bluuebunny/crossref_metadata_2025 huggingface dataset:
EPA guidance on assessment of negative symptoms in schizophrenia
Authors: Galderisi S. , Mucci A. , Dollfus S. , Nordentoft M. , Falkai P. , Kaiser S. , Giordano G. M. , Vandevelde A. , Nielsen M. Ø. , Glenthøj L. B. , Sabé M. , Pezzella P. , Bitter I. , Gaebel W.
Published: February 2021

Background

During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.

Methods

In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.

Results

Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.

This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.

The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.

Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.

Conclusions

The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.
Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myélodysplasies (GFM)
Authors: Cluzeau Thomas , Sebert Marie , Rahmé Ramy , Cuzzubbo Stefania , Lehmann-Che Jacqueline , Madelaine Isabelle , Peterlin Pierre , Bève Blandine , Attalah Habiba , Chermat Fatiha , Miekoutima Elsa , Rauzy Odile Beyne , Recher Christian , Stamatoullas Aspasia , Willems Lise , Raffoux Emmanuel , Berthon Céline , Quesnel Bruno , Loschi Michael , Carpentier Antoine F. , Sallman David A. , Komrokji Rami , Walter-Petrich Anouk , Chevret Sylvie , Ades Lionel , Fenaux Pierre
Published: February 2021

PURPOSE

TP53-mutated ( TP53m) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have very poor outcome irrespective of the treatment received, including 40% responses (20% complete remission [CR]) with azacitidine (AZA) alone, short response duration, and a median overall survival (OS) of approximately 6 months. Eprenetapopt (APR-246), a novel first-in-class drug, leads to p53 protein reconformation and reactivates its proapoptotic and cell-cycle arrest functions.

PATIENTS AND METHODS

This phase II study assessed the safety and efficacy of eprenetapopt in combination with AZA in untreated high or very high International Prognostic Scoring System-R TP53m MDS and AML patients.

RESULTS

Fifty-two TP53m patients (34 MDS, 18 AML [including seven with more than 30% blasts]) were enrolled. In MDS, we observed an overall response rate (ORR) of 62%, including 47% CR, with a median duration of response at 10.4 months. In AML, the ORR was 33% including 17% CR (27% and 0% CR in AML with less than and more than 30% marrow blasts, respectively). Seventy-three percent of responders achieved TP53 next-generation sequencing negativity (ie, variant allele frequency < 5%). The main treatment-related adverse events were febrile neutropenia (36%) and neurologic adverse events (40%), the latter correlating with a lower glomerular filtration rate at treatment onset ( P < .01) and higher age ( P = .05), and resolving with temporary drug interruption without recurrence after adequate eprenetapopt dose reduction. With a median follow-up of 9.7 months, median OS was 12.1 months in MDS, and 13.9 and 3.0 months in AML with less than and more than 30% marrow blasts, respectively.

CONCLUSION

In this very high-risk population of TP53m MDS and AML patients, eprenetapopt combined with AZA was safe and showed potentially higher ORR and CR rate, and longer OS than reported with AZA alone.
Erythrocytosis in a Large Cohort of Trans Men Using Testosterone: A Long-Term Follow-Up Study on Prevalence, Determinants, and Exposure Years
Authors: Madsen Milou Cecilia , van Dijk Dennis , Wiepjes Chantal Maria , Conemans Elfi Barbara , Thijs Abel , den Heijer Martin
Published: February 2021

Context

Erythrocytosis is a known side effect of testosterone therapy that can increase the risk of thromboembolic events.

Objectives

To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone.

Methods

A 20-year follow-up study in adult trans men who started testosterone therapy and had monitoring of hematocrit at our center (n = 1073).

Results

Erythrocytosis occurred in 11% (hematocrit > 0.50 L/L), 3.7% (hematocrit > 0.52 L/L), and 0.5% (hematocrit > 0.54 L/L) of trans men. Tobacco use (odds ratio [OR] 2.2; 95% CI, 1.6-3.3), long-acting undecanoate injections (OR 2.9; 95% CI, 1.7-5.0), age at initiation of hormone therapy (OR 5.9; 95% CI, 2.8-12.3), body mass index (BMI) (OR 3.7; 95% CI, 2.2-6.2), and pulmonary conditions associated with erythrocytosis and polycythemia vera (OR 2.5; 95% CI, 1.4-4.4) were associated with hematocrit > 0.50 L/L. In the first year of testosterone therapy hematocrit increased most: 0.39 L/L at baseline to 0.45 L/L after 1 year. Although there was only a slight continuation of this increase in the following 20 years, the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 10 years).

