bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association Between the Decision to Withdraw Life-Sustaining Therapy and Patient Mortality in U.K. ICUs*
Authors: Maharaj Ritesh , Harrison David A. , Rowan Kathryn 
Published: August 2021

OBJECTIVES:
Differences in decisions to limit life-sustaining therapy are often supported by perceptions that patients receive unnecessary and expensive treatment which provide negligible survival benefit. However, the assumption behind those beliefs—that is, that life-sustaining therapy provides no significant marginal survival benefit—remains unproven. Our objective was to quantify the effects of variations in decisions to withdraw or withhold life-sustaining treatment on 180-day mortality in critically ill patients.

DESIGN:
Retrospective observational cohort study of a national clinical database.

SETTING:
Adult ICUs participating in the Intensive Care National Audit and Research Center Case Mix Program in the United Kingdom.

PATIENTS:
Adult patients admitted to general ICUs between April 1, 2009, and March 31, 2016.

MEASUREMENTS AND MAIN RESULTS:
During the study period, 795,721 patients were admitted to 247 ICUs across the United Kingdom. A decision to withdraw or withhold life-sustaining treatment was made for 92,327 patients (11.6%). A multilevel model approach was used to estimate ICU-level practice variation. The ICU-level practice variation was then used as an instrument to measure the effects of decision to withdraw or withhold life-sustaining treatment on 180-day mortality. The marginal population was estimated to be 5.9% of the total cohort. A decision to withdraw or withhold life-sustaining treatment was associated with a marginal increase in 180-day mortality of 25.6% (95% CI, 23.2–27.9%).

CONCLUSIONS:
Decision to withdraw or withhold life-sustaining treatment in critically ill adults in the United Kingdom was associated with increased 180-day mortality in the marginal patients. The increased mortality from a decision to withdraw or withhold life-sustaining treatment in the marginal patient may be informative when establishing patients’ preferences and evaluating the cost-effectiveness of intensive treatments.
The effect of a nurse-led advice line and virtual clinic on inflammatory bowel disease service delivery: an Australian study
Authors: Karimi Neda , Sechi Alexandra J. , Harb Martin , Sawyer Elise , Williams Astrid-Jane , Ng Watson , Connor Susan J. 
Published: August 2021

Background
This retrospective cohort study investigated the economic impact of implementing a nurse-led inflammatory bowel disease (IBD) advice-line and virtual clinic on the Australian healthcare system. The advice line is a telephone and email service managed by IBD specialist nurses. The virtual clinic is a planned, formal communication between the gastroenterologist and the specialist IBD nurse the result of which is communicated to the patient electronically

Methods
Advice line telephone calls and virtual clinic consultations registered between 1 June 2015 and 1 June 2016 were reviewed and analyzed in terms of outcome: avoidance of general practitioner (GP) consultation, IBD outpatient consultation, emergency department (ED) presentation, or hospital admission. Cost-benefit analysis was conducted to estimate financial savings.

Results
During the study period, 220 calls were received through the advice line and 1017 virtual clinic consultations occurred. The advice line resulted in the avoidance of 53 GP visits, 159 IBD outpatient department visits, six ED presentations, and one hospital admission. The virtual clinic resulted in the avoidance of four GP visits, 954 IBD outpatient department visits, and 58 ED presentations. This led to an estimated annual cost saving of AUD 169 376.80, with the annual costs incurred estimated to be $58 713. Thus, the annual net benefit of implementing the advice line and the virtual clinic was estimated to be $110 663.80.

