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A 6-year-old boy presented for evaluation after a new onset focal seizure. CT demonstrated a large right hemispheric mass with midline shift ([figure 1A][1]). MRI confirmed a T2 hyperintense tumour with reduced diffusivity, minimal enhancement on postgadolinum sequences, and linear calcifications on

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

In this study, the authors present the outcomes of 4 patients with a severe form of Crouzon syndrome characterized by mutation of fibroblast growth factor receptor 2 (FGFR2) c.1040 CG p.Ser347Cys or the pathogenic c.1061CG p.Ser354Cys variant of FGFR2, who underwent posterior vault distraction osteogenesis (PVDO) to alleviate elevated intracranial pressure.Patients with diagnosed Crouzon syndrome who were found by genetic testing to have an FGFR2 c.1040 CG p.Ser347Cys mutation or the c.1061CG p.Ser354Cys variant were included. Outcome data and presence of hydrocephalus, Chiari Malformation type I (CMIs), and the presence/absence of a tracheostomy were recorded.Three patients with the FGFR2 c.1040 CG p.Ser347Cys mutation and 1 with the pathogenic FGFR2 c.1061CG p.Ser354Cys variant were identified as having characteristics of severe Crouzon syndrome. The mean age at PVDO was 15 months and the mean posterior advancement was 20 mm. All 4 patients experienced sufficient relief of the elevated intracranial pressure from the PVDO to prevent the need for shunt placement, stabilize the ventricular dimensions (n = 2), and resolve the CMIs (n = 2). Intracranial pressure screening ruled out malignant cerebrospinal fluid volume increase.PVDO effectively prevented hydrocephalus and resolved CMIs, successfully alleviating intracranial pressure and maximizing clinical outcomes for patients with severe Crouzon syndrome.

The United Nations (UN) established an umbrella of organizations to manage distinct clusters of humanitarian aid. The World Health Organization (WHO) oversees the health cluster, giving it responsibility for global, national, and local medical responses to natural disasters. However, this centralized structure insufficiently engages local players, impeding robust local implementation. The Gorkha earthquake struck Nepal on April 25, 2015, becoming Nepal’s most severe natural disaster since the 1934 Nepal-Bihar earthquake. In coordinated response, 2 organizations, Empower Nepali Girls and International Neurosurgical Children’s Association, used a hybrid approach integrating continuous communication with local recipients. Each organization mobilized its principal resource strengths—material medical supplies or human capital—thereby efficiently deploying resources to maximize the impact of the medical response. In addition to efficient resource use, this approach facilitates dynamic medical responses from highly mobile organizations. Importantly, in addition to future earthquakes in Nepal, this medical response strategy is easily scalable to other natural disaster contexts and other medical relief organizations. Preemptively identifying partner organizations with complementary strengths, continuous engagement with recipient populations, and creating disaster- and region-specific response teams may represent viable variations of the WHO cluster model with greater efficacy in local implementation of treatment in acute disaster scenarios.

Human cortical organoids, three-dimensional neuronal cell cultures derived from human induced pluripotent stem cells, have recently emerged as promising models of human brain development and dysfunction. Transplantation of human brain organoids into the mouse brain has been shown to be a successful in vivo model providing vascularization for long term chronic experiments. However, chronic functional connectivity and responses evoked by external sensory stimuli has yet to be demonstrated, due to limitations of chronic recording technologies. Here, we develop an experimental paradigm based on transparent graphene microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human organoids transplanted in the mouse cortex. The transparency of graphene microelectrodes permits visual and optical inspection of the transplanted organoid and the surrounding cortex throughout the chronic experiments where local field potentials and multi-unit activity (MUA) are recorded during spontaneous activity and visual stimuli. These experiments reveal that visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in the power of the gamma and MUA bands as well as phase locking of MUA events to slow oscillations evoked by visual stimuli suggest functional connectivity established between the human and mouse tissue. Optical imaging through the transparent microelectrodes shows vascularization of the organoids. Postmortem histological analysis exhibits morphological integration and synaptic connectivity with surrounding mouse cortex as well as migration of organoid cells into the surrounding cortex. This novel combination of stem cell and neural recording technologies could serve as a unique platform for comprehensive evaluation of organoids as models of brain development and dysfunction and as personalized neural prosthetics to restore lost, degenerated, or damaged brain regions.

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options. Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids. Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.

Brain organoids recapitulate in vitro the specific stages of in vivo human brain development, thus offering an innovative tool by which to model human neurodevelopmental disease. We review here how brain organoids have been used to study neurodevelopmental disease and consider their potential for both technological advancement and therapeutic development.

