People waiting to receive information about a personally relevant future event often become increasingly pessimistic as the event draws near. These temporal declines in expectations have been demonstrated robustly across both naturalistic and laboratory settings. However, the low-level cognitive processes that give rise to temporal declines in expectations remain unclear. Here, we investigated the temporal boundary conditions of this effect. In a controlled cognitive task involving repeated probabilistic gambles, we assessed the dynamics of participants' reward expectations over a 12-second waiting period prior to revelation of the gamble outcome. Across two experiments (total N = 120), we found no evidence for temporal declines in expectations over this short waiting period, no matter whether expectations were measured via direct probability report (Experiment 1) or via an incentive-compatible `cash-out' decision (Experiment 2). These results demonstrate that temporal declines in expectations are not an invariant characteristic of human expectations regarding personally relevant future events.

This study evaluates the impact of depression treatment on economic behavior in Karnataka, India. We cross-randomized pharmacotherapy and livelihoods assistance among 1000 depressed adults and evaluated impacts on depression severity, socioeconomic outcomes, and several potential pathways over 26 months. The pharmacotherapy treatments reduce depression severity, with benefits that persist after treatment concludes. They substantially increase child human capital investment, particularly for older children, and reduce risk intolerance and the incidence of negative shocks. These findings suggest two pathways through which depression may perpetuate poverty.

BACKGROUND: Extremity CT angiography (CTA) is frequently used to assess for vascular injury among patients with extremity trauma. The injured extremity index (IEI), defined as the ratio of systolic occlusion pressure between injured and uninjured extremities, has been implemented to screen patients being considered for CTA. Physical examination together with IEI is extremely sensitive for significant extremity vascular injury. Unfortunately, IEI cannot always be calculated. This study aimed to determine whether patients with normal pulse examinations and no hard signs of vascular injury benefitted from further imaging with CTA. We hypothesized that CTA has become overused among patients with extremity trauma, as determined by the outcome of vascular abnormalities that underwent vascular intervention but were missed by physical examination. METHODS: The charts of traumatically injured patients who underwent extremity CTA were retrospectively reviewed. This study was performed at a level 1 trauma center for patients who presented as trauma activations from September 1, 2019 to September 1, 2020. RESULTS: One hundred and thirty-six patients with 167 injured limbs were included. Eight limbs (4.8%) underwent an open vascular operation, whereas five limbs (3.0%) underwent an endovascular procedure. One of the 167 limbs (0.6%) had a vascular injury seen on CTA and underwent intervention that was not associated with a pulse abnormality or hard signs of vascular injury. This patient presented in a delayed fashion after an initially normal IEI and examination. Proximity injuries and fractures alone were not highly associated with vascular injuries. DISCUSSION: Many patients with normal pulse examination and no hard signs of vascular injury underwent CTA; the vast majority of these patients did not then have a vascular intervention. Given the consequences of missed vascular injuries, further work is required to prospectively assess the utility of CTA among patients with extremity trauma. LEVEL OF EVIDENCE: III.

Lipedematous alopecia is a rare, non-androgenic form of alopecia that is challenging to diagnose, often requiring clinical-pathological correlation. The condition has been reported predominantly in African-American females, but more recently has been described in a broader demographic [1,2]. We describe a rare case of a young Caucasian man with isolated lipedematous alopecia who presented with a boggy, erythematous plaque with alopecia of the occipital scalp and subcutaneous thickening with lymphocytic dermal infiltrate and decreased anagen hairs on histology.

Purpose

The purpose of this study was to characterize the benign biological variance of fixational microsaccades in a control population using a tracking scanning laser ophthalmoscope (TSLO), accounting for machine accuracy and precision, to determine ideal testing conditions to detect pathologic change in fixational eye motion (FEM).

Methods

We quantified the accuracy and precision of the TSLO, analyzing measurements made by three operators on a model eye. Repeated, 10-second retinal motion traces were then recorded in 17 controls, 3 times a day (morning, afternoon, and evening), on 3 separate days. Microsaccade metrics (MMs) of frequency, average amplitude, peak velocity, and peak acceleration were extracted. Trace to trace, interday, and intraday variability were calculated across all subjects.