Conclusion
Specialized-IBD-nurse-led advice line and virtual clinic improves IBD patients’ access to services and reduces healthcare costs. This highlights the importance of a proactive multidisciplinary approach in optimizing the care of patients with IBD.
The influence of SARS-CoV-2 variants of concern on national case fatality rates
Authors: Barletta William A. 
Published: August 2021

AbstractBackgroundDuring 2021 several new variants of the SARS-CoV-2 virus appeared with both increased levels of transmissibility and virulence with respect to the original wild variant. The Delta (B.1.617.2) variation, first seen in India, dominates COVID-19 infections in several large countries including the United States and India. Most recently, the Lambda variant of interest with increased resistance to vaccines has spread through much of South America.ObjectiveThis research explores the degree to which new variants of concern 1) generate spikes and waves of fluctuations in the daily case fatality rates (CFR) across countries in several regions in the face of increasing levels of vaccination of national populations and 2) may increase the vulnerability of persons with certain comorbidities.MethodsThis study uses new, openly available, epidemiological statistics reported to the relevant national and international authorities for countries across the Americas, Europe, Africa, Asia and the Middle East. Daily CFRs and correlations of fatal COVID-19 infections with potential cofactors are computed for the first half of 2021 that has been dominated by the wide spread of several “variants of concern” as denoted by the World Health Organization.ResultsThe analysis yields a new quantitative measure of the temporal dynamics of mortality due to SARS-CoV-2 infections in the form of variations of a proxy case fatality rate compared on a country to-country basis in the same region. It also finds minimal variation of correlation between the cofactors based on WHO data and on the average apparent case fatality rate.
Immunogenicity and safety of inactivated whole virion Coronavirus vaccine with CpG (VLA2001) in healthy adults aged 18 to 55: a randomised phase 1 /2 clinical trial
Authors: Lazarus Rajeka , Taucher Christian , Brown Claire , Corbic Irena , Danon Leon , Dubischar Katrin , Duncan Christopher J.A. , Eder-Lingelbach Susanne , Faust Saul N , Green Christopher , Gokani Karishma , Hochreiter Romana , Wright Johanna Kellett , Kwon Dowan , Middleditch Alexander , Munro Alasdair P.S. , Naker Kush , Penciu Florentina , Price David , Querton Benedicte , Riaz Tawassal , Ross-Russell Amy , Sanchez-Gonzalez Amada , Wardle Hayley , Warren Sarah , Finn Adam ,   the Valneva Phase 1 Trial Group
Published: August 2021

AbstractBackgroundWe assessed the safety, tolerability and immunogenicity of VLA2001 is a whole-virion inactivated SARS-CoV-2 vaccine adsorbed to alum with a toll-like receptor 9 agonist adjuvant in healthy volunteers aged 18-55.MethodsThe first 15 participants were enrolled, in groups of 5, to receive two doses, separated by 21 days, of one of three dose concentrations, administered intramuscularly. 138 further participants were randomised 1:1:1 to receive the same 3 dose concentrations, in a double blinded manner. Primary outcomes were solicited adverse reactions 7 days after each vaccination and neutralising antibody geometric mean titres (GMT) against SARS-CoV-2, 2 weeks after the second vaccination (day 36), measured by live microneutralisation assay against wild-type virus (MNA50). Secondary outcomes included unsolicited adverse events, and humoral and cellular responses at day 36, measured by IgG ELISA against Spike protein and interferon-γ secreting T-cells by ELISpot stimulated with multiple SARS-CoV-2 antigens. (ClinicalTrials.govNCT04671017, ISRCTN 82411169)FindingsBetween December 16, 2020 and January 21, 2021, 153 participants were enrolled and randomised evenly between the dose groups. The rates of solicited reactions were similar after the first and second doses and between the three dose groups. The most frequent local reactions were tenderness (58·2%) and pain (41·8%) and systemic reactions were headache (46%) and fatigue (39·2%).In the high dose group, two weeks following the second dose, the geometric mean titres were 530.4 (95% CI: 421·49, 667·52) for neutralizing antibodies and 2147·9 (95% CI: 1705·98, 2704·22) for S-binding antibodies. There was a dose dependent response with 90·0% (95% CI:78·0%.,97·0%) seroconversion (4-fold rise) at day 36 in the high dose group, which was significantly higher than rates in both the medium (73.5%; 95% CI: 59%,85%), CIs) and low dose (51%; 95%CI: 37%,65%) rate, CIs) groups (both p < 0.001). Antigen-specific interferon-γ T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49% of high dose recipients, respectively.InterpretationVLA2001-201 was well tolerated and produced both humoral and cellular immune responses, with a clear dose-response effect.FundingThis study was funded by the Department of Health and Social Care, UKThe funder had no role in the study design, implementation or analysis.
Food interactions observed in a pharmacokinetic investigation comparing two marketed cold preparations (BNO1016 and ELOM-080) after administration to male beagle dogs
Authors: Seibel Jan , Neumann Astrid , Müller Anne , Wonnemann Meinolf 
Published: August 2021

AbstractThe cold remedies Sinupret extract (BNO 1016) and Gelomyrtol forte (ELOM-080) represent the two top-selling cold remedies in Germany nowadays. Whereas BNO 1016 is a typical immediate release coated tablet, ELOM-080 is an enteric-coated soft gelatin capsule. The latter formulation, however, is at risk of pharmacokinetic interactions affecting absorption especially in the case of concomitant food intake. In the present pilot study, we investigated the risk of a possible food effect on BNO 1016 in comparison to ELOM-080 in three male beagle dogs. Single doses of BNO 1016 and ELOM-80 at 80 mg/kg and 160 mg/kg, respectively, were administered under fasting and fed conditions according to a 4-period, 4-treatment within-design. Blood sampling took place until up to 30 hp.a.and plasma concentrations of gentiopicroside, verbenalin and from a further marker analyte (BNO 1016 analytes) as well as 1,8-cineole, limonene and perillic acid (ELOM-080 analytes) were determined. Pharmacokinetic parameters focusing on rate and extent of absorption were derived. BNO 1016 analytes demonstrated a homogenous course in all animals in both, the fasted and fed state. Pharmacokinetic characteristics of a typical immediate release drug formulation were observed for all analytes and a food effect could be ruled out. ELOM-080 analytes also showed a homogeneous picture in the fasted state. However, lag-times (tlag) of up to 2 hp.a.with corresponding tmaxvalues of 3 to 4 h were observed, reflecting a longer gastric residence time of the formulation. In the fed state, ELOM-080 showed significant pharmacokinetic characteristics suggesting a clear food effect. A major observation was a double peak phenomenon that could be observed in two out of three dogs. Furthermore, lag-times of some analytes up to 3-4 h and corresponding tmaxvalues of up to 6-8 h occurred. In contrast to BNO 1016, these findings suggest that, as with other enteric-coated formulations, there may be a significant risk for food effects with ELOM-080 also in humans.
Covid-19 vaccine immunogenicity in people living with HIV-1
Authors: Nault Lauriane , Marchitto Lorie , Goyette Guillaume , Tremblay-Sher Daniel , Fortin Claude , Martel-Laferrière Valérie , Trottier Benoît , Richard Jonathan , Durand Madeleine , Kaufmann Daniel , Finzi Andrés , Tremblay Cécile 
Published: August 2021

AbstractIntroductionCOVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals’ response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals.MethodsHIV-positive individuals (n=121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naïve to SARS CoV-2 was used. The participants’ Anti-RBD IgG responses were measured by ELISA at baseline and 3 to 4 weeks after receiving the first dose of an mRNA vaccine).ResultsEleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between between the HIV negative control group (n=20) and the combined HIV+ group (n=106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm3. (p<0.0001). Increasing age was independently associated with decreased immunogenicity.ConclusionHIV-positive individuals with CD4 counts over 250 cells/mm3have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm3) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose.
Nucleoporin107 mediates female sexual differentiation via Dsx
Authors: Shore Tikva , Levi Tgst , Kalifa Rachel , Dreifuss Amatzia , Rekler Dina , Weinberg-Shukron Ariella , Nevo Yuval , Bialistoky Tzofia , Moyal Victoria , Gold Merav Yaffa , Leebhoff Shira , Zangen David , Deshpande Girish , Gerlitz Offer 
Published: August 2021

