bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Quality in Children and Adults with Rett Syndrome
Authors: Leven Y. , Wiegand F. , Wilken B.
Published: March 2020

Background Over 80% of individuals suffering from Rett syndrome (RTT) are affected over their life period by sleeping disorders. Little is known about the impact of those on the quality of life and a clinical approach to the treatment of sleep disturbances is lacking.

Aims Primary aim was to assess sleep quality in children and adults. Secondary aim was to assess behavioral disorders and their relationship to sleep quality. The medication taken by the subjects was also included.

Methods Sleep quality and medication were assessed using the sleeping questionnaire for children with neurological and other complex diseases (SNAKE). Behavioral disorders were assessed by the Rett Syndrome Behavior Questionnaire (RSBQ). Questionnaires were sent to the 700 members of the Elternhilfe für Kinder mit Rett Syndrom in Deutschland e.V. (Rett Aid) of which 287 were included. Questionnaires were filled out by the primary caregivers.

Results Sleep quality was rated as very good to good by over 60% of caregivers in contrast to data available in the literature. Behavioral disorders related to regression such as loss of acquired hand skills (p = 0.046) and isolation (p = 0.002) were found to be associated with sleep quality. Melatonin showed a significant association (p = 0.007) with sleep quality.

Conclusion Our study showed sleep dysfunction to be less prevalent in RTT-affected individuals than evidence from past studies has suggested. Nevertheless, this remains a subjective assessment of sleep quality and therefore the need to find objective, disorder-specific parameters that measure sleep quality in RTT patients persists.
Gestational Age at Birth and Risk of Developmental Delay: The Upstate KIDS Study
Authors: Hochstedler Kimberly A. , Bell Griffith , Park Hyojun , Ghassabian Akhgar , Bell Erin M. , Sundaram Rajeshwari , Grantz Katherine L. , Yeung Edwina H.
Published: March 2020

Objective The aim of this study is to model the association between gestational age at birth and early child development through 3 years of age.

Study Design Development of 5,868 children in Upstate KIDS (New York State; 2008–2014) was assessed at 7 time points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking, and plurality.

Results Compared with gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at <32, 32–34, 35–36, 37, 38, and 40 weeks of gestational age were 5.32 (3.42–8.28), 2.43 (1.60–3.69), 1.38 (1.00–1.90), 1.37 (0.98–1.90), 1.29 (0.99–1.67), 0.73 (0.55–0.96), and 0.51 (0.32–0.82). Similar risks of being eligible for Early Intervention Program services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 [ref], 0.92, and 0.78 respectively for <32, 32–34, 37, 38, 39 [ref], 40, and 41 weeks).

Conclusion Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks, but it is notable that deliveries at 40 weeks exhibited further lower risk.
New metamaterial as a broadband absorber of sunlight with extremely high absorption efficiency
Authors: Akafzade Hussein , Sharma Suresh C.
Published: March 2020

We present computer simulations on the design and performance of a broadband and extremely highly efficient (∼98%) CMOS-compatible metamaterial nanostructure for solar energy applications. An optimized unit cell of the nanostructure consists of a 300 nm × 300 nm × 100 nm titanium nitride (TiN) base covered with 60 nm thick SiO2. A 50 nm high TiN disk of 90 nm radius sits over the SiO2 dielectric. The TiN disk is capped with another disk of HfO2 of 90 nm radius and 30 nm height into which six Au nanoparticles (NPs) are symmetrically placed. A periodic array of such unit cells of 300 nm periodicity covers an underlying solar panel. We investigate the performance of the absorber as functions of wavelength, angle of incidence, and polarization of incident sunlight by utilizing the COMSOL Multiphysics software. We observe an impressive absorption of approximately 98% for normal incidence and the broadband range of wavelengths from 250 nm to 1100 nm. Additionally, the absorption is almost independent of the polarization of light and remains higher than 90% for a wide range of incidence angles.
Broad-band measurements of dielectric permittivity in coaxial line using partially filled circular waveguide
Authors: Svirskas Šarūnas , Jablonskas Džiugas , Rudys Saulius , Lapinskas Saulius , Grigalaitis Robertas , Banys Jūras
Published: March 2020

