Simulating and Predicting Dynamical Systems With Spatial Semantic Pointers.

While neural networks are highly effective at learning task-relevant representations from data, they typically do not learn representations with the kind of symbolic structure that is hypothesized to support high-level cognitive processes, nor do they naturally model such structures within problem domains that are continuous in space and time. To fill these gaps, this work exploits a method for defining vector representations that bind discrete (symbol-like) entities to points in continuous topological spaces in order to simulate and predict the behavior of a range of dynamical systems. These vector representations are spatial semantic pointers (SSPs), and we demonstrate that they can (1) be used to model dynamical systems involving multiple objects represented in a symbol-like manner and (2) be integrated with deep neural networks to predict the future of physical trajectories. These results help unify what have traditionally appeared to be disparate approaches in machine learning.

Treatment of Psoriasis With Biologics and Apremilast in Patients With a History of Malignancy: A Retrospective Chart Review

Introduction: Biologics have transformed the management of moderate-to-severe psoriasis. The risk of developing a malignancy during treatment is an important consideration, and many studies have been conducted to determine the magnitude of this risk. However, there is little research on the use of biologic treatment in psoriasis patients with a history of established malignancy. Methods: We preformed a retrospective chart review of patients with psoriasis and a history of malignancy that were treated with biologics or apremilast. A list was created containing the 690 patients with psoriasis who were treated in our clinic with biologics or apremilast between January 1st, 2012 and May 31, 2018. The charts were examined, and 16 patients were found to have a history of malignancy excluding non-melanoma skin cancer. Results: Sixteen patients met criteria to be included in this review. The average time from cancer diagnosis to initiation of biologics or apremilast was 4.7 years, and 9 patients (56%) started treatment within five years. Three patients (19%) received concurrent cancer therapy during biologic treatment. None of the 16 patients had recurrence or progression of their cancer noted clinically or radiographically during biologic or apremilast treatment. Most patients had improvement of their psoriasis. Discussion: The data reviewed here show successful treatment on biologics despite concurrent malignancy, though confirmatory research is needed. J Drugs Dermatol. 2019;18(4):387-390.

Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.

BACKGROUND: Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. OBJECTIVE: We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. METHODS: This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20. RESULTS: Of 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53-99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4-43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne. LIMITATIONS: Limitations of the study include the small sample size and open-label study design. CONCLUSIONS: Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo.

Systemic Treatment of Recalcitrant Pediatric Psoriasis: A Case Series and Literature Review.

BACKGROUND/PURPOSE: No systemic drugs are approved by the Food and Drug Administration to treat pediatric psoriasis due to a lack of supporting data. The purpose of this study is to present cases demonstrating the use of systemic drugs in pediatric psoriasis. METHODS: In this case series, data were collected on patients ≤ 18 years old with moderate-to-severe psoriasis treated with systemic medications (traditional systemic drugs or biologics) from 2008 through 2014. Efficacy was measured using the validated simple measure for assessing psoriasis activity (S-MAPA), and the product of the body surface area and Physician Global Assessment. RESULTS: Twenty-seven patients aged 5 to 18 years were eligible, and 56 treatment courses were analyzed. Methotrexate (MTX) was the most frequently prescribed systemic (70%), followed by etanercept (59%). Clearance rates were highest on biologic medications (67% for etanercept and adalimumab, 33% for ustekinumab). Phototherapy, cyclosporine, and MTX were less effective in clearing psoriasis, although they were successful in improving S-MAPA ≥ 50% from baseline 100%, 67%, and 36% of the time, respectively. The most common adverse events were sunburn for patients on narrowband ultraviolet B phototherapy (14%), gastrointestinal intolerance and minor infections for patients on MTX (16% each), and minor infections for patients on etanercept (25%) and adalimumab (33%). The most common reasons for discontinuation were secondary failure (38% for etanercept, 33% for adalimumab) or lack of response (37% for MTX, 33% for cyclosporine). CONCLUSION: Although phototherapy, MTX, and cyclosporine are effective for controlling resistant pediatric psoriasis, concerns about long-term safety or inconvenience have led people to consider biologics in their place. However, there is a lack of literature on the use of biologics in pediatric psoriasis. These cases attest to the safety and efficacy of etanercept, adalimumab, and ustekinumab in pediatric psoriasis, expanding the treatment repertoire and guiding dermatologists in better managing recalcitrant pediatric psoriasis.

Clearance of psoriasis: the impact of private versus public insurance.

