with different ranking abilities are used to provide judgment ranks. The judgment ranks are then combined to produce a strength of agreement measure for each observation. This strength measure is implemented in the maximum likelihood estimation of model parameters via a suitable expectation maximization algorithm. Simulation studies are conducted to evaluate the performance of the estimators with or without the extra rank information. Results are applied to bone mineral density data from the third National Health and Nutrition Examination Survey to estimate the prevalence of osteoporosis in adult women aged 50 and over.
Amorphous Iron(III)‐Borate Nanolattices as Multifunctional Electrodes for Self‐Driven Overall Water Splitting and Rechargeable Zinc–Air Battery
Authors: Zhao Weinan , Xu Tao , Li Tao , Wang Yuankun , Liu Hui , Feng Jianze , Ding Shujiang , Li Zhongtao , Wu Mingbo
Published: September 2018

Highly stable and low‐cost electrocatalysts with multi‐electrocatalytic activities are in high demand for developing advanced energy conversion devices. Herein, a unique trifunctional amorphous iron‐borate electrode is developed, which is capable of boosting hydrogen evolution, oxygen evolution, and oxygen reduction reactions simultaneously. The amorphous iron borate can self‐assemble into well‐defined nanolattices on electrode surface through a facile hydrothermal process, which possess more active sites and charge transfer pathways. As a result, the asymmetry overall water‐splitting cell that adopts the amorphous electrodes as anode and cathode can be driven at 1.56 V with the current density of 10 mA cm−2, which is lowest in state‐of‐the‐art catalysts. Moreover, the water‐splitting devices can be powered by a two‐series‐connected amorphous electrode–based zinc–air battery with high stability and Faradic efficiency (96.3%). The result can offer a potential and promising alternative way to develop metal‐borate electrode for multifunctional applications.
Potential immunomodulatory and antioxidant effects of walnut Juglans regia vegetable oil against lead‐mediated hepatic damage and their interaction with lipase activity in rats
Authors: Soussi Ahlem , Gargouri Manel , El Feki Abdelfattah
Published: September 2018

Environmental pollutants, particularly lead, pose a serious threat to human and animal health that causes disturbances of several functions, including hepatotoxicity. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. This study was carried out to investigate the protective efficacy of Juglans regia vegetable oil (JRVO) against the hepatotoxicity induced by lead. To achieve this aim, adults male rats were treated for 10 days with Pb (0.344 g/kg bw) associated or not with JRVO (0.9 g/kg bw). The rats intoxicated by lead exhibited oxidative stress determined by TBARS, protein carbonyls, liver tumor necrosis factor‐α (TNF‐α), caspase‐3, and antioxidant status: SOD, CAT, GPx, and GSH. Administration of lead increased the levels of plasma hepatic markers (AST, ALT, LDH) and bilirubin, the lipid profiles (total cholesterol, triglycerides, VLDL‐Ch, LDL‐Ch levels, TBARS, NOx, and PCO), the plasmatic lipase activity and the inflammatory markers, while the plasmatic ALP decreased. Coadministration of JRVO restored all the hepatic markers, the lipid profiles and the antioxidants to near‐normal values and lowered the plasmatic lipase activity as well as the elevated thiobarbituric acid reactive substances. Hepatic histological studies confirmed the beneficial role of JRVO through the amelioration of all biochemical parameters. Our results suggest that Juglans regia vegetable oil contains promising substances to counteract the lead intoxication and may be efficient in the prevention of hepatotoxicity complications.
Introduction
Authors: Crane Jennifer
Published: September 2018

This chapter positions Child Protection in England within long histories of child protection, childhood, and family. Situating this book as a history of modern Britain, it also discusses how the voluntary organisations studied relate to broader historiographical examinations of voluntary action and public participation in the post-war period. This introduction also explores the theoretical underpinning of this book in terms of thinking around expertise, experience, and emotion; complex and shifting constructs which have nonetheless become significant—and visible—in late twentieth-century Britain.
The Battered Child Syndrome: Parents and Children as Objects of Medical Study
Authors: Crane Jennifer
Published: September 2018