Conclusion

Erythrocytosis occurs in trans men using testosterone. The largest increase in hematocrit was seen in the first year, but also after the first years a substantial number of people present with hematocrit > 0.50 L/L. A reasonable first step in the care for trans men with erythrocytosis while on testosterone is to advise them to quit smoking, to switch to a transdermal administration route, and if BMI is high, to lose weight.
Laocoön’s Scream; or, Lessing Redux
Authors: Gyenge Andrea
Published: February 2021

This article returns to the figure of the mouth in Gotthold Ephraim Lessing’s Laocoön: An Essay on the Limits of Painting and Poetry. While many scholars treat Lessing’s attention to the statue’s mouth as a sign of his contempt for the body, the article argues that Lessing’s interest in orality is a test of the limits of the eighteenth century’s neoclassicism. The article concludes that Lessing is thus not a representative of conservative aesthetics but a proto-Freudian thinker who inadvertently challenged the foundations of his own aesthetic project.
What IsLeitkultur?
Authors: Cattien Jana
Published: February 2021

This article interrogates the discursive regimes that underpin Leitkultur (guiding culture) discourse in contemporary Germany and argues that Leitkultur conjures Germany’s imagined “freedom from history” from within Enlightenment temporalities of liberal freedom. This requires that liberal Germany mark its limits in certain moments of German history—namely, National Socialism—while disavowing its role in the constitution of German colonialism. The return to the Enlightenment implied in hegemonic formulations of Leitkultur restores Germany’s freedom from an ugly past; this imagined return can carry the promise of a “diverse” and “inclusive” Germany only insofar as Germany’s colonial heritage is suppressed. The article aims to expose how Germany’s colonial legacy underpins dominant Leitkultur discourse while it is nevertheless hidden from it.
The Possibility of Translation
Authors: Gillespie Susan H.
Published: February 2021

Translation, by highlighting the incommensurability of human language, sheds light on essential philosophical insights into the limited, historically and socially embedded nature of meaning while simultaneously offering theoretical and practical tools for overcoming differences and divisions. The author’s experience as a translator, the concept of determinate negation as developed by Theodor W. Adorno, the translation theory of Walter Benjamin, and a poem by Paul Celan support claims that translation is a dialectical process that works both ways: it influences the translator’s language and changes the language from which a work is translated. Translatability offers concepts, techniques, and tools for negotiating difference that are preferable to multiculturalism. Its practices of analytical guesswork, informed critique, careful listening to tone and resonance, and recognition of the ultimately nonfinalizable character of immediate outcomes as it “gestures toward eternity” (Benjamin) can help humans address contemporary crises while preserving the hope of a better world.
Combined heterogeneity in cell size and deformability promotes cancer invasiveness
Authors: Asadullah  , Kumar Sandeep , Saxena Neha , Sarkar Madhurima , Barai Amlan , Sen Shamik
Published: February 2021

Phenotypic heterogeneity is increasingly acknowledged to confer several advantages to cancer progression and drug resistance. Here, we probe the collective importance of heterogeneity in cell size and deformability in breast cancer invasion. A computational model of invasion of a heterogeneous cell aggregate predicts that combined heterogeneity in cell size and deformability enhances invasiveness of the whole population, with maximum invasiveness at intermediate cell-cell adhesion. We then show that small cells of varying deformability, a subpopulation predicted to be enriched at the invasive front, exhibit considerable overlap with the biophysical properties of cancer stem cells (CSCs). In MDA-MB-231 cells, these include CD44hi CD24− mesenchymal CSCs, which are small and soft, and CD44hi CD24+ hybrid CSCs, which exhibit a wide range of size and deformability. We validate our predictions by tracking the pattern of cell invasion from spheroids implanted in three-dimensional collagen gels, wherein we show temporal enrichment of CD44hi cells at the invasive front. Collectively, our results illustrate the advantages imparted by biophysical heterogeneity in enhancing cancer invasiveness.

This article has an associated First Person interview with the first author of the paper.
Why Join a Team?
Authors: Cooper David J. , Saral Krista , Villeval Marie Claire
Published: February 2021

We present experiments exploring why high ability workers join teams with less able coworkers when there are no short-term financial benefits. We distinguish between two explanations: prosocial preferences and expected long-term financial gains from teaching future teammates. Participants perform a real-effort task and decide whether to work independently or join a two-person team. Treatments vary the payment scheme (piece rate or revenue sharing), whether teammates can communicate, and the role of teaching. High ability workers are more willing to join teams in the absence of revenue sharing and less willing to join teams when they cannot communicate. When communication is possible, the choice of high ability workers to join teams is driven by expected future financial gains from teaching rather than some variety of prosocial preferences. This result has important implications for the role of adverse selection in determining the productivity of teams.

