Probabilistic County-Level Population Projections.

Population projections provide predictions of future population sizes for an area. Historically, most population projections have been produced using deterministic or scenario-based approaches and have not assessed uncertainty about future population change. Starting in 2015, however, the United Nations (UN) has produced probabilistic population projections for all countries using a Bayesian approach. There is also considerable interest in subnational probabilistic population projections, but the UN's national approach cannot be used directly for this purpose, because within-country correlations in fertility and mortality are generally larger than between-country ones, migration is not constrained in the same way, and there is a need to account for college and other special populations, particularly at the county level. We propose a Bayesian method for producing subnational population projections, including migration and accounting for college populations, by building on but modifying the UN approach. We illustrate our approach by applying it to the counties of Washington State and comparing the results with extant deterministic projections produced by Washington State demographers. Out-of-sample experiments show that our method gives accurate and well-calibrated forecasts and forecast intervals. In most cases, our intervals were narrower than the growth-based intervals issued by the state, particularly for shorter time horizons.

A patient with bullous pemphigoid presenting with haemorrhagic oral erosions, oral haematoma and haemoptysis.

We present a case of a patient with bullous pemphigoid presenting with acquired haemophilia A. This is characterized by formation of antibodies or inhibitors against coagulation Factor VIII, leading to a prolonged activated partial thromboplastin time with normal prothrombin time and international normalized ratio. Our case emphasizes the need for increased awareness among dermatologists of this uncommon and potentially life-threatening condition. Click here for the corresponding questions to this CME article.

Iodinated Contrast Extravasation on Post-Revascularization Computed Tomography Mimics Magnetic Resonance Hyperintense Acute Reperfusion Marker: A Case Study.

Hyperintense reperfusion marker (HARM) on post-contrast magnetic resonance imaging (MRI) fluid attenuated inversion recovery (FLAIR) represents gadolinium contrast extravasation in the setting of acute ischemic stroke and is a common finding after revascularization therapies. Clinically, it is a marker of blood brain barrier (BBB) disruption, predictor of hemorrhagic transformation, and predictor of poor clinical outcome in ischemic stroke. Here, we describe a case where a patient underwent mechanical thrombectomy and was later found to have evidence of contrast extravasation on CT imaging, in the same locations found on the post-contrast FLAIR MRI, demonstrating that MRI-HARM and CT contrast extravasation may mimic similar phenomena. Thus, this case demonstrates that we may be able to extrapolate what we know about HARM detected on MRI to a CT imaging biomarker that would be more readily obtainable in most stroke patients.

Impairment of TrkB-PSD-95 signaling in Angelman syndrome.

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction.

An Evaluation of Projection Methods for Detailed Small Area Projections: An Application and Validation to King County, Washington.

Population projections are used by a number of local agencies to better prepare for the future resource needs of counties, ensuring that educational, health, housing, and economic demands of individuals are met. Meeting the specific needs of a county's population, such as what resources to provide, where to target resources, and ensure an equitable distribution of those resources, requires population projections which are both demographically detailed, such as by age, race, and ethnicity, and geographically precise, such as at the census tract level. Despite this need, an evaluation of which methods are best suited to produce population projections at this level are lacking. In this study, we evaluate the accuracy of several cohort-based methods for small area population projections by race and ethnicity. We apply these methods to population projections of King County, Washington and assess the validity of projections using past population estimates. We find a clear pattern that demonstrates while simplified methods perform well in near term forecasts, methods which employ smoothing strategies perform better in long-term forecasting scenarios. Furthermore, we demonstrate that model's incorporating multiple stages of smoothing can provide detailed insights into the projected population size of King county and the places and groups which will most contribute to this growth. Detailed projections, such as those provided by multi-stage smoothing methods, enable city planners and policy makers a detailed view of the future structure of their county's population and provide for them a resource to better meet the needs of future populations.

Acute Cerebral Ischemia Temporally Associated with Marijuana Use.

The cerebrovascular effects of marijuana use are not well described. With increasing legalization of cannabis for medical and recreational use in North America, identification of potential risks of the drug is necessary. We present the case of a 31-year-old man who had two ischemic infarctions in different vascular distributions, without other identifiable etiology, which were temporally associated with marijuana use. We additionally identified the level of metabolites in his system and discussed the need for a systematic description of these cases to determine whether a dose-dependent effect exists.

The EHD protein Past1 controls postsynaptic membrane elaboration and synaptic function.

Membranes form elaborate structures that are highly tailored to their specialized cellular functions, yet the mechanisms by which these structures are shaped remain poorly understood. Here, we show that the conserved membrane-remodeling C-terminal Eps15 Homology Domain (EHD) protein Past1 is required for the normal assembly of the subsynaptic muscle membrane reticulum (SSR) at the Drosophila melanogaster larval neuromuscular junction (NMJ). past1 mutants exhibit altered NMJ morphology, decreased synaptic transmission, reduced glutamate receptor levels, and a deficit in synaptic homeostasis. The membrane-remodeling proteins Amphiphysin and Syndapin colocalize with Past1 in distinct SSR subdomains and collapse into Amphiphysin-dependent membrane nodules in the SSR of past1 mutants. Our results suggest a mechanism by which the coordinated actions of multiple lipid-binding proteins lead to the elaboration of increasing layers of the SSR and uncover new roles for an EHD protein at synapses.