‘The Battered Child Syndrome’ explores the re-emergence of public and political concerns about child protection in the post-war period, and the role of medical communities in constructing this. It assesses the work of paediatric radiologists in Britain and America, who worked in the 1940s and 1950s to use x-ray technology to ‘make visible’ the healing injuries of children. In England, the NSPCC drew on this work to conduct early studies about the ‘battered child syndrome’. The chapter demonstrates that much of this work examined children and parents as objects of study. Nonetheless, early concerns about the emotions of children and parents were present, and this foreshadowed the development of experiential movements traced by the rest of this book.
Collective Action by Parents and Complicating Family Life
Authors: Crane Jennifer
Published: September 2018

This chapter explores how groups of parents formed collective action groups, of various forms, looking to contest child protection policy and practice in the late twentieth century. Such activism first emerged in the late 1960s, initially in the form of peer support groups for parents who had harmed, or felt at risk of harming, their children. In the 1980s, multiple groups developed to support parents who had been falsely accused of abuse. These spaces of activism complicated visions of family life and also made public the emotional toil of interacting with statutory agencies around child protection. As such, and for the first time, parents acted collectively to critique professional intervention, constructing a visible, public, and powerful notion of experiential and familial expertise. Parents also demanded that social workers, lawyers, and clinicians themselves discussed their own experiences and emotions, looking to blur the lines between the personal and the professional.
Conclusion
Authors: Crane Jennifer
Published: September 2018

The conclusion discusses the key findings of this book. It argues that understandings of child protection have developed rapidly over the late twentieth century. This process has not only been driven by media, public policy, and research, as previous analyses have emphasised, but also by children, concerned parents, and survivors. These groups have acted in conflict and collaboration with media, social policy, and medicine, challenging long-standing professionals to display and perform experiential and emotional expertise. The conclusion traces the extent to which this forging of experience and emotion as expert, and the place of the voluntary sector in this process, has historical precedents, and argues that these phenomena were distinct to, and are revealing of, the specific contexts of Britain in the post-1960s moment. The conclusion finally explores the contemporary relevance of this work, notably in terms of making visible the politicisation of child protection and the fragility of child protection concerns.
Modelling heterogeneity in detection probabilities in land and aerial abundance surveys in humpback whales (Megaptera novaeangliae)
Authors: Dudgeon Christine L. , Dunlop Rebecca A. , Noad Michael J.
Published: September 2018

The effective management and conservation of animal populations relies on statistically‐sound and replicable surveys to obtain estimates of abundance and assess trends. Surveys of cetaceans, such as humpback whalesMegaptera novaeangliae, are difficult to conduct and are particularly affected by bias in detection probability. For example, the probability of detection of whales from land decreases substantially with increased distance from the platform. This distance effect is also true for aerial surveys, combined with the problem that animals are unavailable for detection (underwater) whilst in the field of view. We present a novel approach that combines corrected double‐platform land surveys with corrected aerial surveys to obtain a robust estimate ofg(0), the probability of detection on the survey line, for aerial surveys of migrating humpback whales. Several sources of heterogeneity in detection probabilities were identified within the land and aerial surveys (including group composition, bearing of first sighting, number of groups being tracked simultaneously and cloud cover). After including these into our estimate ofĝ(0), we found that only 29% of available whales are being detected on the survey line (ĝ(0) = 0.288), which is a considerably smaller estimate than many available for humpback whales using other methods. Incorporating heterogeneity into the population surveys shows that we are likely to be underestimating the population size of whales on the east coast of Australia. The implications of this result for their conservation and management in light of increased whale‐human conflict is discussed.
Myocarditis and Early Markers of Cardiac Response Associated with Scorpion Stings in Children
Authors: Gökay Sinem S. , Kendir Özlem T. , Güllü Utku U. , Nalbant Tuğçe , Ekinci Faruk , Matyar Selçuk , Ünal İlker , Erdem Sevcan , Yildizdaş Riza D. , Yilmaz Hayri L.
Published: September 2018

Introduction

A clinical course ranging from mild local findings to life-threatening systemic findings may occur after scorpion stings. The purpose of this study was to identify priority markers indicating scorpion sting–related cardiac involvement.

Methods

Our study was performed between July 2014, and September 2015 in the Çukurova University medical faculty pediatric emergency department, in Adana, Turkey. Patients admitted with scorpion sting–related cardiac involvement and a control group consisting of patients with no scorpion sting–related cardiac involvement were included in the study. Troponin I at time of presentation and at 6 and 24 h, N-terminal prohormone of brain natriuretic peptide (NTproBNP), ejection fraction as determined by echocardiography at 24 h, and peak and end of T wave (Tp-e) and Tp-e/QTc ratios with echocardiography at 24 h were evaluated.

Results

A patient group consisting of 7 cases of scorpion envenomation–related myocarditis and a control group of 30 cases of scorpion intoxication without myocarditis findings were enrolled. Statistically significantly high glucose, white blood cell values, creatine kinase MB, troponin I, and NTproBNP values were identified in the scorpion sting–related myocarditis group ( P<0.05). Ejection fractions determined by echocardiography at time of presentation were significantly lower in the patients with myocarditis compared with the control group ( P<0.05). A statistically significant difference was identified between Tp-e/corrected QT interval (QTc) ratios investigated in DI and V2 derivations in patient and control group echocardiograms ( P<0.05).

Conclusions

We think that use can be made of NTproBNP in addition to echocardiography and troponin I in the early diagnosis of scorpion sting–related myocarditis and that Tp-e and Tp-e/QTc ratios identified via echocardiography can be used as early markers; however, further studies with larger numbers are needed to confirm this.
The Global Laboratory of Investment Law Reform Alternatives
Authors: Alschner Wolfgang
Published: September 2018

There are two ways of thinking about institutional choice in the context of multilateral investment law reform. One starts from abstract principles, asking what policy goal investment law is supposed to achieve and what institutional choice most effectively advances that goal. The other draws on practical experimentation, asking what institutional choices states are making and how these choices perform in real life. Sergio Puig and Gregory Shaffer present a compelling analytical framework for the former, top-down approach to investment law reform. In this essay, I will scrutinize their analysis and argue that the latter, bottom-up approach is more promising.
Who's Afraid of Reform? Beware the Risk of Fragmentation
Authors: Titi Catharine
Published: September 2018

With multilateral negotiations to reform investor-state dispute settlement (ISDS) now underway, it is legitimate to wonder about the outcome. Many seem to hope for a single, global reform, but that may be unrealistic in the near future. Indeed, the article by Sergio Puig and Gregory Shaffer and the essay by Anthea Roberts both suggest that states are pursuing a wide range of changes to the current system, some of which are incompatible with one another. A number of states prefer investment arbitration. Others favor an investment court. Still others reject international dispute settlement altogether. In this essay, I identify a collection of these options and argue that their number and variety, combined with the intensity of state preferences on the matter of ISDS reform, are likely to preclude a multilateral solution for the foreseeable future and lead to continued fragmentation.
Generic behavior of a measure-preserving transformation
Authors: ETEDADIALIABADI MAHMOOD
Published: September 2018

Del Junco–Lemańczyk [Generic spectral properties of measure-preserving maps and applications. Proc. Amer. Math. Soc., 115 (3) (1992)] showed that a generic measure-preserving transformation satisfies certain orthogonality conditions. More precisely, there is a dense $G_{\unicode[STIX]{x1D6FF}}$ subset of measure preserving transformations such that, for every $T\in G$ and $k(1),k(2),\ldots ,k(l)\in \mathbb{Z}^{+}$, $k^{\prime }(1),k^{\prime }(2),\ldots ,k^{\prime }(l^{\prime })\in \mathbb{Z}^{+}$, the convolutions $$\begin{eqnarray}\unicode[STIX]{x1D70E}_{T^{k(1)}}\ast \cdots \ast \unicode[STIX]{x1D70E}_{T^{k(l)}}\quad \text{and}\quad \unicode[STIX]{x1D70E}_{T^{k^{\prime }(1)}}\ast \cdots \ast \unicode[STIX]{x1D70E}_{T^{k^{\prime }(l^{\prime })}},\end{eqnarray}$$ where $\unicode[STIX]{x1D70E}_{T^{k}}$ is the maximal spectral type of $T^{k}$, are mutually singular, provided that $(k(1),k(2),\ldots ,k(l))$ is not a rearrangement of $(k^{\prime }(1),k^{\prime }(2),\ldots ,k^{\prime }(l^{\prime }))$. We will introduce analogous orthogonality conditions for continuous unitary representations of the group of all measurable functions with values in the circle, $L^{0}(\unicode[STIX]{x1D707},\mathbb{T})$, which we denote by the DL-condition. We connect the DL-condition with a result of Solecki [Unitary representations of the groups of measurable and continuous functions with values in the circle. J. Funct. Anal., 267 (2014), pp. 3105–3124] which identifies continuous unitary representations of $L^{0}(\unicode[STIX]{x1D707},\mathbb{T})$ with a collection of measures $\{\unicode[STIX]{x1D706}_{\unicode[STIX]{x1D705}}\}$, where $\unicode[STIX]{x1D705}$ runs over all increasing finite sequence of non-zero integers. In particular, we show that the ‘probabilistic’ DL-condition translates to ‘deterministic’ orthogonality conditions on the measures $\unicode[STIX]{x1D706}_{\unicode[STIX]{x1D705}}$. As a corollary, we show that the same orthogonality conditions as in the result by Del Junco–Lemańczyk hold for a generic unitary operator on a separable infinite-dimensional Hilbert space.
Buoyancy effects on large-scale motions in convective atmospheric boundary layers: implications for modulation of near-wall processes
Authors: Salesky S. T. , Anderson W.
Published: September 2018

