bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline
Authors: Daley Charles L , Iaccarino Jonathan M , Lange Christoph , Cambau Emmanuelle , Wallace Richard J , Andrejak Claire , Böttger Erik C , Brozek Jan , Griffith David E , Guglielmetti Lorenzo , Huitt Gwen A , Knight Shandra L , Leitman Philip , Marras Theodore K , Olivier Kenneth N , Santin Miguel , Stout Jason E , Tortoli Enrico , van Ingen Jakko , Wagner Dirk , Winthrop Kevin L 
Published: March 2020

AbstractNontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
China Through the Lens of Modernity
Authors: Buzan Barry , Lawson George 
Published: March 2020

Abstract
This article examines China’s encounter with modernity from the 19th century to the present day. It builds on the historical narrative of modernity developed by Buzan and Lawson (2015), and two theoretical perspectives: uneven and combined development, and differentiation theory. The article opens with a short history of modernity, establishing that it is not a static phenomenon, but a continuously unfolding process. It then explores five periods of China’s encounter with modernity: imperial decline and resistance to modernization; civil war and Japanese invasion; Mao’s radical communist project; Deng’s market socialism; and Xi’s attempt to synthesize Confucius, Mao, and Deng. It explores both how China fits into the general trajectory of modernity, and how it has evolved from rejection of it to constructing its own distinctive version of ‘modernity with Chinese characteristics’. The article ends by reflecting on what issues remain within China’s version of modernity, and how it fits, and doesn’t fit with other forms of modernity already established within global international society.
Hepatic function in mononucleosis induced by Epstein-Barr virus and cytomegalovirus.
Authors: Horwitz C A , Burke M D , Grimes P , Tombers J 
Published: March 2020

Abstract
We evaluated serial enzyme and bilirubin determinations as aids to diagnosis of Epstein-Barr virus-induced infectious mononucleosis (121 cases) and the heterophil-negative mononucleosis-like illness due to cytomegalovirus (33 cases). Laboratory evidence for either type of mononucleosis includes mild to moderate hepatic dysfunction, with aspartate aminotransferase activity increased, but lower than commonly encountered in active viral hepatitis. Of the enzymes commonly assayed in evaluating liver function, aspartate aminotransferase activity was the most commonly abnormal: in 96.7% of those with Epstein-Barr virus disease and 87.9% with cytomegalovirus disease. Values for alkaline phosphatase were increased in 94.2% of the Epstein-Barr virus cases and 63.6% of the cytomegalovirus cases, and gamma-glutamyltransferase values were increased in 90.9% and 75.8%, respectively. We conclude that, in serially studied patients, normal results for liver-function studies or very high aspartate aminotransferase activities (greater than 1000 U/L) eliminate, for practical purposes, both Epstein-Barr virus and cytomegalovirus as diagnostic considerations.
Qualitative testing for circulating immune complexes by use of zone electrophoresis on agarose.
Authors: Kelly R H , Scholl M A , Harvey V S , Devenyi A G 
Published: March 2020

Abstract
On binding of antibody to antigen an immune complex is formed that has a net surface charge different from that of either of the two components. This, together with clonal restriction of the antibody response, gives rise to distinctive patterns that are readily apparent in stained agarose gels after routine zone electrophoresis. Most circulating immune complexes appear as a rectangular pattern, with well-defined edges, located in the gamma-region. The identity of the material responsible for these patterns has been established by three different experimental approaches: analysis of tetanus/anti-tetanus complexes formed in vitro, analysis of sera from rabbits with experimental immune complex disease, and analysis of human type II and type III cryoglobulins. Studies of reproducibility, interfering substances, and correlation with other assays for detecting immune complexes indicate that zone electrophoresis in agarose gel is a sensitive, highly specific technique for immune complex detection, of potential value as a screening tool.
Auto-Scale Resource Provisioning In IaaS Clouds
Authors: Salmanian Zolfaghar , Izadkhah Habib , Isazadeh Ayaz 
Published: March 2020