AbstractWe recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modelling of the human mutation in Drosophila or specific knockdown of Nup107 in the gonadal soma resulted in ovarian-dysgenesis-like phenotypes. Transcriptomic analysis identified the somatic sex-determination gene doublesex (dsx) as a target of Nup107. Establishing Dsx as a primary relevant target of Nup107, either loss or gain of Dsx in the gonadal soma is sufficient to mimic or rescue the phenotypes induced by Nup107 loss. Importantly, the aberrant phenotypes induced by compromising either Nup107 or dsx are reminiscent of BMP signaling hyperactivation. Remarkably, in this context, the metalloprotease AdamTS-A, a transcriptional target of both Dsx and Nup107, is necessary for the calibration of BMP signaling. As modulation of BMP signaling is a conserved critical determinant of soma-germline interaction, the sex and tissue specific deployment of Dsx-F by Nup107 seems crucial for the maintenance of the homeostatic balance between the germ cells and somatic gonadal cells.
Desolvation Energy Explains Partitioning of Client Proteins into Condensates
Authors: Villegas José A. , Levy Emmanuel D. 
Published: August 2021

AbstractMembraneless organelles are cellular compartments that form by liquid-liquid phase separation of one or more components. Other molecules, such as other proteins and nucleic acids, will distribute between the cytoplasm and the liquid compartment in accordance with the thermodynamic drive to lower the free energy of the system. The resulting distribution colocalizes molecular species, to carry out a diversity of functions. Two factors could drive this partitioning: the difference in solvation between the dilute versus dense phase, and intermolecular interactions between the client and scaffold proteins. Here, we develop a set of knowledge-based potentials that allow for the direct comparison between desolvation energy and pairwise interaction energy terms, and use these to examine experimental data from two systems: protein cargo dissolving within phase-separated droplets made from FG repeat proteins of the nuclear pore complex, and client proteins dissolving within phase-separated FUS droplets. We find close agreement between desolvation energies of the client proteins and the experimentally determined values of the partition coefficients, while pairwise interaction energies between client and scaffold show weaker correlations. These results show that client stickiness is sufficient to explain differential partitioning of clients within these two phase-separated systems without taking into account the composition of the condensate. This suggests that selective trafficking of client proteins to distinct membraneless organelles requires recognition elements beyond the client sequence composition.
Specific length and structure rather than high thermodynamic stability enable regulatory mRNA stem-loops to pause translation
Authors: Bao Chen , Zhu Mingyi , Nykonchuk Inna , Wakabayashi Hironao , Mathews David H. , Ermolenko Dmitri N. 
Published: August 2021

SUMMARYTranslating ribosomes unwind mRNA secondary structures by three basepairs each elongation cycle. Despite the ribosome helicase, certain mRNA stem-loops stimulate programmed ribosomal frameshift by inhibiting translation elongation. Here, using mutagenesis, biochemical and single-molecule experiments, we examine whether high stability of three basepairs, which are unwound by the translating ribosome, is critical for inducing ribosome pauses. We find that encountering frameshift-inducing mRNA stem-loops from the E. coli dnaX mRNA and the gag-pol transcript of Human Immunodeficiency Virus (HIV) hinders A-site tRNA binding and slows down ribosome translocation by 15-20 folds. By contrast, unwinding of first three basepairs adjacent to the mRNA entry channel slows down the translating ribosome by only 2-3 folds. Rather than high thermodynamic stability, specific length and structure enable regulatory mRNA stem-loops to stall translation by forming inhibitory interactions with the ribosome. Our data provide the basis for rationalizing transcriptome-wide studies of translation and searching for novel regulatory mRNA stem-loops.
Value relevance of accounting information during IFRS convergence period: comparative evidence between India and Indonesia
Authors: Srivastava Anubha , Muharam Harjum 
Published: August 2021

Purpose
This study aims to examine the financial reporting quality during the International Financial Reporting Standards (IFRS) enforcement period in the emerging markets of India and Indonesia by using Ohlson’s (1995) valuation model. The study further endeavors to compare the quality of the reporting environment and its impact on stock prices for both these emerging economies by using a price model during the IFRS conversion period.