A number of recent studies have demonstrated the existence of so-called large- and very-large-scale motions (LSM, VLSM) that occur in the logarithmic region of inertia-dominated wall-bounded turbulent flows. These regions exhibit significant streamwise coherence, and have been shown to modulate the amplitude and frequency of small-scale inner-layer fluctuations in smooth-wall turbulent boundary layers. In contrast, the extent to which analogous modulation occurs in inertia-dominated flows subjected to convective thermal stratification (low Richardson number) and Coriolis forcing (low Rossby number), has not been considered. And yet, these parameter values encompass a wide range of important environmental flows. In this article, we present evidence of amplitude modulation (AM) phenomena in the unstably stratified (i.e. convective) atmospheric boundary layer, and link changes in AM to changes in the topology of coherent structures with increasing instability. We perform a suite of large eddy simulations spanning weakly ($-z_{i}/L=3.1$) to highly convective ($-z_{i}/L=1082$) conditions (where $-z_{i}/L$ is the bulk stability parameter formed from the boundary-layer depth $z_{i}$ and the Obukhov length $L$) to investigate how AM is affected by buoyancy. Results demonstrate that as unstable stratification increases, the inclination angle of surface layer structures (as determined from the two-point correlation of streamwise velocity) increases from $\unicode[STIX]{x1D6FE}\approx 15^{\circ }$ for weakly convective conditions to nearly vertical for highly convective conditions. As $-z_{i}/L$ increases, LSMs in the streamwise velocity field transition from long, linear updrafts (or horizontal convective rolls) to open cellular patterns, analogous to turbulent Rayleigh–Bénard convection. These changes in the instantaneous velocity field are accompanied by a shift in the outer peak in the streamwise and vertical velocity spectra to smaller dimensionless wavelengths until the energy is concentrated at a single peak. The decoupling procedure proposed by Mathis et al. (J. Fluid Mech., vol. 628, 2009a, pp. 311–337) is used to investigate the extent to which amplitude modulation of small-scale turbulence occurs due to large-scale streamwise and vertical velocity fluctuations. As the spatial attributes of flow structures change from streamwise to vertically dominated, modulation by the large-scale streamwise velocity decreases monotonically. However, the modulating influence of the large-scale vertical velocity remains significant across the stability range considered. We report, finally, that amplitude modulation correlations are insensitive to the computational mesh resolution for flows forced by shear, buoyancy and Coriolis accelerations.
EAT, PRAY, REGULATE: THE INDONESIAN ULAMA COUNCIL AND THE MANAGEMENT OF ISLAMIC AFFAIRS
Authors: Fenwick Stewart
Published: September 2018

Indonesia's national ulama council, the Majelis Ulama Indonesia, or MUI, has successfully transformed itself during the reform era reversing its earlier relationship with government. It is the MUI that now sets the agenda on appropriate ways to recognize, protect, and promote the majority faith. However it does not operate entirely separate to the state, indeed, there are numerous points of contact and mutual dependence between this group of Islamic scholars and state agencies.