Chemical weed control remains a widely used component of integrated weed management strategies because of its cost-effectiveness and rapid removal of crop pests. Additionally, dicamba-plus-glyphosate mixtures are a commonly recommended herbicide combination to combat herbicide resistance, specifically in recently commercially released dicamba-tolerant soybean and cotton. However, increased spray drift concerns and antagonistic interactions require that the application process be optimized to maximize biological efficacy while minimizing environmental contamination potential. Field research was conducted in 2016, 2017, and 2018 across three locations (Mississippi, Nebraska, and North Dakota) for a total of six site-years. The objectives were to characterize the efficacy of a range of droplet sizes [150 µm (Fine) to 900 µm (Ultra Coarse)] using a dicamba-plus-glyphosate mixture and to create novel weed management recommendations utilizing pulse-width modulation (PWM) sprayer technology. Results across pooled site-years indicated that a droplet size of 395 µm (Coarse) maximized weed mortality from a dicamba-plus-glyphosate mixture at 94 L ha–1. However, droplet size could be increased to 620 µm (Extremely Coarse) to maintain 90% of the maximum weed mortality while further mitigating particle drift potential. Although generalized droplet size recommendations could be created across site-years, optimum droplet sizes within each site-year varied considerably and may be dependent on weed species, geographic location, weather conditions, and herbicide resistance(s) present in the field. The precise, site-specific application of a dicamba-plus-glyphosate mixture using the results of this research will allow applicators to more effectively utilize PWM sprayers, reduce particle drift potential, maintain biological efficacy, and reduce the selection pressure for the evolution of herbicide-resistant weeds.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are now well-documented. To experimentally determine whether SARS-CoV-2 could replicate in and affect human brain cells, we infected iPSC-derived human brain organoids. Here, we show that SARS-CoV-2 can productively replicate and promote death of neural cells, including cortical neurons. This phenotype was accompanied by loss of excitatory synapses in neurons. Notably, we found that the U.S. Food and Drug Administration (FDA)-approved antiviral Sofosbuvir was able to inhibit SARS-CoV-2 replication and rescued these neuronal alterations in infected brain organoids. Given the urgent need for readily available antivirals, these results provide a cellular basis supporting repurposed antivirals as a strategic treatment to alleviate neurocytological defects that may underlie COVID-19- related neurological symptoms.

Probable rapid eye movement (REM) sleep behavior disorder (pRBD) is a synucleinopathy-associated parasomnia in which loss of REM sleep muscle atonia results in motor behavior during REM sleep, including dream enactment. Traumatic brain injury is independently associated with increased risk of pRBD and Lewy body disease, and both pRBD and Lewy body disease are often observed in chronic traumatic encephalopathy (CTE). However, the frequency and pathological substrate of pRBD in CTE have not been formally studied and remain unknown. Of the total sample of 247 men, age at death of 63.1 ± 18.8 years (mean ± SD), 80 [32%] were determined by informant report to have symptoms of pRBD. These participants had played more years of contact sports (18.3 ± 11.4) than those without pRBD (15.1 ± 6.5; P = 0.02) and had an increased frequency of Lewy body disease (26/80 [33%] vs 28/167 [17%], P = 0.005). Of the 80 participants with pRBD, 54 [68%] did not have Lewy body disease; these participants were more likely to have neurofibrillary tangles and pretangles in the dorsal and median raphe (41 of 49 [84%] non-LBD participants with pRBD symptoms vs 90 of 136 [66%] non-LBD participants without pRBD symptoms, P = 0.02), brainstem nuclei with sleep regulatory function. Binary logistic regression modeling in the total study sample showed that pRBD in CTE was associated with dorsal and median raphe nuclei neurofibrillary tangles (OR = 3.96, 95% CI [1.43, 10.96], P = 0.008), Lewy body pathology (OR = 2.36, 95% CI [1.18, 4.72], P = 0.02), and years of contact sports participation (OR = 1.04, 95% CI [1.00, 1.08], P = 0.04). Overall, pRBD in CTE is associated with increased years of contact sports participation and may be attributable to Lewy body and brainstem tau pathologies.

Background Pesticide applications using a specific droplet size and carrier volume could maximize herbicide efficacy while mitigating particle drift in a precise and efficient manner. The objectives of this study were to investigate the influence of spray droplet size and carrier volume on dicamba and glufosinate efficacy, and to determine the plausibility of droplet-size based site-specific weed management strategies. Results Generally, across herbicides and carrier volumes, as droplet size increased, weed control decreased. Increased carrier volume (187 L ha-1 ) buffered this droplet size effect, thus greater droplet sizes could be used to mitigate drift potential while maintaining sufficient levels of weed control. To mitigate drift potential and achieve satisfactory weed control (≥ 90% of maximum observed control), a 900 µm (Ultra Coarse) droplet size paired with 187 L ha-1 carrier volume is recommended for dicamba applications and a 605 µm (Extremely Coarse) droplet size across carrier volumes is recommended for glufosinate applications. Although general droplet size recommendations were created, optimum droplet sizes for weed control varied significantly across site-years. Conclusion Convoluted interactions occur between droplet size, carrier volume, and other application parameters. Recommendations for optimizing herbicide applications based on droplet size should be based on a site-specific management approach to better account for these interactions. © 2018 Society of Chemical Industry.

A 12-year-old boy with Down syndrome (DS), myeloproliferative disorder and autism spectrum disorder presented for new-onset seizures. The patient did not report any headaches, weakness, nausea or vomiting, and neurological examination was non-focal. MRI revealed a mixed solid and cystic 13 mm mass

A 14-year-old girl presented with 10 months of worsening headaches with associated nausea and 1 month of visual impairment, including blurry and double vision. Her headaches initially occurred monthly but increased in frequency and became intractable to medical management. Physical examination was

Background Facial baroparesis is a palsy of the seventh cranial nerve resulting from increased pressure compressing the nerve along its course through the middle ear cavity. It is a rare condition, most commonly reported in barotraumatic environments, in particular scuba diving and high-altitude air travel. We report here an unusual case of highly frequent baroparesis, workup, and successful treatment. Case presentation A 57-year-old Caucasian male frequent commercial airline traveler presented with a 4-year history of recurrent episodes of right-sided facial paralysis and otalgia, increasing in both frequency and severity. Incidents occurred almost exclusively during rapid altitude changes in aircraft, mostly ascent, but also during rapid altitude change in an automobile. Self-treatment included nasal and oral decongestants, nasal corticosteroids, and warm packs. Temporal bone computed tomography (CT) scan revealed possible right-sided dehiscence of the tympanic bone segment; audiogram and magnetic resonance imaging of the internal auditory canals were unremarkable. After a diagnosis of facial nerve baroparesis was made, the patient underwent myringotomy with insertion of a pressure equalization tube (PET) into the right tympanic membrane. Despite re-exposure to altitude change multiple times weekly post-treatment, the patient reported being symptom-free for more than 6 months following intervention. Conclusions Prompt PET insertion may represent the preferred treatment for individuals who suffer recurrent episodes of facial baroparesis. Education regarding this rare condition may prevent unnecessary testing and treatment of affected patients. Future studies should explore the pathophysiology and risk factors, compare therapeutic options, and provide follow-up data to optimize the management of affected patients.

Chronic traumatic encephalopathy (CTE) is a progressive, neurodegenerative tauopathy associated with exposure to repetitive head injury, including concussions and subconcussions. Clinical features of CTE consist of abnormalities in behavior, including explosivity, impulsivity, and suicidality; mood, including depressed mood and hopelessness; cognition, including executive dysfunction, memory loss, and dementia; and movement, including parkinsonism. Neuropathologically, there is often generalized cortical atrophy, which may be most severe in the frontal and temporal lobes; abnormalities of the septum pellucidum, such as cavum septum or fenestrations; enlargement of the lateral and third ventricles; atrophy of the diencephalon; and depigmentation of the substantia nigra and locus coeruleus. Microscopically, CTE is defined by the perivascular accumulation of hyperphosphorylated tau (p-tau) in neurons and neuronal processes as neurofibrillary tangles (NFTs) and disordered neurites and in astrocytes, irregularly distributed in the cerebral cortex, with a predilection for the sulcal depths. In the mildest forms of CTE, a few perivascular CTE lesions are found in the cortex; in advanced CTE, p-tau NFTs and neurites are widely distributed in other cortical regions, often in the superficial layers of cortex, as well as the hypothalamus, thalamus, and brainstem. Most of the knowledge about CTE has been gained from the careful clinical characterization and comprehensive postmortem pathological analysis of brain donors. Although these studies have been essential to understanding the clinicopathological features of CTE and its molecular pathogenesis, current tissue-based research efforts have expanded to include developing in vivo biomarkers and diagnostics, characterizing risk factors, and developing methods to prevent and treat CTE.

