bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Imputation for Cure Rate Quantile Regression with Censored Data
Authors: Wu Yuanshan , Yin Guosheng
Published: August 2016

The main challenge in the context of cure rate analysis is that one never knows whether censored subjects are cured or uncured, or whether they are susceptible or insusceptible to the event of interest. Considering the susceptible indicator as missing data, we propose a multiple imputation approach to cure rate quantile regression for censored data with a survival fraction. We develop an iterative algorithm to estimate the conditionally uncured probability for each subject. By utilizing this estimated probability and Bernoulli sample imputation, we can classify each subject as cured or uncured, and then employ the locally weighted method to estimate the quantile regression coefficients with only the uncured subjects. Repeating the imputation procedure multiple times and taking an average over the resultant estimators, we obtain consistent estimators for the quantile regression coefficients. Our approach relaxes the usual global linearity assumption, so that we can apply quantile regression to any particular quantile of interest. We establish asymptotic properties for the proposed estimators, including both consistency and asymptotic normality. We conduct simulation studies to assess the finite-sample performance of the proposed multiple imputation method and apply it to a lung cancer study as an illustration.
Psychological and behavioral acculturation in a social network of Mexican Americans in the United States and use of dental services
Authors: Maupome G. , McConnell W. R. , Perry B. L. , Marino R. , Wright E. R.
Published: August 2016

Objectives

We used data from the TalaSurvey study to examine associations between dental health experiences, social network characteristics, and levels of behavioral and psychological acculturation in one location in the American Midwest.

Methods

Starting in parishes and community organizations, we identified adults of Mexican origin living in Indianapolis, who were 1st‐ or 2nd‐generation immigrants from Tala, Mexico. Using a social networks methodology and following extensive formative research, we created an egocentric social network survey and administered it via face‐to‐face interviews. We identified the peers (alters) in interviewees’ (egos) personal networks. We asked egos about multiple oral health and dental care variables for self and for alters. Acculturation (psychological and behavioral) was measured with a validated tool. Through logistic and negative binomial regression, we examined the effects of acculturation and network composition on ego's dental insurance status, dental office visits, and the reason for most recent dental office visit.

Results

A total of 332 egos (mean age 36; 63% female) were interviewed: 90% were born in Mexico; 45% had completed elementary school or lower; and most had low income. Each ego named 3.9 (SD±1.9) alters in his/her personal network, for a total of 1299 alters (mean age 39; 61% female). Both behavioral acculturation and psychological acculturation were moderately associated with dental insurance coverage, and greater behavioral acculturation predicted more frequent dental care. More psychologically acculturated egos were more likely to seek preventive care. Further, egos with more highly educated networks sought care more frequently and for preventive purposes, net of ego's own education and acculturation.

Conclusions

This study contextualizes acculturation of Mexican Americans within the personal networks in which oral health discussion takes place. The findings underscore the critical importance of acculturation and social network factors in shaping a subgroup of Latinos’ orientation toward dental care.
4D Reconstruction of Blooming Flowers
Authors: Zheng Qian , Fan Xiaochen , Gong Minglun , Sharf Andrei , Deussen Oliver , Huang Hui
Published: August 2016

Flower blooming is a beautiful phenomenon in nature as flowers open in an intricate and complex manner whereas petals bend, stretch and twist under various deformations. Flower petals are typically thin structures arranged in tight configurations with heavy self‐occlusions. Thus, capturing and reconstructing spatially and temporally coherent sequences of blooming flowers is highly challenging. Early in the process only exterior petals are visible and thus interior parts will be completely missing in the captured data. Utilizing commercially available 3D scanners, we capture the visible parts of blooming flowers into a sequence of 3D point clouds. We reconstruct the flower geometry and deformation over time using a template‐based dynamic tracking algorithm. To track and model interior petals hidden in early stages of the blooming process, we employ an adaptively constrained optimization. Flower characteristics are exploited to track petals both forward and backward in time. Our methods allow us to faithfully reconstruct the flower blooming process of different species. In addition, we provide comparisons with state‐of‐the‐art physical simulation‐based approaches and evaluate our approach by using photos of captured real flowers.
War and socialism: why eastern Europe fell behind between 1950 and 1989†
Authors: Vonyó Tamás
Published: August 2016

This article reconsiders the relative growth performance of centrally planned economies in the broader context of postwar growth in Europe. It reports a new dataset of revised estimates for investment rates in eastern European countries between 1950 and 1989. Complemented with data on other growth determinants, this evidence is used to re‐evaluate the socialist growth record in a conditional convergence framework with a panel of 24 European countries. After controlling for relative backwardness, investment rates, and improvements in human capital, the findings show that centrally planned economies underperformed due to their relative inefficiency only after the postwar golden age. In the 1950s and 1960s, eastern Europe was falling behind mainly due to relatively low levels of investment and weak reconstruction dynamics. Both are explained, in part, by the lack of labour‐supply flexibility that, in turn, resulted from the comparatively much larger negative impact of the war on population growth in eastern Europe.
Britain as a debtor: Indian sterling balances, 1940–53
Authors: de Paiva Abreu Marcelo
Published: August 2016

