A System Dynamics Approach for Hospital Waste Management in a City in a Developing Country: The Case of Nablus, Palestine

Hospitals and health centers provide a variety of healthcare services and normally generate hazardous waste as well as general waste. General waste has a similar nature to that of municipal solid waste and therefore could be disposed of in municipal landfills. However, hazardous waste poses risks to public health, unless it is properly managed. The hospital waste management system encompasses many factors, i.e., number of beds, number of employees, level of service, population, birth rate, fertility rate, and not in my back yard (NIMBY) syndrome. Therefore, this management system requires a comprehensive analysis to determine the role of each factor and its influence on the whole system. In this research, a hospital waste management simulation model is presented based on the system dynamics technique to determine the interaction among these factors in the system using a software package, ithink. This model is used to estimate waste segregation as this is important in the hospital waste management system to minimize risk to public health. Real data has been obtained from a case study of the city of Nablus, Palestine to validate the model. The model exhibits wastes generated from three types of hospitals (private, charitable, and government) by considering the number of both inpatients and outpatients depending on the population of the city under study. The model also offers the facility to compare the total waste generated among these different types of hospitals and anticipate and predict the future generated waste both infectious and non-infectious and the treatment cost incurred

Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need for accurate identification and interpretation of novel variants. In a large Mendelian cohort of 4577 molecularly characterized families, numerous scenarios in which variant identification and interpretation can be challenging are encountered. We describe categories of challenges that cover the phenotype (e.g. novel allelic disorders), pedigree structure (e.g. imprinting disorders masquerading as autosomal recessive phenotypes), positional mapping (e.g. double recombination events abrogating candidate autozygous intervals), gene (e.g. novel gene-disease assertion) and variant (e.g. complex compound inheritance). Overall, we estimate a probability of 34.3% for encountering at least one of these challenges. Importantly, our data show that by only addressing non-sequencing-based challenges, around 71% increase in the diagnostic yield can be expected. Indeed, by applying these lessons to a cohort of 314 cases with negative clinical exome or genome reports, we could identify the likely causal variant in 54.5%. Our work highlights the need to have a thorough approach to undiagnosed diseases by considering a wide range of challenges rather than a narrow focus on sequencing technologies. It is hoped that by sharing this experience, the yield of undiagnosed disease programs globally can be improved

Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS. Keywords: KMT2A; MLL1; Wiedemann-Steiner syndrome; hypertrichosis; syndromic intellectual disability; syndromic short stature.Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Advancing Translational Sciences (NCATS) United States Department of Health & Human Services National Institutes of Health (NIH) - USA Hartwell Foundatio