Traumatic brain injury has been associated with increased risk of Parkinson disease and parkinsonism, and parkinsonism and Lewy body disease (LBD) can occur with chronic traumatic encephalopathy (CTE). To test whether contact sports and CTE are associated with LBD, we compared deceased contact sports athletes (n = 269) to cohorts from the community (n = 164) and the Boston University Alzheimer disease (AD) Center (n = 261). Participants with CTE and LBD were more likely to have β-amyloid deposition, dementia, and parkinsonism than CTE alone (p 8 years of play best predicted neocortical LBD (ROC analysis, OR = 6.24, 95% CI = 1.5–25, p = 0.011), adjusting for age, sex, and APOE ɛ4 allele status. Clinically, dementia was significantly associated with neocortical LBD, CTE stage, and AD; parkinsonism was associated with LBD pathology but not CTE stage. Contact sports participation may increase risk of developing neocortical LBD, and increased LBD frequency may partially explain extrapyramidal motor symptoms sometimes observed in CTE.

Pesticide applications using a specific droplet size and carrier volume could maximize herbicide efficacy while mitigating particle drift in a precise and efficient manner. The objectives of this study were to investigate the influence of spray droplet size and carrier volume on dicamba and glufosinate efficacy, and to determine the plausibility of droplet-size based site-specific weed management strategies.Generally, across herbicides and carrier volumes, as droplet size increased, weed control decreased. Increased carrier volume (187 L haConvoluted interactions occur between droplet size, carrier volume, and other application parameters. Recommendations for optimizing herbicide applications based on droplet size should be based on a site-specific management approach to better account for these interactions. © 2018 Society of Chemical Industry.

Yellow toadflax (Linaria vulgaris P. Mill.) infestations in North Dakota increased 300-fold from 1997 to 2011, when the plant was added to the state noxious weed list. Long-term control of other invasive species had included biological control agents, but no effective agents for yellow toadflax had been identified, so a control program using herbicides was needed. The objective was to shift from short-term control with picloram applied in the fall at maximum allowed rates to long-term management with minimal nontarget species impact with an adaptive management approach. Yellow toadflax control was increased from an average of 64% with picloram at 1,120 g ha−1 alone 12 mo after treatment (MAT) to over 90% when applied with diflufenzopyr while the picloram rate was reduced 50%. Yellow toadflax control with aminocyclopyrachlor applied at 140 g ha−1 ranged from 91 to 49% 12 MAT when applied in June or September, respectively. In contrast, yellow toadflax control with picloram plus dicamba plus diflufenzopyr averaged > 90% regardless of application date during the growing season. Land managers now have at least two options for long-term yellow toadflax control with a wide window of application timing. The goal of replacing a single high-use–rate herbicide treatment was met but both picloram and aminocyclopyrachlor can injure many desirable forbs. However, application timing can now be adjusted to have the least impact on nontarget species. The adaptive development program led to a 58% reduction in yellow toadflax infestations in North Dakota by 2014.

The Sheyenne National Grassland (SNG) is a native tall grass and mixed grass prairie located in southeastern North Dakota. Approximately half of the SNG has been invaded by leafy spurge (Euphorbia esulaL.) and control methods have been limited. Many herbicides cannot be utilized at the SNG due to sandy soils (> 80%) and shallow groundwater, nor can they be applied near the western prairie fringed orchid (Platanthera praeclaraSheviak and Bowles), a federally listed threatened plant found on the SNG. Quinclorac and aminocyclopyrachlor were considered for use on the SNG but potential to enter the groundwater was unclear. Movement of quinclorac and aminocyclopyrachlor was evaluated in 70 cm soil columns that simulated field conditions from five ecological sites. Quinclorac leached further following the heavy rainfall event of 15 cm in 48 h compared to the annual precipitation of 51 cm applied over 9 wk. Quinclorac leached approximately 45 cm into the soil profile averaged over all soil types and both precipitation events but never exceeded 65 cm regardless of soil type. Aminocyclopyrachlor leaching was greater than quinclorac and moved through all soil types into the leachate following both watering regimes. Desorption of both herbicides was incomplete. Approximately 10 and 32% of applied aminocyclopyrachlor and quinclorac, respectively, remained in the top 5 cm of soil regardless of soil type or watering regime. Quinclorac but not aminocyclopyrachlor was considered suitable for use at the SNG to control leafy spurge and has the added benefit of not harming the western prairie fringed orchid.

In 2010, an estimated 4.7% of people aged 60+ had dementia (Sosa-Ortiz, Acosta-Castillo, & Prince, 2012), leading to a global economic burden estimated at $604 billion (Wimo, Jonsson, Bond, Prince, & Winblad, 2013). The greatest predictor of dementia is increasing age (Plassman et al., 2007); as the number of older adults in the population continues to grow (Sosa-Ortiz, Acosta-Castillo, & Prince, 2012), early identification of neurodegenerative disease is increasingly essential. The rise in dementia prevalence creates the need for parallel improvements in treatment and palliative care. Research investment in the early characterization and treatment of dementia is an important public health goal. One challenge related to the early detection of dementia continues to be the identification of subtle cognitive changes in what is considered its “pre-clinical” phase. These subtle cognitive deficits may occur years before a clinical diagnosis is made, as biomarker evidence suggests that Alzheimer’s disease (AD) and related pathologies accumulate decades before clinical diagnosis (Albert et al., 2011; Howieson et al., 2008; Sperling et al., 2011). Detection of the earliest and most subtle cognitive changes should coincide with detection of the earliest and most subtle functional changes, which affect an individual’s ability to perform daily tasks in the natural environment (Chaytor & Schmitter-Edgecombe, 2003). A promising area for additional research in this field involves the latent dementia construct referred to as “δ” by Royall and colleagues (Royall & Palmer, 2012; Royall, Palmer, & O’Bryant, 2012), which may represent a recent advancement toward the goal of detecting early and subtle cognitive changes and concomitant functional decline. This construct, which is derived from Spearman’s general intelligence factor g (Spearman, 1904), represents a further subdivision of Spearman’s g into the two independent factors g’ (g prime) and δ. Royall et al. describe the δ construct, the focus of the current investigation, as representing the “cognitive correlates of functional status” (Royall et al., 2007; Royall & Palmer, 2012); as such, g’ reflects the component of one’s general cognitive ability that is separate from the functional decline caused by neurodegenerative disease. The δ and g’ constructs differ only slightly. Though both are thought to represent the latent variables underlying cognitive task performance, only δ is theorized to underlie one’s ability to function independently and perform activities of daily living (ADL). According to Royall and colleagues, g’ explains the largest proportion of the variance in cognitive test results, but δ most strongly correlates with dementia severity (Royall & Palmer, 2012). Most approaches to cognitive assessment of dementia focus on observed scores, which contain measurement error. In contrast, the latent variable modeling approach taken by Royall, which utilizes confirmatory factor analysis (CFA), can be used to quantify dementia severity with error in estimation but not in measurement (McArdle, 2009; Weston & Gore, 2006;). Latent variable models that fit the data well can be interpreted as providing evidence for a latent trait underlying observed test scores. The model proposed by Royall and colleagues should not be dependent upon the use of specific cognitive tests to measure the construct of dementia, which has a categorical latent structure (Gavett & Stern, 2012). If the model proposed by Royall and colleagues provides a valid representation of the latent dementia phenotype, then δ represents an important construct that could advance neurodegenerative disease research, especially as it pertains to the use of cognitive tests to aid in the detection of the earliest co-occurring changes in cognition and ADLs (Albert et al., 2011; Howieson et al., 2008; Sperling et al., 2011). To ensure that the δ construct is invariant to sample and assessment methods (i.e., cognitive test battery), Royall and colleagues’ model for δ requires validation in other samples and with different cognitive tests. The hypothesized model, which treats δ and g’ as independent constructs, has been validated in demented individuals (Royall, Palmer, & O’Bryant, 2012), cognitively healthy adults (Royall & Palmer, 2012) and in an ethnically diverse sample (Royall & Palmer, 2013). The goal of the current study is to further cross-validate the δ construct in a national clinical case series of older adult participants from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) (Beekly, Ramos, & Lee, 2007; Morris et al., 2006; Weintraub et al., 2009), both cross-sectionally and longitudinally. The UDS, maintained by NACC, contains longitudinal assessment data that reflect both the cognitive and functional changes that occur in healthy aging and as a result of AD, mild cognitive impairment (MCI), and other neurodegenerative diseases (Morris et al., 2006). As such, the UDS provides a unique opportunity for cross-validation of the δ construct through use of its large, diverse, and cognitively heterogeneous sample. In addition, the UDS includes a different battery of neuropsychological and functional tests than Royall’s initial δ validations (Royall & Palmer, 2012; Royall & Palmer, 2013; Royall, Palmer, & O’Bryant, 2012) and maintains approximately annual data relevant to ADLs and multiple cognitive domains, including attention, speed of processing, executive function, episodic memory, language, and behavioral symptoms (Weintraub et al., 2009). In validating the δ construct cross-sectionally, we hypothesize that the Royall et al. (Royall & Palmer, 2012; Royall, Palmer & O’Bryant, 2012) model, where δ represents the latent variable underling both cognitive and functional status and g’ represents the latent variable underlying the component of cognitive ability not related to functional decline, will fit the baseline data from the NACC UDS well. In cross-validating the δ construct longitudinally, we hypothesize that participants’ latent dementia status, as measured by δ on an approximately annual basis, will change in conjunction with participants’ latent dementia status as measured approximately annually by the Clinical Dementia Rating Sum of Boxes (CDR-SB), one of the most commonly used methods of rating an individual’s cognitive and functional status in the context of a neurodegenerative disease (O’Bryant et al., 2010).

The serial position effect reveals that recall of a supraspan list of words follows a predictable pattern, whereby words at the beginning (primacy) and end (recency) of a list are recalled more easily than words in the middle. This effect has typically been studied using single list-learning trials, but in neuropsychology, multi-trial list-learning tests are more commonly used. The current study examined trends in learning for primacy, middle, and recency effects across multiple trials in younger and older age cohorts. Participants were 158 volunteers, including 79 adults aged 17-36 ("younger" group) and 79 adults aged 54-89 years ("older" group). Each participant completed four learning trials and one delayed (5-10 min) recall trial from the Memory Assessment Scales. Scores were divided into primacy (first four words), middle (middle four words), and recency (final four words) scores for all trials. For list acquisition, mixed effects modeling examined the main effects of and interactions between learning slope (logarithmic), age group, and serial position. Rate of learning increased logarithmically over four trials and varied by serial position, with growth of middle and recency word acquisition increasing more rapidly than recall of primacy words; this interaction did not differ by age group. Delayed retention differed according to age group and serial position; both older and younger adults demonstrated similar retention for primacy words, but older adults showed reduced retention for middle and recency words. Although older adults acquired less information across learning trials, the reason for this reduced acquisition was related to initial learning, not to rate of learning over time. Older compared to younger adults were less efficient at transferring middle and recency words from short-term to long-term memory.

Neuropsychological research frequently uses non-clinical undergraduate participants to evaluate neuropsychological tests. However, a recent study by An and colleagues (2012, Archives of Clinical Neuropsychology, 27, 849-857) called into question that the extent to which the interpretation of these participants' performance on neuropsychological tests is valid. This study found that in a sample of 36 participants, 55.6% exhibited performance invalidity at an initial session and 30.8% exhibited performance invalidity at a follow-up session. The current study attempted to replicate these findings in a larger, more representative sample using a more rigorous methodology. Archival data from 133 non-clinical undergraduate research participants were analyzed. Participants were classified as performance invalid if they failed any one PVT. In the current sample, only 2.26% of participants exhibited performance invalidity. Thus, concerns regarding insufficient effort and performance invalidity when using undergraduate research participants appear to be overstated.

Introduction Chronic traumatic encephalopathy (CTE) is a progressive neurodegeneration associated with repetitive head impacts. Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) is a U01 project recently funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Biomedical Imaging and Bioengineering. The goal of the UNITE project is to examine the neuropathology and clinical presentation of brain donors designated as “at risk” for the development of CTE based on prior athletic or military exposure. Here, we present the rationale and methodology for UNITE. Methods Over the course of 4 years, we will analyze the brains and spinal cords of 300 deceased subjects who had a history of repetitive head impacts sustained during participation in contact sports at the professional or collegiate level or during military service. Clinical data are collected through medical record review and retrospective structured and unstructured family interviews conducted by a behavioral neurologist or neuropsychologist. Blinded to the clinical data, a neuropathologist conducts a comprehensive assessment for neurodegenerative disease, including CTE, using published criteria. At a clinicopathological conference, a panel of physicians and neuropsychologists, blinded to the neuropathological data, reaches a clinical consensus diagnosis using published criteria, including proposed clinical research criteria for CTE. Results We will investigate the validity of these clinical criteria and sources of error by using recently validated neuropathological criteria as a gold standard for CTE diagnosis. We also will use statistical modeling to identify diagnostic features that best predict CTE pathology. Conclusions The UNITE study is a novel and methodologically rigorous means of assessing clinicopathological correlation in CTE. Our findings will be critical for developing future iterations of CTE clinical diagnostic criteria.