The full-wave analysis was applied for a coaxial line (i.e., transmission line) that has a “short-circuited” discontinuity. The discontinuity has a radius less than or equal to the inner radius of the coaxial line. The “sample region” can be considered as a partially filled circular waveguide. Such a structure is very practical and is of particular interest for the dielectric spectroscopy applications. It takes into account the inhomogeneous field distribution, which is the limiting factor for the determination of high dielectric permittivity values at microwave frequencies. The direct problem was solved by using the mode-matching technique, and the relationship between the complex reflection coefficient and the dielectric permittivity of the cylindrical sample was obtained. By solving the inverse problem, it is possible to obtain the complex dielectric permittivity from the experimental values of the scattering matrix. The results were verified by the finite element modeling of the system and applied for particular materials. The correspondence between these approaches is excellent. This method is very suitable for the determination of permittivity, which exceeds several thousands (it is applicable for any type of material). It extends the frequency range where the permittivity can be determined reliably. There is no necessity to prepare samples with different geometries (i.e., surface area and thickness).
Indexing brain state-dependent pupil dynamics with simultaneous fMRI and optical fiber calcium recording
Authors: Pais-Roldán Patricia , Takahashi Kengo , Sobczak Filip , Chen Yi , Zhao Xiaoning , Zeng Hang , Jiang Yuanyuan , Yu Xin
Published: March 2020

Pupillometry, a noninvasive measure of arousal, complements human functional MRI (fMRI) to detect periods of variable cognitive processing and identify networks that relate to particular attentional states. Even under anesthesia, pupil dynamics correlate with brain-state fluctuations, and extended dilations mark the transition to more arousable states. However, cross-scale neuronal activation patterns are seldom linked to brain state-dependent pupil dynamics. Here, we complemented resting-state fMRI in rats with cortical calcium recording (GCaMP-mediated) and pupillometry to tackle the linkage between brain-state changes and neural dynamics across different scales. This multimodal platform allowed us to identify a global brain network that covaried with pupil size, which served to generate an index indicative of the brain-state fluctuation during anesthesia. Besides, a specific correlation pattern was detected in the brainstem, at a location consistent with noradrenergic cell group 5 (A5), which appeared to be dependent on the coupling between different frequencies of cortical activity, possibly further indicating particular brain-state dynamics. The multimodal fMRI combining concurrent calcium recordings and pupillometry enables tracking brain state-dependent pupil dynamics and identifying unique cross-scale neuronal dynamic patterns under anesthesia.
Speaking for the Nation
Authors: Sicurella Federico Giulio
Published: March 2020

The book explores the nexus of intellectual activity and nation-building from a critical discourse-analytical perspective. By examining how public intellectuals from Serbia, Croatia, and Bosnia and Herzegovina commented on key national events in editorials and opinion pieces, it offers unique insights into contemporary nation-building discourses in an enlarging Europe. Through a detailed reconstruction of the debates concerning the selected events, the book also provides fresh empirical evidence of the implications and challenges of post-socialist transition, post-conflict reconciliation, democratisation and European integration in the post-Yugoslav region. Its versatile framework, which innovatively combines sociological and linguistic approaches to the discursive positioning of intellectuals, may be readily applied to the analysis of intellectual engagement with current affairs and public life in general.
Agency and Trauma in the Palestinian Struggle to Remain
Authors: Nassar Maha
Published: March 2020

Adel Manna’s Nakba and Survival: The Story of the Palestinians Who Remained in Haifa and the Galilee, 1948–1956 appeared in Arabic and Hebrew in 2016–2017. Manna’s book gives voice to the experience of the first generation of Palestinians living within the State of Israel. Here, four scholars of Palestinian and Israeli history review Nakba and Survival and weigh its importance for reckoning with the entangled history of the creation of Israel and the related dispossession of Palestinians during and after 1948.
Incidence of Prehypertension and Hypertension in Rural India, 2012–2018: A Sex-Stratified Population-Based Prospective Cohort Study
Authors: Rai Rajesh Kumar , Kumar Chandan , Singh Prashant Kumar , Singh Lucky , Barik Anamitra , Chowdhury Abhijit
Published: March 2020

BACKGROUND

India is home to the largest number of hypertensive individuals, and factors responsible for the incidence of hypertension are poorly understood. This study examines predictors of transition to different stages of hypertension—incidence of hypertension, incidence of prehypertension, and incidence of prehypertension to hypertension.

METHODS

Population-based survey data from the Birbhum Population Project, located in West Bengal, India were used. A cohort of 8,977 individuals (male: 3,934, female: 5,043), participated in the 2012–13 survey, and were followed up for resurvey in 2017–18. The Seventh Report of the Joint National Committee (JNC 7) guidelines were followed to define hypertension. Bivariate and multivariate Poisson regression analyses were conducted to attain the study objective.

RESULTS

The incidence of hypertension, prehypertension among males (7.9% and 45.3%, respectively) is higher than that among females (5.9% and 32.7%, respectively). However, the incidence of prehypertension to hypertension is lower among males (23.6%) than among females (33.6%). Among both sexes, with age, the incidence of hypertension, and incidence of prehypertension to hypertension appeared to increase, whereas incidence of prehypertension among females increased with age. Findings indicate a diverse gradient of socioeconomic, behavioral, and anthropometric characteristics influencing the incidence of different stages of hypertension.

CONCLUSIONS

With a focus on females and the richest individuals, this study proposes that an appropriate intervention be designed in keeping with the socioeconomic, behavioral gradient of incidence of different stages of hypertension. The role of anthropometric indicators in hypertension is proposed to be further studied for better population-based screening.
Unique and highly specific cyanogenic glycoside localization in stigmatic cells and pollen in the genus Lomatia (Proteaceae)
Authors: Ritmejerytė Edita , Boughton Berin A , Bayly Michael J , Miller Rebecca E
Published: March 2020

Background and Aims

Floral chemical defence strategies remain understudied despite the significance of flowers to plant fitness, and the fact that many flowers contain secondary metabolites that confer resistance to herbivores. Optimal defence and apparency theories predict that the most apparent plant parts and/or those most important to fitness should be most defended. To test whether within-flower distributions of chemical defence are consistent with these theories we used cyanogenic glycosides (CNglycs), which are constitutive defence metabolites that deter herbivores by releasing hydrogen cyanide upon hydrolysis.

Methods

We used cyanogenic florets of the genus Lomatia to investigate at what scale there may be strategic allocation of CNglycs in flowers, what their localization reveals about function, and whether levels of floral CNglycs differ between eight congeneric species across a climatic gradient. Within-flower distributions of CNglycs during development were quantified, CNglycs were identified and their localization was visualized in cryosectioned florets using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI).

Key Results

Florets of all congeneric species studied were cyanogenic, and concentrations differed between species. Within florets there was substantial variation in CNglyc concentrations, with extremely high concentrations (up to 14.6 mg CN g−1 d. wt) in pollen and loose, specialized surface cells on the pollen presenter, among the highest concentrations reported in plant tissues. Two tyrosine-derived CNglycs, the monoglycoside dhurrin and diglycoside proteacin, were identified. MALDI-MSI revealed their varying ratios in different floral tissues; proteacin was primarily localized to anthers and ovules, and dhurrin to specialized cells on the pollen presenter. The mix of transient specialized cells and pollen of L. fraxinifolia was ~11 % dhurrin and ~1.1 % proteacin by mass.

Conclusions

Tissue-specific distributions of two CNglycs and substantial variation in their concentrations within florets suggests their allocation is under strong selection. Localized, high CNglyc concentrations in transient cells challenge the predictions of defence theories, and highlight the importance of fine-scale metabolite visualization, and the need for further investigation into the ecological and metabolic roles of CNglycs in floral tissues.
How Religious Jewish and Muslim Students of Social Work Cope in a Secular College
Authors: Ranz Rebecca , Allassad Alhuzail Nuzha
Published: March 2020

The social work profession’s worldview, which is expressed through education and practice, is ‘almost exclusively secular in colour and context’. This qualitative study in the phenomenological tradition of ten religious Jewish and ten religious Arab-Muslim students of social work in Israel found that both groups coped similarly with the secularity, despite their ethnic, national and religious differences. Most of them adopted emotion-focussed coping strategies that isolated them from their academic surroundings. The religious students who adopted a problem-focussed strategy opened themselves to new knowledge. Knowing about these strategies may help faculty and other personnel in social work schools not only to be better acquainted with this minority but also to provide an environment that is receptive to and respectful of the religious student.
Read-through transcripts in lung: germline genetic regulation and correlation with the expression of other genes
Authors: Maspero Davide , Dassano Alice , Pintarelli Giulia , Noci Sara , De Cecco Loris , Incarbone Matteo , Tosi Davide , Santambrogio Luigi , Dragani Tommaso A , Colombo Francesca
Published: March 2020