This paper was accepted by Yan Chen, decision analysis.
Supply Chains and Antitrust Governance
Authors: Jain Nitish , Hasija Sameer , Netessine Serguei
Published: February 2021

Antitrust regulations are meant to promote fair competition in the market, but balancing administrative and legal costs with enforcement can be difficult when multilayered supply chains are involved. The canonical example of this challenge is the landmark Illinois Brick ruling, which limits antitrust damages to only the direct purchasers of a product; for instance, consumers can file antitrust claims against colluding retailers but not against colluding manufacturers—only retailers can file claims against manufacturers. This controversial ruling was meant to reduce legal costs, but it can clearly lead to missed enforcement opportunities. In this paper, we demonstrate how the Illinois Brick ruling interacts with contracts adopted in the supply chain, and we show that otherwise equivalent supply chain arrangements can have markedly different effects. In particular, we find that wholesale price, minimum order quantity, revenue sharing, and quantity discount contracts lead retailers to take legal action against manufacturers in the event of collusive behavior. However, the wholesale price plus fixed fee contract structure (also known as a two-part tariff or slotting fee contract) facilitates collusion among the manufacturers with retailers compensated by the fixed fee and not filing the antitrust litigation. We further demonstrate that collusion is more likely under high demand uncertainty and high competition at the retail level but is less likely under high competition at the manufacturer level. Our paper helps public enforcers identify market conditions conducive to antitrust violations.

This paper was accepted by Vishal Gaur, operations management.
REPRESENTASI KELUGASAN BERANDA LAMAN WWW.COVID19.GO.ID: TINJAUAN ANALISIS WACANA KRITIS
Authors: Suswandi Irwan
Published: February 2021

The digital era has encourages information providers to innovate by utilizing the internet to convey information quickly. No exception for the government in a way to provide information and news related to Covid-19 which has become a global pandemic.  Using a website as a source of information can give quick access for people to obtain actual and valid information relating to Covid-19.  Through www.covid19.go.id, the government provides a facility for people to be able to access all information about Covid-19 matters. In this research, the researcher will analyze how government gives simplicity in providing information related to Covid-19, which is represented on the www.covid19.go.id homepage. The researcher used CDA (critical discourse analysis) theory from Fairclough to analyze the text found on the www.covid19.go.id homepage.  Then, the results of critical discourse analysis were linked with the reputation theory of Charles J. Fombrun.  The analysis produced information in the form of language units of www.covid19.go.id homepage which contains a simplicity matter in the delivery of information.  From this analysis, the researcher can conclude that the simplicity in www.covid19.go.id homepage was represented through the website components, content, and propositions contained in the homepage.  The simplicity matter also found in the use of modes, those were descriptive, persuasive, and interrogative mode.
Steroids in inflammatory bowel disease: a clinical review
Authors: Hussenbux Arif , De Silva Aminda
Published: February 2021

Corticosteroids are effective at inducing remission in inflammatory bowel disease (IBD). Acute severe ulcerative colitis and Crohn's disease are managed with intravenous steroids. In mild-to-moderate disease, corticosteroids can be given orally or topically. Long-term use should be limited to prevent commonly associated adverse effects. Corticosteroids should not be used to maintain remission. Blood pressure, body mass index and blood glucose monitoring are crucial while on steroids. Acid suppression along with calcium and vitamin D supplementation should be co-prescribed to all patients on long-term corticosteroids. Bridging these patients to a steroid-sparing agent early prevents steroid-refractory and steroid-dependent disease. GP education, IBD helplines, IBD clinics, multidisciplinary team meetings and regular auditing should be encouraged to prevent corticosteroid overprescribing.
Variations on a deadly theme: How COVID-19 is changing
Authors: Greener Mark
Published: February 2021

Mark Greener looks at how the virus is evolving over time and what that means for us
Organising health visiting services in the UK: Frontline perspectives
Authors: Whittaker Karen , Appleton Jane V , Peckover Sue , Adams Cheryll
Published: February 2021

The organisation of health visitor work is an important part of service design, which can have an impact on when and where services are provided and who gains access. This article reports a 2018 survey of UK health visitors conducted to provide an overview of the range of ways in which health visitor cases and workloads are organised. The 584 respondents confirmed the operation of three broad types of health visitor service delivery models; namely, the individual case, the corporate case and the combination model. Themes that emerged from practitioners' experiences of working with the different models reflected concerns about continuity and staffing, accommodating different needs and different services in different places. Overall, the data indicated a lack of consistency in health visitor service across the UK. The advantages and disadvantages of each workload model are detailed and considered with respect to markers of a quality service, including achieving relationships with clients and sufficient communication within and across teams.
Waveguide-based absorption measurement system for visible wavelength applications
Authors: Neutens P. , Jansen R. , Woronoff G. , Rutowska M. , Hosseini N. , Buja F. , Humbert A. , Colle F. , Stakenborg T. , Van Roy W.
Published: February 2021

