Islam and Chiefship in Northern Mozambique

Muslim leadership of Northern Mozambique historically has incorporated Islamic authority and chiefship at once. Throughout the colonial period, Muslim chiefs defended their version of Islam against non-local conceptions of Islam, such as Sufism and Wahhabism. After independence the links between chiefship and Islam in northern Mozambique became less visible. This resulted primarily from the policies of the post-colonial government, which saw African chiefship and Islam as two separate spheres. Islam was viewed as an “organized faith” similar to Christianity, while chiefship was understood to represent African “traditional authority.

Pharmacokinetic and neurochemical correlates of context-dependent behavioral sensitization

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The use of the Arabic script in northern Mozambique

Northern Mozambican Muslim population has been using the Arabic script for writing in KiSwahili and local African languages for centuries. Even today, many people continue using this script in private correspondence. Despite the abundance of the documents in this script that are housed at the Mozambique Historical Archives as well as in private hands, these documents have never been addressed or researched either from linguistic, historical, cultural or religious vantage points. For the last seven years, the Archives have been trying to draw attention of the scholars and obtain funds for the preservation and research of the documents. In this article two short letters from the collection of the Mozambique Historical Archives are transcribed and translated with the help of a local shaykh who was educated within the regional historical Islamic literacy tradition. Then, the content and the protagonists of the letters were identified and analyzed with the reference to the historical context and the events of the time. Besides serving as the evidence for historical occurrences, the letters also provide a general public with a unique opportunity of “hearing the voices” of the authors and in their own words (in first person)

A teoria do “encerramento do Ijtihad” no direito islâmico

O postulado da jurisprudência islâmica clássica sobre o “encerramento dos portões do ijtihad”, ou a teoria da abdicação da aplicação do raciocínio humano para a extrapolação da lei a partir das escrituras sagradas, foi indicado por orientalistas como uma das razões da alegada incapacidade das sociedades islâmicas de acompanhar o desenvolvimento moderno, do qual o Ocidente desfrutava. O fecho do ijtihad pareceu ser a causa plausível da aparente estagnação e da falta de criatividade da jurisprudência muçulmana. Apesar de juristas pré-modernos islâmicos e os orientalistas concordarem sobre o encerramento do ijtihad, este, nos dias que correm, tem sido objecto de estudos mais aprofundados e de discussões acesas entre académicos, sendo opinião comum que nem o exercício nem a teoria da lei islâmica manifestaram alguma vez a ausência do ijtihad ou da criatividade jurídica.The postulate of classic Islamic jurisprudence of the ‘closing of the doors of ijtihad’, or the theory of abdicating from applying human reasoning to the extrapolation of law from sacred scripture, was posited by Orientalists as one of the reasons for the alleged inability of Islamic societies to stay abreast of the modern development which the West enjoyed. The closing of the doors of ijtihad appeared to be the credible cause for the seeming stagnation and lack of creativity of Muslim jurisprudence. Although pre-modern Islamic legal scholars and Orientalists agreed on the closing of the doors of ijtihad, the latter, in our time, has been the object of more acute study and of heated debate among academics. It is a commonly held view that neither the exercise nor the theory of Islamic law ever evinced the absence of ijtihad or of juridical creativity.Le postulat de la jurisprudence islamique classique sur la “fermeture des portes du Ijtihad”, ou la théorie de l’abdication de l’application du raisonnement humain dans l’extrapolation de la loi à partir des écritures sacrées, a été interprété par les orientalistes comme une des raisons de la soi-disant incapacité des sociétés islamiques d’accompagner le développement moderne, dont l’Occident bénéficiait. La fermeture du Ijtihad a semblé être la cause plausible de l’apparente stagnation et du manque de créativité dans le domaine de la jurisprudence islamique. Quoique les juristes pré-modernes islamiques et les orientalistes s’entendent bien sur la fermeture du Ijtihad, celui-ci, à nos jours, a été l’objet des études les plus approfondies et de discussions enflammées entre les académiques, l’opinion commune admettant que ni l’exercice ni la théorie de la loi islamique n’ont jamais témoigné de l’absence du Ijtihad ni de la créativité juridique

