Patterns of overlapping habitat use of juvenile white shark and human recreational water users along southern California beaches.

Juvenile white sharks (JWS) of the Northeastern Pacific population are present in nearshore southern California waters and form mixed size class (~1.5-3 m) aggregations for weeks to months, often within 500 m of shore. These nearshore beach habitats are heavily used for human recreation (e.g., surfing, swimming, body boarding, wading, and standup paddleboarding) and the amount of spatio-temporal overlap between JWS and humans is currently unknown. Increases in human population and the Northeastern Pacific population of white sharks have raised concern over human beach safety. To determine spatio-temporal JWS-human overlap at various spatial scales (e.g., across the entire southern California coastline, across different distances from shore, and within specific beach locations), 26 beach locations across southern California were surveyed monthly resulting in 1644 aerial drone surveys between January 2019 to March 2021. Thirteen environmental variables were assessed to predict when spatio-temporal overlap between JWS and water users was highest. Coast-wide distribution of JWS was clumped, limiting human-shark co-occurrence to specific locations, with 1096 of 1204 JWS observations occurring at Carpinteria and Del Mar Beach locations. Nearshore distribution indicated JWS are often close enough to the wave break to interact with some water users (median = 101 m, range = 2-702 m), although JWS had the most spatial overlap with stand-up paddlers. Daily human-shark co-occurrence was 97% at beaches where JWS aggregations had formed, and human activity showed high spatial overlap at shark aggregation sites. Although there is higher seasonal human-shark spatio-temporal overlap where aggregations form in southern California, the number of unprovoked shark bites across southern California is extremely low. This study provides evidence that high human-shark spatio-temporal overlap does not lead to an increased bite frequency in southern California, and there are a number of possible explanations as to why JWS are not biting water users despite daily encounters.

Diverging patterns at the forest edge: Soil respiration dynamics of fragmented forests in urban and rural areas.

As urbanization and forest fragmentation increase around the globe, it is critical to understand how rates of respiration and carbon losses from soil carbon pools are affected by these processes. This study characterizes soils in fragmented forests along an urban to rural gradient, evaluating the sensitivity of soil respiration to changes in soil temperature and moisture near the forest edge. While previous studies found elevated rates of soil respiration at temperate forest edges in rural areas compared to the forest interior, we find that soil respiration is suppressed at the forest edge in urban areas. At urban sites, respiration rates are 25% lower at the forest edge relative to the interior, likely due to high temperature and aridity conditions near urban edges. While rural soils continue to respire with increasing temperatures, urban soil respiration rates asymptote as temperatures climb and soils dry. Soil temperature- and moisture-sensitivity modeling shows that respiration rates in urban soils are less sensitive to rising temperatures than those in rural soils. Scaling these results to Massachusetts (MA), which encompasses 0.25 Mha of the urban forest, we find that failure to account for decreases in soil respiration rates near urban forest edges leads to an overestimate of growing-season soil carbon fluxes of >350,000 Mg C. This difference is almost 2.5 times that for rural soils in the analogous comparison (underestimate of <143,000 Mg C), even though rural forest area is more than four times greater than urban forest area in MA. While a changing climate may stimulate carbon losses from rural forest edge soils, urban forests may experience enhanced soil carbon sequestration near the forest edge. These findings highlight the need to capture the effects of forest fragmentation and land use context when making projections about soil behavior and carbon cycling in a warming and increasingly urbanized world.

Rewilding the small stuff: the effect of ecological restoration on prokaryotic communities of peatland soils.

To investigate the effect that restoration has on the microbiome of wetland soils, we used 16S amplicon sequencing to characterize the soil prokaryotic communities of retired cranberry farms that were restored to approximate the peat wetlands they once were. For comparison, we also surveyed the soil communities of active cranberry farms, retired cranberry farms and natural peat wetlands that were never farmed. Our results show that the prokaryotic communities of active cranberry farms are distinct from those of natural peat wetlands. Moreover, 4 years after restoration, the prokaryotic community structure of restored cranberry farms had shifted, resulting in a community more similar to natural peat wetlands than to active farms. Meanwhile, the prokaryotic communities of retired cranberry farms remained similar to those of active farms. The observed differences in community structure across site types corresponded with significant differences in inferred capacity for denitrification, methanotrophy and methanogenesis, and community composition was also correlated with previously published patterns of denitrification and carbon sequestration measured from the same soil samples. Taken together, these results suggest that ecological restoration efforts have the potential to restore ecosystem functions of soils and that they do so by 'rewilding' the communities of resident soil microbes.

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors.

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

Assessing a single targeted next generation sequencing for human leukocyte antigen typing protocol for interoperability, as performed by users with variable experience.

BACKGROUND: A simplified protocol for HLA-typing -by NGS, developed for use with the Illumina MiSeq, was performed by technologists with varying NGS experience to assess accuracy and reproducibility. METHODS: Technologists from six laboratories typed the same 16 samples at HLA-A, B, C, DRB1, and DQB1. The protocol includes long range PCR, library preparation, and paired-end 250bp sequencing. Two indexing strategies were employed: locus-specific indexing whereby each locus was tagged uniquely and sample-specific indexing whereby all 5 loci for a sample were pooled prior to library preparation. Sequence analysis was performed with two software packages, Target HLA (Omixon) and NGSengine (GenDx). RESULTS: The average number of sequence reads per library was 387,813; however, analysis was limited to 40,000 reads for locus-indexed libraries and 200,000 reads for sample-indexed libraries resulting in an average depth of coverage of 1444 reads per locus. Sufficient reads for genotype analysis were obtained for 98.4% of libraries. Genotype accuracy was >97% in pooled amplicons and >99% in individual amplicons by both software analysis. Inter-laboratory reproducibility was 99.7% and only cause of discordance was cross-contamination of a single amplicon. CONCLUSIONS: This NGS HLA-typing protocol is simple, reproducible, scalable, highly accurate and amenable to clinical testing.

Experience with antibody-mediated rejection in kidney allograft recipients.

In our case series, AMR occurred in patients who had DSA. Twelve of the 21 patients (57%) who developed de novo antibodies post-transplant had biopsy-proven episodes of either rejection (of any Banff classification) and/or chronic allograft nephropathy. Only one-third of these 12 patients with rejection episodes were classified as AMR. It is unclear when and how often measurements for DSA should be performed after transplantation. When AMR is suspected, the detection of anti-HLA antibodies should be done using very sensitive assays. An increase in PRA and/or the detection of anti-HLA antibodies specific to previous sensitization events may precede an episode of AMR, even in the absence of DSA. Prospective clinical trials are needed to assess the predictive value of the presence of DSA after transplant. It is uncertain which therapeutic response should follow after the detection of these antibody responses in the absence of clinical symptoms. AMR requires intensive therapy, but no standard treatment has been established. Three patients who had AMR at our center were treated with rituximab in addition to various combinations of plasmapheresis, methylprednisolone, OKT3, and intravenous immune globulin. Only one patient responded to this treatment. Well-controlled clinical trials would help to evaluate the efficacy and benefit of B-cell depletion in combination with other immunosuppressive agents.