Data from: Noninvasive sampling reveals short-term genetic rescue in an insular red fox population

Genetic factors in the decline of small populations are extremely difficult to study in nature. We leveraged a natural experiment to investigate evidence of inbreeding depression and genetic rescue in a remnant population of subalpine-specialized Sierra Nevada red foxes (Vulpes vulpes necator) using noninvasive genetic monitoring during 2010–2017. Only 7 individuals were detected in the first 2 years. These individuals assigned genetically to the historical population and exhibited genetic hallmarks of inbreeding and no evidence of reproduction. Two years into the study, we detected 2 first-generation immigrant males from a recently expanding population of red foxes in the Great Basin Desert. Through annual resampling of individuals (634 red fox DNA samples, 41 individuals) and molecular reconstruction of pedigrees, we documented 1–3 litters/yr for 5 years, all descended directly or indirectly from matings involving immigrant foxes. The observed heterozygosity and allelic richness of the population nearly doubled in 2 years. Abundance increased, indicative of a rapidly expanding population. Throughout the study, adult survival was high. Restoration of gene flow apparently improved the demographic trajectory of this population in the short term. Whether these benefits continue in the longer-term could depend on numerous factors, such as maintenance of any locally adapted alleles. This study highlights the value of noninvasive genetic monitoring to assess rapidly shifting conditions in small populations. Uncertainties about the longer-term trajectory of this population underscore the need to continue monitoring and to research potential for both negative and positive aspects of continued genetic infusion

Contrasting genetic trajectories of endangered and expanding red fox populations in the western U.S.

As anthropogenic disturbances continue to drive habitat loss and range contractions, the maintenance of evolutionary processes will increasingly require targeting measures to the population level, even for common and widespread species. Doing so requires detailed knowledge of population genetic structure, both to identify populations of conservation need and value, as well as to evaluate suitability of potential donor populations. We conducted a range-wide analysis of the genetic structure of red foxes in the contiguous western U.S., including a federally endangered distinct population segment of the Sierra Nevada subspecies, with the objectives of contextualizing field observations of relative scarcity in the Pacific mountains and increasing abundance in the cold desert basins of the Intermountain West. Using 31 autosomal microsatellites, along with mitochondrial and Y-chromosome markers, we found that populations of the Pacific mountains were isolated from one another and genetically depauperate (e.g., estimated Ne range = 3-9). In contrast, red foxes in the Intermountain regions showed relatively high connectivity and genetic diversity. Although most Intermountain red foxes carried indigenous western matrilines (78%) and patrilines (85%), the presence of nonindigenous haplotypes at lower elevations indicated admixture with fur-farm foxes and possibly expanding midcontinent populations as well. Our findings suggest that some Pacific mountain populations could likely benefit from increased connectivity (i.e., genetic rescue) but that nonnative admixture makes expanding populations in the Intermountain basins a non-ideal source. However, our results also suggest contact between Pacific mountain and Intermountain basin populations is likely to increase regardless, warranting consideration of risks and benefits of proactive measures to mitigate against unwanted effects of Intermountain gene flow

Nonlinear Optics

This chapter provides a brief introduction into the basic nonlinear-optical phenomena and discusses some of the most significant recent advances and breakthroughs in nonlinear optics, as well as novel applications of nonlinear-optical processes and devices. Nonlinear optics is the area of optics that studies the interaction of light with matter in the regime where the response of the material system to the applied electromagnetic field is nonlinear in the amplitude of this field. At low light intensities, typical of non-laser sources, the properties of materials remain independent of the intensity of illumination. The superposition principle holds true in this regime, and light waves can pass through materials or be reflected from boundaries and interfaces without interacting with each other. Laser sources, on the other hand, can provide sufficiently high light intensities to modify the optical properties of materials. Light waves can then interact with each other, exchanging momentum and energy, and the superposition principle is no longer valid. This interaction of light waves can result in the generation of optical fields at new frequencies, including optical harmonics of incident radiation or sum- or difference-frequency signals

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee