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Although human fragmentation of freshwater habitats is ubiquitous, the genetic consequences of isolation and a roadmap to address them are poorly documented for most fishes. This is unfortunate, because translocation for genetic rescue could help mitigate problems. We used genetic data (32 SNPs) from 203 populations of westslope cutthroat trout (Oncorhynchus clarkii lewisi) to (1) document the effect of fragmentation on genetic variation and population structure, (2) identify candidate populations for genetic rescue, and (3) quantify the potential benefits of strategic translocation efforts. Human-isolated populations had substantially lower genetic variation and elevated genetic differentiation, indicating that many populations are strongly influenced by random genetic drift. Based on simple criteria, 23 populations were candidates for genetic rescue, which represented a majority (51%) of suitable populations in one major region (Missouri drainage). Population genetic theory suggests that translocation of a small number of individuals (∼5 adults) from nearby populations could dramatically increase heterozygosity by up to 58% (average across populations). This effort provides a clear template for future conservation of westslope cutthroat trout, while simultaneously highlighting the potential need for similar efforts in many freshwater species.

Background/Objectives: Remote assessment of children’s visual acuity became necessary during the COVID19 pandemic. We aimed to assess the extent of agreement between hospital-based clinical testing and clinician-led home-based testing.Subjects/Methods: 50 children aged 2–16 years attending hospital eye services at two UK hospitals had routine hospital-based acuities compared with subsequent online, orthoptist-supervised home visual acuities. Agreement was assessed using Bland-Altman plots, as was test-retest (TRT) agreement of two, repeated home acuity tests.Results: Monocular acuities tested at hospital and at home were obtained from all 50 children; 33 also had binocular acuities in both settings and 35 had acuities retested immediately at home. Most children were tested at home using a computer or tablet: two were tested with a smartphone. No mean test differences were found for hospital vs home testing, and limits of agreement (LOAs) were ± 0.32 and ± 0.35 logMAR for binocular and monocular testing respectively. LOAs for inter-ocular acuity differences were -0.15–0.25 logMAR. TRT agreement was excellent, with LOA of ± 0.14 logMAR.Conclusions: We found excellent agreement between hospital and home acuity testing. LOAs were in keeping with multiple changes between measures (test; setting; time; tester) and a cohort including patients as young as two years old. Even smartphone testing proved feasible. Inability of the supervising orthoptist to check test distance or device calibration/orientation were limitations likely contributing to breadth of LOAs. Home vision testing is feasible and accurate, but its precision, acceptability, health economic impact and carbon impact require more attention.

Telemedicine is introducing new paradigms in the delivery of ophthalmology services. This work will explore the Scottish experience in delivering remote live decision support and remote visual assessment.

Background: The Covid-19 pandemic necessitated social distancing restrictions, which placed limitations on access to ophthalmic care to only those who had an imminent risk of sight loss. All other face-to-face consultations were converted to telephone consultations or were postponed. We investigated whether parents were able to test their child’s vision using available home vision testing applications, with an aim to aid decision making during a telephone consultation. Methods: Families with follow-up consultations at Birmingham Children’s Hospital were asked to test their child’s vision at home. Instructions for the use of Peek acuity, or iSight Pro, were emailed to a parent. Parents chose to use a particular app based on available devices at home. Parents were asked to test uniocular visual acuity twice. Home versus hospital acuity was correlated. Home acuity test-retest reliability was acquired. Parental feedback was obtained through questionnaires. Results: One hundred and three families were contacted, 15 families completed home vision testing. Ten families used Peek acuity, five families used iSight Pro. Uniocular visual acuity test-retest reliability was 0.03 LogMAR. Home-hospital acuity testing had a bias of 0.14 LogMAR, hospital acuity yielding a lower LogMAR score. Most families who completed testing found it easy to do; however, some struggled, and 81 families did not undertake home vision testing. Conclusions: Uptake of home vision testing was limited by parental engagement, most likely influenced by the current pandemic. Most families who undertook home vision testing were able to generate results that could be used for clinical decision making. Extending the impact of parental vision testing will require education by clinicians and further study to increase sample sizes and to improve confidence.

