Community-wide correlations between species richness, abundance and population genomic diversity in a freshwater biodiversity hotspot.

Understanding patterns of diversity across macro (e.g. species-level) and micro (e.g. molecular-level) scales can shed light on community function and stability by elucidating the abiotic and biotic drivers of diversity within ecological communities. We examined the relationships among taxonomic and genetic metrics of diversity in freshwater mussels (Bivalvia: Unionidae), an ecologically important and species-rich group in the southeastern United States. Using quantitative community surveys and reduced-representation genome sequencing across 22 sites in seven rivers and two river basins, we surveyed 68 mussel species and sequenced 23 of these species to characterize intrapopulation genetic variation. We tested for the presence of species diversity-abundance correlations (i.e. the more-individuals hypothesis, MIH), species-genetic diversity correlations (SGDCs) and abundance-genetic diversity correlations (AGDCs) across all sites to evaluate relationships between different metrics of diversity. Sites with greater cumulative multispecies density (a standardized metric of abundance) had a greater number of species, consistent with the MIH hypothesis. Intrapopulation genetic diversity was strongly associated with the density of most species, indicating the presence of AGDCs. However, there was no consistent evidence for SGDCs. Although sites with greater overall densities of mussels had greater species richness, sites with higher genetic diversity did not always exhibit positive correlations with species richness, suggesting that there are spatial and evolutionary scales at which the processes influencing community-level diversity and intraspecific diversity differ. Our work reveals the importance of local abundance as indicator (and possibly a driver) of intrapopulation genetic diversity.

Identifying potential drivers of distribution patterns of invasive Corbicula fluminea relative to native freshwater mussels (Unionidae) across spatial scales.

This study aimed to identify the importance of ecological factors to distribution patterns of the invasive Clam (Corbicula fluminea) relative to native mussels (family: Unionidae) across seven rivers within the Mobile and Tennessee basins, Southeast United States. We quantitatively surveyed dense, diverse native mussel aggregations across 20 river reaches and estimated mussel density, biomass, and species richness along with density of invasive C. fluminea (hereafter Corbicula). We measured substrate particle size, velocity, and depth in quadrats where animals were collected. Additionally, we characterized reach scale environmental parameters including seston quantity and quality (% Carbon, % Nitrogen, % Phosphorous), water chemistry (ammonium [ NH 4 + ], soluble reactive phosphorous [SRP]), and watershed area and land cover. Using model selection, logistic regression, and multivariate analysis, we characterized habitat features and their association to invasive Corbicula within mussel beds. We found that Corbicula were more likely to occur and more abundant in quadrats with greater mussel biomass, larger substrate size, faster water velocity, and shallower water depth. At the reach scale, Corbicula densities increased where particle sizes were larger. Mussel richness, density, and biomass increased with watershed area. Water column NH 4 + increased at reaches with more urban land cover. No land cover variables influenced Corbicula populations or mussel communities. The strong overlapping distribution of Corbicula and mussels support the hypothesis that Corbicula are not necessarily limited by habitat factors and may be passengers of change in rivers where mussels have declined due to habitat degradation. Whether Corbicula is facilitated by mussels or negatively interacts with mussels in these systems remains to be seen. Focused experiments that manipulate patch scale variables would improve our understanding of the role of species interactions (e.g., competition, predation, facilitation) or physical habitat factors in influencing spatial overlap between Corbicula and native mussels.

The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

Diurnal stability of cell-free DNA and cell-free RNA in human plasma samples.

Many emerging technologies are reliant on circulating cell-free DNA (cfDNA) and cell-free RNA (cfRNA) applications in the clinic. However, the impact of diurnal cycles or daily meals on circulating analytes are poorly understood and may be confounding factors when developing diagnostic platforms. To begin addressing this knowledge gap, we obtained plasma from four healthy donors serially sampled five times during 12 h in a single day. For all samples, we measured concentrations of cfDNA and cfRNA using both bulk measurements and gene-specific digital droplet PCR. We found no significant variation attributed to blood draw number for the cfDNA or cfRNA. This indicated that natural diurnal cycles and meal consumption do not appear to significantly affect abundance of total cfDNA, total cfRNA, or our two selected cfRNA transcripts. Conversely, we observed significant variation between individual donors for cfDNA and one of the cfRNA transcripts. The results of this work suggest that it will be important to consider patient-specific baselines when designing reliable circulating cfDNA or cfRNA clinical assays.

Circulating tumor DNA dynamics using patient-customized assays are associated with outcome in neoadjuvantly treated breast cancer.

Pathological complete response (pCR) is an accurate predictor of good outcome following neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. The presence of circulating-tumor DNA (ctDNA) has recently been reported to be strongly predictive of poor outcome in similar patient groups. We monitored ctDNA levels from 10 women undergoing NAC for locally advanced breast cancer using a patient-specific, hybrid-capture sequencing technique sensitive to the level of one altered allele in 10,000. Plasma was collected prior to the start of NAC, prior to each infusion of NAC, and during follow-up for between 350 and 1150 d after the start of NAC. Prior to the start of NAC, ctDNA was detectable in 3/3 triple negative, 3/3 HER2+, and 2/4 HER2-, ER+ breast cancer patients. Total cell-free DNA levels were considerably higher when patients were on NAC than at other times. ctDNA dynamics during NAC showed that patients with pCR experienced rapid declines in ctDNA levels, whereas patients without pCR typically showed evidence of residual ctDNA after initiation of treatment. Intriguingly, two of three patients that showed marked increases in ctDNA while on NAC experienced rapid recurrences (<2 yr following start of NAC). The third patient that had increases in ctDNA levels while on NAC had low-grade ER+ disease and showed residual ctDNA after surgery, which became undetectable after local radiation. Taken together, these results demonstrate the ability of our approach to sensitively serially monitor ctDNA during NAC, and identifies a need to further investigate the possibility of stratifying patients who need additional treatment or identify therapies that are ineffective.

Factors and barriers influencing influenza vaccination among students at Brigham Young University.

BACKGROUND: To identify the prevalence of influenza vaccination and factors associated with vaccination among students at Brigham Young University. MATERIAL/METHODS: A Cross-sectional survey of seven general education classes, size 30 to 200 students each, was conducted the week of November 25, 2007. A 34 item paper-pencil questionnaire was administered, taking 5-10 minutes to complete. The response rate was 90%, with 421 completed surveys. RESULTS: Prevalence of influenza vaccination was 12% in the current influenza season. Influenza vaccination was significantly influenced by place of work, frequency of being around children, place of residence, and selected area of academic study. Students that received the influenza vaccination were more motivated by perceived severity of influenza than by perceived risk of contracting the illness. Physicians or nurses were the most influential at encouraging influenza vaccination, followed by parents, then the university or student health center, and then the media. The percentage of students that received influenza vaccination information from physicians or nurses was 14%, from parents was 15%, from the student health center was 25%, and from the general media was 45%. CONCLUSIONS: Influenza vaccination is low among college students, but impacted by perceived severity of the illness, place of employment or residence, and who encourages influenza vaccination.