Temporal Analysis of Effective Population Size and Mating System in a Social Wasp.

Highly social species are successful because they cooperate in obligately integrated societies. We examined temporal genetic variation in the eusocial wasp Vespula maculifrons to gain a greater understanding of evolution in highly social taxa. First, we wished to test if effective population sizes of eusocial species were relatively low due to the reproductive division of labor that characterizes eusocial taxa. We thus estimated the effective population size of V. maculifrons by examining temporal changes in population allele frequencies. We sampled the genetic composition of a V. maculifrons population at 3 separate timepoints spanning a 13-year period. We found that effective population size ranged in the hundreds of individuals, which is similar to estimates in other, non-eusocial taxa. Second, we estimated levels of polyandry in V. maculifrons in different years to determine if queen mating system varied over time. We found no significant change in the number or skew of males mated to queens. In addition, mating skew was not significant within V. maculifrons colonies. Therefore, our data suggest that queen mate number may be subject to stabilizing selection in this taxon. Overall, our study provides novel insight into the selective processes operating in eusocial species by analyzing temporal genetic changes within populations.

Applying community ecological theory to maximize productivity of cultivated biocrusts.

Degraded rangelands around the world may benefit from the reestablishment of lost biological soil crusts (biocrusts, soil surface cryptogamic-microbial communities). Cultivation of biocrust organisms is the first step in this process, and may benefit from harnessing species interactions. Species interactions are a dominant force structuring ecological communities. One key element of community structure, species richness, is itself important because it can promote the productivity of the entire community. Here, we use biological soil crusts as a model to test the effects of species interactions on production of biocrust materials for use in ecosystem rehabilitation. We screened eight different moss and lichen species from semiarid rangelands of Montana, USA, for growth potential under two watering regimes. Mosses generally grew well, but we were unable to cultivate the selected lichen species. We produced a >400% increase in the biomass of one species (Ceratodon purpureus). We tested whether a parasite-host relationship between two lichens could be used to enhance productivity of the parasite species, but this also resulted in no net gain of lichen productivity. Finally, we constructed all possible community combinations from a pool of five moss species to test for overyielding (community productivity exceeding that expected from the growth of community members in monoculture), and to determine both if, and the mode in which, species richness increases productivity. Polycultures yielded more than would be expected based upon the production of community constituents in monoculture. Using structural equation models, we determined that there was a modest effect of species richness on community productivity (r = 0.24-0.25), which was independent of a stronger effect of the identity of species in the community (r = 0.41-0.50). These results will contribute to the optimization of biocrust cultivation, promoting the development of this emerging ecological rehabilitation technology.

Narrative review: Revised Principles and Practice Recommendations for Adolescent Substance Use Treatment and Policy.

OBJECTIVE: In 2014, the U.S. National Institute on Drug Abuse released the "Principles of Adolescent Substance Use Disorder Treatment," summarizing previously established evidence and outlining principles of effective assessment, treatment, and aftercare for substance use disorders (SUD). Winters et al. (2018) updated these principles to be developmentally appropriate for adolescents. This review builds on that formative work and recommends updated adolescent assessment, treatment, and aftercare principles and practices. METHOD: The Cochrane, MEDLINE-PubMed, and PsychInfo databases were searched for relevant studies with new data about adolescent substance use services. This article updates the 13 original principles; condenses the 8 original modalities into 5 practices; and highlights implications for public policy approaches, future funding, and research. RESULTS: Key recommendations from the principles include integrating care for co-occurring mental health disorders and SUDs, improving service accessibility including through the educational system, maintaining engagement, and addressing tension between agencies when collaborating with other youth service systems. Updates to the treatment practices include adoption of Screening, Brief Intervention and Referral to Treatment (SBIRT), investment in social programs and family involvement in treatment, expanding access to behavioral therapies and medications, increasing funding to harm reduction services, supporting reimbursement for continuing care services, and increasing investment in research. CONCLUSION: These revised principles of adolescent assessment, treatment, and aftercare approaches and practices aim to establish guidance and evidence-based practices for treatment providers, while encouraging necessary support from policymakers and funding agencies to improve the standard of care for adolescent SUD services.

Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study.

Stroke is a major cause of death and long-term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open-label trial to assess the safety and feasibility of a single IV infusion of non-human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3-9 days post-stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well-tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post-treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non-HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo-controlled phase 2 study. Stem Cells Translational Medicine 2018;7:521-529.

Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial.

