Locally adaptive, spatially explicit projection of US population for 2030 and 2050.

Localized adverse events, including natural hazards, epidemiological events, and human conflict, underscore the criticality of quantifying and mapping current population. Building on the spatial interpolation technique previously developed for high-resolution population distribution data (LandScan Global and LandScan USA), we have constructed an empirically informed spatial distribution of projected population of the contiguous United States for 2030 and 2050, depicting one of many possible population futures. Whereas most current large-scale, spatially explicit population projections typically rely on a population gravity model to determine areas of future growth, our projection model departs from these by accounting for multiple components that affect population distribution. Modeled variables, which included land cover, slope, distances to larger cities, and a moving average of current population, were locally adaptive and geographically varying. The resulting weighted surface was used to determine which areas had the greatest likelihood for future population change. Population projections of county level numbers were developed using a modified version of the US Census's projection methodology, with the US Census's official projection as the benchmark. Applications of our model include incorporating multiple various scenario-driven events to produce a range of spatially explicit population futures for suitability modeling, service area planning for governmental agencies, consequence assessment, mitigation planning and implementation, and assessment of spatially vulnerable populations.

Do the effects of adolescent employment differ by employment intensity and neighborhood context?

Research on the effects of adolescent employment on primarily middle-class youth suggests that intense employment, working more than 15 or 20 hours during the school year, is associated with increased participation in risky behavior. Despite these findings, scholars who focus on the development of youth living in low-income urban areas often hypothesize that adolescent employment will have beneficial effects on this population. There is some evidence that adolescent employment is associated with increased educational achievement and adult employment for low-income urban youth. The impact of adolescent employment on future engagement in risky behavior across levels of neighborhood deprivation and employment intensity was investigated on a sample of 1,057 adolescents from the Project on Human Development in Chicago Neighborhoods, a longitudinal study of neighborhood effects on development. After controlling for individual characteristics, intense employment during adolescence did predict increased use of cigarettes and alcohol and having a greater number of sexual partners 2 years after employment was measured. There were no significant interactions between neighborhood SES and adolescent employment status on involvement in risky behavior. These findings suggest that intense adolescent employment is associated with detrimental developmental outcomes for youth regardless neighborhood context.

Safety and efficacy of intradermal injection of botulinum toxin for the treatment of oily skin.

OBJECTIVE: To evaluate the safety and efficacy of intradermal injection of abobotulinumtoxinA for the treatment of oily skin. METHODS AND MATERIALS: Twenty-five patients with oily skin were treated in the forehead region with intradermal injections of botulinum toxin. Baseline and post-treatment sebum production was measured using a sebometer. Photographs were taken. Patients were also asked to rate their satisfaction with the treatment in terms of improvement in their oily skin. RESULTS: Treatment with botulinum toxin resulted in significantly lower sebum production at 1 week and 1, 2, and 3 months after injection (p < .001, t-test). Twenty-one patients (91%) reported that they were satisfied (50-75% improvement) with intradermal botulinum toxin as a treatment for oily skin. [Correction added after online publication 7-Jan-2013: the number of satisfied patients has been updated] CONCLUSION: Intradermal injection of botulinum toxin significantly reduced sebum production in the forehead region, with a high degree of patient satisfaction. Intradermal botulinum toxin may be an effective treatment to reduce sebum production in patients with oily skin. Larger, randomized, blinded, placebo-controlled studies are warranted.

Successful treatment of facial telangiectasias using a micropulse 1,064-nm neodymium-doped yttrium aluminum garnet laser.

OBJECTIVES: To evaluate the safety and efficacy of a microsecond 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for the treatment of facial telangiectasias. METHODS: Subjects ages 35-70 with Fitzpatrick skin types I to III and facial telangiectasias underwent two treatments with a micropulse (0.65 ms) 1,064-nm Nd:YAG laser. Treatments were spaced 30 days apart, with a final evaluation 60 days after the second treatment. Evaluation included digital photography and an assessment of the degree of improvement on a scale from 1 to 5 by the subject and a nontreating investigator. RESULTS: Twenty subjects (18 women, two men) with Fitzpatrick skin type II and III completed the study. The nontreating investigator rated the objective clinical response as total clearance (100% clear) in 10% (n = 2) of subjects, significant clearance (≥50% clear) in 75% (n = 15), and some clearance (0-49% clear) in 15% (n = 3). None of the subjects was rated as having no clearance or worsening. In terms of subjective clearance reported by subjects, 80% (n = 16) reported significant clearance, with the remainder reporting some clearance. No adverse events were reported. CONCLUSION: The micropulse 1,064-nm Nd:YAG successfully treated facial telangiectasias with a high degree of patient satisfaction, minimal discomfort, and no adverse events.