We present a miniaturized waveguide-based absorption measurement system operating at a wavelength of 635 nm, based on a silicon nitride integrated photonic platform, suitable for lab-on-chip applications. We experimentally demonstrate a high correlation between the bulk dye concentration and the measured absorption loss levels in the waveguides. We explain a photonic design process for choosing the ideal waveguide to minimize the coefficient of variation on the analyte concentration. The approach is designed for camera readout, allowing multiple readouts and easy integration for lab-on chip cartridge approach.
Oxidation of aluminum thin films protected by ultrathin MgF2 layers measured using spectroscopic ellipsometry and X-ray photoelectron spectroscopy
Authors: Johnson Brian I. , Avval Tahereh G. , Turley R. Steven , Linford Matthew R. , Allred David D.
Published: February 2021

To maintain high, broad-band reflectance, thin transparent fluoride layers, such as MgF2, are used to protect aluminum mirrors against oxidation. In this study, we present, for the first time, combined X-ray photoelectron spectroscopy (XPS) and spectroscopic ellipsometric (SE) studies of aluminum oxidation as a function of MgF2 overlayer thickness (thickness 0-5 nm). Dynamic SE tracks the extent of oxide growth every ca. 2s over a period of several hours after the evaporated Al + MgF2 bilayer is removed from the deposition chamber. Aluminum oxidation changes under the fluoride layer were quantitatively verified with XPS. Changes in chemical state from Al metal to Al oxide were directly observed. Oxide growth is computed from relative XPS peak areas as corrected for electron attenuation through the MgF2 overlayer. An empirical formula fits time-dependent data for aluminum surfaces protected by MgF2 as a function of MgF2 layer thickness: aluminum-oxide thickness = kSE*log(t)+bSE. The slope depends only on MgF2 thickness, decreasing monotonically with increasing MgF2 thickness. This method of employing SE coupled with XPS can be extendable to the study of other metal/overlayer combinations.
Paradoxes Datenschutzverhalten
Authors: Lasarov Wassili , Hoffmann Stefan
Published: February 2021

Einhergehend mit der Digitalisierung vieler Lebensbereiche werden große Mengen persönlicher Daten von Konsument*innen durch Unternehmen und Institutionen erfasst und analysiert. Daher ist der verantwortungsvolle Umgang mit diesen Daten eines der drängendsten Themen der Gegenwart. Zwar gibt es zahlreiche gesetzliche Verordnungen (z. B. GDPR) sowie eine zunehmende Anzahl von Unternehmen, die sich freiwillig dem Datenschutz verpflichten, allerdings nutzen auch viele Unternehmen und Institutionen die Unachtsamkeit von Konsument*innen aus. Dies wird dadurch begünstigt, dass viele Konsument*innen zwar angeben, dass sie auf ihre Privatsphäre achten, aber nur wenige die dafür notwendigen Maßnahmen ergreifen. Diese Einstellungs-Verhaltens-Diskrepanz (Privatsphäre-Paradoxon) lässt sich einerseits durch ein rationales Kosten-Nutzen-Kalkül erklären, in dem Konsument*innen den Nutzen bestimmter Produkte (z. B. durch Personalisierung) mit der Preisgabe ihrer Daten verrechnen. Andererseits können situative Einflüsse (z. B. wenig Zeit) oder kognitive Verzerrungen (z. B. Kontrollillusion) Datenschutzbedenken in diesen Situationen verringern. Vor diesem Hintergrund führen wir in das Privatsphäre-Paradoxon ein und zeigen den Stand des Schrifttums auf, wobei wir auf situative und kognitiven Verzerrungen fokussieren. Abschließend wird das Konzept der drei Privatsphäre-Gaps eingeführt und ein Rahmen für zukünftige Forschung entwickelt.
Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition
Authors: Cabrera-Quio Luis Enrique , Schleiffer Alexander , Mechtler Karl , Pauli Andrea
Published: February 2021

Post-transcriptional regulation of gene expression is crucial during the oocyte-to-embryo transition, a highly dynamic process characterized by the absence of nuclear transcription. Thus, changes to the RNA content are solely dependent on RNA degradation. Although several mechanisms that promote RNA decay during embryogenesis have been identified, it remains unclear which machineries contribute to remodeling the maternal transcriptome. Here, we focused on the degradation factor Ski7 in zebrafish. Homozygous ski7 mutant fish had higher proportions of both poor quality eggs and eggs that were unable to develop beyond the one-cell stage. Consistent with the idea that Ski7 participates in remodeling the maternal RNA content, transcriptome profiling identified hundreds of misregulated mRNAs in the absence of Ski7. Furthermore, upregulated genes were generally lowly expressed in wild type, suggesting that Ski7 maintains low transcript levels for this subset of genes. Finally, GO enrichment and proteomic analyses of misregulated factors implicated Ski7 in the regulation of redox processes. This was confirmed experimentally by an increased resistance of ski7 mutant embryos to reductive stress. Our results provide first insights into the physiological role of vertebrate Ski7 as a post-transcriptional regulator during the oocyte-to-embryo transition.
A novel role for Dun1 in the regulation of origin firing upon hyper-acetylation of H3K56
Authors: Gershon Lihi , Kupiec Martin
Published: February 2021

During DNA replication newly synthesized histones are incorporated into the chromatin of the replicating sister chromatids. In the yeast Saccharomyces cerevisiae new histone H3 molecules are acetylated at lysine 56. This modification is carefully regulated during the cell cycle, and any disruption of this process is a source of genomic instability. Here we show that the protein kinase Dun1 is necessary in order to maintain viability in the absence of the histone deacetylases Hst3 and Hst4, which remove the acetyl moiety from histone H3. This lethality is not due to the well-characterized role of Dun1 in upregulating dNTPs, but rather because Dun1 is needed in order to counteract the checkpoint kinase Rad53 (human CHK2) that represses the activity of late firing origins. Deletion of CTF18, encoding the large subunit of an alternative RFC-like complex (RLC), but not of components of the Elg1 or Rad24 RLCs, is enough to overcome the dependency of cells with hyper-acetylated histones on Dun1. We show that the detrimental function of Ctf18 depends on its interaction with the leading strand polymerase, Polε. Our results thus show that the main problem of cells with hyper-acetylated histones is the regulation of their temporal and replication programs, and uncover novel functions for the Dun1 protein kinase and the Ctf18 clamp loader.
A family-based intervention for prevention and self-management of disabilities due to leprosy, podoconiosis and lymphatic filariasis in Ethiopia: A proof of concept study
Authors: van‘t Noordende Anna T. , Wubie Aycheh Moges , Tadesse Tesfaye , Hagens Tanny , Haverkort Eva , Schippers Alice P.
Published: February 2021

A key issue for persons with leprosy-, lymphatic filariasis- and podoconiosis-related disabilities is the life-long need to practice self-management routines. This is difficult to sustain without regular encouragement and support of others. Family-based support may be a sustainable and feasible strategy to practice self-management routines. This proof of concept study aimed to develop and pilot a family-based intervention to support prevention and self-management of leprosy, lymphatic filariasis and podoconiosis-related disabilities in Ethiopia.

We used a quasi-experimental pre/post intervention study design with a mixed methods approach. The study population included persons affected by leprosy, lymphatic filariasis and podoconiosis and their family members. All persons affected had visible impairments due to their condition. We collected physical impairment outcomes, data on activity limitations, stigma and family quality of life using the SALSA scale (range 0–80), the SARI stigma scale (range 0–63) and the Beach Centre Family Quality of Life scale (range 0–125) and conducted in-depth interviews and focus group discussions. Quantitative data were analysed using paired t-tests, unequal variances t-tests, linear regression and binary logistic regression. Qualitative data were coded using open, inductive coding and content analysis.

The family-based intervention consisted of self-management of disabilities, awareness raising and socio-economic empowerment. The intervention was delivered over several monthly group meetings over the course of several months. A total of 275 (100%) persons affected attended at least one session with a family member, and 215 (78%) attended at least three sessions. There was no significant improvement in eye and hand problems after the intervention. However, foot and leg impairments, number of acute attacks, lymphedema and shoe wearing all significantly improved at follow-up. In addition, family quality of life significantly improved from 67.4 at baseline to 89.9 at follow-up for family members and from 76.9 to 84.1 for persons affected (p<0.001). Stigma levels significantly decreased from 24.0 at baseline to 16.7 at follow-up (p<0.001). Activity levels improved, but not significantly.

This proof of concept study showed that the family-based intervention had a positive effect on impairments and self-management of disabilities, family quality of life and stigma. We recommend a large-scale efficacy trial, using a randomised controlled trial and validated measurement tools, to determine its effectiveness and long-term sustainability.
Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India
Authors: Dhakulkar Shubhangi , Das Mrinalini , Sutar Narendra , Oswal Vikas , Shah Daksha , Ravi Shilpa , Vengurlekar Dipa , Chavan Vijay , Rebello Lorraine , Meneguim Augusto C. , Iyer Aparna , Mansoor Homa , Kalon Stobdan , Acharya Shrikala , Ferlazzo Gabriella , Isaakidis Petros , Thakur Harshad P.
Published: February 2021

Background

Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB.

Methods

This is a descriptive study including children (0–9 years) and adolescents (10–19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020.

Result

A total of 268 patients were included; 16 (6%) of them were children (0–9 years). The median(min-max) age was 17(4–19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10–25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3–4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3–4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3–13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome.

