Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Data from: Niche and range size patterns suggest that speciation begins in small, ecologically diverged populations in North American monkeyflowers (Mimulus spp.)

Closely related species (e.g., sister taxa) often occupy very different ecological niches and can exhibit large differences in geographic distributions despite their shared evolutionary history. Budding speciation is one process that may partially explain how differences in niche and distribution characteristics may rapidly evolve. Budding speciation is the process through which new species form as initially small colonizing populations that acquire reproductive isolation. This mode of species formation predicts that, at the time of speciation, sister species should have highly asymmetrical distributions. We tested this hypothesis in North American monkeyflowers, a diverse clade with a robust phylogeny, using data on geographical ranges, climate, and plant community attributes. We found that recently diverged sister pairs have highly asymmetrical ranges and niche breadths, relative to older sister pairs. Additionally, we found that sister species occupy distinct environmental niche positions, and that 80% of sister species have completely or partially overlapping distributions (i.e., are broadly sympatric). Together, these results suggest that budding speciation has occurred frequently in Mimulus, that it has likely taken place both inside the range and on the range periphery, and that observed divergences in habitat and resource use could be associated with speciation in small populations

Niche and range size patterns suggest that speciation begins in small, ecologically diverged populations in North American monkeyflowers (Mimulus spp.).

Closely related species (e.g., sister taxa) often occupy very different ecological niches and can exhibit large differences in geographic distributions despite their shared evolutionary history. Budding speciation is one process that may partially explain how differences in niche and distribution characteristics may rapidly evolve. Budding speciation is the process through which new species form as initially small colonizing populations that acquire reproductive isolation. This mode of species formation predicts that, at the time of speciation, sister species should have highly asymmetrical distributions. We tested this hypothesis in North American monkeyflowers, a diverse clade with a robust phylogeny, using data on geographical ranges, climate, and plant community attributes. We found that recently diverged sister pairs have highly asymmetrical ranges and niche breadths, relative to older sister pairs. Additionally, we found that sister species occupy distinct environmental niche positions, and that 80% of sister species have completely or partially overlapping distributions (i.e., are broadly sympatric). Together, these results suggest that budding speciation has occurred frequently in Mimulus, that it has likely taken place both inside the range and on the range periphery, and that observed divergences in habitat and resource use could be associated with speciation in small populations

Data from: Niche and range size patterns suggest that speciation begins in small, ecologically diverged populations in North American monkeyflowers (Mimulus spp.)

Closely related species (e.g., sister taxa) often occupy very different ecological niches and can exhibit large differences in geographic distributions despite their shared evolutionary history. Budding speciation is one process that may partially explain how differences in niche and distribution characteristics may rapidly evolve. Budding speciation is the process through which new species form as initially small colonizing populations that acquire reproductive isolation. This mode of species formation predicts that, at the time of speciation, sister species should have highly asymmetrical distributions. We tested this hypothesis in North American monkeyflowers, a diverse clade with a robust phylogeny, using data on geographical ranges, climate, and plant community attributes. We found that recently diverged sister pairs have highly asymmetrical ranges and niche breadths, relative to older sister pairs. Additionally, we found that sister species occupy distinct environmental niche positions, and that 80% of sister species have completely or partially overlapping distributions (i.e., are broadly sympatric). Together, these results suggest that budding speciation has occurred frequently in Mimulus, that it has likely taken place both inside the range and on the range periphery, and that observed divergences in habitat and resource use could be associated with speciation in small populations

phylogeny

This file contains a nexus formatted file with a subsample of 900 trees from the posterior distribution of trees from the BEAST analysis. Additionally, three log files are included

occurrence_data

This file contains raw environmental data for each species used in our analysis