BACKGROUND: Psoriasis treatments and therapeutic response as they relate to private versus public patient insurance in the United States have not yet been reviewed. Improved understanding could clarify factors challenging optimal psoriasis management and offer insight for dermatologists treating psoriasis within our healthcare system. METHODS: 258 subjects were included from a database of psoriasis patients seen at Tufts Medical Center (Boston, MA) during 2008-2014. Insurance was classified as primarily private or public (Medicare or MassHealth/Medicaid). Patients required a minimum of two consecutive visits per treatment and at least 8 weeks within one of four treatment categories: biologics, oral systemics/ phototherapy, combined biologics and oral systemics/phototherapy, or topicals only. Primary endpoint was the Simple-Measure for Assessing Psoriasis Activity (S-MAPA) calculated by multiplying Physician Global Assessment by Body Surface Area. S-MAPA<3 constituted absolute clearance. Insurance type was evaluated as a predictor of prescribed treatment categories, maximum S-MAPA improvement from baseline, and total drugs used per treatment course ("drug-switching"). RESULTS: 80.2% (n=207) and 19.8% (n=51) had primarily private and public insurance, respectively. 69.6% with private insurance were prescribed biologics versus 66.7% (public insurance) (P=0.689). 54% (private) versus 49% (public) achieved clearance (P=0.514). However, S-MAPA decreased 78.35% from baseline in those with private insurance compared to 61.48% (public) (P=0.036). On average, privately insured patients used at least twice as many same-category treatments, most commonly biologics, than publicly insured individuals (P=0.003). Drug-switching was significantly associated with clearance (P=0.024). Multivariate analysis demonstrated no significant differences in prescribed treatment categories, drug efficacy, clearance, S-MAPA, or drugswitching with respect to patient age. CONCLUSIONS: Treatment categories were comparably prescribed between insurance subgroups. However, privately insured patients achieved significantly greater degrees of clearance and switched between more medications within biologic and systemic categories, potentially explaining their overall improved therapeutic response. Further studies including cost-analysis could clarify any difference in the effectiveness of prescribed therapy for these two patient populations.

A randomized, prospective, sham-controlled study of localized narrow-band UVB phototherapy in the treatment of plaque psoriasis.

IMPORTANCE: UV phototherapy remains a useful and frequently employed treatment for chronic plaque psoriasis. In those patients with plaque body surface area less than 10%, targeted treatment is the safest and most effective modality. OBJECTIVE: We aimed to evaluate the efficacy of the Levia® localized NB-UVB phototherapy machine in the treatment of patients with symmetrical psoriatic lesions. DESIGN: We performed a prospective, double-blinded, sham-treatment controlled study of this device beginning March 2012 through April 2014. SETTING: a comprehensive dermatology clinic in the northeastern United States. PARTICIPANTS: 21 subjects with chronic plaque psoriasis. INTERVENTIONS: Each patient had one lesion randomized to receive the Levia treatment and one lesion (the control) treated with visible light. Treatment was administered three times a week for twelve weeks. Target lesion score (TLS), a rating of 0-4 each of erythema, scaling, and thickness, was measured biweekly by a blinded assessor, and visual analogue scale of pruritus was recorded by subjects. MAIN OUTCOMES AND MEASURES: The primary outcome, formulated prior to study initiation, was the percentage of lesions achieving clear or almost clear TLS after 12 weeks of treatment. Secondary endpoints included changes in target lesion pruritus VAS, percentage improvement in TLS, and the percentage of subjects achieving 50% improvement in TLS (TLS-50). RESULTS: The primary endpoint, TLS of three or less, was not achieved (P=0.118), but the secondary endpoints of percentage improvement in TLS (P=0.043) and TLS-50 (P=0.0195) were significantly superior in treated compared to sham-treated lesions. Percentage improvement in pruritus VAS was not significant (P=0.0565). CONCLUSIONS AND RELEVANCE: This device was found to be efficacious, though not necessarily to the point of clearance, in the treatment of psoriasis over a 12-week period. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT02107482, http://clinicaltrials.gov/show/NCT02107482

Prevalence of the metabolic syndrome in children with psoriatic disease.

Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1 mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no statistically significant differences in the other four components of MetS, BMI, BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that children with psoriasis have higher rates of MetS than age- and sex-matched controls. It may therefore be important to evaluate children with psoriasis for components of MetS to prevent future CVD morbidity and mortality.

Exploiting semantic information in a spiking neural SLAM system.

To navigate in new environments, an animal must be able to keep track of its position while simultaneously creating and updating an internal map of features in the environment, a problem formulated as simultaneous localization and mapping (SLAM) in the field of robotics. This requires integrating information from different domains, including self-motion cues, sensory, and semantic information. Several specialized neuron classes have been identified in the mammalian brain as being involved in solving SLAM. While biology has inspired a whole class of SLAM algorithms, the use of semantic information has not been explored in such work. We present a novel, biologically plausible SLAM model called SSP-SLAM-a spiking neural network designed using tools for large scale cognitive modeling. Our model uses a vector representation of continuous spatial maps, which can be encoded via spiking neural activity and bound with other features (continuous and discrete) to create compressed structures containing semantic information from multiple domains (e.g., spatial, temporal, visual, conceptual). We demonstrate that the dynamics of these representations can be implemented with a hybrid oscillatory-interference and continuous attractor network of head direction cells. The estimated self-position from this network is used to learn an associative memory between semantically encoded landmarks and their positions, i.e., an environment map, which is used for loop closure. Our experiments demonstrate that environment maps can be learned accurately and their use greatly improves self-position estimation. Furthermore, grid cells, place cells, and object vector cells are observed by this model. We also run our path integrator network on the NengoLoihi neuromorphic emulator to demonstrate feasibility for a full neuromorphic implementation for energy efficient SLAM.