Transcripts originating from the transcriptional read through of two adjacent, similarly oriented genes have been identified in normal and neoplastic tissues, but their functional role and the mechanisms that regulate their expression are mostly unknown. Here, we investigated whether the expression of read-through transcripts previously identified in the non-involved lung tissue of lung adenocarcinoma patients was genetically regulated. Data on genome-wide single nucleotide variant genotypes and expression levels of 10 read-through transcripts in 201 samples of lung tissue were combined to identify expression quantitative trait loci (eQTLs). Then, to identify genes whose expression levels correlated with the 10 read-through transcripts, we used whole transcriptome profiles available for 154 patients. For 8 read-though transcripts, we identified 60 eQTLs (false discovery rate <0.05), including 17 cis-eQTLs and 43 trans-eQTLs. These eQTLs did not maintain their behavior on the ‘parental’ genes involved in the read-through transcriptional event. The expression levels of 7 read-through transcripts were found to correlate with the expression of other genes: CHIA–PIFO and CTSC–RAB38 correlated with CHIA and RAB38, respectively, while 5 other read-through transcripts correlated with 43 unique non-parental transcripts; thus offering indications about the molecular processes in which these chimeric transcripts may be involved. We confirmed 9 eQTLs (for 4 transcripts) in the non-involved lung tissue from an independent series of 188 lung adenocarcinoma patients. Therefore, this study indicates that the expression of four read-through transcripts in normal lung tissue is under germline genetic regulation, and that this regulation is independent of that of the genes involved in the read-through event.
Optimization and Validation of HPTLC Method for Estimation of Ulipristal Acetate in Presence of Its Forced Degradation Products
Authors: Kamdar Gulzar , Desai Sonal
Published: March 2020

Ulipristal acetate (UPA) is used as emergency contraceptive and for uterine fibroids. No validated method has been reported to estimate UPA in presence of its degradation products. Therefore it is mandatory to develop method which can accurately measure it in presence of impurity. A simple and sensitive high-performance thin-layer chromatography (HPTLC) method was developed for the estimation of UPA. Pre-coated silica gel 60F254 TLC plates were as stationary phase and ethyl acetate:toluene:glacial acetic acid (4:7:0.3, v/v/v) was used as mobile phase. Drug was subjected to acid and alkali hydrolysis, oxidation, photo degradation and thermal degradation to study its degradation behavior. UPA eluted with Rf value 0.38 ± 0.02. The method was found to be linear in the concentration range of 400–3,600 ng/band. Limit of detection and limit of quantitation were found to be 72.7786 ng/band and 220.5412 ng/band, respectively. The % recovery of the proposed method was found to be 100.05–100.65%. The proposed method was specific to measure UPA in presence of degradants. The method was found to be accurate, precise, robust and can be useful for routine analysis of formulations containing UPA in presence of its degradation products.
Derivation and Validation of a Novel Severity Scoring System for Pneumonia at Intensive Care Unit Admission
Authors: Carmo Thomas A , Ferreira Isabella B , Menezes Rodrigo C , Telles Gabriel P , Otero Matheus L , Arriaga Maria B , Fukutani Kiyoshi F , Neto Licurgo P , Agareno Sydney , Filgueiras Filho Nivaldo M , Andrade Bruno B , Akrami Kevan M
Published: March 2020

Background

Severity stratification scores developed in intensive care units (ICUs) are used in interventional studies to identify the most critically ill. Studies that evaluate accuracy of these scores in ICU patients admitted with pneumonia are lacking. This study aims to determine performance of severity scores as predictors of mortality in critically ill patients admitted with pneumonia.

Methods

Prospective cohort study in a general ICU in Brazil. ICU severity scores (Simplified Acute Physiology Score 3 [SAPS 3] and Sepsis-Related Organ Failure Assessment [qSOFA]), prognostic scores of pneumonia (CURB-65 [confusion, urea, respiratory rate, blood pressure, age] and CRB-65 [confusion, respiratory rate, blood pressure, age]), and clinical and epidemiological variables in the first 6 hours of hospitalization were analyzed.

