Glaucoma Agreement in New Zealand (GAINZ).

CLINICAL RELEVANCE: With an ageing population, ophthalmologists are becoming burdened with glaucoma management, and patient care can be delayed. Therefore, the use of optometrists in glaucoma management can help alleviate the burden. BACKGROUND: The ageing population and subsequent rise of glaucoma prevalence are putting a strain on the public health system in New Zealand. Glaucoma collaborative care between optometrists and ophthalmologists has been gaining support with the aim to reduce this burden on ophthalmologists. There has been little investigation of the agreement in care and management of mild-to-moderate severity glaucoma patients by optometrists and ophthalmologists. METHODS: One hundred and three glaucomatous eyes were used in a survey where clinical history and examination, intraocular pressures (IOPs), visual field testing and optical coherence tomography (OCT) imaging were evaluated for glaucoma progression and decision-making regarding subsequent management by four participants. Two participants were glaucoma-credentialled optometrists (Group 1), and the other two were glaucoma specialists (Group 2). RESULTS: With respect to glaucoma progression, Spearman coefficients identified strong agreement between the two groups for IOP, visual fields and overall status and moderate agreement for OCT imaging. A confusion matrix was used to analyse management and found 80% ± 10% agreement between the two groups. Review periods gave an agreement of 55% ± 20% between the two groups. CONCLUSION: There was strong agreement in the assessment of glaucoma progression between the two groups. The 80% level of agreement for subsequent management between the two groups is comparable to other published reports. These results provide some reassurance that a collaborative care system can perform safely and as intended.

The Pelagic Species Trait Database, an open data resource to support trait-based ocean research.

Trait-based frameworks are increasingly used for predicting how ecological communities respond to ongoing global change. As species range shifts result in novel encounters between predators and prey, identifying prey 'guilds', based on a suite of shared traits, can distill complex species interactions, and aid in predicting food web dynamics. To support advances in trait-based research in open-ocean systems, we present the Pelagic Species Trait Database, an extensive resource documenting functional traits of 529 pelagic fish and invertebrate species in a single, open-source repository. We synthesized literature sources and online resources, conducted morphometric analysis of species images, as well as laboratory analyses of trawl-captured specimens to collate traits describing 1) habitat use and behavior, 2) morphology, 3) nutritional quality, and 4) population status information. Species in the dataset primarily inhabit the California Current system and broader NE Pacific Ocean, but also includes pelagic species known to be consumed by top ocean predators from other ocean basins. The aim of this dataset is to enhance the use of trait-based approaches in marine ecosystems and for predator populations worldwide.

Treatment of ocular-involving monkeypox virus with topical trifluridine and oral tecovirimat in the 2022 monkeypox virus outbreak.

Purpose: To report a case of ocular involving monkeypox infection in the United States during the 2022 outbreak, and to review the literature regarding its clinical manifestations and management known to date. Observations: A 36-year-old man with well controlled HIV presented to the emergency department with anal pain, diffuse rash, right eye pain, and right eye redness after he tested positive for monkeypox one week prior. Ocular examination showed bilateral periorbital vesicular lesions, right eye conjunctival injection, and a single white plaque on his right medial bulbar conjunctiva. Macular, vesicular, and pustular lesions were noted throughout his body, including the genital and perianal region. His ocular and systemic symptoms completely resolved after treatment with a ten-day course of 1% trifluridine and moxifloxacin drops in both eyes, as well as two weeks of oral tecovirimat. Conclusion and Importance: In July of 2022, monkeypox virus was declared a global health emergency by the World Health Organization; however, there are no standard guidelines for monkeypox treatment. Data on its clinical presentation and course, especially pertaining to ocular manifestations, is limited. We highlight the importance of recognizing ophthalmic manifestations of monkeypox virus and a possible therapeutic approach to help guide the management of these patients.

The energetic costs of sub-lethal helminth parasites in mammals: a meta-analysis.