Biologically-Based Computation: How Neural Details and Dynamics Are Suited for Implementing a Variety of Algorithms.

The Neural Engineering Framework (Eliasmith & Anderson, 2003) is a long-standing method for implementing high-level algorithms constrained by low-level neurobiological details. In recent years, this method has been expanded to incorporate more biological details and applied to new tasks. This paper brings together these ongoing research strands, presenting them in a common framework. We expand on the NEF's core principles of (a) specifying the desired tuning curves of neurons in different parts of the model, (b) defining the computational relationships between the values represented by the neurons in different parts of the model, and (c) finding the synaptic connection weights that will cause those computations and tuning curves. In particular, we show how to extend this to include complex spatiotemporal tuning curves, and then apply this approach to produce functional computational models of grid cells, time cells, path integration, sparse representations, probabilistic representations, and symbolic representations in the brain.

A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis.

OBJECTIVE: Evaluate the efficacy and safety of apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, in subjects with recalcitrant moderate to severe atopic dermatitis (AD) or allergic contact dermatitis (ACD). RESEARCH DESIGN AND METHODS: This was a proof-of-concept, phase 2, open-label, single institution trial that evaluated the efficacy and safety of apremilast, 20 mg twice daily, for twelve weeks, in ten subjects with either AD and/or ACD. The primary endpoint was a ?2 point improvement in Investigator Global Assessment (IGA) score after 12 weeks of treatment. Secondary endpoints included a 75% reduction in the Eczema Assessment Severity Index (EASI-75), EASI-50, and the maximum EASI response. RESULTS: The primary endpoint of improvement in IGA by two or more points was met by 20% of subjects. Ten percent of subjects achieved EASI-75 and another 10% reached EASI-50. All subjects tolerated apremilast well with no serious adverse events or withdrawal due to side effects. Common adverse events associated with apremilast included headache, nausea, and soft stool. LIMITATIONS: This study was limited by its small sample size and lack of a comparison group to serve as a control. CONCLUSIONS: Apremilast was well tolerated in all subjects. Apremilast was minimally effective in AD and ACD and results were inferior to previous trials of apremilast in psoriasis.

Assessor-blinded study of the metabolic syndrome and surrogate markers of increased cardiovascular risk in children with moderate-to-severe psoriasis compared with age-matched population of children with warts.

Adult patients with psoriasis have an increased prevalence of the metabolic syndrome (MetS) and cardiovascular disease (CVD) risk factors due to elevations of Tumor Necrosis Factor and other inflammatory cytokines.1,2 Recently, higher rates of hyperlipidemia, obesity, hypertension, and diabetes mellitus were seen in patients with juvenile psoriasis.3 Here, we report the interim results of an ongoing study of MetS and CVD risk factors in pediatric psoriasis patients.

Concomitant atopic dermatitis and psoriasis - a retrospective review.

INTRODUCTION: At one time considered opposing diseases, it is now recognized that atopic dermatitis (AD) and psoriasis can coexist. There are limited data characterizing this population of patients. In this study, we characterize the population of patients diagnosed with both AD and psoriasis and summarize their response to therapy. METHODS: A retrospective chart review was performed and data was recorded for patients with a diagnosis of psoriasis (n = 1390), AD (n = 912) and psoriasis plus AD (n = 30) within the Tufts Medical Center Department of Dermatology between January 1, 2012 and May 1, 2019. RESULTS: The prevalence of concomitant AD and psoriasis was 1.5%. Of those with both AD and psoriasis, hand involvement was high (63%). Systemic therapy was used in 73% of patients. Of those on biologics, 30% required more than one biologic consecutively and 22% required more than one biologic simultaneously to achieve clinically significant results. CONCLUSION: Patients with overlapping AD and psoriasis have a high prevalence of hand involvement, poor response to topical therapy, and may require multiple systemic agents to treat. In a patient with known history of psoriasis with recalcitrant hand disease involvement, AD should be considered.

Improving health literacy and treatment understanding of hidradenitis suppurativa using group educational interventions.

Background: Hidradenitis suppurativa (HS) is a chronic immune-mediated skin disorder characterized by inflamed, painful abscesses most commonly located in the intertriginous regions that may lead to significant scarring and social stigma. It is unclear how much patients with HS understand about their disease. Objective: We sought to evaluate baseline knowledge of patients who have HS, as well as to evaluate if an educational intervention of a teaching session about the disease will help increase patient's knowledge of their ailment and treatment options. These sessions also act as a support group for the participants, during which they have time to connect with one another and discuss their experiences with HS. Methods: Participants were recruited at Tufts Medical Center by searching for an ICD-10 code of HS or were identified via advertisement. Eligible subjects were given a study specific questionnaire pre- and post an educational lecture on HS. Results: Twenty subjects participated in the study, conducted from June 2017 through January 2018. Mean test score improved from 62.7% to 82.7% (p < .0001). Additionally, participants reported an average of 20.3% (p = .0002) improvement in their knowledge of HS postintervention. Conclusions: Group information sessions can be an effective means to educate patients with hidradenitis suppurativa and were preferable to the majority of participants in this study.