Results

Intra-operator and machine variation contributed minimally to total variation, with only 0.007% and 0.14% contribution for frequency and amplitude respectively. Bias was detected, with lower accuracy for higher amplitudes. Participants had an average (SD) microsaccade frequency of 0.84 Hz (0.52 Hz), amplitude of 0.32 degrees (0.11 degrees), peak velocity of 43.68 degrees/s (14.02 degrees/s), and peak acceleration of 13,920.04 degrees/s2 (4,186.84 degrees/s2). The first trace recorded within a session significantly differed from the second two in both microsaccade acceleration and velocity (P < 0.05), and frequency was 0.098 Hz higher in the evenings (P < 0.05). There was no MM difference between days and no evidence of a session-level learning effect (P > 0.05).

Conclusions

The TSLO is both accurate and precise. However, biological inter- and intra-individual variance is present. Trace to trace variability and time of day should be accounted for to optimize detection of pathologic change.

Introduction

Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking.

Methods

Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants.

Results

Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations.

Discussion

Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.

Introduction

The reporting of approaches facilitating the most efficient and timely recruitment of Alzheimer's disease (AD) patients into pharmacologic trials is fundamental to much-needed therapeutic progress.

Methods

T2 Protect AD (T2), a phase 2 randomized placebo-controlled trial of troriluzole in mild to moderate AD, used multiple recruitment strategies.

Results

T2 exceeded its recruitment target, enrolling 350 participants between July 2018 and December 2019 (randomization rate: 0.87 randomizations/site/month, or 3-fold greater than recent trials of mild to moderate AD). The vast majority (98%) of participants were enrolled during a 10-month window of intense promotion in news media, TV and radio advertisements, and social media. The distribution of primary recruitment sources included: existing patient lists at participating sites (72.3%), news media (12.3%), physician referral (6.0%), word of mouth (3.1%), and paid advertising (2.9%).

Discussion

The rapid recruitment of participants with mild to moderate AD was achieved through a range of approaches with varying success.

No single neuroimaging technique or sequence is capable of reflecting the functional deficits manifest in MS. Given the interest in imaging biomarkers for short- to medium-term studies, we aimed to assess which imaging metrics might best represent functional impairment for monitoring in clinical trials. Given the complexity of functional impairment in MS, however, it is useful to isolate a particular functionally relevant pathway to understand the relationship between imaging and neurological function. We therefore analyzed existing data, combining multiparametric MRI and OCT to describe MS associated visual impairment. We assessed baseline data from fifty MS patients enrolled in ReBUILD, a prospective trial assessing the effect of a remyelinating drug (clemastine). Subjects underwent 3T MRI imaging, including Neurite Orientation Dispersion and Density Imaging (NODDI), myelin content quantification, and retinal imaging, using OCT. Visual function was assessed, using low-contrast letter acuity. MRI and OCT data were studied to model visual function in MS, using a partial, least-squares, regression analysis. Measures of neurodegeneration along the entire visual pathway, described most of the observed variance in visual disability, measured by low contrast letter acuity. In those patients with an identified history of ON, however, putative myelin measures also showed correlation with visual performance. In the absence of clinically identifiable inflammatory episodes, residual disability correlates with neurodegeneration, whereas after an identifiable exacerbation, putative measures of myelin content are additionally informative.

Introduction

Apolipoprotein E (APOE) ε4, the strongest non-Mendelian genetic risk factor for Alzheimer's disease (AD), has been shown to affect brain capillaries in mice, with potential implications for AD-related neurodegenerative disease. However, human brain capillaries cannot be directly visualized in vivo. We therefore used retinal imaging to test APOE ε4 effects on human central nervous system capillaries.

Methods

We collected retinal optical coherence tomography angiography, cognitive testing, and brain imaging in research participants and built statistical models to test genotype-phenotype associations.

Results

Our analyses demonstrate lower retinal capillary densities in early disease, in cognitively normal APOE ε4 gene carriers. Furthermore, through regression modeling with a measure of brain perfusion (arterial spin labeling), we provide support for the relevance of these findings to cerebral vasculature.

Discussion

These results suggest that APOE ε4 affects capillary health in humans and that retinal capillary measures could serve as surrogates for brain capillaries, providing an opportunity to study microangiopathic contributions to neurodegenerative disorders directly in humans.