Design/methodology/approach
This paper aspires to obtain insights about the value relevance of accounting information during the IFRS enforcement period for India and its Southeast Asian neighbor, Indonesia which is identical in terms of inclusive growth and development. In that context, 3,325 Indian (National Stock Exchange indexed) and 815 Indonesian (Indonesian stock exchange indexed) firm-year observations were examined by using Ohlson’s price valuation model for five years, representing the IFRS adherence period.

Findings
The findings of the paper insinuated that the value relevance of book values and earnings, both, have increased throughout the IFRS enforcement period for both economies. However, the investigation revealed that the incremental interpretive power of earnings is more substantial and evident during the IFRS adherence phase than book values which indicates investor’s inclination toward earnings management over book values.

Research limitations/implications
The findings may assist the regulators, investors, firms and standard setters of both economies in examining the effectiveness of financial reporting curriculums as it brings forth informational improvement in the financial market. This study also outstretches the discussion on the subject in other emerging nations where the market is imperfect with insufficient information, poor enforcement and limited regulations. This investigation has few limitations such as limited data and period, only two emerging economies and two control variables, thus provide scope for future research.

Social implications
This paper endeavors to investigate and compare the value relevance of accounting information during IFRS convergence period between India and Indonesia with an aim to assist in improved decision making for both, regulatory bodies and market participants in both the countries.

Originality/value
The key contribution of the study is to examine whether the accounting information is value relevant during the IFRS convergence period for the two fastest-growing economies in Asia, India and Indonesia and it is the first such empirical research to the best of the author’s knowledge. The study is an extended contribution to the modest research administered in developing nations.
Regulatory dilemma: a changing dynamics of the Cochin international airport
Authors: Damodaran Akhil , Dhingra Tarun , Dwivedi Prasoom 
Published: August 2021

Learning outcomes
The case study helps students to understand how public-private partnership (PPP) airports runs their business, how regulatory policies impact their business. The case also explains why the Cochin International Airport business model is so unique compared to any airport in India.

Case overview/synopsis
In 2016, Airport Economic Regulatory Authority released a new tariff regime for Cochin International Airport Limited (CIAL).CIAL has undergone challenges because of the tariff changes (changes every five years), which were implemented in 2017. This has impacted their business model. The CFO of CIAL was under pressure to share the impacts with the shareholders and to provide a way forward for the business. Cochin International was known to be one of the cheapest aeronautical tariff charging airports. The case discusses the issues of a public utility when it is under a regulatory price regime. The case explains different regulatory mechanisms (single till: the whole commercial revenue is cross-subsidized). The case discusses issues regarding Cochin International Airport, which is a public utility under PPP mode. Since 2016, regulator has changed the price regulatory regime from light touch (no price regulation only monitoring) to hybrid till regulation (a percentage of commercial revenue is cross-subsidized). The case explains what made Cochin International Airport so unique. It explores the challenges because of the regulatory regime, how it affects Cochin airport’s strategy for business. How should the management of CIAL to act on the above issue? What will be the impact? Will they need to change their business models?

Complexity academic level
The case is basically focused on MBA level students who are in their final year. There are various MBA courses in which this can be taught, which can be infrastructure management, infrastructure regulation, domain courses such as airport management. The student should have basic knowledge of economics, public utility and business strategy. The case helps them understand the impact of regulation, the role of the regulator and its impact on business strategy.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS: 10 Public Sector Management.