Roots of Diversity in Mozambican Islam

This paper explores historical roots for the existing diversity of the conceptions of Islam among African Sunni Muslims of Mozambique. This diversity is frequently expressed by internal Muslim debates and competitions centred on the nature of Islamic authority and on the definition of ‘orthodoxy.’ After identifying roughly three divergent conceptions of Islamic authority and ritual among Mozambican Muslims, the author analyses specific historical contexts within which each of these conceptions of Islam emerged and confronted one another. In particular, the paper focuses on changes with respect to religious authority and ritual. One of the central arguments of this paper is that on the emergence of each new conception, local Muslims set upon redefining what constituted the centre and the margin of Islam in Mozambique, but despite the attempts to the contrary, the old conceptions have persisted and continuously posed challenges to the newly-established centre.Este artigo explora as razões históricas para a existência das diversas concepções do Islão entre os muçulmanos sunnitas africanos de Moçambique. A diversidade de concepções é expressa através de debates e competições internos entre os muçulmanos em torno de natureza da autoridade islâmica e da definição de “ortodoxia” islâmica. Após ter identificado três concepções divergentes, a autora analisa contextos históricos específicos nos quais cada uma destas emergiu e confrontou as outras concepções. O artigo foca em particular as mudanças da autoridade religiosa e dos ritos. Um dos argumentos centrais de artigo é que com a emergência de cada uma das novas concepções, os muçulmanos locais se envolverem na definição do centro e da margem do Islão. No entanto, apesar de esforços de elimina-los, as concepções anteriores não desapareceram e continuaram desafiando os novos centros do Islão a partir de margens a que foram supostamente relegados.Cet article explore les racines historiques de la diversité existant actuellement dans les conceptions de l’Islam parmi les musulmans sunnites africains du Mozambique. Cette diversité s’exprime souvent par des discussions et des rivalités musulmanes internes, centrées sur la nature de l’autorité islamique et sur la définition de l’« orthodoxie ». Après avoir identifié en gros trois conceptions divergentes de l’autorité et du rituel islamique parmi les Musulmans du Mozambique, l’auteur analyse les contextes historiques spécifiques au sein desquels chacune de ces conceptions de l’Islam a émergé et fait face aux autres. Plus particulièrement, l’article se concentre sur les changements concernant l’autorité religieuse et le rituel. L’un des arguments principaux de cet article est que, face à l’émergence de chaque nouvelle conception, les Musulmans locaux ont entrepris de redéfinir ce qui constituait le centre et la marge de l’Islam au Mozambique, mais malgré les tentatives dans l’autre sens, les anciennes conceptions ont persisté et représenté des défis continuels pour le centre nouvellement établi

Pharmacodynamics of isavuconazole in experimental invasive pulmonary aspergillosis: implications for clinical breakpoints

OBJECTIVES: Isavuconazole, a novel triazole antifungal agent, has broad-spectrum activity against Aspergillus spp. and other pathogenic fungi. The isavuconazole exposure–response relationship in experimental invasive pulmonary aspergillosis using galactomannan index (GMI) suppression as a marker of disease clearance was explored. METHODS: The impact of exposure on GMI suppression in persistently neutropenic rabbits treated with isavuconazonium sulphate (isavuconazole-equivalent dosages of 20, 40 or 60 mg/kg every 24 h, after a 90 mg/kg loading dose) for 12 days was linked using mathematical modelling. Bridging to humans using population pharmacokinetic (PK) data from a clinical trial in invasive aspergillosis was performed using Monte Carlo simulations. RESULTS: Mean plasma isavuconazole AUC/MIC (EC(50)) of 79.65 (95% CI 32.2, 127.1) produced a half-maximal effect in GMI suppression. The inhibitory sigmoid E(max) curve dropped sharply after an AUC/MIC of ≥30 and was near maximum (EC(80)) at ∼130. Bridging the experimental PK/pharmacodynamic (PD) target to human population PK data was then used to return to the rabbit model to determine a clinically relevant PD endpoint. The clinical dosing regimen used in the trial would result in a mean GMI of 4.3 ± 1.8, which is a 50% reduction from the starting GMI in the experiment. CONCLUSIONS: The clinical trial results showing the non-inferiority of isavuconazole to voriconazole for all-cause mortality further support the PK-PD endpoint, thereby demonstrating the usefulness of the rabbit model and endpoint for isavuconazole and implications on interpretive breakpoints. Importantly, the analysis supports this model as an important tool for development of antifungal agents

Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study)

Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.

Two heads are better than one: current landscape of integrating QSP and machine learning

Quantitative systems pharmacology (QSP) modeling is applied to address essential questions in drug development, such as the mechanism of action of a therapeutic agent and the progression of disease. Meanwhile, machine learning (ML) approaches also contribute to answering these questions via the analysis of multi-layer ‘omics’ data such as gene expression, proteomics, metabolomics, and high-throughput imaging. Furthermore, ML approaches can also be applied to aspects of QSP modeling. Both approaches are powerful tools and there is considerable interest in integrating QSP modeling and ML. So far, a few successful implementations have been carried out from which we have learned about how each approach can overcome unique limitations of the other. The QSP ? ML working group of the International Society of Pharmacometrics QSP Special Interest Group was convened in September, 2019 to identify and begin realizing new opportunities in QSP and ML integration. The working group, which comprises 21 members representing 18 academic and industry organizations, has identified four categories of current research activity which will be described herein together with case studies of applications to drug development decision making. The working group also concluded that the integration of QSP and ML is still in its early stages of moving from evaluating available technical tools to building case studies. This paper reports on this fast-moving field and serves as a foundation for future codification of best practices

Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi

Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT)