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Health outcomes and health service use during armed conflicts:a comparison of conflict and non-conflict areas in Northern Nigeria
No full textIn conflict-affected regions, persistent violence and instability severely hinder access to healthcare, deepen inequalities and introduce new barriers to service delivery. This dissertation investigates the impact of armed conflict on health systems and outcomes in Northern Nigeria, with a specific focus on women and children, populations most vulnerable during crises.Each chapter of the study builds a comprehensive understanding of healthcare dynamics in conflict-affected settings. It begins with a critical literature review, then empirically examines the effects of conflict on maternal health service utilization, child nutrition, and neonatal outcomes using geo-referenced national survey data. The findings reveal a high burden of unmet health needs in conflict-exposed communities and demonstrate how conflict weakens routine service access. The dissertation concludes by offering targeted, evidence-based policy recommendations and programming strategies aimed at strengthening healthcare delivery in fragile settings, while also identifying pathways for future research to build more resilient and equitable health systems
Osimertinib Cost Minimization in Non-Small Cell Lung Cancer (NSCLC) Treatment:Hypothesis Generation for a Population Pharmacokinetic Approach for Equivalent Dose Optimization of Osimertinib in Combination With Cobicistat
No full textPharmacokinetic boosting can be a strategy to enhance osimertinib exposure and reduce treatment associated costs. The OSIBOOST trial demonstrated that it was feasible to boost low osimertinib plasma trough levels with cobicistat. The current study aims to establish the equivalent dose of cobicistat boosted osimertinib compared to osimertinib 80 mg once daily (QD) by population pharmacokinetic (popPK) modeling. A popPK model was developed on the pharmacokinetic data from the OSIBOOST study using NONMEM 7.4.4. Simulations were performed with cobicistat boosted osimertinib dosing regimens to evaluate their equivalence to the standard of osimertinib 80 mg QD. A dose level was assumed equivalent when the 90% confidence interval (CI) of the geometric mean ratios (GMR) for the area under the curve over 144 h (AUC 0-144h) and maximum osimertinib concentration (C max) were in the acceptance range of 0.8-1.25. Cobicistat decreased osimertinib CL/F by 29.6% compared to osimertinib monotherapy (P <.0001). Osimertinib 80 mg 2 days on, 1 day off, boosted with cobicistat 150 mg QD was equivalent for osimertinib AUC 0-144h (GMR [90% CI] = 0.96 [0.94-0.98]) and C max (GMR [90% CI] = 1.06 [1.04-1.08]) compared to osimertinib 80 mg QD monotherapy. However, this regimen was not equivalent for AZ5104 AUC 0-144h (GMR [90% CI] = 0.67 [0.66-0.68]) and C max (GMR [90% CI] = 0.74 [0.73-0.76]). Theoretically, this reduced dose of cobicistat boosted osimertinib can potentially save approximately 33% in osimertinib treatment associated costs whilst maintaining adequate osimertinib exposure.</p
Reimagining social protection:financialised futures among ageing migrant domestic workers in Asia
No full textA common narrative among Filipino migrant domestic workers in Singapore and Hong Kong is that their work abroad is to guarantee a better future for their families. Migrant women frequently extend their temporary contracts, sometimes over decades to support family life projects. Yet their contracts can only be extended until retirement age, after which they must return to their countries of origin. This paper focuses on migrant women approaching this critical juncture as they begin to shift their focus towards themselves, in the face of precarious futures with limited state-based forms of social protection and uncertainties around kinship care in later life. As a consequence, domestic workers increasingly enrol in courses on 'financial literacy' to prepare for their retirement. Such courses are led by an array of state, corporate and non-governmental actors. They generate new financialised aspirations among migrant women which revolve around self-responsibility for success and security in later life. This cultivation of a self-oriented and 'purpose-driven' ethos remains entangled in existing (inter)dependencies in migrant women's lives. Financialised modes of thinking furthermore exist alongside, and in tension with alternative imaginaries around social protection and how to live a meaningful life
The Ex-utero intrapartum treatment procedure:a narrative review
No full textThe "Ex Utero Intrapartum Treatment" (EXIT) procedure is a specialized surgical technique used during cesarean delivery to perform life-saving fetal interventions while maintaining placental circulation. By preserving feto-placental gas exchange, EXIT enables the treatment of severe conditions such as predictable severe breathing difficulties at birth. EXIT's origins date back to removing tracheal occlusion devices used for congenital diaphragmatic hernias. It has since expanded to treat conditions such as congenital high airway obstruction syndrome and airway compression by masses. Despite the risks of adverse maternal and fetal events, it shows high perinatal survival rates. The success of EXIT depends on an accurate prenatal diagnosis through fetal ultrasound and magnetic resonance imaging. Anesthetic management differs from standard cesarean sections, balancing the need for uterine relaxation and avoiding maternal-fetal risks. Inhaled anesthetics are preferred, although recent studies suggest the potential of neuraxial anesthesia combined with tocolytics. Although the EXIT procedure can be performed safely in specialized centers, it does carry risks for both the mother and the fetus. Neonatal mortality and complications vary depending on indications and postnatal management. Research and clinical practice must advance to improve safety and efficacy
Urban Transition Toward Environmental Sustainability:Instrumentation and Institutionalization of Co-Creation
No full textThe transition in cities toward environmental sustainability requires transforming urban subsystems such as energy, transport, and waste infrastructure. Based on the frameworks of strategic spatial planning (SSP) and urban transition management (UTM), the urban transition is conceptualized as a long-term process in which stakeholders co-create a vision and a strategic plan, which is subsequently implemented in multiple relatively short-term projects transforming these urban subsystems. While co-creation is emerging in urban planning, ambiguity remains regarding the development and use of co-creation instruments in transforming urban subsystems. This article therefore has two aims: first, to develop a typology of co-creation instruments for urban transition planning and management; and second, to examine the institutionalization of their development and use. The article follows an iterative inductive-deductive search method to make an inventory of instruments, after which four main types are identified: participatory planning and communication tools, expert planning support systems, urban living labs, and virtual transformation labs. Several challenges in using these instruments are identified, including the need to acquire governance and digital skills, and to keep tools and data up to date. This article subsequently examines the capabilities that need to be institutionalized to support the use and development of these instruments across multiple projects. Capabilities needed are stakeholder engagement and collaborative governance, the participatory design and updating of digital tools, maintenance of urban subsystem and city development models, definition of transition scenarios and experiments, and interpretation of (simulation) results. Additional capabilities are needed to manage the project portfolio and facilitate learning within and across projects. Ultimately, a "Transition Planning Office" is proposed to institutionalize these capabilities and, by doing so, to complement UTM's focus on independent vision and agenda formulation with sustained involvement in long-term planning, and to support SSP's call for more strategic urban planning through project portfolio management and instrument use and development
A head-to-head comparison of soluble dietary fibers on microbiota composition and short-chain fatty acid production using the<i> in</i><i> vitro</i> TIM-2 system
No full textSoluble dietary fibers (SDFs) are recognized for their health benefits through their fermentation and gut microbiota modulation. Previous studies focused on individual SDFs without sufficient structural information and a comparative analysis using different SDFs on microbiota composition and function is lacking. The present study aimed to determine key structural features of different SDFs, including soluble resistant starch (SRS), inulin (INU), four structurally diverse pectins (PS1 to PS4), one pectic derivative (PS5) and larch arabinogalactan (AG). Their effects on gut microbiota composition and function were investigated by 72 h experiments in TIM-2 in vitro colon system with pooled feces, upon constant feeding (2.5 mL/h, total of 7.5 g/day) of test compounds. The tested SDFs were structurally different, inducing distinct effects on the relative abundance of specific bacterial genera and overall microbiota composition. AG, PS2, PS3, PS5, and SRS demonstrated marked changes compared to control in the overall community structure over time. SCFA production increased over time for all SDFs, but only PS1 to PS4 resulted in significantly higher SCFA levels compared to control. These findings demonstrate that structurally different SDFs exhibit different effects on the gut microbiota composition and function, however this could not be solely explained by Mw and monosaccharide composition
Inference on data with both multiplicative and additive measurement errors