Conclusion

High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.
Acoustic analysis of vowel formant frequencies in genetically-related and non-genetically related speakers with implications for forensic speaker comparison
Authors: Cavalcanti Julio Cesar , Eriksson Anders , Barbosa Plinio A.
Published: February 2021

The purpose of this study was to explore the speaker-discriminatory potential of vowel formant mean frequencies in comparisons of identical twin pairs and non-genetically related speakers. The influences of lexical stress and the vowels’ acoustic distances on the discriminatory patterns of formant frequencies were also assessed. Acoustic extraction and analysis of the first four speech formants F1-F4 were carried out using spontaneous speech materials. The recordings comprise telephone conversations between identical twin pairs while being directly recorded through high-quality microphones. The subjects were 20 male adult speakers of Brazilian Portuguese (BP), aged between 19 and 35. As for comparisons, stressed and unstressed oral vowels of BP were segmented and transcribed manually in the Praat software. F1-F4 formant estimates were automatically extracted from the middle points of each labeled vowel. Formant values were represented in both Hertz and Bark. Comparisons within identical twin pairs using the Bark scale were performed to verify whether the measured differences would be potentially significant when following a psychoacoustic criterion. The results revealed consistent patterns regarding the comparison of low-frequency and high-frequency formants in twin pairs and non-genetically related speakers, with high-frequency formants displaying a greater speaker-discriminatory power compared to low-frequency formants. Among all formants, F4 seemed to display the highest discriminatory potential within identical twin pairs, followed by F3. As for non-genetically related speakers, both F3 and F4 displayed a similar high discriminatory potential. Regarding vowel quality, the central vowel /a/ was found to be the most speaker-discriminatory segment, followed by front vowels. Moreover, stressed vowels displayed a higher inter-speaker discrimination than unstressed vowels in both groups; however, the combination of stressed and unstressed vowels was found even more explanatory in terms of the observed differences. Although identical twins displayed a higher phonetic similarity, they were not found phonetically identical.
Visual scanning strategies in the cockpit are modulated by pilots’ expertise: A flight simulator study
Authors: Lounis Christophe , Peysakhovich Vsevolod , Causse Mickaël
Published: February 2021

During a flight, pilots must rigorously monitor their flight instruments since it is one of the critical activities that contribute to update their situation awareness. The monitoring is cognitively demanding, but is necessary for timely intervention in the event of a parameter deviation. Many studies have shown that a large part of commercial aviation accidents involved poor cockpit monitoring from the crew. Research in eye-tracking has developed numerous metrics to examine visual strategies in fields such as art viewing, sports, chess, reading, aviation, and space. In this article, we propose to use both basic and advanced eye metrics to study visual information acquisition, gaze dispersion, and gaze patterning among novices and pilots. The experiment involved a group of sixteen certified professional pilots and a group of sixteen novice during a manual landing task scenario performed in a flight simulator. The two groups landed three times with different levels of difficulty (manipulated via a double task paradigm). Compared to novices, professional pilots had a higher perceptual efficiency (more numerous and shorter dwells), a better distribution of attention, an ambient mode of visual attention, and more complex and elaborate visual scanning patterns. We classified pilot’s profiles (novices—experts) by machine learning based on Cosine KNN (K-Nearest Neighbors) using transition matrices. Several eye metrics were also sensitive to the landing difficulty. Our results can benefit the aviation domain by helping to assess the monitoring performance of the crews, improve initial and recurrent training and ultimately reduce incidents, and accidents due to human error.
Effect of bilateral contraction on the ability and accuracy of rapid force production at submaximal force level
Authors: Ohta Yoichi
Published: February 2021

The present study aims to clarify the effects of bilateral contraction on the ability and accuracy of rapid force production at the submaximal force level. Eleven right-handed participants performed rapid gripping as fast and precisely as they could in unilateral (UL) and bilateral (BL) contractions in a standing position. Participants were required to impinge a grip force of 30% and 50% of their maximal voluntary contraction (MVC). Ability and accuracy of rapid force production were evaluated using the rate of force development (RFD) and force error, respectively. The data analysis did not observe a significant difference in the RFD between UL and BL contractions in both 30% (420±86 vs. 413±106%MVC/s, p = 0.34) and 50% of MVC (622±84 vs. 619±103%MVC/s, p = 0.77). Although the RFD to peak force ratio (RFD/PF) in BL contraction was lower than in UL in 30% of MVC (12.8±2.8 vs. 13.4±2.7, p = 0.003), it indicated a small effect size (d = 0.22) of the difference between UL and BL in RFD/PF. The absolute force error of BL contraction was higher than of UL contraction in 30% (4.67±2.64 vs. 3.64±1.13%MVC, p = 0.005) and 50% of MVC (5.53±2.94 vs. 3.53±0.71%MVC, p = 0.009). In addition, medium and large effect sizes were observed in absolute force error from 30% (d = 0.51) and 50% of MVC (d = 0.94), respectively. In conclusion, results indicated that the bilateral contraction reduced in the ability and accuracy of rapid force production at the submaximal force level. Nevertheless, the present results suggest that the noticeable effect of bilateral contraction is more prominent on the accuracy than in the ability of rapid force production at the submaximal force level.
Demographic and behavioural drivers of intra-urban mobility of migrant street children and youth in Kampala, Uganda
Authors: Bwambale Mulekya Francis , Bukuluki Paul , Moyer Cheryl A. , Borne Bart H. W. van den
Published: February 2021