The number of effective breeders (Nb) has been touted as a means to monitor freshwater fishes, but the realized application of Nbhas been limited. Using genetic monitoring data for two Arctic grayling (Thymallus arcticus) populations of conservation concern, we describe temporal trends in genetic variation and Nb, determine how sampling and variance in reproductive success influence estimates of Nb, and quantify the relationship among Nb, effective population size (Ne), and adult abundance (Nc). Temporal trends in allelic richness (AR) and Nbtracked known or suspected population trajectories. Nbincreased in one population where there has been extensive conservation action, and both Nband ARtracked a decline in the other population where harsh winter conditions have resulted in overwinter mortality events. After accounting for population demography, Neestimates for each population were 190.7 and 308.8. Overall, this study demonstrates that temporal genetic data effectively resolve demographic and evolutionary status and trend in Arctic grayling, provides insight into the demographic factors that influence genetic variation, and emphasizes the value of temporal genetic data for conservation and management.

AimTo report disability and visual outcomes following suspected abusive head trauma (AHT) in children under 2 years.MethodsWe present a retrospective case series (1995–2017) of children with suspected AHT aged ≤24 months. King’s Outcome Score of Childhood Head Injury (KOSCHI) was used to assess disability outcomes at hospital discharge and at follow-up. The study used a retinal haemorrhage score (RHS) to record findings at presentation and a visual outcome score at follow-up.ResultsWe included 44 children (median age 16 weeks). At presentation, 98% had a subdural haemorrhage and 93% had a retinal haemorrhage. At discharge, 61% had moderate-to-severe disability, and 34% a good recovery. A higher RHS was observed in those with more disability (r=−0.54, p=0.0002). At follow-up, 14% had a worse KOSCHI score (p=0.055). 35% children had visual impairment, including 9% with no functional vision. Those with poorer visual function had a higher RHS (r=0.53, p=0.003). 28% attended mainstream school without support; 50% were in foster care or had been adopted, 32% lived with birth mother and 18% with extended family.ConclusionIt is known that injuries from suspected AHT result in high levels of morbidity; our cohort showed significant rates of disability and visual impairment. Those with higher disability at discharge and poorer visual function showed more significant retinal changes. The extent of disability was not always apparent at hospital discharge, impacting on provision of prognostic information and targeted follow-up.

Released hatchery-origin fish must survive and reproduce for supplementation to recover collapsed native populations, yet monitoring fitness is challenging, because physical tags are not passed from parent to offspring. Parentage-based tagging (PBT) is a method in which all captive-bred parents are genotyped (i.e., given a molecular tag), and their wild-caught hatchery offspring are identified via genetic pedigree analysis. The sauger (Sander canadensis) is a highly migratory, freshwater percid (perch species), native to central and eastern North America. In the Wind River basin, Wyoming the species’ abundance has declined considerably since 2002, and in 2013 stakeholders initiated a hatchery program to recover the population. We estimated the statistical sensitivity and accuracy of PBT using 17 microsatellites to identify hatchery-origin saugers captured in the wild. We completed in vitro and in silico experiments that demonstrated 98% sensitivity and 99% accuracy of PBT in distinguishing hatcher...

BackgroundThe travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, pConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.

​Background The clinical severity of disease in neurofibromatosis type 2 (NF2) is variable. Patients affected with a constitutional truncating NF2 mutation have severe disease, while missense mutations or mosaic mutations present with a milder attenuated phenotype. Genotype-derived natural history data are important to inform discussions on prognosis and management. Methods We have assessed NF2 clinical phenotype in 142 patients in relation to the UK NF2 Genetic Severity Score to validate its use as a clinical and research tool. Results The Genetic Severity Score showed significant correlations across 10 measures, including mean age at diagnosis, proportion of patients with bilateral vestibular schwannomas, presence of intracranial meningioma, spinal meningioma and spinal schwannoma, NF2 eye features, hearing grade, age at first radiotherapy, age at first surgery and age starting bevacizumab. In addition there was moderate but significant correlation with age at loss of useful hearing, and weak but significant correlations for mean age at death, quality of life, last optimum Speech Discrimination Score and total number of major interventions. Patients with severe disease presented at a younger age had a higher disease burden and greater requirement of intervention than patients with mild and moderate disease. Conclusions This study validates the UK NF2 Genetic Severity Score to stratify patients with NF2 for both clinical use and natural history studies.

