28 research outputs found
A coordinated response to the needs of the learner: How deworming and school meals together will contribute to the global recovery from the COVID-19 pandemic
A systematic literature review of schistosomiasis in urban and peri-urban settings.
BACKGROUND: Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural-urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap. METHODOLOGY: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic computer-aided literature review was carried out using PubMed, ScienceDirect, and the World Health Organization Database in November 2019, which was updated in March 2020. Only papers for which at least the abstract was available in English were used. Relevant publications were screened, duplicates were removed, guidelines for eligibility were applied, and eligible studies were reviewed. Studies looking at human Schistosoma infections, prevalence, and intensity of infection in urban and peri-urban settings were included as well as those focusing on the intermediate host snails. PRINCIPAL FINDINGS: A total of 248 publications met the inclusion criteria. The selected studies confirm that schistosomiasis is prevalent in peri-urban and urban areas in the countries assessed. Earlier studies report higher prevalence levels in urban settings compared to data extracted from more recent publications, yet the challenge of migration, rapid uncontrolled urbanization, and resulting poor living conditions highlight the potential for continuous or even newly established transmission to take place. CONCLUSIONS: The review indicates that schistosomiasis has long existed in urban and peri-urban areas and remains a public health problem. There is, however, a challenge of comparability of settings due to the lack of a clear definition of what constitutes urban and peri-urban. There is a pressing need for improved monitoring of schistosomiasis in urban communities and consideration of treatment strategies
Resisting the denial of coevalness in International Relations: provincializing, perspectivism, border thinking
Safety and efficacy of vanzacaftorâtezacaftorâdeutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials
Background
Elexacaftorâtezacaftorâivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.
Methods
We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftorâtezacaftorâdeutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftorâtezacaftorâdeutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftorâdeutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)âtezacaftorâdeutivacaftor or tezacaftorâivacaftor active control for 4 weeks, following a 4-week tezacaftorâivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete.
Findings
In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3¡1 percentage points (95% CI â0¡8 to 7¡0) and 2¡7 percentage points (â1¡0 to 6¡5) from baseline at week 12, respectively, versus â0¡8 percentage points (â6¡2 to 4¡7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)âtezacaftorâdeutivacaftor (n=9), vanzacaftor (10 mg)âtezacaftorâdeutivacaftor (n=19), vanzacaftor (20 mg)âtezacaftorâdeutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4¡6 percentage points (â1¡3 to 10¡6), 14¡2 percentage points (10¡0 to 18¡4), 9¡8 percentage points (5¡7 to 13¡8), and 1¡9 percentage points (â4¡1 to 8¡0), respectively, in sweat chloride concentration of â42¡8 mmol/L (â51¡7 to â34¡0), â45¡8 mmol/L (95% CI â51¡9 to â39¡7), â49¡5 mmol/L (â55¡9 to â43¡1), and 2¡3 mmol/L (â7¡0 to 11¡6), respectively, and in CFQ-R respiratory domain score of 17¡6 points (3¡5 to 31¡6), 21¡2 points (11¡9 to 30¡6), 29¡8 points (21¡0 to 38¡7), and 3¡3 points (â10¡1 to 16¡6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)âtezacaftorâdeutivacaftor (n=18) and tezacaftorâivacaftor (n=10) had mean changes relative to baseline (taking tezacaftorâivacaftor) at day 29 in ppFEV1 of 15¡9 percentage points (11¡3 to 20¡6) and â0¡1 percentage points (â6¡4 to 6¡1), respectively, in sweat chloride concentration of â45¡5 mmol/L (â49¡7 to â41¡3) and â2¡6 mmol/L (â8¡2 to 3¡1), respectively, and in CFQ-R respiratory domain score of 19¡4 points (95% CI 10¡5 to 28¡3) and â5¡0 points (â16¡9 to 7¡0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftorâtezacaftorâdeutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity.
Interpretation
Once-daily dosing with vanzacaftorâtezacaftorâdeutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftorâtezacaftorâdeutivacaftor in phase 3 clinical trials compared with elexacaftorâtezacaftorâivacaftor.
Funding
Vertex Pharmaceuticals
Verlauf von Schulabsentismus 1.5 bis 3 Jahre nach Erstvorstellung: Prädiktoren, psychosoziales Funktionsniveau und Inanspruchnahme von Hilfen
Untersucht wurden der Verlauf bei schulvermeidenden Patientinnen und Patienten hinsichtlich Symptomatik, Schulbesuch, Funktionsniveau und Inanspruchnahmeverhalten eineinhalb bis drei Jahre nach Erstvorstellung und Einflussfaktoren auf diesen Verlauf. Methodik: Von einer Inanspruchnahme-Stichprobe von 237 Schulvermeiderinnen und -vermeidern wurden eineinhalb bis drei Jahre nach Erstvorstellung 108 fĂźr ein Telefoninterview mit den Eltern erreicht. Es wurde die Elternversion des 'Strenghts and Difficulties Questionnaire' (SDQ) durchgefĂźhrt und das Inanspruchnahmeverhalten sowie der aktuelle Schulbesuch erfragt. Als Prädiktoren wurden u. a. das AusmaĂ der Schulvermeidung, die Diagnosen, die Art der Schulvermeidung (Schulverweigerung versus Schulschwänzen versus gemischte Gruppe) sowie die Werte im 'Inventar Schulvermeidendes Verhalten' (ISV) analysiert. Ergebnisse: Es wurde eine hohe Inanspruchnahme sowohl von kinder- und jugendpsychiatrischen als auch von JugendhilfemaĂnahmen gefunden, bei 40,7 % kam es zu wiederholten teil- oder vollstationären Behandlungen. Beim Follow-up wurde der SDQ-Gesamtwert bei 46,3 % als grenzwertig oder auffällig angegeben, wobei emotionale Probleme und Probleme mit Gleichaltrigen dominierten. Das Funktionsniveau, insbesondere der Schulbesuch, wurde bei etwa einem Drittel als problematisch eingeschätzt. Die ISV-Skalen Aggression, Probleme mit Peers und Probleme mit Lehrerinnen und Lehrern sowie die Diagnose einer StĂśrung des Sozialverhaltens waren mit Schwierigkeiten beim Schulbesuch oder erhĂśhten Fehlzeiten beim Follow-upverbunden. Schlussfolgerungen: Die Ergebnisse betonen die Bedeutung externalisierender Symptome und einhergehender sozialer Belastungen fĂźr einen negativen Verlauf von Schulabsentismus. Implikationen fĂźr prospektive Verlaufsstudien werden diskutiert
Cortical capacity constraints for visual working memory: dissociation of fMRI load effects in a fronto-parietal network
Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached
Sociology and international relations: legacies and prospects
While sociological concepts have often been implicitly used in International Relations (IR), recent years have seen a more explicit engagement between IR and Sociology. As with any such interdisciplinary assignation, there are both possibilities and challenges contained within this move: possibilities in terms of reducing IR's intellectual autism and opening the discipline towards potentially fertile terrain that was never, actually, that distant; challenges in that interdisciplinary raiding parties can often serve as pseudonyms for cannibalism, shallowness and dilettantism. This forum reviews the sociological turn in IR and interrogates it from a novel vantage pointâhow sociologists themselves approach IR concepts, debates and issues. Three sociological approachesâclassical social theory, historical sociology and Foucauldian analysisâare critically deployed to illuminate IR concerns. In this way, the forum offers the possibility of (re)establishing exchanges between the two disciplines premised on a firmer grasp of social theory itself. The result is a potentially more fruitful sociological turn, one with significant benefits for IR as a whole