While research on the nexus of migration and wellbeing of individuals has gained recognition in recent years, far less attention has been devoted to intra-urban mobility especially among the urban poor young populations. We assess the drivers of intra-urban mobility using a random sample of 412 migrant street children and youth in Kampala city, Uganda. This paper draws from a larger cross-sectional survey of circular migration and sexual and reproductive health choices among street children in Kampala, Uganda. We define ‘migrants’ as street children and youth with a rural-urban migration experience and ‘intra-urban mobility’ as the number of places stayed in or moved since migrating to the city, measured on a continuous scale. More than half (54.37%) of the migrant street children and youth had lived in two or more places since migrating to the city. Multivariate negative binomial regression analysis reveals migrant street children and youth’s intra-urban mobility to be associated with gender (aIRR = 0.71, 95%CI 0.53–0.96), sex work (aIRR = 1.38, 95%CI 1.01–1.88), a daily income of one USD or more (aIRR = 1.57, 95%CI 1.16–2.13) and duration of stay in the city (aIRR = 1.54, 95%CI 1.17–2.01). Other drivers of intra-urban mobility included availability of causal work, personal safety and affordability of rental costs. Our findings suggest the need for urban housing and health policies to take into account street children and youth’s intra-urban mobility and its drivers. Future research on all drivers of street children and youth’s intra-urban mobility and its linkage with their health outcomes is recommended.
Determination of modifiable risk factors for length-for-age z-scores among resource-poor Indonesian infants
Authors: Diana Aly , Haszard Jillian J. , Sari Sri Y. Irda , Rahmannia Sofa , Fathonah Annisha , Sofiah Wina Nur , Rizqi Haidar , Haekal Raulia , Gilmartin Allissia , Harper Michelle , Petri William , Houghton Lisa , Gibson Rosalind
Published: February 2021

To reduce the burden of early-life linear growth faltering in low- and middle-income countries, interventions have focused on nutrition strategies, sometimes combined with water quality, sanitation, and hygiene (WASH). However, even when combined, their effects on linear growth have been inconsistent. Here, we investigate potential predictors of length-for-age z-scores (LAZ) in a cohort of resource-poor rural Indonesian infants to inform the optimal strategies to reduce linear growth faltering. Apparently healthy rural breastfed Indonesian infants were randomly selected from birth registries at age 6 months (n = 230) and followed up at 9 (n = 202) and 12 (n = 190) months. Using maximum likelihood estimation, we examined longitudinal relationships among socio-demographic status, maternal height, infant sex, age, water source, sanitation facility, energy, protein, micronutrient intakes and biomarkers (serum ferritin, zinc, retinol binding protein (RBP), selenium–adjusted for inflammation), and α-1-acid glycoprotein (AGP) and C-reactive protein (CRP) (systemic inflammation biomarkers) at age 6 and 9 months on LAZ at age 9 and 12 months. Stunting (LAZ <-2) at 6, 9, and 12 months was 15.7%, 19.3%, and 22.6%, respectively. In the full model, the predictor variable at age 6 months that was most strongly associated with infant LAZ at 9 months was maternal height (0.18 (95% CI 0.03, 0.32) SD). At age 9 months, the strongest predictors of LAZ at 12 months were improved drinking water source (-0.40 (95% CI -0.65, -0.14) vs. not improved), elevated AGP compared to not elevated (0.26 (95%CI -0.06, 0.58), maternal height (0.16 (95% CI 0.02, 0.31) SD), sex (0.22 (95% CI -0.02,0.45) female vs. male), serum RBP (0.12 (95% CI -0.01, 0.25) SD), and protein intake (0.17 (95% CI -0.01, 0.35) SD). Health promotion that includes exclusive breastfeeding up to the first six months and follows microbial water quality guidelines to ensure water intake is always safe should be considered.
Winter is coming–Temperature affects immune defenses and susceptibility to Batrachochytrium salamandrivorans
Authors: Carter Edward Davis , Bletz Molly C. , Le Sage Mitchell , LaBumbard Brandon , Rollins-Smith Louise A. , Woodhams Douglas C. , Miller Debra L. , Gray Matthew J.
Published: February 2021