AbstractUsers of cloud computing technology can lease resources instead of spending an excessive charge for their ownership. For service delivery in the infrastructure-as-a-service model of the cloud computing paradigm, virtual machines (VMs) are created by the hypervisor. This software is installed on a bare-metal server, called the host, and acted as a broker between the hardware of the host and its VMs. The host is responsible for the allocation of required resources, such as CPU, RAM and network bandwidth, for VMs. Therefore, allocating resources to a VM is equivalent to finding the location of the VM on the hosts. In this paper, we propose a model for resource allocation of a datacenter that includes clusters of hosts. This model is based on the birth–death process of queueing systems and continuous-time Markov chains. We will focus on RAM-intensive VMs and consider the allocation of RAM for a VM as a job in the queueing systems. The purpose of this modeling is to keep the number of running hosts minimum while guaranteeing the quality of service in terms of response. When the utilization of active hosts reaches a predefined threshold value, a new host is added to prevent response time violation, and when host utilization is reduced to a certain threshold, one of the hosts can be deactivated. The experimental results show that, in the long run, the odds of working with more jobs are increased.
Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme
Authors: Sandborn William J , Nguyen Deanna D , Beattie David T , Brassil Patrick , Krey Whitney , Woo Jacky , Situ Eva , Sana Reuben , Sandvik Erik , Pulido-Rios M Teresa , Bhandari Raj , Leighton Jonathan A , Ganeshappa Ravi , Boyle David L , Abhyankar Brihad , Kleinschek Melanie A , Graham Richard A , Panes Julian 
Published: March 2020

Abstract

Background and Aims
Oral systemic pan-Janus kinase [JAK] inhibition is effective for ulcerative colitis [UC] but is limited by toxicities. We describe preclinical to clinical translation of TD-1473—an oral gut-selective pan-JAK inhibitor—from in vitro characterization through a Phase 1b study in patients with UC.

Methods
TD-1473 JAK inhibition potency was evaluated in vitro; plasma pharmacokinetics, safety and efficacy were assessed in mice. In a first-time-in-human study, plasma pharmacokinetics and safety were assessed after single and multiple [14 days] ascending doses administered orally to healthy subjects. The Phase 1b study randomized patients with moderately to severely active UC to receive once-daily oral TD-1473 20, 80 or 270 mg, or placebo for 28 days. Plasma and colonic tissue concentrations were measured; safety was assessed; and efficacy was evaluated by UC clinical parameters, disease-surrogate biomarkers, endoscopy, histology and colonic tissue JAK signalling.

Results
TD-1473 exhibited potent pan-JAK inhibitory activity in vitro. Oral TD-1473 administration to mice achieved high, biologically active colonic tissue concentrations with low plasma exposure and decreased oxazolone-induced colitis activity without reducing blood cell counts vs placebo. TD-1473 administration in healthy human subjects and patients with UC yielded low plasma exposure and was generally well tolerated; treatment in patients with UC resulted in biologically active colonic tissue concentrations and descriptive trends toward reduced clinical, endoscopic and histological disease activity vs placebo.

Conclusion
Gut-selective pan-JAK inhibition with TD-1473 administration resulted in high intestinal vs plasma drug exposure, local target engagement, and trends toward reduced UC disease activity. [Clinicaltrials.gov NCT02657122, NCT02818686]
General practitioners and decision-making capacity assessment: the experiences and educational needs of New Zealand general practitioners
Authors: Vara Alisha , Young Greg , Douglass Alison , Sundram Frederick , Henning Marcus , Cheung Gary 
Published: March 2020

Abstract

Background
Assessing decision-making capacity to health care is within the scope of practice for all doctors, yet the experience of GPs in this area is unknown.

Objective
To explore the experiences, perspectives, approaches and challenges for GPs in New Zealand when conducting decision-making capacity assessments.

Methods
Qualitative study design comprising individual in-depth semi-structured interviews conducted with a convenience sample of GPs. Interview transcripts were transcribed verbatim and analysed using a thematic analysis approach.

Results
Twelve participants were recruited. The following themes emerged: (i) GPs’ roles and responsibilities in decision-making capacity assessments; (ii) GPs lack formal training, knowledge, and confidence in decision-making capacity assessments; (iii) the legal interface of decision-making capacity assessments; (iv) GPs’ relationships with specialists and the resulting impact on their confidence in decision-making capacity assessments; and (v) opportunities to improve GPs’ knowledge and confidence in decision-making capacity assessments.

Conclusions
GPs take responsibility for decision-making capacity assessments; however, assessments can be complex. There is a need to develop specific curriculum and training resources for GPs to improve their clinical skills and legal knowledge in decision-making capacity assessments.
How many firms benefit from a window of opportunity? Knowledge spillovers, industry characteristics, and catching up in the Chinese biomass power plant industry
Authors: Hansen Teis , Hansen Ulrich Elmer 
Published: March 2020

Abstract
The literature on the catching up of latecomer countries has pointed at windows of opportunity as a precondition for catching up. Previous research has however failed to illuminate the determining factors affecting the number of firms benefitting from windows of opportunity. The current article addresses this gap by combining insights on the nature of knowledge spillovers with sectoral characteristics. This perspective is applied empirically by analyzing the number of firms benefitting from a ‘green’ window of opportunity in the Chinese biomass power plant industry, specifically related to changes in the institutional framework conditions in the form of a feed-in tariff and specified targets for renewable energy. The article finds that while a single Chinese firm constituted the initial phase of the catch-up cycle, domestic knowledge spillovers allowed a larger number of Chinese firms to benefit from the window of opportunity in the later stage of the catch-up cycle. The article points at the importance of combining sectoral characteristics with the degree of domestic knowledge spillovers as key determinants for the number of firms profiting from windows of opportunity.
Exponential Moments and Piecewise Thinning for the Bessel Point Process
Authors: Charlier Christophe 
Published: March 2020

Abstract
We obtain exponential moment asymptotics for the Bessel point process. As a direct consequence, we improve on the asymptotics for the expectation and variance of the associated counting function and establish several central limit theorems. We show that exponential moment asymptotics can also be interpreted as large gap asymptotics, in the case where we apply the operation of a piecewise constant thinning on several consecutive intervals. We believe our results also provide important estimates for later studies of the global rigidity of the Bessel point process.
Oral antibiotics for infective endocarditis: a clinical review
Authors: Brown Evelyn , Gould F Kate 
Published: March 2020

Abstract
Current guidelines for management of infective endocarditis (IE) advise 4–6 weeks of IV antibiotics. This is based on historical data from animal models, which set a precedent for high peak serum antimicrobial levels, thought to be only achievable with IV therapy. However, there has been increasing recent interest in oral antibiotics as an alternative to prolonged parenteral therapy, not limited to treatment of IE. This review examines the theory behind parenteral antibiotic administration with reference to the MICs of relevant pathogens. By comparing published serum antimicrobial levels after oral and IV administration we suggest that safe levels of commonly used antibiotics can be achieved orally. We have then reviewed the literature to date on oral antibiotics for IE. The largest randomized controlled trial (RCT) in this area, the POET trial, concluded that oral therapy was non-inferior to prolonged IV therapy in stable patients with left-sided IE. Additionally, there have been two smaller RCTs published, as well as a number of observational studies over the last 50 years, utilizing a variety of different patient groups, methods and treatment strategies. This body of evidence gives weight to a potential shift in practice towards oral therapy, primarily as a step-down treatment. We conclude that pharmacological data offer theoretical reassurance for the safety of oral therapy. This is coupled with a growing evidence base for non-inferiority of oral antimicrobials compared with prolonged parenteral therapy in practice.
Inhaled tigecycline is effective against Mycobacterium abscessus in vitro and in vivo
Authors: Pearce Camron , Ruth Mike M , Pennings Lian J , Wertheim Heiman F L , Walz Amanda , Hoefsloot Wouter , Ruesen Carolien , Muñoz Gutiérrez Juan , Gonzalez-Juarrero Mercedes , van Ingen Jakko 
Published: March 2020

Abstract

Background
Mycobacterium abscessus causes chronic pulmonary infections. Owing to its resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%. Tigecycline is active against M. abscessus, but severe toxicity and the need for IV administration limit its use.

Objectives
To assess the potential of inhaled tigecycline as a treatment for M. abscessus pulmonary disease, by measuring its efficacy in a mouse model of chronic M. abscessus pulmonary disease, establishing the intracellular activity of tigecycline against M. abscessus in human macrophages and measuring the activity of tigecycline in the sputum of cystic fibrosis patients.

Methods
We infected GM-CSF knockout mice with M. abscessus by intrapulmonary aerosol. Infected mice were treated with tigecycline in 0.25, 1.25 and 2.5 mg doses, by inhalation, or untreated, for 28 days. Tigecycline was added to human peripheral blood-derived macrophages infected with M. abscessus to assess its intracellular activity. We performed a time–kill kinetics experiment of tigecycline against M. abscessus with and without sputum of cystic fibrosis patients.

Results
Inhaled tigecycline proved highly effective against M. abscessus in GM-CSF knockout mice. The effect was dose dependent. Tigecycline showed potent activity against M. abscessus in macrophages and retained most of its activity in the presence of sputum of cystic fibrosis patients.

Conclusions
Inhaled tigecycline may represent a viable treatment option for M. abscessus pulmonary disease, where treatment outcomes are currently very poor. A stable and safe formulation is required to proceed to further pharmacodynamic studies and ultimately clinical trials.
Using and improving distributed data networks to generate actionable evidence: the case of real-world outcomes in the Food and Drug Administration’s Sentinel system
Authors: Brown Jeffrey S , Maro Judith C , Nguyen Michael , Ball Robert 
Published: March 2020

Abstract
The US Food and Drug Administration (FDA) Sentinel System uses a distributed data network, a common data model, curated real-world data, and distributed analytic tools to generate evidence for FDA decision-making. Sentinel system needs include analytic flexibility, transparency, and reproducibility while protecting patient privacy. Based on over a decade of experience, a critical system limitation is the inability to identify enough medical conditions of interest in observational data to a satisfactory level of accuracy. Improving the system’s ability to use computable phenotypes will require an “all of the above” approach that improves use of electronic health data while incorporating the growing array of complementary electronic health record data sources. FDA recently funded a Sentinel System Innovation Center and a Community Building and Outreach Center that will provide a platform for collaboration across disciplines to promote better use of real-world data for decision-making.
Roles of GPRC5 family proteins: focusing on GPRC5B and lipid-mediated signalling
Authors: Hirabayashi Yoshio , Kim Yeon-Jeong 
Published: March 2020

Abstract
In the past decade, physiological roles and molecular functions of GPRC5 family receptors, originally identified as retinoic acid-induced gene products, have been uncovered, even though their intrinsic agonists are still a mystery. They are differentially distributed in certain tissues and cells in the body suggesting that cell-type-specific regulations and functions are significant. Molecular biological approaches and knockout mouse studies reveal that GPRC5 family proteins have pivotal roles in cancer progression and control of metabolic homeostasis pathways. Remarkably, GPRC5B-mediated tyrosine-phosphorylation signalling cascades play a critical role in development of obesity and insulin resistance through dynamic sphingolipid metabolism.
A bottom-up algorithm for solving ♯2SAT
Authors: De Ita Guillermo , Marcial-Romero J Raymundo , HernÁndez-ServÍn J A 
Published: March 2020

