bluuebunny/crossref_metadata_2025_split huggingface dataset:
Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case‒control study
Authors: van Velzen Alice S. , Eckhardt Corien L. , Peters Marjolein , Oldenburg Johannes , Cnossen Marjon , Liesner Ri , Morfini Massimo , Castaman Giancarlo , McRae Simon , van der Bom Johanna G. , Fijnvandraat Karin ,   the INSIGHT consortium
Published: March 2020

SummaryInhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma‐derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case‒control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case‒control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2–40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma‐derived FVIII concentrates (adjusted odds ratio 0·96, 95% confidence interval (CI) 0·36–2·52) or for specific types of FVIII concentrates.
The application of ‘omics’ to pulmonary arterial hypertension
Authors: Harbaum Lars , Rhodes Christopher J. , Otero‐Núñez Pablo , Wharton John , Wilkins Martin R. 
Published: March 2020

Recent genome‐wide analyses of rare and common sequence variations have brought greater clarity to the genetic architecture of pulmonary arterial hypertension and implicated novel genes in disease development. Transcriptional signatures have been reported in whole lung tissue, pulmonary vascular cells and peripheral circulating cells. High‐throughput platforms for plasma proteomics and metabolomics have identified novel biomarkers associated with clinical outcomes and provided molecular instruments for risk assessment. There are methodological challenges to integrating these datasets, coupled to statistical power limitations inherent to the study of a rare disease, but the expectation is that this approach will reveal novel druggable targets and biomarkers that will open the way to personalized medicine. Here, we review the current state‐of‐the‐art and future promise of ‘omics’ in the field of translational medicine in pulmonary arterial hypertension.LINKED ARTICLESThis article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc
A cross‐cultural qualitative study of the ethical aspects in the transition from child mental health services to adult mental health services
Authors: O'Hara Lesley , Holme Ingrid , Tah Priya , Franic Tomislav , Vrljičak Davidović Nikolina , Paul Moli , Singh Swaran Preet , Street Cathy , Tuomainen Helena , Schulze Ulrike , McNicholas Fiona ,   The MILESTONE Consortium
Published: March 2020

BackgroundTransitioning from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) raises novel ethical aspects for healthcare professionals, as well as for young people, their parents and carers.MethodFocus groups were conducted in Croatia, Ireland and the United Kingdom with youth mental health groups and youth representatives with no mental health (MH) remit. One hundred and eleven participants, aged from 16 to 60 years, contributed to discussions.ResultsPerpetuation of stigma, autonomy and decision‐making were central themes as both enablers and deterrents of successful transition. The tension between professional (and at times parental) paternalism and young persons' growing autonomy was well captured in the themes; (a) desired practice, (b) who should decide, (c) the process of decision‐making and (d) potential harm(s).ConclusionsThis study provides insight into the ethical values, particularly autonomy and collaboratively working, which people expect to underpin the transition between CAMHS and AMHS.Key Practitioner Message

Engaging young people early in making decisions about their future care can enhance trust between practitioner and the young person.

In addition to diagnosis, a number of factors (such as moving home; waiting lists and stigma) may need to be taken into account when considering the direction of future health care.

When possible, alternatives to AMHS should be considered if considered by the young person to be a less‐stigmatising treatment option.
The elephant in the room: Madagascar's rosewood stocks and stockpiles
Authors: Wilmé Lucienne , Innes John L. , Schuurman Derek , Ramamonjisoa Bruno , Langrand Marion , Barber Charles V. , Butler Rhett A. , Wittemyer George , Waeber Patrick O. 
Published: March 2020

AbstractTo prevent the illegal trade in wild species, stock management is critical given stocks function as a buffer to supply chains during lean periods or as a mechanism for market speculation. The Madagascar government with backing by the World Bank recently promoted the sale of confiscated rosewood to reach a zero‐stocks situation. To better assess options, we contrast the risks and rewards of four stock management options. Stock destruction broadcasts a potent conservation message, but provides little economic benefit. National trade can be beneficial to local socioeconomic development goals, but can lead to laundering of illegal products. International trade is fraught with risks related to illegal trade and is perceived to achieve the least related to forest and socioeconomic indicators. Lastly, banking stocks act to postpone decisions. No management option ensures a sustainable solution, but critical analyses allow better insight to the strengths and weaknesses of the available approaches.
Detecting illicit opioid content on Twitter
Authors: Tofighi Babak , Aphinyanaphongs Yindalon , Marini Christina , Ghassemlou Shouron , Nayebvali Peyman , Metzger Isabel , Raghunath Ananditha , Thomas Shailin 
Published: March 2020