Results

Two hundred patients were included between 2015 and 2018, with a median age of 81 years (interquartile range, 67–90 years) and female predominance (52%), primarily admitted from the emergency department (65%) with community-acquired pneumonia (CAP, 80.5%). SAPS 3, CURB-65, CRB-65,and qSOFA all exhibited poor performance in predicting mortality. Multivariate regression identified variables independently associated with mortality that were used to develop a novel pneumonia-specific ICU severity score (Pneumonia Shock score) that outperformed SAPS 3, CURB-65, and CRB-65. The Shock score was validated in an external multicenter cohort of critically ill patients admitted with CAP.

Conclusions

We created a parsimonious score that accurately identifies patients with pneumonia at highest risk of ICU death. These findings are critical to accurately stratify patients with severe pneumonia in therapeutic trials that aim to reduce mortality.
Modeling Infectious Diseases in Healthcare Network (MInD-Healthcare) Framework for Describing and Reporting Multidrug-resistant Organism and Healthcare-Associated Infections Agent-based Modeling Methods
Authors: Slayton Rachel B , O’Hagan Justin J , Barnes Sean , Rhea Sarah , Hilscher Rainer , Rubin Michael , Lofgren Eric , Singh Brajendra , Segre Alberto , Paul Prabasaj
Published: March 2020

Mathematical modeling of healthcare-associated infections and multidrug-resistant organisms improves our understanding of pathogen transmission dynamics and provides a framework for evaluating prevention strategies. One way of improving the communication among modelers is by providing a standardized way of describing and reporting models, thereby instilling confidence in the reproducibility and generalizability of such models. We updated the Overview, Design concepts, and Details protocol developed by Grimm et al [11] for describing agent-based models (ABMs) to better align with elements commonly included in healthcare-related ABMs. The Modeling Infectious Diseases in Healthcare Network (MInD-Healthcare) framework includes the following 9 key elements: (1) Purpose and scope; (2) Entities, state variables, and scales; (3) Initialization; (4) Process overview and scheduling; (5) Input data; (6) Agent interactions and organism transmission; (7) Stochasticity; (8) Submodels; and (9) Model verification, calibration, and validation. Our objective is that this framework will improve the quality of evidence generated utilizing these models.
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

Nontuberculous 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

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

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

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

Users 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

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

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

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

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

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

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

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

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

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

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

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.
The Role of Multimicronutrient Supplementation in Pediatric HIV Management in Nigeria: A Randomized Controlled Study
Authors: Esiovwa Regina , Rankin Jean , David Agatha , Disu Elizabeth , Wapmuk Agatha , Amoo Olufemi
Published: March 2020

Background

We aimed to compare the immunologic and hematologic effects of 3 multimicronutrient supplements in human immunodeficiency virus–positive children in Lagos, Nigeria.

Methods

This double-blind, randomized controlled study included 190 children, aged 5–12 years, in Lagos, Nigeria. Sixty-four, 63, and 63 participants were assigned to multimicronutrient group A, B, or C, respectively, for 6 months. Supplements A, B, and C contained 7 micronutrients at the recommended daily allowance (RDA) (comparable to standard-of-care multivitamin), 22 micronutrients at the RDA, and 22 micronutrients at 3 times the recommended daily allowance (3RDA), respectively. Using paired sample t tests and factorial repeat-measures analysis of variance (ANOVA), within- and between-group changes in CD4 count and hemoglobin levels were evaluated after 6 months.

Results

After 6 months of supplementation, paired-sample t test showed that CD4 cell count did not significantly differ from baseline for all 3 groups. Between-subject effect also did not significantly differ in the 3 groups after 6 months (factorial repeat-measures ANOVA (F [degrees of freedom {df} = 2, 187] = 0.846; P = .436; partial η 2 = 0.009). Hemoglobin levels were significantly increased after supplementation in all 3 supplement groups. Increases were not significantly different between groups (factorial repeat-measures ANOVA (F [df = 2, 187] = 0.549; P = .591; partial η 2 = 0.006).

Conclusions

Equivalent effects were observed. After 6 months of supplementation, mean CD4 count was not significantly different between groups. Hemoglobin concentration was significantly increased in all 3 groups, but increase did not differ between groups.

Clinical Trials Registration

NCT02552602.