This article offers two case studies on religious freedom demonstrating different aspects of the MUI's self-appointed role of national mufti. The first case study demonstrates how the MUI has taken control of the high ground of religious doctrine. Through its response to blasphemy cases and deviant Muslim activities the MUI defines appropriate, orthodox Muslim conduct. The second case study deals with the revised regime of halal food certification. Here the state has sought to bring the MUI back into its embrace, partly as a result of corruption scandals. In doing so, however, Islam continues to be further entrenched in state law and regulation.

Indonesian Islam was said to be deconfessionalized, reflecting the nature of the former authoritarian and bureaucratic state's engagement with various Islamic institutions. The changing role of the MUI demonstrates that the state and law are becoming increasingly confessionalized. This change has significant implications for Indonesia's democratic constitutional framework, evident in what these cases say about the enjoyment of the fundamental right of citizenship.
A room with a view in English nuisance law: exploring modernisation hidden within the ‘textbook tradition’
Authors: Pontin Ben
Published: September 2018

The paper critically examines the consensus among tort scholars that an injured view can never be actionable in nuisance. The consensus, it is argued, is based on a problematic understanding of the permanence of early modern nuisance authority, and a neglect of modernisation in the definition of actionable injury in the nineteenth century, in response to industrialisation, urbanisation and, crucially, suburbanisation. David Sugarman's ‘textbook tradition’ provides a valuable disciplinary explanation for the mismatch between scholarly portrayals of doctrine and authoritative judicial formulations in decided cases.
Fatty acids composition as an indicator of food intake inMerluccius hubbsilarvae
Authors: Temperoni Brenda , Massa Agueda , Viñas María Delia
Published: September 2018

Fatty acids (FA) analysis is a well-established approach for qualitatively studying feeding preferences. In the Argentinean Continental Shelf, Argentine hakeMerluccius hubbsisupports the major demersal finfish fishery. The Patagonian stock of the species spawns and nurses in austral summer in the north Patagonian shelf (NPS, 43°–45°30′S). Previous studies about larval feeding in the NPS have solely focused on gut contents, indicating selectivity upon calanoid copepods. Hence, our main objective was to apply the FA approach to confirm and/or broadenM. hubbsilarval food selection. Hake larvae and copepod FA profiles overlapped significantly, dominated by the saturated FA 16:0, the monounsaturated FAs 18:1n-9 and 22:1n-9, and the polyunsaturated FA 22:6n-3. Moreover, identified markers typical of bacteria (15:0, 17:0) and dinoflagellates (18:4n-3, 22:6n-3) suggest a microbial input at the base of the NPS food web, with the latter probably acting as an intermediate step between bacteria and hake larvae. Possible direct predation upon protozoans by larvae is postulated, broadening the known trophic spectrum derived from classical diet analyses. The FA approach allowed us to clarify feeding preferences in the NPS, with data being relevant in the context of hake recruitment studies.
Epidemiology and associated risk factors of giardiasis in a peri-urban setting in New South Wales Australia
Authors: Zajaczkowski P. , Mazumdar S. , Conaty S. , Ellis J. T. , Fletcher-Lartey S. M.
Published: September 2018

Giardiasis is one of the most important non-viral causes of human diarrhoea. Yet, little is known about the epidemiology of giardiasis in the context of developed countries such as Australia and there is a limited information about local sources of exposure to inform prevention strategies in New South Wales. This study aimed to (1) describe the epidemiology of giardiasis and (2) identify potential modifiable risk factors associated with giardiasis that are unique to south-western Sydney, Australia. A 1:2 matched case-control study of 190 confirmed giardiasis cases notified to the South-Western Local Health District Public Health Unit from January to December 2016 was employed to investigate the risk factors for giardiasis. Two groups of controls were selected to increase response rate; Pertussis cases and neighbourhood (NBH) controls. A matched analysis was carried out for both control groups separately. Variables with a significant odds ratio (OR) in the univariate analysis were placed into a multivariable regression for each matched group, respectively. In the regression model with the NBH controls, age and sex were controlled as potential confounders. Identified risk factors included being under 5 years of age (aOR = 7.08; 95% confidence intervals (CI) 1.02–49.36), having a household member diagnosed with a gastrointestinal illness (aOR = 15.89; 95% CI 1.53–164.60) and having contact with farm animals, domestic animals or wildlife (aOR = 3.03; 95% CI 1.08–8.54). Cases that travelled overseas were at increased risk of infection (aOR = 19.89; 95% CI 2.00–197.37) when compared with Pertussis cases. This study provides an update on the epidemiology and associated risk factors of a neglected tropical disease, which can inform enhanced surveillance and prevention strategies in the developed metropolitan areas.
Self-reported patient history to assess hepatitis B virus serological status during a large screening campaign
Authors: Boyd A. , Gozlan J. , Carrat F. , Rougier H. , Girard P.-M. , Lacombe K. , Bottero J.
Published: September 2018

When assessing hepatitis B virus (HBV) status in clinical settings, it is unclear whether self-reports on vaccination history and previous HBV-test results have any diagnostic capacity. Of 3997 participants in a multi-centre HBV-screening study in Paris, France, 1090 were asked questions on their last HBV-test result and vaccination history. Discordance between self-reported history compared with infection status (determined by serology) was calculated for participants claiming ‘negative’, ‘effective vaccine’, ‘past infection’, or ‘chronic infection’ HBV-status. Serological testing revealed that 320 (29.4%) were non-immunised, 576 (52.8%) were vaccinated, 173 (15.9%) had resolved the infection and 21 (1.9%) were hepatitis B surface antigen positive. In total 208/426 (48.8%) participants with a self-reported history of ‘negative’ infection had a discordant serological result, in whom 128 (61.5%) were vaccinated and 74 (35.6%) had resolved infections. A total of 153/599 (25.5%) participants self-reporting ‘effective vaccine’ had a discordant serological result, in whom 100 (65.4%) were non-immunised and 50 (32.7%) were resolved infections. Discordance for declaring ‘past’ or ‘chronic infection’ occurred in 9/55 (16.4%) and 3/10 (30.0%) individuals, respectively. In conclusion, self-reported HBV-status based on participant history is partially inadequate for determining serological HBV-status, especially between negative/vaccinated individuals. More adapted patient education about HBV-status might be helpful for certain key populations.
Retirement Pension Reforms in Six European Social Insurance Schemes between 2000 and 2017: More Financial Sustainability and More Gender Inequality?
Authors: Arcanjo Manuela
Published: September 2018

In 2000, the European Union established three principles that should guide Member State pension systems and their reforms: the financial sustainability of pension systems; adequacy of pensions; and the modernisation of systems. The latter included the achievement of greater gender equality and sought to respond to the significant gender gaps in public pension systems. This article demonstrates how the reforms carried out over the period 2000–2017 have focused on strengthening the financial sustainability of systems but may also have contributed to even greater gender inequality in old age protection. To this end, we examine the major legislative amendments concerning eligibility criteria and entitlement conditions in six countries (Austria, Belgium, France, Germany, Portugal and Spain), as representative of the social insurance scheme.
Analyses of the internal transcribed rDNA spacers (ITS1 and ITS2) of Indian weevils of Odoiporus longicollis (Olivier) reveal gene flow between locations
Authors: Kumar Lalitha Sunil , Shankar Pallavi , Kulkarni Vishvas M.
Published: September 2018

An important step towards developing a successful integrated pest management (IPM) programme for the control of banana pseudostem weevil,Odoiporus longicollis(Olivier), a serious pest of banana in India, is the study of the population structure of the pest. In the present study, the genetic variation among 30 individual weevils ofO.longicolliscollected from six different locations was assessed by analysing the primary nucleotide sequences of the rDNA ITS1 and ITS2 regions. AMOVA, Mantel test, and the maximum likelihood trees of the haplotypes failed to reveal any phylogeographic structuring, which was confirmed by haplotype analysis and genetic differentiation estimates. The results indicate that the locations are not differentiated, i.e. there is gene flow between the locations. The star-shaped networks revealed a signature of demographic expansion that was confirmed by the different demographic tests. These results provide important information, which is essential for the development of suitable strategies for the control of this banana pest, as well as management of its resistance to insecticides.
Processes Controlling the Composition and Abundance of Arctic Aerosol
Authors: Willis Megan D. , Leaitch W. Richard , Abbatt Jonathan P.D.
Published: September 2018

The Arctic region is a harbinger of global change and is warming at a rate higher than the global average. While Arctic warming is driven by increases in anthropogenic greenhouse gases' in combination with local feedback mechanisms, short‐lived climate forcing agents, such as tropospheric aerosol, are also important drivers of Arctic climate. Arctic aerosol‐climate impacts vary seasonally as a result of the interplay between aerosol and different cloud types, available solar radiation, sea ice, surface albedo, Arctic and lower latitude removal processes, and atmospheric transport patterns. Photochemistry and efficient wet aerosol removal have low impact in winter but become important in spring to summer, dramatically altering aerosol chemical composition, and driving the size distribution from a pronounced accumulation mode toward a dominance of smaller particles. Retreating sea ice, increasing solar insolation and warmer temperatures in summer result in enhanced emissions from Arctic marine and terrestrial ecosystems, and anthropogenic sources, with impacts on the composition of gas and particle phases. Fractional cloud cover reaches a maximum in Arctic summer, in parallel with decreasing sea ice extent and surface albedo. This seasonal variation corresponds to significant changes in the net cloud radiative effect; changes that are affected by aerosol. This review summarizes our current knowledge of processes that control Arctic aerosol properties. We highlight both natural and anthropogenic processes that will be impacted by current and future sea ice loss. Efforts are needed to better constrain aerosol removal rates, characterize aerosol precursors, and constrain the seasonality and magnitude of aerosol‐cloud‐climate impacts.
Shark genomes provide insights into elasmobranch evolution and the origin of vertebrates
Authors: Hara Yuichiro , Yamaguchi Kazuaki , Onimaru Koh , Kadota Mitsutaka , Koyanagi Mitsumasa , Keeley Sean D. , Tatsumi Kaori , Tanaka Kaori , Motone Fumio , Kageyama Yuka , Nozu Ryo , Adachi Noritaka , Nishimura Osamu , Nakagawa Reiko , Tanegashima Chiharu , Kiyatake Itsuki , Matsumoto Rui , Murakumo Kiyomi , Nishida Kiyonori , Terakita Akihisa , Kuratani Shigeru , Sato Keiichi , Hyodo Susumu , Kuraku Shigehiro
Published: September 2018

Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and skates) and chimaeras, and the lack of established whole-genome sequences for the former has prevented our understanding of early vertebrate evolution and the unique phenotypes of elasmobranchs. Here we present de novo whole-genome assemblies of brownbanded bamboo shark and cloudy catshark and an improved assembly of the whale shark genome. These relatively large genomes (3.8–6.7 Gbp) contain sparse distributions of coding genes and regulatory elements and exhibit reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox C genes previously hypothesized to have been lost, as well as distinct gene repertories of opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and epigenomic resources, provides a foundation for the comprehensive, molecular exploration of phenotypes unique to sharks and insights into the evolutionary origins of vertebrates.
Genetic inhibition of an ATP synthase subunit extends lifespan in C. elegans
Authors: Xu Chen , Hwang Wooseon , Jeong Dae-Eun , Ryu Youngjae , Ha Chang Man , Lee Seung-Jae V. , Liu Lulu , He Zhi Ming
Published: September 2018

Mild inhibition of mitochondrial respiration leads to longevity. Disruption of mitochondrial respiratory components extends lifespan in Caenorhabditis elegans, but the effects appear to be complex and the underlying mechanism for lifespan regulation by mitochondrial respiratory genes is still not fully understood. Here, we investigated the role of Y82E9BR.3, a worm homolog of the ATP synthase subunit C, in modulating longevity in C. elegans. We found that the Y82E9BR.3 protein is localized in mitochondria and expressed in various tissues throughout development. RNAi knockdown of Y82E9BR.3 extends lifespan, decreases the accumulation of lipofuscin, and affects various physiological processes, including development delay, reproduction impairment and slow behavior. Further tissue-specific RNAi analysis showed that the intestine is a crucial organ for the longevity effects conferred by Y82E9BR.3 RNAi. Moreover, we demonstrated that lifespan extension by Y82E9BR.3 RNAi is associated with reduced mitochondrial function, as well as the suppression of complex I activity in mitochondria. Unexpectedly, Y82E9BR.3 RNAi knock down did not influence the whole-worm ATP level. Our findings first reveal the crucial role of Y82E9BR.3 in mitochondrial function and the underlying mechanism of how Y82E9BR.3 regulates lifespan in C. elegans.