AbstractIntroduction and AimsThis article examines the feasibility of leveraging Twitter to detect posts authored by people who use opioids (PWUO) or content related to opioid use disorder (OUD), and manually develop a multidimensional taxonomy of relevant tweets.Design and MethodsTwitter messages were collected between June and October 2017 (n = 23 827) and evaluated using an inductive coding approach. Content was then manually classified into two axes (n = 17 420): (i) user experience regarding accessing, using, or recovery from illicit opioids; and (ii) content categories (e.g. policies, medical information, jokes/sarcasm).ResultsThe most prevalent categories consisted of jokes or sarcastic comments pertaining to OUD, PWUOs or hypothetically using illicit opioids (63%), informational content about treatments for OUD, overdose prevention or accessing self‐help groups (20%), and commentary about government opioid policy or news related to opioids (17%). Posts by PWUOs centered on identifying illicit sources for procuring opioids (i.e. online, drug dealers; 49%), symptoms and/or strategies to quell opioid withdrawal symptoms (21%), and combining illicit opioid use with other substances, such as cocaine or benzodiazepines (17%). State and public health experts infrequently posted content pertaining to OUD (1%).Discussion and ConclusionsTwitter offers a feasible approach to identify PWUO. Further research is needed to evaluate the efficacy of Twitter to disseminate evidence‐based content and facilitate linkage to treatment and harm reduction services.
Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval
Authors: Jefferys John G. R. , Ashby‐Lumsden Alexander , Lovick Thelma A. 
Published: March 2020

AbstractObjectiveTo determine electrical changes in the heart in a chronic, nonstatus model of epilepsy.MethodsElectrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks.ResultsEpileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds. Ictal changes in heart rate include tachycardia and in the case of convulsive seizures, bradyarrhythmias resembling Mobitz type 1 second‐degree atrioventricular block; notably the P‐R interval increased before block. Postictally, the amplitude of T wave increases. Interictally, QT dependence on RR is modest and conventional QT corrections prove ineffective. Interictal QT intervals, measured at a heart rate of 400 bpm, increased from 65 to 75 ms, an increase dependent on seizure incidence over the preceding 10‐14 days.SignificanceRepeated seizures induce a sustained tachycardia and increase in QT interval of the ECG and evoke arrhythmias including periods of atrioventricular block during Racine type 4 and 5 seizures. These changes in cardiac function may predispose to development in fatal arrhythmias and sudden death in humans with epilepsy.
Upregulation of lactate dehydrogenase A in a chronic model of temporal lobe epilepsy
Authors: Sada Nagisa , Suto Shogo , Suzuki Mana , Usui Shoichiro , Inoue Tsuyoshi 
Published: March 2020

AbstractThe ketogenic diet treatment is effective for drug‐resistant epilepsy. Because its antiepileptic effect is associated with lactate dehydrogenase (LDH), drug development is possible by targeting LDH enzymes. Seizures in rodent models are suppressed by inhibiting LDH; however, it remains unclear whether LDH in the brain is changed by seizures. In the present study, we examined the expression of LDH subunits (LDHA and LDHB) in a chronic model of temporal lobe epilepsy, in which seizures were induced by the microinjection of kainate into the mouse hippocampus. Using Western blot analyses, we found that LDHA expression was increased in the hippocampus of the chronic seizure model, whereas LDHB expression was not. Lactate levels in the hippocampus were also increased in this seizure model, suggesting elevated LDH enzymatic activities. Furthermore, the inhibition of LDHA suppressed spontaneous paroxysmal discharges in vivo in the chronic seizure model. In conclusion, our results show that chronic seizures increase LDHA, and conversely, the inhibition of LDHA suppresses seizures, which supports LDHA as a molecular target for the development of new antiepileptic drugs.
Land remediation, event spaces and the pursuit of Olympic legacy
Authors: Gold John R. , Gold Margaret M. 
Published: March 2020

AbstractThis paper explores the links between remediating land for Olympic event spaces and the pursuit of legacy. In particular, it considers ways in which redevelopment of the sizeable spaces prepared for staging the event take their place in broader strategies intended to bring long‐term benefits to the host city and society in order to compensate for the costs and inconvenience originally incurred in hosting the Games. There are six main sections. The first analyses the diverse nature of brownfield land and highlights salient characteristics of its remediation for use in urban regeneration. The second supplies background to Olympic legacy and indicates the importance of the changing climate of ideas in understanding the formulation of legacy over the past two decades. The third section documents the role of remediation as an option employed recently by Games' organisers when needing to find spaces of suitable size to stage the Olympics, noting how choosing remediation ab initio involves commitment to legacy. The fourth and fifth parts analyse approaches to implementing remediation, with respect to the key event spaces for 2 of 21 century's Summer Games: Homebush Bay, which housed the Olympic Park for Sydney 2000; and the Lower Lea Valley, which served the same function for London 2012. The final section provides commentary on the wider narratives of transformation associated with deployment of remediated sites for Olympic event spaces and indicates the significance of the values that have underpinned those narratives.
Cultural festivals and the city
Authors: Finkel Rebecca , Platt Louise 
Published: March 2020

