Genome-wide patterns of polymorphism in an inbred line of the African malaria mosquito Anopheles gambiae.

Anopheles gambiae is a major mosquito vector of malaria in Africa. Although increased use of insecticide-based vector control tools has decreased malaria transmission, elimination is likely to require novel genetic control strategies. It can be argued that the absence of an A. gambiae inbred line has slowed progress toward genetic vector control. In order to empower genetic studies and enable precise and reproducible experimentation, we set out to create an inbred line of this species. We found that amenability to inbreeding varied between populations of A. gambiae. After full-sib inbreeding for ten generations, we genotyped 112 individuals--56 saved prior to inbreeding and 56 collected after inbreeding--at a genome-wide panel of single nucleotide polymorphisms (SNPs). Although inbreeding dramatically reduced diversity across much of the genome, we discovered numerous, discrete genomic blocks that maintained high heterozygosity. For one large genomic region, we were able to definitively show that high diversity is due to the persistent polymorphism of a chromosomal inversion. Inbred lines in other eukaryotes often exhibit a qualitatively similar retention of polymorphism when typed at a small number of markers. Our whole-genome SNP data provide the first strong, empirical evidence supporting associative overdominance as the mechanism maintaining higher than expected diversity in inbred lines. Although creation of A. gambiae lines devoid of nearly all polymorphism may not be feasible, our results provide critical insights into how more fully isogenic lines can be created

Observed and Modeled Bio-Optical, Bioluminescent, and Physical Properties During a Coastal Upwelling Event in Monterey Bay, California

During spring and summer time, coastal upwelling influences circulation and ecosystem dynamics of the Monterey Bay, California, which is recognized as a National Marine Sanctuary. Observations of physical, bio‐optical properties (including bioluminescence) together with results from dynamical biochemical and bioluminescence models are used to interpret the development of the upwelling event during August 2003 in Monterey Bay, California. Observations and the biochemical model show the development of a phytoplankton bloom in the southern portion of Monterey Bay. Model results show an increase of nutrients in the southern portion of the bay, where nutrient‐rich water masses are brought in by the southward flow and cyclonic circulation inside the bay. This increase in nutrients together with the sluggish circulation in the southern portion of the bay provides favorable conditions for phytoplankton growth. Our observations and models suggest that with the development of upwelling the offshore water masses with the subsurface layer of bioluminescent zooplankton were replaced by water masses advected from the northern coast of the bay with a relatively high presence of mostly nonbioluminescent phytoplankton. Inshore observations from autonomous underwater vehicles (AUVs) show consistent coincidence of chlorophyll, backscatter, and bioluminescence maxima during upwellingdevelopment. Offshore AUV observations (taken at the entrance to the bay) show a deeper bioluminescence maximum below the surface layers of high chlorophyll and backscatter values during the earlier stages of upwelling development. Later, the observed deep offshore bioluminescence maximum disappeared and became a shallower and much weaker signal, coinciding with high chlorophyll and backscatter values offshore. Based on the biochemical and bioluminescence models, a methodology for estimating the nighttime water leaving radiance due to stimulated bioluminescence is demonstrated and evaluated

Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: A review of the National Cancer Database

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival

Can vertical migrations of dinoflagellates explain observed bioluminescence patterns during an upwelling event in Monterey Bay, California?

Extensive AUVs surveys showed that during the development of upwelling, bioluminescent dinoflagellates from the northern part of the Monterey Bay, California (called the upwelling shadow area), were able to avoid advection by southward flowing currents along the entrance to the Bay, while non-bioluminescent phytoplankton were advected by currents. It is known that vertical swimming of dinoflagellates to deeper layers helps them avoid losses due to advection. In the present paper, we investigate if modeling dinoflagellates’ vertical swimming can explain the observed dinoflagellates’ ability to avoid advection during the upwelling development. The dynamics of a dinoflagellate population is modeled with the tracer model with introduced vertical swimming velocity. Three swimming behaviors are considered: sinking, swimming to the target depth and diel vertical migration. Velocities in all swimming cases are considered in the ranges of documented velocities for the observed dinoflagellates species during the upwelling development in the Monterey Bay. Our modeling confirmed that observed bioluminescent dinoflagellates’ avoidance of advection during the upwelling development can be explained by their vertical swimming ability. In the case of swimming with 20 m/day (which is half of observed maximum swimming velocity), around 40% of dinoflagellates population from the northern part of the Bay were advected along the entrance to the Bay in comparison to the case without swimming. This is in agreement with the ratio of around 45% of observed mean bioluminescence intensity at the entrance to the Bay to the observed mean intensity in the northern part of the Bay. This mechanism also helps explain the general persistence of dinoflagellates in this part of the coastline

Linking Life Skills and Norms with adolescent substance use and delinquency in South Africa

We examined factors targeted in two popular prevention approaches with adolescent drug use and delinquency in South Africa. We hypothesized adolescent life skills to be inversely related, and perceived norms to be directly related to later drug use and delinquency. Multiple regression and a relative weights approach were conducted for each outcome using a sample of 714 South African adolescents ages 15 to 19 years (M = 15.8 years, 57% female). Perceived norms predicted gateway drug use. Conflict resolution skills (inversely) and perceived peer acceptability (directly) predicted harder drug use and delinquency. The “culture of violence” within some South African schools may make conflict resolution skills more salient for preventing harder drug use and delinquency.Department of HE and Training approved lis

Modeling the cost of bird strikes to US civil aircraft

The objective of our analysis is to develop a model of damage costs that arise from collisions between aircraft and birds, based on data drawn from the Federal Aviation Administration National Wildlife Strike Database (NWSD). We develop a two-part model, composed of two separate statistical models, that accounts for the effects of aircraft mass category, engine type, component of the aircraft struck, and the size and number of birds struck. Our results indicate the size of bird, number of birds, and engine ingestions are the largest determinants of strike-related costs. More generally, our result is a model that provides a better understanding of the determinants of damage costs and that can be used to interpolate the substantial amount of missing data on damage costs that currently exists within the NWSD. A more complete accounting of damage costs will allow a better understanding of how damage costs vary geographically and temporally and, thus, enable more efficient allocation of management resources across airports and seasons

Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.9b00063.Multiple sclerosis represents the world’s most common cause of neurological disability in young people and is attributed to a loss of immune tolerance toward proteins of the myelin sheath. Typical treatment options for MS patients involve immunomodulatory drugs, which act non-specifically, resulting in global immunosuppression. The study discussed herein aims to demonstrate the efficacy of antigen-specific immunotherapies involving conjugation of disease causing auto-antigen, PLP139–151, and a potent immunosuppressant, dexamethasone. Antigen-drug conjugates (AgDCs) were formed using copper-catalyzed azide-alkyne cycloaddition chemistry with the inclusion of a hydrolyzable linker to maintain activity of released dexamethasone. Subcutaneous administration of this antigen-drug conjugate to SJL mice induced with experimental autoimmune encephalomyelitis protected the mice from symptom onset throughout the 25-day study, demonstrating enhanced efficacy in comparison to dexamethasone treatment. These results highlight the benefits of co-delivery of auto-antigens with immunosuppressant drugs as AgDCs for the treatment of autoimmune diseases.National Institutes of Health Graduate Training Program in Dynamic Aspects of Chemical Biology Grant (T32 GM008545)Howard Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of KansasNational Institutes of Health Biotechnology Training Grant (NIH0073415)NIH Shared Instrumentation Grant # S10RR024664NSF Major Research Instrumentation Award # 162592

Acute versus delayed reverse total shoulder arthroplasty for proximal humerus fractures in the elderly: Mid-term outcomes

Background: Treatment of proximal humerus fractures (PHFs) via reverse total shoulder arthroplasty (RTSA) has shown early promise when compared to historical treatment modalities. Ideal surgical timing remains unclear. The purpose of this study was to compare the outcomes of early versus delayed RTSA for PHF. We hypothesized that acute RTSA would display superior outcomes compared to those receiving delayed surgical intervention. Methods: This multicenter study retrospectively analyzed 142 patients who underwent RTSA for fracture. Patients treated within 4 weeks of injury were placed in the acute group (n = 102), and patients treated longer than 4 weeks after injury were placed in the chronic group (n = 38). A comprehensive panel of patient reported outcome measures, VAS pain scores, range of motion, and patient satisfaction were evaluated. Results: The acute group had significantly better final follow-up SPADI scores (20.8 ± 23.9 vs. 30.7 ± 31.7) (p\u3c0.05). No further differences were detected in other postoperative range of motion measurements, subjective outcomes, or VAS scores. Conclusions: Our results suggest that patients treated acutely display similar mid-term outcomes to those who receive delayed treatment. With this in mind, surgeons may first give consideration to a period of nonoperative treatment. Level of evidence: Level II

Soil microbial communities in diverse agroecosystems exposed to the herbicide glyphosate

© 2020 American Society for Microbiology. Despite glyphosate\u27s wide use for weed control in agriculture, questions remain about the herbicide\u27s effect on soil microbial communities. The existing scientific literature contains conflicting results, from no observable effect of glyphosate to the enrichment of agricultural pathogens such as Fusarium spp. We conducted a comprehensive field-based study to compare the microbial communities on the roots of plants that received a foliar application of glyphosate to adjacent plants that did not. The 2-year study was conducted in Beltsville, MD, and Stoneville, MS, with corn and soybean crops grown in a variety of organic and conventional farming systems. By sequencing environmental metabarcode amplicons, the prokaryotic and fungal communities were described, along with chemical and physical properties of the soil. Sections of corn and soybean roots were plated to screen for the presence of plant pathogens. Geography, farming system, and season were significant factors determining the composition of fungal and prokaryotic communities. Plots treated with glyphosate did not differ from untreated plots in overall microbial community composition after controlling for other factors. We did not detect an effect of glyphosate treatment on the relative abundance of organisms such as Fusarium spp