Lichen sclerosus et atrophicus.

Morphea and lichen sclerosus et atrophicus (LSA) have similar clinical presentations. Reports of patients with overlapping clinical and histopathologic features of both conditions have led some to speculate that they may represent different presentations along the same disease spectrum. It has been postulated that there is a common etiologic agent, which may involve autoimmunity, response to trauma, or infection. The link between Borrelia infection and both morphea and LSA has been widely studied but remains controversial. We present a case of a patient with lesions characterized by overlapping features of morphea and LSA with rapid decrease in joint mobility.

Livedo reticularis.

Livedo reticularis (LR) is a net-like, violaceous, hyperpigmented pattern on the skin that reflects an underlying change in cutaneous blood flow. The causes of LR are many and most commonly include connective tissue diseases, vasculitis, hypercoagulability, and embolic events. We describe a 49-year-old man who presented with painful LR and ulcers on the lower extremities as a manifestation of chronic natural killer cell leukemia (CNKL). There have been only a few cases previously reported in the literature. We report an additional case of a patient with both LR and CNKL and suggest a possible mechanism that explains this association.

Syringocystadenoma.

We present a case of a 35-year-old woman with a yellow, verrucous, and itchy plaque on her scalp. Within this plaque, there was an erythematous, bleeding papule. Histopathologic findings were compatible with a diagnosis of syringocystadenoma papilliferum within a nevus sebaceous. We present a brief review of the natural history of nevus sebaceus, its pathogenesis, and management.

Interprofessional education on autism and intellectual disabilities: Program description and initial evaluation.

Project INTERprofessional Autism Collaborative Training (INTERACT) is an interprofessional education program designed to prepare graduate students in psychology, special education, and speech-language pathology to work with autistic children with moderate to severe intellectual disabilities. The rising prevalence of autism, coupled with increased appreciation for interprofessional approaches to service delivery, indicates the need for university training programs to prepare graduate students to work interprofessionally with this population; yet descriptions of such programs and their effectiveness are not reported in the literature. In this article, we explain the process through which an interprofessional faculty team developed Project INTERACT, describe the sequence of coursework and team-based clinical experiences that comprise the program, and present preliminary data regarding its effectiveness. Twenty-four graduate students in psychology, special education, and speech-language pathology participated in this quantitative study. We report results from three rating scales that participants completed at program entry, midpoint, and program exit. Participants endorsed positive attitudes toward interprofessional practice and demonstrated high levels of knowledge about autism. Self-rated knowledge and abilities in interprofessional practice increased significantly by program exit. Project INTERACT scholars developed knowledge and skills related to understanding, assessing, and treating autistic children with intellectual disabilities, through the lens of team-based interprofessional collaboration. We discuss implications for practice with Project INTERACT. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.

The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.

Impact of race on survival in patients with clinically nonmetastatic prostate cancer who deferred primary treatment.

BACKGROUND: Prostate cancer (PCa) racial disparity studies typically focus on survival differences after curative treatment. The authors of this report hypothesized that comparing mortality rates between African American (AA) and Caucasian American (CA) patients who deferred primary treatment for clinically nonmetastatic PCa may provide a better assessment of the impact of race on the natural course of PCa. METHODS: The pathology database of the New York Veterans Administration Medical Center (VAMC), an equal access-of-care facility, was searched for patients with biopsy-proven PCa. Inclusion criteria included 1) no evidence of metastatic disease or death within 3 years after diagnosis, 2) no primary treatment, and 3) a minimum of 5 years of follow-up for survivors. RESULTS: In total, 518 patients met inclusion criteria between 1990 and 2005. AA patients were younger (P = .02) and had higher median prostate-specific antigen (PSA) levels (P = .001) at the time of diagnosis compared with CA patients. In a multivariate model, higher Gleason score and PSA level were associated with increased mortality (P = .001 and P = .03, respectively), but race was not a predictor of death from PCa. CONCLUSIONS: The current data suggested that race did not have a major impact on survival in patients with PCa who deferred primary treatment for clinically nonmetastatic disease.

Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor.

The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly up-regulated in human melanoma cell lines and tissue samples; this up-regulation correlates with gene copy number in a subset of melanoma cell lines. Moreover, miR-182 ectopic expression stimulates migration of melanoma cells in vitro and their metastatic potential in vivo, whereas miR-182 down-regulation impedes invasion and triggers apoptosis. We further show that miR-182 over-expression promotes migration and survival by directly repressing microphthalmia-associated transcription factor-M and FOXO3, whereas enhanced expression of either microphthalmia-associated transcription factor-M or FOXO3 blocks miR-182's proinvasive effects. In human tissues, expression of miR-182 increases with progression from primary to metastatic melanoma and inversely correlates with FOXO3 and microphthalmia-associated transcription factor levels. Our data provide a mechanism for invasion and survival in melanoma that could prove applicable to metastasis of other cancers and suggest that miRNA silencing may be a worthwhile therapeutic strategy.