Investigation of the genetic population structure of Bull Trout Salvelinus confluentus is useful for developing biologically sound conservation and management strategies. We focused on the East Fork Bitterroot River (hereafter, East Fork), Montana, because it is a relatively undisturbed, connected watershed that contains a migratory life history form of Bull Trout. Fin clips were collected from 17 sites: nine East Fork tributaries, the main-stem East Fork, and seven other tributaries across the Bitterroot River drainage. Considering all the population samples, principal components analysis of allele frequencies at 15 microsatellite loci indicated that the East Fork samples formed a cluster that was distinct from the other Bitterroot River tributary samples. Within the East Fork, there was significant divergence among population samples, with pairwise FST ranging from 0.016 to 0.188 and a global FST of 0.063. Relative to other Bull Trout studies, levels of genetic variation within our samples were...

Hybridization with introduced rainbow trout threatens most native westslope cutthroat trout populations. Understanding the genetic effects of hybridization and introgression requires a large set of high-throughput, diagnostic genetic markers to inform conservation and management. Recently, we identified several thousand candidate single-nucleotide polymorphism (SNP) markers based on RAD sequencing of 11 westslope cutthroat trout and 13 rainbow trout individuals. Here, we used flanking sequence for 56 of these candidate SNP markers to design high-throughput genotyping assays. We validated the assays on a total of 92 individuals from 22 populations and seven hatchery strains. Forty-six assays (82%) amplified consistently and allowed easy identification of westslope cutthroat and rainbow trout alleles as well as heterozygote controls. The 46 SNPs will provide high power for early detection of population admixture and improved identification of hybrid and nonhybridized individuals. This technique shows promise as a very low-cost, reliable and relatively rapid method for developing and testing SNP markers for nonmodel organisms with limited genomic resources.

We analyzed 11 microsatellite loci to determine the genetic population structure of saugers and to describe the amount and pattern of hybridization with widely introduced walleyes in the upper Missouri River drainage. We detected significant genetic differentiation among saugers spawning upstream and downstream of the confluence of the Bighorn and Yellowstone Rivers. Samples from upstream of the confluence had significantly lower heterozygosity and allelic richness. We suspect this reflects isolation at the periphery of the species’ range and possibly genetic drift resulting from recent population contractions due to dams, diversions, and water development. We detected only eighteen hybrids out of 925 individuals analyzed. Hybridization appeared recent, as nearly 50% of the hybrids showed significant evidence for having a non-hybrid ancestor within two generations. All but one hybrid were detected in the Yellowstone River drainage, despite a substantially higher rate of walleye stocking in the Missouri River drainage, suggesting conditions in the Yellowstone may be more conducive to hybridization. Rarity of hybridization is unexpected, given both massive walleye releases and previous findings of more frequent hybridization in the study area. Introgression of walleye genes into native saugers does not appear to be an immediate threat.

Acta Ophthalmol. 2010: 88: 786–790 Abstract. Purpose: Endophthalmitis is a rare but sight-threatening complication of intraocular surgery. β-Defensins are antimicrobial peptides that appear to be important components of the ocular immune response. We propose that variation in defensin genes may alter susceptibility to endophthalmitis. Methods: Post-cataract endophthalmitis patients (n = 28) and post-cataract controls (n = 75) were recruited and DNA samples extracted. The β-defensin 1 gene (DEFB1) was screened for single-nucleotide polymorphisms (SNPs) using bidirectional sequencing. Case–control statistical assessment was undertaken for both the individual polymorphic loci observed and combined haplotypes using PHASE software. Results: We identified 19 SNPs and observed strong linkage disequilibrium within the gene. We found that the three-SNP haplotype −688C/−44C/−20A was associated strongly with endophthalmitis [odds ratio (OR) = 8.88 (1.74, 45.42), corrected p = 0.0095]. Furthermore, we uncovered several trends, including increased prevalence of the −44CC genotype in the endophthalmitis group. Conclusion: We have shown previously that the −44CC SNP genotype was present in a single case of bilateral endophthalmitis. In this study, we found this genotype to be more common in the endophthalmitis group and a mini-haplotype including this SNP was associated strongly with endophthalmitis. There is functional evidence that this genetic profile decreases transcription of the β-defensin 1 peptide and could therefore reduce the innate ocular immune defence.