Abstract
Counting models for a two conjunctive formula (2-CF) $F$, a problem known as $\sharp $2Sat, is a classic $\sharp $P complete problem. Given a 2-CF $F$ as input, its constraint graph $G$ is built. If $G$ is acyclic, then $\sharp $2Sat($F$) can be computed efficiently. In this paper, we address the case when $G$ has cycles.
When $G$ is cyclic, we propose a decomposition on the constraint graph $G$ that allows the computation of $\sharp $2Sat($F$) in incremental way. Let $T$ be a cactus graph of $G$ containing a maximal number of independent cycles, and let $\overline{T}=(E(G)-E(T))$ be a subset of frond edges from $G$. The clauses in $\overline{T}$ are ordered in connected components $\{K_1, \ldots , K_r\}$. Each $(G \cup K_i), i=1,\ldots ,r$ is a knot (a set of intersected cycles) of the graph.
The arrangement of the clauses of $\overline{T}$ allows the decomposition of $G$ in knots and provides a way of computing $\sharp $2Sat(F) in an incremental way. Our procedure has a bottom-up orientation for the computation of $\sharp $2Sat($F$). It begins with $F_0 = T$. In each iteration of the procedure, a new clause $C_i \in \overline{T}$ is considered in order to form $F_i = (F_{i-1} \wedge C_i)$ and then to compute $\sharp $2Sat$(F_i)$ based on the computation of $\sharp $2Sat$(F_{i-1})$.
Generic Entry Before the Agreed-Upon Date in Pharmaceutical Patent Settlements
Authors: Drake Keith M , McGuire Thomas G 
Published: March 2020

ABSTRACT
Drug patent litigation settlements specify a date for generic entry and typically include a so-called acceleration clause allowing the generic to enter earlier in certain circumstances. An agreed-upon date between a brand and a generic with “first-filer” status is particularly salient because this date also affects when other generics may enter. It has been unclear the degree to which acceleration clauses increase competition—by accelerating entry—or decrease competition, by deterring pursuit of entry by potential generic competitors. This paper documents the entry outcome after first-filer-brand settlements by tracking how often acceleration clauses in these settlements in fact accelerate entry. In no case was a first filer’s 180-day exclusivity period accelerated because of a later filing generic winning patent litigation or settling for an earlier entry date. In the cases where early entry occurred, the first filer had lost its right to the exclusivity period, typically by failing to receive tentative FDA approval within 30 months of its filing; or other generics shared first-filer status. An acceleration clause paired with the 180-day exclusivity period appears to effectively deter other generics and, at least in the instances we observed, never to have resulted in an actual “accelerated” entry.
Collaboration and Competition Policy in a Market-Based Hospital System: A Case Study from the Netherlands
Authors: van der Schors Wouter , Kemp Ron , Varkevisser Marco 
Published: March 2020

Abstract
In the Dutch healthcare system, provider competition is used as a tool to improve efficiency. From a competition policy perspective, little is known about how collaboration among healthcare providers contributes to overall patient welfare, and how a balance is achieved between scale benefits and preventing anti-competitive collusion. This paper examines the ex-post effects of a Dutch case study in which three competing hospitals have collaborated to provide high-complexity low-volume cancer surgery, an arrangement that tests the limits of permissibility under the Dutch cartel prohibition. Our preliminary empirical research demonstrated only a modest increase in price and travel time for some of the tumour surgeries. Volume analysis showed that the intended centralization of surgical procedures has not been fully realized. Our findings highlight the importance of a comprehensive self-assessment by the collaborating hospitals to ex-ante assess (potential) efficiencies and antitrust risks. Such self-assessments could benefit from research focused on which collaborations are most appropriate to achieve quality gains. For the ex-post assessment by competition authorities following the cartel prohibition, a more thorough insight into the (long-term) changes in hospital prices, profitability, and quality after collaboration is needed.