Necrobiotic xanthogranuloma.

Necrobiotic xanthogranuloma (NXG) is a rare, chronic, progressive, non-Langerhans histiocytosis that is strongly associated with hematologic malignant conditions. Only about 100 cases have been reported in the literature since it was first described in 1980. It is important for dermatologists to recognize NXG and initiate a prompt hematologic evaluation. IgG kappa is the most frequently discovered monoclonal gammopathy (65%), followed by IgG lambda (35%), and, much less commonly, IgA. Although no modality has been shown to be consistently effective, therapeutic options include glucocorticoids (topical, intralesional, and/or systemic), alkylating agents (chlorambucil and cyclophosphamide). interferon alpha, antimetabolites, antibiotics, thalidomide, and plasmaphersis.

Spatial and Temporal Characterization of Activity in Public Space, 2019-2020.

The data reported here characterize spatial and temporal variation in the ratio of short-to-long-duration visits in public places (i.e., points of interest) in the United States for each week between January 2019 and December 2020. The underlying data on anonymized and aggregated foot traffic to public places is curated by SafeGraph, a geospatial data provider. In this work, we report the estimated number and duration of "short" (i.e., <4 hours) and "long" (i.e., >4 hours) visits to public places at the US census block group level. Long visits are shown to be a good proxy for workers based on formal economic data. We propose that short visits are more likely to represent nonobligate activities: people visiting a public place for leisure, shopping, entertainment, or civic or cultural engagement. Our work constructs a ratio of short to long visits, which can be used to inform population estimates for nonworker use of public space. These data may be useful for understanding how people's use of public space has changed during the COVID-19 pandemic and, more generally, for understanding activity patterns in public.

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1.

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment. Meta-analysis and other bioinformatic analyses of the combined data show that bacteria associated with favorable response are confined within the Actinobacteria phylum and the Lachnospiraceae/Ruminococcaceae families of Firmicutes. Conversely, Gram-negative bacteria were associated with an inflammatory host intestinal gene signature, increased blood neutrophil-to-lymphocyte ratio, and unfavorable outcome. Two microbial signatures, enriched for Lachnospiraceae spp. and Streptococcaceae spp., were associated with favorable and unfavorable clinical response, respectively, and with distinct immune-related adverse effects. Despite between-cohort heterogeneity, optimized all-minus-one supervised learning algorithms trained on batch-corrected microbiome data consistently predicted outcomes to programmed cell death protein-1 therapy in all cohorts. Gut microbial communities (microbiotypes) with nonuniform geographical distribution were associated with favorable and unfavorable outcomes, contributing to discrepancies between cohorts. Our findings shed new light on the complex interaction between the gut microbiome and response to cancer immunotherapy, providing a roadmap for future studies.

A high proliferative index of recurrent melanoma is associated with worse survival.

OBJECTIVE: Previous melanoma studies evaluating prognostic factors of survival at recurrence have focused on primary tumor characteristics and clinical variables at first recurrence. We examined the prognostic relevance of recurrent tumor proliferation. METHODS: 114 melanoma patients with available recurrent tissues who were prospectively enrolled at New York University Medical Center were studied. Standard of care prognostic variables (e.g. stage at initial diagnosis and lactate dehydrogenase level) and recurrent tissue expression of proliferative marker Ki-67 were evaluated for their association with overall survival. RESULTS: High Ki-67 expression was observed in 57 (50%) of the 114 recurrent melanomas. On univariate analysis, the median overall survival of patients whose recurrent tumors overexpressed Ki-67 was significantly shorter than that of patients whose recurrent tumors had low Ki-67 expression (3.6 vs. 9.5 years, p = 0.03). On multivariate analysis, a high proliferative index of the recurrent melanoma remained an independent predictor of worse overall survival, controlling for stage at initial diagnosis, disease-free survival, and stage at first recurrence [HR = 2.09 (95% CI 1.24-3.54), p = 0.006]. CONCLUSIONS: Our results demonstrate the prognostic relevance of tumor proliferation in recurrent melanoma patients. Data also support restratification of risk assessment upon recurrence that considers tumor biology in addition to clinical variables evaluated as part of the standard of care.

Cheilitis granulomatosa.

Melkersson-Rosenthal Syndrome (MRS) is a rare syndrome that is characterized by a triad of facial paralysis, chronic edema of the lip, and a fissured tongue. Most commonly, one element of the triad precedes the development of the other symptoms. We present a case of cheilitis granulomatosa (CG) as a manifestation of incomplete MRS. As the etiology remains unknown, treatment of CG is challenging. Intralesional glucocorticoids remain the first-line treatment, but recurrences are common. We discuss alternative treatment strategies that include combination therapy with other anti-inflammatory agents and biologics, such as infliximab.

Erythrodermic lichen planus.

Lichen planus (LP) is a relatively common papulosquamous disorder that is characterized by pruritic, polygonal papules in a characteristic distribution. We present a case of a 71-year-old man with erythroderma, who was ultimately diagnosed with severe, generalized LP. Treatment of severe LP is challenging, and there are few, robust, clinical trials in the literature to guide the selection of appropriate treatment. We discuss the treatment options for generalized LP and the evidence in support of these agents.

Effects of PEERS® Social Skills Training on Young Adults with Intellectual and Developmental Disabilities During College.

The Program for the Education and Enrichment of Relational Skills (PEERS®) was used to provide weekly social skills training to a group of 10 college students with intellectual and developmental disabilities (IDD) between ages 18 and 26 attending an inclusive residential postsecondary college program. Additionally, Circles curriculum was used to supplement the PEERS curriculum for teaching social relationship boundaries. An average of 12 sessions per semester of PEERS® training sessions were conducted over each academic year. The present study examines the impact of the program on social skills, friendship qualities, and conversational skills. Results showed increased social skill knowledge, friendship quality, and conversational skills from pretest to posttest intervention. In this paper, we discuss the training program, results, implications for practice, limitations, and future research needs.

Dendritic cell vaccines targeting tumor blood vessel antigens in combination with dasatinib induce therapeutic immune responses in patients with checkpoint-refractory advanced melanoma.

BACKGROUND: A first-in-human, randomized pilot phase II clinical trial combining vaccines targeting overexpressed, non-mutated tumor blood vessel antigens (TBVA) and tyrosine kinase inhibitor dasatinib was conducted in human leukocyte antigen (HLA)-A2+ patients with advanced melanoma. METHODS: Patient monocyte-derived type-1-polarized dendritic cells were loaded with HLA-A2-presented peptides derived from TBVA (DLK1, EphA2, HBB, NRP1, RGS5, TEM1) and injected intradermally as a vaccine into the upper extremities every other week. Patients were randomized into one of two treatment arms receiving oral dasatinib (70 mg two times per day) beginning in week 5 (Arm A) or in week 1 (Arm B). Trial endpoints included T cell response to vaccine peptides (interferon-γ enzyme-linked immunosorbent spot), objective clinical response (Response Evaluation Criteria in Solid Tumors V.1.1) and exploratory tumor, blood and serum profiling of immune-associated genes/proteins. RESULTS: Sixteen patients with advanced-stage cutaneous (n=10), mucosal (n=1) or uveal (n=5) melanoma were accrued, 15 of whom had previously progressed on programmed cell death protein 1 (PD-1) blockade. Of 13 evaluable patients, 6 patients developed specific peripheral blood T cell responses against ≥3 vaccine-associated peptides, with further evidence of epitope spreading. All six patients with specific CD8+ T cell response to vaccine-targeted antigens exhibited evidence of T cell receptor (TCR) convergence in association with preferred clinical outcomes (four partial response and two stabilization of disease (SD)). Seven patients failed to respond to vaccination (one SD and six progressive disease). Patients in Arm B (immediate dasatinib) outperformed those in Arm A (delayed dasatinib) for immune response rate (IRR; 66.7% vs 28.6%), objective response rate (ORR) (66.7% vs 0%), overall survival (median 15.45 vs 3.47 months; p=0.0086) and progression-free survival (median 7.87 vs 1.97 months; p=0.063). IRR (80% vs 25%) and ORR (60% vs 12.5%) was greater for females versus male patients. Tumors in patients exhibiting response to treatment displayed (1) evidence of innate and adaptive immune-mediated inflammation and TCR convergence at baseline, (2) on-treatment transcriptional changes associated with reduced hypoxia/acidosis/glycolysis, and (3) increased inflammatory immune cell infiltration and tertiary lymphoid structure neogenesis. CONCLUSIONS: Combined vaccination against TBVA plus dasatinib was safe and resulted in coordinating immunologic and/or objective clinical responses in 6/13 (46%) evaluable patients with melanoma, particularly those initiating treatment with both agents. TRIAL REGISTRATION NUMBER: NCT01876212.

Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.

Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.