Human-mediated hybridization is a leading cause of biodiversity loss worldwide. How hybridization affects fitness and what level of hybridization is permissible pose difficult conservation questions with little empirical information to guide policy and management decisions. This is particularly true for salmonids, where widespread introgression among non-native and native taxa has often created hybrid swarms over extensive geographical areas resulting in genomic extinction. Here, we used parentage analysis with multilocus microsatellite markers to measure how varying levels of genetic introgression with non-native rainbow trout (Oncorhynchus mykiss) affect reproductive success (number of offspring per adult) of native westslope cutthroat trout (Oncorhynchus clarkii lewisi) in the wild. Small amounts of hybridization markedly reduced fitness of male and female trout, with reproductive success sharply declining by approximately 50 per cent, with only 20 per cent admixture. Despite apparent fitness costs, our data suggest that hybridization may spread due to relatively high reproductive success of first-generation hybrids and high reproductive success of a few males with high levels of admixture. This outbreeding depression suggests that even low levels of admixture may have negative effects on fitness in the wild and that policies protecting hybridized populations may need reconsideration.

Women infected with clade A human immunodeficiency virus type 1 harbor a virus population that is genetically diverse in the envelope gene, a fact that contrasts with the homogeneous virus population identified in newly infected men. It is not known whether viral genetic diversity at this early stage of infection is manifested as phenotypic diversity. This is a significant question because phenotypic diversity in the viral population that establishes infection in women may have important implications for pathogenesis and therapeutic intervention. Thus, in this study we compared the biological properties of three pairs of chimeric viruses that contained envelope genes representative of variant groups in each of three infected women—Q23, Q45, and Q47. Envelope chimeras were evaluated for replication in stimulated and resting peripheral blood mononuclear cells alone and in competition, for coreceptor use, and for neutralization sensitivity. All viruses utilized CCR5 exclusively and had a non-syncytium-inducing phenotype on MT-2 cells and in primary culture. There were no significant differences in replication parameters between paired variants in individual cultures. However, in competition experiments, one chimera of each variant pair always dominated. The dominant virus from Q23 and Q47, but not from Q45, infected a significantly higher number of CCR5- and CD4-expressing GHOST cells than the weaker chimeras. Significantly, chimeric viruses from Q47 and Q45 showed markedly different neutralization sensitivity to antibodies to CCR5 and gp120, respectively. These data indicate that distinct envelope genotypes identified in clade A-infected women near seroconversion confer unique phenotypes that affect viral fitness and that may be due, in part, to different requirements for relative configuration of CD4 and CCR5 on infected cells.

Factors that restrict a virus from establishing productive infection in a new host species are important to understand because cross-species transmission events are often associated with emergent viral diseases. To determine the evolutionary pressures on viruses in new host species, we evaluated the molecular evolution of a feline immunodeficiency virus derived from a wild cougar, Puma concolor , during infection of domestic cats. Analyses were based on the coding portion of genome sequences recovered at intervals over 37 weeks of infection of six cats inoculated by either intravenous or oral-nasal routes. All cats inoculated intravenously, but only one inoculated orally-nasally, became persistently viremic. There were notable accumulations of lethal errors and predominance of G-to-A alterations throughout the genome, which were marked in the viral polymerase gene, pol . Viral structural ( env and gag ) and accessory ( vif and orfA ) genes evolved neutrally or were under purifying selection. However, sites under positive selection were identified in reverse transcriptase that involved residues in the nucleotide binding pocket or those contacting the RNA-DNA duplex. The findings of extensive G-to-A alterations in this cross-species infection are consistent with the recently described editing of host cytidine deaminase on lentivirus genomes. Additionally, we demonstrate that the primary site of hypermutation is the viral pol gene and the dominant selective force acting on this feline immunodeficiency virus as it replicates in a new host species is on key residues of the virus polymerase.

KIE: Many scientific societies have begun to re-examine their standards of conduct and procedures for investigating alleged misconduct by members in light of recent litigation involving professional codes of ethics and an increase in reported incidences of misconduct by academic researchers. Painter summarizes a Spring 1984 meeting of the American Association for the Advancement of Science Professional Ethics Group, at which speakers outlined general guidelines for revising professional codes and for investigating complaints against members. Among the issues discussed were confidentiality, institutional obligations to inform third parties of investigations, due process requirements, professional liability insurance, and professional duties to the public.