No full textMeasurement errors are omnipresent in many fields and can lead to serious problems in statistical analysis. In the literature, measurement errors are often assumed to be either additive or multiplicative. We consider the case where a variable is subject to both additive and multiplicative errors. We establish the identifiability and propose a moment-based estimator for the variances of these two types of errors, which is shown to be consistent. We further derive the asymptotic distribution of the estimator and conduct hypothesis tests to examine the existence of the two types of errors. We also develop a likelihood-based method to approximate the density of the error-prone variable. We apply our strategy in the context of linear regression and study its effect on the estimation of regression parameters in combination with Regression Calibration and Simulation Extrapolation. The proposed methodology is numerically investigated through simulations and is implemented in a real data application
Lower Urinary Tract Dysfunction in Uncommon Neurological Diseases - Part IV:Infections, Inflammatory, Toxic, and Structural Disorders - A NUPC Report
No full textThe manuscript examines the impact of various rare neurological disorders on lower urinary tract dysfunction (LUTD), building upon previous parts of this series. It discusses several infections and their sequelae, such as Neuroborreliosis (Lyme Disease), Herpes Zoster (HZ), and Neurosyphilis. Lyme Disease is a vector-borne infection leading to storage and voiding symptoms. Herpes Zoster (HZ) is associated with various types of LUTD due to its effect on spinal nerves. Neurosyphilis, historically, is a common cause of LUTD due to the degeneration of the spinal cord. In the manuscript, other miscellaneous conditions, such as Radiation Myelopathy, Decompression Sickness and Charcot Spine, are also discussed. Radiation Myelopathy is a chronic condition affecting bladder function post-radiation therapy. Decompression Sickness occurs in scuba divers and can lead to LUTD as a neurological complication. Charcot Spine represents a destructive spinal condition that can lead to LUTD and may require intensive management. Some degenerative disorders such as Progressive Multifocal Leucoencephalopathy (PML), Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), RSF1 related disorder-CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome), Acute Disseminated Encephalomyelitis (ADEM) and Spinal Cord Sarcoidosis which have varying impacts on LUT function are also included in this report. Additionally, the paper includes two metabolic and toxic myelopathies (severe B12 deficiency and Nitrous oxide myelopathy), which may cause LUTD. The document emphasizes the necessity for urologists to recognize and manage LUTD in patients with these uncommon neurological conditions, promoting a comprehensive understanding of their overlaps in clinical symptoms. The overall goal is to better inform clinicians and aid in patient management by summarizing current knowledge and encouraging further research. This serves as the fourth installment in a series aiming to provide insights into rare neuro-urological diseases
Fibrin clot lysis predicts anticoagulant-associated bleeding in atrial fibrillation:ready for clinical use?
No full textTargeted ablation of the distal Purkinje-myocardium interface for premature ventricular complex-induced cardiomyopathy by delayed Purkinje conduction-induced re-excitation:a case report
No full textBackground In structurally normal hearts, premature ventricular complexes (PVCs) are primarily driven by enhanced automaticity or afterdepolarization-dependent triggered activity. Traditionally, re-entrant excitation has only been associated with cardiac conditions involving scar formation, such as post-myocardial infarction or cardiac sarcoidosis.Case summary We present a case of an asymptomatic 28-year-old patient with a high burden of monomorphic PVCs originating near the posteromedial papillary muscle. Left ventricular (LV) dilatation with reduced systolic function (ejection fraction 45%) was diagnosed as PVC-induced cardiomyopathy, given the absence of fibrosis and coronary artery disease. During an electrophysiological study, a 2-cm2 region was identified where abnormal Purkinje potentials (P1), exhibiting markedly reduced conduction velocity (0.88 mm/ms), consistently followed the rapid conduction via the left posterior fascicle (LPF). Local activation time velocity vectors of P1 pinpointed the earliest abnormal Purkinje activation at the proximal LPF. The impulse excited the distal one-third of the interventricular septum before conducting retrogradely to the LPF. Radiofrequency ablation targeted at the Purkinje-myocardial pivot point successfully eliminated the PVCs, restoring LV systolic function at follow-up.Discussion Even in the absence of structural heart disease, delayed anterograde Purkinje conduction can facilitate monomorphic PVCs via re-excitation. This highlights the potential for targeted ablation at the distal Purkinje network as an effective treatment strategy