The British war effort in the Second World War depended on US Lend‐Lease and the accumulation of sterling balances by other countries, including the Empire. By the end of the war outstanding balances were equivalent to 60 per cent of British net receipts under Lend‐Lease. Of the total sterling balances, about a third was accumulated by India. This article seeks to evaluate the costs incurred by India in the reduction of balances after the war. The accumulation of balances and their use to repatriate India's sterling debt is described. British efforts to convince India to accept a partial cancellation of the balances are analysed, singling out the crucial role of Keynes. The negotiations after independence are detailed, including releases, transfers to Pakistan, settlement of pensions, purchase of military stores, and gold sales. The possible contribution of British divestment to reduce outstanding balances is assessed. The Indian case is compared with those of other holders, such as Portugal, Brazil, Argentina, and Egypt. The links between the accumulation of sterling balances and inflation are considered. In the end there was a significant reduction in the purchasing power of sterling balances, but not for the reasons anticipated by London.
Good collateral circulation predicts favorable outcomes in intravenous thrombolysis: a systematic review and meta‐analysis
Authors: Leng X. , Lan L. , Liu L. , Leung T. W. , Wong K. S.
Published: August 2016

Background and purpose

Baseline collateral status has been correlated with outcomes of acute ischaemic stroke patients receiving intravenous thrombolysis (IVT) in previous studies. We carried out the current systematic review and meta‐analysis to synthesize currently available evidence regarding such correlations.

Methods

Full‐text articles published since 2000 were retrieved and screened. The overall effect sizes of good versus poor collateral status over a series of outcomes and certain baseline features were estimated by random‐effects models and presented in risk ratios (RRs) or mean differences.

Results

Overall, 28 (3057 patients) and 14 (1584 patients) studies were included in qualitative and quantitative synthesis, respectively. Compared with poor pre‐treatment collateral status, good collaterals showed a beneficial effect over the primary outcome of a favorable functional outcome at 3 or 6 months [RR, 2.45; 95% confidence interval, 1.94–3.09; P < 0.001] in acute ischaemic stroke patients receiving IVT treatment. However, such an effect tended to be different between studies with prescribed time windows of 3, 4.5 and > 4.5 h (up to 7 h), with the RRs being 2.21, 2.48 and 5.00, respectively (I2 = 53%). Good pre‐treatment collaterals were also associated with a smaller infarct size at baseline, and a lower rate of symptomatic intracranial hemorrhage and a higher rate of neurological improvement early after IVT treatment.

Conclusions

The present study has demonstrated the prognostic value of baseline collateral circulation for outcomes of acute ischaemic stroke patients receiving intravenous reperfusion therapies, studied with different time windows of up to 7 h after ictus for IVT therapy.
The Role of Multiple Large Shareholders in the Choice of Debt Source
Authors: Boubaker Sabri , Rouatbi Wael , Saffar Walid
Published: August 2016

This paper examines the effect of multiple large shareholders (MLS) on debt choice. Using a sample of 654 French‐listed firms over the period 1998‐2013, we find that reliance on bank debt increases with the presence and voting power of MLS. This result is robust to endogeneity concerns and to several sensitivity tests. Moreover, we find that the effect of MLS on debt choice is more pronounced when agency problems between controlling and minority shareholders are more severe. Taken together, our results suggest that MLS reduce the controlling owner's incentive to avoid bank monitoring, leading to greater reliance on bank debt.
Circadian oscillations of KaiA‐KaiC and KaiB‐KaiC complex formations in an in vitro reconstituted KaiABC clock oscillator
Authors: Murakami Reiko , Mutoh Risa , Ishii Ketaro , Ishiura Masahiro
Published: August 2016

The circadian clock is an endogenous biological mechanism that generates autonomous daily cycles in physiological activities. The phosphorylation levels of KaiC oscillated with a period of 24 h in an ATP‐dependent clock oscillator reconstituted in vitro from KaiA, KaiB and KaiC. We examined the complex formations of KaiA and KaiB with KaiC in the KaiABC clock oscillator by fluorescence correlation spectrometry (FCS) analysis. The formation of KaiB‐containing protein complex(es) oscillated in a circadian manner, with a single peak at 12 h and single trough at 24 h in the circadian cycle, whereas that of KaiA‐containing protein complex(es) oscillated with two peaks at 12 and 24 h. FCS and surface plasmon resonance analyses showed that the binding affinity of KaiA for a mutant KaiC with Ala substitutions at the two phosphorylation sites considered to mimic the nonphosphorylated form of KaiC (np‐KaiC) was higher than that for a mutant KaiC with Asp substitutions at the two phosphorylation sites considered to mimic the completely phosphorylated form of KaiC (cp‐KaiC). The results from the study suggest that a KaiA‐KaiB‐cp‐KaiC ternary complex and a KaiA‐np‐KaiC complex were formed at 12 and 24 h, respectively.
Psychometric field testing of the HemoLatin‐QoL questionnaire
Authors: Remor E.
Published: August 2016

Purpose

The present work aims to describe the psychometric field testing of the Latin American Hemophilia‐Specific Quality of Life Assessment Measure for Adults (the HemoLatin‐QoL questionnaire) in 306 adults (age range 16–80) with haemophilia living in seven Latin American countries (i.e. Argentina, Brasil, Chile, Nicaragua, Panama, Uruguay and Venezuela).

Methods

The HemoLatin‐QoL questionnaire is a patient‐reported outcomes instrument that evaluates relevant health‐related quality‐of‐life domains for haemophilia, selected by an exploratory qualitative study with patients, and taking into account healthcare specialists in haemophilia also. Psychometric examination involved the assessment of the data quality, scaling assumptions, reliability (internal consistency and test–retest) and evidences for validity (dimensionality, convergent and external‐related clinical criterion).

Results

A 27‐item version with a six‐factor structure (e.g. physical functioning, pain, emotional functioning, social functioning, mental health, environment conditions) was psychometrically tested using exploratory factor analysis. The instrument and its subscales fulfilled the construct (dimensionality, convergent and criterion‐related) validity hypotheses. The criteria for adequate internal consistency and test–retest reliability of the HemoLatin‐QoL instrument were also met.

Conclusion

The HemoLatin‐QoL showed acceptable psychometric properties with respect to responses from haemophilia patients. The questionnaire is now available for adult assessment and is ready for use in research in Latin America.
Long‐Term Use and Safety of Migraine Preventive Medications
Authors: VanderPluym Juliana , Evans Randolph W. , Starling Amaal J.
Published: August 2016

Migraine preventive medications are used to reduce the frequency, severity, and disability of migraine attacks. Once migraine preventive therapy is initiated, the question of how long to maintain this therapy arises. This article will explore the literature pertaining to the long‐term use of migraine preventive medications, including length of treatment and safety with long‐term exposure.
Australian Girls' Reading in the First Half of the Twentieth Century: A Survey of the Necessary Approaches
Authors: Lowe Bronwyn
Published: August 2016

Although the history of girlhood has attracted growing attention around the world, there still remains a lot to uncover, particularly in the Australian context. This article addresses the history of girls' reading habits in the first half of the twentieth century: examining where progress has been made in this area, and looking at avenues for further discussion – particularly in the examination of gender roles and in notions of growing up. This article argues that in completing a history of girls' reading habits, new light can be shed on these important areas of study. The article also addresses questions of methodology, examining autobiographies and memoirs as a particularly rich source for memories about girls' reading.
Presentation for care and antenatal management of HIV in the UK, 2009−2014
Authors: French CE , Thorne C , Byrne L , Cortina‐Borja M , Tookey PA
Published: August 2016

Objectives

Despite very low rates of vertical transmission of HIV in the UK overall, rates are higher among women starting antenatal antiretroviral therapy (ART) late. We investigated the timing of key elements of the care of HIV‐positive pregnant women [antenatal care booking, HIV laboratory assessment (CD4 count and HIV viral load) and antenatal ART initiation], to assess whether clinical practice is changing in line with recommendations, and to investigate factors associated with delayed care.

Methods

We used the UK's National Study of HIV in Pregnancy and Childhood for 2009−2014. Data were analysed by fitting logistic regression and Cox proportional hazards models.

Results

A total of 5693 births were reported; 79.5% were in women diagnosed with HIV prior to that pregnancy. Median gestation at antenatal booking was 12.1 weeks [interquartile range (IQR) 10.0–15.6 weeks] and booking was significantly earlier during 2012–2014 vs. 2009–2011 (P < 0.001), although only in previously diagnosed women. Overall, 42.2% of pregnancies were booked late (≥ 13 gestational weeks). Among women not already on treatment, antenatal ART commenced at a median of 21.4 (IQR18.1–24.5) weeks and started significantly earlier in the most recent time period (P < 0.001). Compared with previously diagnosed women, those newly diagnosed during the current pregnancy booked later for antenatal care and started antenatal ART later (both P < 0.001). Multivariable analyses revealed demographic variations in access to or uptake of care, with groups including migrants and parous women initiating care later.

Conclusions

Although women are accessing antenatal and HIV care earlier in pregnancy, some continue to face barriers to timely initiation of antenatal care and ART.
Elvitegravir concentrations in seminal plasma in HIV‐1‐infected men
Authors: Imaz A , Niubó J , Kashuba AD , Ferrer E , Sykes C , Rozas N , Acerete L , Vila A , Podzamczer D
Published: August 2016

Objectives

The aim of the study was to quantify elvitegravir (EVG) concentrations in the semen of HIV‐1‐infected men receiving antiretroviral therapy (ART) consisting of an elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) single‐tablet regimen.

Methods

A phase IV, cross‐sectional study was carried out including HIV‐1‐infected male adults with suppressed plasma HIV‐1 RNA who switched ART to EVG/COBI/FTC/TDF. Total EVG concentrations at the end of the dosing interval (C24 h) and HIV‐1 RNA were measured in paired seminal plasma (SP) and blood plasma (BP) samples 4 weeks after switching to EVG/COBI/FTC/TDF. Validated liquid chromatography−tandem mass spectrometry (LC‐MS/MS) was used to quantify EVG concentrations, and HIV‐1 RNA was determined by real‐time polymerase chain reaction (PCR).

Results

Ten men were included. Their median age was 40 years (range 24–47 years), the median time on ART was 50 months (range 10–186 months), the median time with plasma HIV‐1 RNA < 40 copies/mL was 37 months (range 7–113 months), and the median CD4 count was 737 cells/μL (range 190–1122 cells/μL). Four weeks after switching to EVG/COBI/FTC/TDF, all subjects had HIV‐1 RNA < 40 copies/mL in both BP and SP. Median EVG C24 h was 277 ng/mL (range 64.8–1790 ng/mL) in BP and 169 ng/mL (range 12.8–792 ng/mL) in SP. A significant correlation was observed between BP and SP EVG concentrations (Spearman rho 0.952; P < 0.001). The median SP:BP EVG concentration ratio was 0.39 (range 0.20–0.92). EVG C24 h in SP was at least 23‐fold the in vitro protein‐unbound 50% effective response (EC50) of HIV‐1 clinical isolates (0.04–0.55 ng/mL). In all but one individual, EVG C24 h in SP was also higher than the blood plasma protein binding‐adjusted 95% inhibitory concentration (IC95) of wild‐type HIV‐1 (45 ng/mL).

Conclusions

Seminal EVG concentrations in HIV‐infected men treated with EVG/COBI/FTC/TDF sufficed to contribute to maintaining HIV‐1 RNA suppression in this compartment.
Direct‐acting antivirals in hepatitis C virus (HCV)‐infected and HCV/HIV‐coinfected patients: real‐life safety and efficacy
Authors: Milazzo L , Lai A , Calvi E , Ronzi P , Micheli V , Binda F , Ridolfo AL , Gervasoni C , Galli M , Antinori S , Sollima S
Published: August 2016

Objectives

Clinical trials of all‐oral direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting.

Methods

In this prospective observational study, all the HCV‐monoinfected and HCV/HIV‐coinfected patients undergoing HCV treatment with all‐oral DAA regimens in a routine clinical setting from December 2014 to December 2015 were included in the analysis. Sustained virological response 12 weeks after the end of therapy (SVR12) and reported adverse events (AEs) were evaluated. Resistance‐associated variants (RAVs) were analysed in a subgroup of patients at baseline and at the time of viral rebound in those with virological failure.

Results

One‐hundred and nine patients (51 HCV‐infected and 58 HCV/HIV‐coinfected) were enrolled in the study. Sixty per cent had cirrhosis and 52% were pegylated interferon and ribavirin (pegIFN/RBV)‐experienced. Thirty‐six per cent received ombitasvir + paritaprevir/ritonavir + dasabuvir, 25% sofosbuvir + daclatasvir, 16% sofosbuvir + simeprevir, 17% sofosbuvir + ribavirin and 6% sofosbuvir + ledipasvir; ribavirin was used in 57% of subjects. The SVR12 rate was 91% and 96% in HIV‐infected and uninfected patients, respectively (P = 0.44). The 4‐week HCV viral decline was similar in the two groups. RAVs were found at baseline in 23 of 49 patients and did not affect SVR12. No predictors of SVR12 were identified in our cohort.

Conclusions

Treatment with all‐oral DAA combinations of patients infected with HCV and with HCV/HIV under real‐life conditions led to high and similar rates of SVR12. Moreover, the historical factors associated with a sustained virological response to pegIFN/RBV were not predictive of the response to all‐oral DAAs.
The Modernization of Colonialism and the Educability of the “Native”: Transpacific Knowledge Networks and Education in the Interwar Years
Authors: McLeod Julie , Paisley Fiona
Published: August 2016

This article focuses on a seminar-conference held in Hawaii in 1936 on the “educability” of native peoples. The seminar-conference was convened by New Zealand anthropologist Felix Keesing and Yale education professor Charles Loram and supported by the Carnegie Corporation, among other organizations. Conference delegates-who came from across the Pacific, including the U.S. mainland, Australia, and New Zealand, and from as far as South Africa-joined to discuss the future of colonial education. The residential conference, which lasted several weeks, resulted in published proceedings and the establishment of extensive transpacific networks. One in a series of international congresses on education that took place during the interwar years, the 1936 Hawaii conference offers unique insight into the transnational dialogue among academics, education practitioners, colonial administrators, and, in some cases, Indigenous spokespeople, concerning the modernization of colonialism and new forms of citizenship in the era of progressive education and cultural internationalism.
Gateways to the West, Part I: Education in the Shaping of the West
Authors: Beadie Nancy , Williamson-Lott Joy , Bowman Michael , Frizell Teresa , Guzman Gonzalo , Hyun Jisoo , Johnson Joanna , Nicholas Kathryn , Phillips Lani , Wellington Rebecca , Yoshida La'akea
Published: August 2016

In 1950, theDenver Catholic Registerpublished an article describing and challenging the varieties of “prejudice” that a military pilot moving from base to base in the United States might encounter. To “successfully transact business” in the vicinity of various “metropolitan landing fields,” the writer admonished, the veteran must:

Remember to be not too sanguine about people of Oriental ethnic origin when talking with a merchant in Seattle, that he must speak about the Jew with a slight sneer in Eastern cities, that the Colored person must be “kept in his place” in Houston, that in reservation country the Indian must be treated as a man would treat a child and that in the San Antonio-Los Angeles-Denver triangle it is wiser to remember that the Mexican-American is a second-class citizen.
The role of breeding phenology and aggregation of waterfowl on avian influenza dynamics in southern Africa
Authors: Mundava Josphine , Caron Alexandre , de Garine‐Wichatitsky Michel , Abolnik Celia , Mundy Peter , Gaidet Nicolas
Published: August 2016

Recent outbreaks of highly pathogenic avian influenza virus (AIV) in birds, humans and other mammalian species calls for a better understanding of virus dynamics in wild bird species and populations that act as maintenance hosts. Host ecology influences the transmission of pathogens and can be used to explore and infer pathogen dynamics. Most of the ecological processes proposed to explain AIV transmission in wild birds have been derived from studies conducted in the temperate and boreal regions of the northern hemisphere. We evaluate the role of two key drivers of AIV dynamics in a waterfowl community in Zimbabwe (southern Africa): (1) the recruitment of young birds and (2) the seasonal aggregation of birds. We analyse the seasonal variation of AIV prevalence in waterfowl and overlay these data with the phenology of reproduction and the seasonal variation in the local abundance of these species. We find that the breeding period of southern Afrotropical waterfowl species is more extended and somewhat less synchronized among species in the community than is the case in temperate and boreal waterfowl communities. Young birds are recorded at most times of the year, and these immunologically naïve individuals can therefore act as new hosts for AIV throughout the year within the wild bird population. Although host aggregation peaks in the cold‐dry to hot‐dry season, birds still aggregate throughout the year and this potentially spreads the opportunities for first infection of juveniles and other naïve birds temporally. We did not find a relationship between season, AIV prevalence in waterfowl, the influx of juveniles or the gradual aggregation of birds during the dry season. Therefore, the main drivers of AIV dynamics (juvenile influx and host abundance/aggregation), although present in Afrotropical regions, could not explain the AIV seasonal patterns in our study in contrast to results reported from temperate and boreal regions. These differences imply variation in the risk of AIV circulation in waterfowl and in the risk of spread to poultry, other animals or humans.
Satisfaction of health‐care providers with electronic health records and perceived barriers to its implementation in the United Arab Emirates
Authors: Bani‐issa Wegdan , Al Yateem Nabeel , Al Makhzoomy Ibtihal Khalaf , Ibrahim Ali
Published: August 2016

The integration of electronic health records (EHRs) has shown promise in improving health‐care quality. In the United Arab Emirates, EHRs have been recently adopted to improve the quality and safety of patient care.

A cross‐sectional survey of 680 health‐care providers (HCPs) was conducted to assess the satisfaction of HCPs in the United Arab Emirates with EHRs' impact on access/viewing, documentation and medication administration and to explore the barriers encountered in their use. Data were collected over 6 months from April to September 2014.

High overall satisfaction with EHRs was reported by HCPs, suggesting their acceptance. Physicians reported the greatest overall satisfaction with EHRs, although nurses showed significantly higher satisfaction with the impact on medication administration compared with other HCPs. The most significant barriers reported by nurses were lack of belief in the value of EHRs for patients and lack of adequate computer skills.

Given the large investment in technology, additional research is necessary to promote the full utilization of EHRs. Nurses need to be aware of the value of EHRs for patient care and be involved in all stages of EHR implementations to maximize its meaningful use for better clinical outcomes.
NOD1 in the modulation of host–microbe interactions and inflammatory bone resorption in the periodontal disease model
Authors: Chaves de Souza João Antônio , Frasnelli Sabrina Cruz Tfaile , Curylofo‐Zotti Fabiana de Almeida , Ávila‐Campos Mário Julio , Spolidório Luis Carlos , Zamboni Dario Simões , Graves Dana T. , Rossa Carlos
Published: August 2016

Periodontitis is a chronic inflammatory condition characterized by destruction of non‐mineralized and mineralized connective tissues. It is initiated and maintained by a dysbiosis of the bacterial biofilm adjacent to teeth with increased prevalence of Gram‐negative microorganisms. Nucleotide‐binding oligomerization domain containing 1 (NOD1) is a member of the Nod‐like receptors (NLRs) family of proteins that participate in the activation of the innate immune system, in response to invading bacteria or to bacterial antigens present in the cytoplasm. The specific activating ligand for NOD1 is a bacterial peptidoglycan derived primarily from Gram‐negative bacteria. This study assessed the role of NOD1 in inflammation‐mediated tissue destruction in the context of host–microbe interactions. We used mice with whole‐genome deletion of the NOD1 gene in a microbe‐induced periodontitis model using direct injections of heat‐killed Gram‐negative or Gram‐negative/Gram‐positive bacteria on the gingival tissues. In vitro experiments using primary bone‐marrow‐derived macrophages from wild‐type and NOD1 knockout mice provide insight into the role of NOD1 on the macrophage response to Gram‐negative and Gram‐negative/Gram‐positive bacteria. Microcomputed tomography analysis indicated that deletion of NOD1 significantly aggravated bone resorption induced by Gram‐negative bacteria, accompanied by an increase in the numbers of osteoclasts. This effect was significantly attenuated by the association with Gram‐positive bacteria. In vitro, quantitative PCR arrays indicated that stimulation of macrophages with heat‐killed Gram‐negative bacteria induced the same biological processes in wild‐type and NOD1‐deficient cells; however, expression of pro‐inflammatory mediators was increased in NOD1‐deficient cells. These results suggest a bone‐sparing role for NOD1 in this model.
Intermittent Capture of the Left Bundle With Permanent His Bundle Pacing: Mechanistic Insights and Implications for an Emerging Field
Authors: FRIEDMAN DANIEL J. , HJORTH MARKUS A. , SUN ALBERT Y. , ATWATER BRETT D.
Published: August 2016

LBBB and His Bundle Pacing

We present a case of a patient with elevated His lead capture thresholds and intermittent recruitment of the left bundle. The patient underwent a noninvasive electrophysiology study and was determined to have a left bundle branch block due to postrepolarization refractoriness. The nature of bundle branch block can have important implications for optimal patient selection and device programming in the emerging field of His bundle pacing.
Does body mass index impact on muscle wasting and recovery following critical illness? A pilot feasibility observational study
Authors: Segaran E. , Wandrag L. , Stotz M. , Terblanche M. , Hickson M.
Published: August 2016

Background

Critical illness is associated with muscle loss, weakness and poor recovery. The impact that illness and the ensuing metabolic response has on obese patients is not known. Objectives were to test if obese patients lose less muscle depth compared to non‐obese patients; if a reduction in muscle depth was associated with reduced strength and recovery; and to assess the feasibility of these methods with a range of body mass index's (BMI).

Methods

A prospective observational pilot study of muscle depth in critically ill patients categorised by BMI was performed. Muscle depth changes were assessed by ultrasound on study days 1, 3, 5, 7, 12 and 14. Strength was measured via handgrip dynamometry and Medical Research Council (MRC) sum score on waking and at discharge from the intensive care unit. Level of dependency was measured with the Barthel index.

Results

44 critically ill patients; 17 had normal BMI, 10 were overweight and 17 were obese. The three groups did not differ in baseline characteristics, except obese patients had significantly greater initial muscle depth. Muscle depth loss was similar between the BMI groups at each of the time points. Handgrip and MRC sum score were only possible in a small number of patients because of reduced alertness and weakness. Majority were deemed fully dependent based on the Barthel index.

Conclusions

Obese patients lost muscle depth in a comparable manner to non‐obese patients, suggesting that BMI may not prevent muscle depth loss. It was not possible to determine the effect on strength because the clinical condition of patients precluded reliable measurements.
Drug Coated Balloon Is Less Effective for Treatment of DES In‐Stent Restenosis Both in Native Coronary Arteries and Saphenous Vein Grafts: Results From a Bicenter Registry
Authors: Resch Markus , Ostheim Patrick , Endemann Dierk H. , Debl Kurt , Buchner Stefan , Birner Christoph , Maier Lars S. , Kerber Sebastian , Luchner Andreas , Griese Daniel P.
Published: August 2016

Background

The paclitaxel drug coated balloon (DCB) is an established treatment for bare metal stent (BMS) in‐stent restenosis (ISR) in native coronary arteries. The evidence of DCB‐application for drug eluting stent (DES) ISR both in native coronaries and saphenous vein grafts (SVG) is limited. Aim of our study was to compare the differential efficacy of DCB for treatment of BMS‐ and DES‐ISR in native coronary vessels and SVGs.

Methods and Results

N = 135 DCB‐treated patients with available follow up (FU) angiography were included in this retrospective study. Patients received treatment between April 2009 and March 2013 at 2 tertiary care hospitals in Germany. DCB was applied in BMS‐ISR (n = 65; 48%) and DES‐ISR (n = 70; 52%). DCB‐treated lesions were located in native coronary arteries (n = 110; 81%; BMS‐ISR: n = 58; 53%; DES‐ISR: n = 52; 47%) and SVGs (n = 25; 19%; BMS‐ISR: n = 7, 28%; DES‐ISR: n = 18, 72%). Median FU was 12 months. Endpoints were binary restenosis and target lesion revascularization (TLR). Binary restenosis (29% vs. 57%; P < 0.01) and TLR (18% vs. 46%; P < 0.01) were significantly more frequent in DES‐ISR versus BMS‐ISR. In SVGs, TLR was required in 72% (DES‐ISR) versus 14% (BMS‐ISR); P = 0.02. In the Kaplan–Meier‐analysis freedom from both endpoints was significantly decreased in the DES‐lesions both in the total population (binary restenosis P < 0.01; TLR P < 0.01) and native coronaries (binary restenosis P = 0.02; TLR P = 0.04).

Conclusions

DCB treatment is less effective in DES‐ISR than in BMS‐ISR. The diminished efficacy of DCB treatment is even more pronounced in DES‐ISR located within degenerated SVGs.
Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis
Authors: Winzeler B. , Lengsfeld S. , Nigro N. , Suter‐Widmer I. , Schütz P. , Arici B. , Bally M. , Blum C. , Bock A. , Huber A. , Müller B. , Christ‐Crain M.
Published: August 2016

Background

Fluid restriction (FR), the first‐line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s‐copeptin and s‐mid‐regional pro‐atrial natriuretic peptide (s‐MR‐proANP), as possible predictors of FR response.

Methods

In this prospective observational study, we included patients with profound hyponatraemia (s‐sodium <125 mmol L−1) due to SIAD. Patients were classified as FR responders (increase in s‐sodium concentration of >3 mmol L−1 within 24 h) or nonresponders (increase of ≤3 mmol L−1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis.

Results

Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u‐sodium and u‐osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4–95.8, P = 0.004 and OR 34.8, 95% CI 1.2–1038.8, P = 0.041, respectively). The association of u‐sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s‐MR‐proANP were associated with nonresponse (OR 0.03, 95% CI 0.003–0.3, P = 0.004), whereas s‐copeptin was not significantly associated with response to FR.

Conclusion

Easily measured laboratory parameters, especially u‐sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD.
Functional characterization of the Aspergillus nidulans glucosylceramide pathway reveals that LCB Δ8‐desaturation and C9‐methylation are relevant to filamentous growth, lipid raft localization and Psd1 defensin activity
Authors: Fernandes C. M. , de Castro P. A. , Singh A. , Fonseca F. L. , Pereira M. D. , Vila T. V. M. , Atella G. C. , Rozental S. , Savoldi M. , Del Poeta M. , Goldman G. H. , Kurtenbach E.
Published: August 2016

C8‐desaturated and C9‐methylated glucosylceramide (GlcCer) is a fungal‐specific sphingolipid that plays an important role in the growth and virulence of many species. In this work, we investigated the contribution of Aspergillus nidulans sphingolipid Δ8‐desaturase (SdeA), sphingolipid C9‐methyltransferases (SmtA/SmtB) and glucosylceramide synthase (GcsA) to fungal phenotypes, sensitivity to Psd1 defensin and Galleria mellonella virulence. We showed that ΔsdeA accumulated C8‐saturated and unmethylated GlcCer, while gcsA deletion impaired GlcCer synthesis. Although increased levels of unmethylated GlcCer were observed in smtA and smtB mutants, ΔsmtA and wild‐type cells showed a similar 9,Me‐GlcCer content, reduced by 50% in the smtB disruptant. The compromised 9,Me‐GlcCer production in the ΔsmtB strain was not accompanied by reduced filamentation or defects in cell polarity. When combined with the smtA deletion, smtB repression significantly increased unmethylated GlcCer levels and compromised filamentous growth. Furthermore, sdeA and gcsA mutants displayed growth defects and raft mislocalization, which were accompanied by reduced neutral lipids levels and attenuated G. mellonella virulence in the ΔgcsA strain. Finally, ΔsdeA and ΔgcsA showed increased resistance to Psd1, suggesting that GlcCer synthesis and fungal sphingoid base structure specificities are relevant not only to differentiation but also to proper recognition by this antifungal defensin.
Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis
Authors: Xiong Fangjie , Zhang Rui , Meng Zhigang , Deng Kexuan , Que Yumei , Zhuo Fengping , Feng Li , Guo Sundui , Datla Raju , Ren Maozhi
Published: August 2016

The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants.

Using engineered rapamycin‐sensitive Binding Protein 12‐2 (BP12‐2) plants, the present study showed that combined treatment with rapamycin and active‐site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis.

Based on this system, we revealed that TOR signaling plays a crucial role in modulating the transition from heterotrophic to photoautotrophic growth in Arabidopsis. Ribosomal protein S6 kinase 2 (S6K2) was identified as a direct downstream target of TOR, and the growth of TOR‐suppressed plants could be rescued by up‐regulating S6K2. Systems, genetic, and biochemical analyses revealed that Brassinosteriod Insensitive 2 (BIN2) acts as a novel downstream effector of S6K2, and the phosphorylation of BIN2 depends on TOR‐S6K2 signaling in Arabidopsis.

By combining pharmacological with genetic and biochemical approaches, we determined that the TOR‐S6K2‐BIN2 signaling pathway plays important roles in regulating the photoautotrophic growth of Arabidopsis.
Demands and challenges for patients with sickle‐cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia
Authors: Alsultan Abdulrahman , Jastaniah Wasil , Al Afghani Sameera , Al Bagshi Muneer H. , Nasserullah Zaki , Al‐Suliman Ahmed M. , Alabdulaali Mohammed K.
Published: August 2016

Allogeneic HSCT is the only curative treatment for SCD. In this study, we estimated the number of Saudi patients with SCD who are candidates for HSCT. We used the presence of overt stroke, recurrent ACS, and frequent severe pain crisis as indications for HSCT. We calculated the frequencies of these complications among a Saudi SCD cohort of 376 patients with SCD, 250 from SW and 126 from Eastern (E) provinces. We found that 59 (23.6%) of SW patients were transplant candidates compared to 22 (17.4%) from E province. It is estimated that about 61 000 patients with SCD live in Saudi Arabia. Thus, the projected number of Saudi patients with SCD who are candidates for HSCT is 10 536 patients. Of those, 2148 are children. The burden of SCD on HSCT centers in Saudi Arabia is substantial and is difficult currently to meet the demand. We recommend recruiting/training more transplant physicians and nurses, expand current capacity of centers if feasible, and open new transplant centers to make HSCT a practical therapeutic option for patients with severe SCD in Saudi Arabia.
Vitamin C supplementation to optimize growth, health and stress resistance in aquatic animals
Authors: Dawood Mahmoud A.O. , Koshio Shunsuke
Published: August 2016

Vitamins are organic compounds that can be synthesized from other essential nutrients; however, they are required in trace amounts from an exogenous source for normal growth, reproduction and health. Vitamin C (ascorbic acid, AA) is an essential micronutrient for normal growth and physiological function of most aquatic animals. In terrestrial animal nutrition, vitamin C has recently spurred scientific interest because of the increasing knowledge on vitamin C involvement in gene expression, cell cycle and reproduction in mammals; in addition, recent advances in molecular biology techniques allow the more effective estimation of the effect of vitamin C on metabolism and physiology. In contrast, this information is scarce in aquatic animal nutrition, as studies have essentially focused on the estimation of minimum vitamin C requirement for maximum growth and immune response as well as for the formulation of least‐cost diet. This scarcity of information is also due to the lack of well‐established indicators of vitamin C status in aquatic organisms. The present review summarizes and discusses information about vitamin C sources, bioavailability, deficiency and requirement in aquatic animals to plan further studies. In the future, vitamin C nutrition studies in aquaculture should also include immune responses, histopathology of the gills, liver, gonad development, gamete quality and quantity, fecundity, larvae survival and gene expression. Dietary vitamin C requirements should be estimated at every life‐history stage of cultured species. All this information will allow a better understanding of the essentiality of vitamin C in aquatic animal growth, development, reproduction and health.
The other face of Eurolegalism: The multifaceted convergence of national enforcement styles
Authors: Bastings Lincey , Mastenbroek Ellen , Versluis Esther
Published: August 2016

This article analyzes the implications of European integration for national regulatory enforcement. More specifically, it tests the Eurolegalism thesis, which holds that the tendency of using more detailed, prescriptive European Union (EU) regulation combined with more public and private enforcement leads to a convergence in national enforcement styles. It does so by developing and applying a fine‐grained conceptualization of enforcement style. This conceptualization forms the basis of a focused comparison of enforcement of the highly detailed and strict EU Packaging Waste Directive in the Netherlands and Germany – two countries known for their opposed enforcement styles. Our analysis shows that although convergence toward a more insistent enforcement style seems to have taken place, the two countries have arrived at this position in markedly different ways. By identifying differences in style underneath the surface of convergence, the article qualifies the Eurolegalism argument, thus, advancing the literature on EU enforcement styles and deepening our understanding of the subtle and divergent ways in which common international regulatory inputs may affect domestic enforcement.
Human Rights: What the United States Might Learn from the Rest of the World and, Yes, from American Sociology
Authors: Blau Judith
Published: August 2016

The U.S. Constitution includes civil and political rights—as individual rights—but does not include what is internationally understood to be “human rights,” namely rights we enjoy as equals, including economic, social, and cultural rights, and protections for vulnerable persons, such as children, minorities, mothers, and refugees. The United States has not ratified any international (United Nations) or regional (Organization of American States) human rights treaty, is not a party to the Rome Statute that established the International Criminal Court, and is no longer a member of the United Nations Educational, Scientific, and Cultural Organization. It might be concluded that Americans do not know what human rights are. It is more complicated than that. While opinion polls show that Americans often endorse individual rights—e. g., the rights of women—they do not frame them as being interdependent or being within the purview of government. Can we conclude that human rights have no place in the United States? Not at all. This article concludes by showing that many U.S. institutions of higher learning have programs in human rights and that some academic associations, including the American Sociological Association, recognize human rights.
Establishing robustness of a spatial dataset in a tolerance‐based vector model
Authors: Belussi Alberto , Migliorini Sara , Negri Mauro , Pelagatti Giuseppe
Published: August 2016

Spatial data are usually described through a vector model in which geometries are represented by a set of coordinates embedded into an Euclidean space. The use of a finite representation, instead of the real numbers theoretically required, causes many robustness problems which are well known in the literature. Such problems are made even worse in a distributed context, where data is exchanged between different systems and several perturbations can be introduced in the data representation.

In order to discuss the robustness of a spatial dataset, two implementation models have to be distinguished: the identity and the tolerance model. The robustness of a dataset in the identity model has been widely discussed in the literature and some algorithms of the Snap Rounding (SR) family can be successfully applied in such contexts. Conversely, this problem has been less explored in the tolerance model. The aim of this article is to propose an algorithm inspired by those of the SR family for establishing or restoring the robustness of a vector dataset in the tolerance model. The main ideas are to introduce an additional operation which spreads instead of snapping geometries, in order to preserve the original relation between them, and to use a tolerance region for such an operation instead of a single snapping location. Finally, some experiments on real‐world datasets are presented, confirming how the proposed algorithm can establish the robustness of a dataset.