Environmental temperature is a key factor driving various biological processes, including immune defenses and host-pathogen interactions. Here, we evaluated the effects of environmental temperature on the pathogenicity of the emerging fungal pathogen,Batrachochytrium salamandrivorans(Bsal), using controlled laboratory experiments, and measured components of host immune defense to identify regulating mechanisms. We found that adult and juvenileNotophthalmus viridescensdied faster due toBsalchytridiomycosis at 14°C than at 6 and 22°C. Pathogen replication rates, total available proteins on the skin, and microbiome composition likely drove these relationships. Temperature-dependent skin microbiome composition in our laboratory experiments matched seasonal trends in wildN.viridescens, adding validity to these results. We also found that hydrophobic peptide production after two months post-exposure toBsalwas reduced in infected animals compared to controls, perhaps due to peptide release earlier in infection or impaired granular gland function in diseased animals. Using our temperature-dependent susceptibility results, we performed a geographic analysis that revealedN.viridescenspopulations in the northeastern United States and southeastern Canada are at greatest risk forBsalinvasion, which shifted risk north compared to previous assessments. Our results indicate that environmental temperature will play a key role in the epidemiology ofBsaland provide evidence that temperature manipulations may be a viable disease management strategy.
Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera
Authors: Rodríguez-García Cristina , Heerman Matthew C. , Cook Steven C. , Evans Jay D. , DeGrandi-Hoffman Gloria , Banmeke Olubukola , Zhang Yi , Huang Shaokang , Hamilton Michele , Chen Yan Ping
Published: February 2021

Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee’s ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.
A novel role of Zebrafish TMEM33 in negative regulation of interferon production by two distinct mechanisms
Authors: Lu Long-Feng , Zhang Can , Li Zhuo-Cong , Zhou Xiao-Yu , Jiang Jing-Yu , Chen Dan-Dan , Zhang Yong-An , Xiong Feng , Zhou Fang , Li Shun
Published: February 2021

The transmembrane protein 33 (TMEM33) was originally identified as an endoplasmic reticulum (ER) protein that influences the tubular structure of the ER and modulates intracellular calcium homeostasis. However, the role of TMEM33 in antiviral immunity in vertebrates has not been elucidated. In this article, we demonstrate that zebrafish TMEM33 is a negative regulator of virus-triggered interferon (IFN) induction via two mechanisms: mitochondrial antiviral signaling protein (MAVS) ubiquitination and a decrease in the kinase activity of TANK binding kinase 1 (TBK1). Upon stimulation with viral components, tmem33 was remarkably upregulated in the zebrafish liver cell line. The IFNφ1 promoter (IFNφ1pro) activity and mRNA level induced by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) were significantly inhibited by TMEM33. Knockdown of TMEM33 increased host ifn transcription. Subsequently, we found that TMEM33 was colocalized in the ER and interacted with the RLR cascades, whereas MAVS was degraded by TMEM33 during the K48-linked ubiquitination. On the other hand, TMEM33 reduced the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA)/IRF3 by acting as a decoy substrate of TBK1, which was also phosphorylated. A functional domain assay revealed that the N-terminal transmembrane domain 1 (TM1) and TM2 regions of TMEM33 were necessary for IFN suppression. Finally, TMEM33 significantly attenuated the host cellular antiviral capacity by blocking the IFN response. Taken together, our findings provide insight into the different mechanisms employed by TMEM33 in cellular IFN-mediated antiviral process.
Ẹnu dùn ń rò’fọ́…: Theatre design, audience cognition and dramatic adaptation of Fagunwa’s texts
Authors: Aderemi Adeoye Michael
Published: February 2021

The stage performance of Langbodo, a play, which Nigerian dramatist Wale Ogunyemi adapted from Soyinka’s The Forest of a Thousand Daemons, which, in turn, is a translation of D. O. Fagunwa’s prose, Ògbójú Ọdẹ Nínú Igbó Irúnmalẹ̀. 'The bold hunter in the daemon-infested forest', exposed the limitation of the text as a bearer of meaning in the theatrical adaptation context. The limitation is analysed in this work to justify the centrality of adaptation in bridging the text-design-audience semiotic gap. This study examines the technical challenges of theatre design in D. O. Fagunwa’s works resulting from their adaptation as drama. The Yoruba apothegmatic idiom, Ẹnu ‘dùn ń rò’fọ́, agada ọwọ́ ṣeé ṣán’ko (which means, literally, that ‘vegetable soup can be prepared orally if a mere hand suffices for a cutlass’), a traditional derision for the inadequacies of the text, and the Barthesian notion of intertextuality serve as a dual theoretical structure in this study. A combination of methodologies including participant observation and ethnographic approach suffice for the retrieval and analysis of performance materials, respectively. Therefore, the study contends that the process of stage adaptation in Wale Ogunyemi’s play, Langbodo, used the technical contributions of theatre design, as a catalyst for connecting Fagunwa’s ideas to the final audience.