Despite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed. We hypothesized that umbilical cord blood-derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain. Accordingly, we conducted a phase I, open-label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials. Twenty-five children, median age 4.6 years (range 2.26-5.97), with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit, were enrolled. Children were evaluated with a battery of behavioral and functional tests immediately prior to cord blood infusion (baseline) and 6 and 12 months later. Assessment of adverse events across the 12-month period indicated that the treatment was safe and well tolerated. Significant improvements in children's behavior were observed on parent-report measures of social communication skills and autism symptoms, clinician ratings of overall autism symptom severity and degree of improvement, standardized measures of expressive vocabulary, and objective eye-tracking measures of children's attention to social stimuli, indicating that these measures may be useful endpoints in future studies. Behavioral improvements were observed during the first 6 months after infusion and were greater in children with higher baseline nonverbal intelligence quotients. These data will serve as the basis for future studies to determine the efficacy of umbilical cord blood infusions in children with ASD. Stem Cells Translational Medicine 2017;6:1332-1339.

TNFerade Biologic: preclinical toxicology of a novel adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene.

TNFerade Biologic (TNFerade) is a second-generation (E1-, E3-, and E4-deleted) replication-deficient adenovector carrying the transgene encoding for human tumor necrosis factor alpha (TNFalpha), regulated by the radiation-sensitive promoter Early Growth Response (Egr-1). We hypothesized that intratumoral injection of TNFerade followed by radiation would result in potentially therapeutic levels of TNFalpha with minimal toxicity. Three preclinical studies were conducted, the purpose of which was to characterize the toxicity and pharmacokinetics of TNFerade in conjunction with radiation in nude as well as immune-competent (Balb/c) mice. A total of 80 mice in the nude mouse toxicology study, all bearing human squamous cell carcinoma xenografts, 120 mice in the Balb/c study, and 33 nude mice in the pharmacokinetic study were used. Doses ranging from 4x10(9) to 4x10(10) particle units (pu) (4x10(11) pu in the Balb/c study) were explored, with and without radiation. In the nude mice studies, TNFerade was injected intratumorally, whereas in the Balb/c study, TNFerade was administered by subcutaneous injection. TNFerade was well tolerated. In the nude mice studies, no significant toxicity occurred in any dose group. In the Balb/c study, 6/40 mice at the top dose (4x10(11) pu) were sacrificed in moribund condition (5/20 in the TNFerade+radiation group, 1/20 in the TNFerade alone group). Necropsy showed local necrosis and ulceration at the site of the injection. No deaths or significant toxicity were observed at the lower dose levels (4x10(9) and 4x10(10) pu), indicating a large safety margin for initial studies in humans. The pharmacokinetic study demonstrated high sustained levels of TNFalpha in the tumor homogenate with no "spillover" to plasma, where TNFalpha levels were below the level of detection. Radiation increased intratumoral levels of TNFalpha by a factor of 12 (from 0.998 to 11.55 ng/g). In conclusion, a gene therapy approach with TNFerade, in combination with radiation, represents a potential way to utilize the potent anticancer activity of TNFalpha without systemic toxicity.

Willingness to communicate organ donation intention.

OBJECTIVE: The study tested an intervention exposing people who planned to donate organs to written information about communicating with family their intention to donate organs. DESIGN: A pretest posttest double-blind experiment compared participants given written information about communicating with family and basic organ donation information, with participants given written information about only basic organ donation information. SAMPLE: Participants included 109 adults who had not yet communicated their plans with family. MEASURES: Participants first responded to previous experience with organ donation, thoughts about organ donation, willingness to communicate with family about organ donation, and knowledge about organ donation. After reading the respective pamphlet, participants again responded to thoughts about communicating with their family and willingness to communicate with family. RESULTS: Both groups responded with the same high willingness to communicate before the intervention and a small but significant increase in willingness to communicate afterwards. CONCLUSIONS: Participants expressed a high degree of willingness to communicate about their organ donation intentions even though they had thus far not communicated their intentions. Factors in addition to willingness to communicate need to be identified in order to encourage better communication about organ donation intentions.

Looking into anti-angiogenic gene therapies for disorders of the eye.

Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR) are the most common causes of visual impairment in the developed world. Because the key factor in AMD and DR is aberrant neovascularization in the retina (DR) or in the choroid (AMD), strategies to inhibit abnormal neovascularization represent a compelling therapeutic approach. Here we review various anti-angiogenic strategies for the treatment of ocular neovascular diseases with special emphasis on gene transfer as a way of achieving high, sustained concentrations of anti-angiogenic proteins in the back of the eye without concomitant systemic toxicity.