AbstractCities have always been hubs for celebration and festivity, bringing people together to escape temporarily from the mundane nature of everyday routines. Festivals have often been bridges between people and places, linking personal geography with collective experiences and therefore increasingly of interest to cultural geographers. However, festivals also have social, economic and political aspects that are constructed by societal influences of the time and place. This article presents some of the key debates ongoing in academic literature across disciplines to demonstrate the contested role that cultural festivals play in urban settings and suggests that urban geography is critical to developing these debates. It is simply no longer possible to say that festivity is a simple rupture in the mundanity of everyday life of urban citizens; rather, contemporary cultural festivals now often exhibit complex and uneasy tensions between the socio‐economic strategies of commercialized neoliberal cities and the cultural needs of diverse communities to gather and celebrate. By reviewing the development of festivals as part of the urban cultural economy utilising a geographic lens, this article sets out how cultural festivals are now more often employed by cities for marketing, tourism and other socio‐economic benefits. We demonstrate that cultural festivals and cities have an ongoing relationship, which is now mainly commercialized and politicized, and this has diverse impacts on communities, urban spaces and cultural identities.
High‐Precision Sr‐Nd‐Hf‐Pb Isotopic Composition of Chinese Geological Standard Glass Reference Materials CGSG‐1, CGSG‐2, CGSG‐4 and CGSG‐5 by MC‐ICP‐MS and TIMS
Authors: Yang Yue‐Heng , Yang Ming , Jochum Klaus Peter , Wu Shi‐Tou , Zhao Han , Xie Lie‐Wen , Huang Chao , Zhan Xiu‐Chun , Yang Jin‐Hui , Wu Fu‐Yuan 
Published: March 2020

To assess the homogeneity of and provide the first Sr‐Nd‐Hf‐Pb isotopic reference values for the Chinese Geological Standard Glasses CGSG‐1, CGSG‐2, CGSG‐4 and CGSG‐5, we measured these isotopes in several measurement sessions over the course of nearly 3 years. The results were obtained by high‐precision MC‐ICP‐MS and TIMS. Our investigation indicates that these CGSG glass reference materials are homogenous with regard to Sr‐Nd‐Hf‐Pb isotopic distribution and are therefore suitable geochemical materials for Sr‐Nd‐Hf‐Pb isotope measurements. Clear differences in Sr‐Nd‐Hf‐Pb isotopic composition were observed between the glasses and the original powdered rock reference materials (CGSG‐2 and GSR‐7, and especially CGSG‐5 and GSR‐2) because of flux addition during preparation of the glasses. The new Sr‐Nd‐Hf‐Pb isotope data provided here might be useful to the geochemical community for in situ and bulk analysis.
PLATFORM COMPETITION WITH ENDOGENOUS HOMING
Authors: Jeitschko Thomas D. , Tremblay Mark J. 
Published: March 2020

AbstractWe consider two‐sided markets in which consumers and firms endogenously determine whether they single‐home, multi‐home, or exit the market. We find that the competitive bottleneck allocation in which consumers single‐home and firms multi‐home is always an equilibrium. In addition, we find equilibria with multi‐homing and single‐homing on each side of the market. However, unlike the standard pricing result where the side that multi‐homes faces higher prices, we find that lower prices coincide with multi‐homing: agents find multi‐homing more attractive when faced with lower prices. We also show that endogenous homing can induce straddle pricing which deters price undercutting between platforms.
Unravelling the relationship between a seasonal environment and the dynamics of forage growth in grazed swards
Authors: Sbrissia André Fischer , Schmitt Daniel , Duchini Paulo Gonçalves , Da Silva Sila Carneiro 
Published: March 2020

AbstractIt is well reported in the scientific literature that pastures can have similar net forage accumulation when managed with contrasting structures. However, we hypothesized that the dynamics of forage accumulation in grazed swards is linked to seasonal‐environmental conditions. Marandu palisadegrass (Brachiaria brizantha [Hochst. ex A. Rich.] was used as the forage species model. The experimental treatments were four grazing heights (10, 20, 30 and 40 cm) allocated to experimental units according to a randomized complete block design with four replicates and evaluated throughout four contrasting environmental seasons (summer, autumn, winter–early spring and late spring). Under rainy and warm periods, greater net forage accumulation was observed in pastures maintained taller; on the contrary, during the mild and dry periods, net forage accumulation rate reduced as grazing height increased. Such patterns of responses were related to compensations between tiller population density and tissues flows during summer and late spring and the reduced capacity of taller canopies to compensate lower population with greater growth rates during autumn and winter–early spring. Grazed swards changed their patterns of forage growth as they transitioned from favourable to more abiotic stressful conditions, suggesting that seasonal adjustments in grazing intensities are necessary in order to maximize forage production.
Economics and Ethics: The Case of Salomon Brothers
Authors: Smith Clifford 
Published: March 2020

The author draws two main lessons from the Treasury bond bidding scandal at Salomon Brothers that took place in the early 1990s, which led to a sharp curtailment of both the firm's franchise value and its future as an independent company:(1) private market forces provide strong deterrents to unethical conduct, thereby reinforcing ethical standards and in some cases limiting the need for regulation; and(2) badly designed laws and regulations—those that effectively provide people with incentives to cheat customers and otherwise game the system—are almost certain to produce the bad corporate culture and ethical lapses that many observers are all too ready to attribute to capitalism and the pursuit of profit.The second of these two lessons appears to have gotten through to the U.S. Treasury, which in 1998 replaced the multiple‐bid procedure that many identified as inviting manipulation with a single‐bid auction that Milton Friedman, among others, recommended as early as the 1970s. And the Treasury auction process has since proved scandal‐free.
Risk and Regulation in Derivatives (or Why Derivatives Are a Blessing, Not a Curse)
Authors: Hentschel Ludger , Smith Clifford 
Published: March 2020

In this article, first published in 1994, the authors aimed to defuse the widespread hysteria about derivatives fueled by media accounts (like Fortune magazine's cover story in the same year) by offering a systematic analysis of the risks to companies, investors, and the entire financial system associated with the operation of the relatively new derivatives markets. Such analysis ended up providing assurances like the following:
As long as most companies are using derivatives mainly to limit their financial exposures and not to enlarge them in efforts to pad their operating profits, reported losses on derivatives should not be a matter for concern. “Complaining about losses on a swap used to hedge a firm's exposure,” as the authors note, “is like objecting to the costs of a fire insurance policy if the building doesn't burn down.”
To the extent that companies are using derivatives to hedge—and what evidence we have suggests that most are—the default risk of derivatives has been greatly exaggerated. An interest rate swap used by a B‐rated company to hedge a large exposure to interest rates will generally have significantly less default risk than a AAA‐rated corporate bond issue.
Thanks to the corporate use of derivatives, much of the impact of economic shocks such as spikes in interest rates or oil prices is being transferred away from the hedging companies to investors and other companies better able to absorb them. And in this fashion, defaults in the economy as a whole, and hence systemic risk, are effectively being reduced, not increased, through the operation of the derivatives markets.
Moreover, the authors warn in closing that the likely effect of then proposed derivatives regulation would be to restrict access to and increase the costs to companies of using derivatives markets. As one example, the excessive capital requirements associated with derivatives facing bank dealers—based on gross rather than net measures of exposure—and which regulators have since proposed extending to nonbank dealers—were expected to have the unintended effect of encouraging dealers to sell precisely the kinds of riskier, leveraged derivatives that Bankers Trust sold Procter & Gamble, and that functioned as Exhibit A in the Fortune article.
The Capital Structure Puzzle: Another Look at the Evidence
Authors: Barclay Michael J. , Smith Clifford 
Published: March 2020

Since the formulation of the Miller and Modigliani propositions over 60 years ago, financial economists have been debating whether there is such a thing as an optimal capital structure—a proportion of debt to equity that can be expected to maximize long‐run shareholder value. Some finance scholars have followed M&M in arguing that both capital structure and dividend policy are irrelevant in the sense of having no significant, predictable effects on corporate market values. Another school of thought holds that corporate financing choices reflect an attempt by corporate managers to balance the tax shields and disciplinary benefits of more debt against the costs of financial distress. Still another theory says that companies do not have capital structure targets, but instead follow a financial pecking order in which retained earnings are generally preferred to outside financing, and debt is preferred to equity when outside funding is required.In reviewing the evidence that has accumulated since M&M, the authors argue that taxes, bankruptcy and other contracting costs, and information costs all appear to play important roles in corporate financing decisions. While much, if not most, of the evidence is consistent with the idea that companies set target leverage ratios, there is also considerable support for the pecking order theory's contention that managements are willing to deviate widely from their targets for long periods of time. According to the authors, the key to reconciling the different theories—and thus to solving the capital structure puzzle—lies in achieving a better understanding of the relation between corporate financing stocks (that is, total amounts of debt and equity) and flows (which security to issue at a particular time). Even when companies have leverage targets, it can make sense to deviate from those targets depending on the costs associated with moving back toward the target. And as the authors argue in closing, a complete theory of capital structure must take account of these adjustment costs and how they affect expected deviations from the targets.