Parasites, by definition, have a negative effect on their host. However, in wild mammal health and conservation research, sub-lethal infections are commonly assumed to have negligible health effects unless parasites are present in overwhelming numbers. Here, we propose a definition for host health in mammals that includes sub-lethal effects of parasites on the host's capacity to adapt to the environment and maintain homeostasis. We synthesized the growing number of studies on helminth parasites in mammals to assess evidence for the relative magnitude of sub-lethal effects of infection across mammal taxa based on this expanded definition. Specifically, we develop and apply a framework for organizing disparate metrics of parasite effects on host health and body condition according to their impact on an animal's energetic condition, defined as the energetic burden of pathogens on host physiological and behavioural functions that relate directly to fitness. Applying this framework within a global meta-analysis of helminth parasites in wild, laboratory and domestic mammal hosts produced 142 peer-reviewed studies documenting 599 infection-condition effects. Analysing these data within a multiple working hypotheses framework allowed us to evaluate the relative weighted contribution of methodological (study design, sampling protocol, parasite quantification methods) and biological (phylogenetic relationships and host/parasite life history) moderators to variation in the magnitude of health effects. We found consistently strong negative effects of infection on host energetic condition across taxonomic groups, with unusually low heterogeneity in effect sizes when compared with other ecological meta-analyses. Observed effect size was significantly lower within cross-sectional studies (i.e. observational studies that investigated a sub-set of a population at a single point in time), the most prevalent methodology. Furthermore, opportunistic sampling led to a weaker negative effect compared to proactive sampling. In the model of host taxonomic group, the effect of infection on energetic condition in carnivores was not significant. However, when sampling method was included, it explained substantial inter-study variance; proactive sampling showing a strongly significant negative effect while opportunistic sampling detected only a weak, non-significant effect. This may partly underlie previous assumptions that sub-lethal parasites do not have significant effects on host health. We recommend future studies adopt energetic condition as the framework for assessing parasite effects on wildlife health and provide guidelines for the selection of research protocols, health proxies, and relating infection to fitness.

A scoping review of the literature on professional learning for MTSS.

This article provides a scoping review of the nascent empirical literature on professional learning for MTSS. We used a systematic search strategy to find studies on the impact of professional learning on educator and implementation outcomes. Seventy-nine studies utilizing a variety of designs were included. We found that research most frequently evaluated training and professional learning community focused interventions in elementary schools. We also observed strong alignment between professional learning interventions and the MTSS model studied, research design used, outcomes evaluated, and methodological rigor (e.g., Professional Learning Communities tended to be evaluated using qualitative methods that varied in rigor). Studies evaluated educator knowledge, skills, and dispositions, as well as implementation of the practices that comprise MTSS; however, educator aspirations were rarely evaluated. Moreover, few studies comprehensively evaluated the relations among professional learning and educator knowledge, skills, and dispositions and how those variables interacted to impact implementation. We call for more rigorous research on the impact of professional learning for MTSS and on factors that facilitate and hinder effectiveness.

A novel approach to studying early knee osteoarthritis illustrates that bilateral medial tibiofemoral osteoarthritis is a heritable phenotype: an offspring study.

To assess the potential of studying offspring of people with and without knee osteoarthritis to understand the risk factors and heritability for knee osteoarthritis. We selected two groups of Osteoarthritis Initiative (OAI) participants from one clinical site: (1) participants with bilateral radiographic medial tibiofemoral osteoarthritis and (2) those without tibiofemoral osteoarthritis. We then invited biological offspring ≥ 18 years old to complete an online survey that inquired about osteoarthritis risk factors and symptoms. Among the survey respondents, we recruited ten offspring of members from each group for a clinic visit with bilateral knee posterior-anterior radiographs and magnetic resonance imaging of the right knee. We established contact with 269/413 (65%) eligible OAI participants. Most (227/269, 84%) had ≥ 1 eligible biological offspring, and 213 (94%) were willing to share information about the new family study with their offspring. Our survey was completed by 188 offspring from 110 OAI participants: mean age of 43.0 (10.4) years, mean body mass index of 23.7 (5.9) kg/m2, 65% female. Offspring obesity (OR = 2.7, 95% CI 1.0-7.3), hypertension (OR = 3.7, 95% CI 1.2-11.3), and Heberden's nodes (OR = 3.6, 95% CI 1.0-13.2) were associated with parental osteoarthritis status; however, adjusted models were not statistically significant. Radiographic tibiofemoral osteoarthritis (16/18 knees vs. 2/20 knees) and meniscal abnormalities (7/9 vs. 2/10 index knees) were more common among offspring with parental osteoarthritis status than not. We established the potential of a novel offspring study design within the OAI, and our results are consistent with bilateral radiographic medial tibiofemoral osteoarthritis being a heritable phenotype of osteoarthritis.

Trait-based approaches to global change ecology: moving from description to prediction.

Trait-based approaches are increasingly recognized as a tool for understanding ecosystem re-assembly and function under intensifying global change. Here we synthesize trait-based research globally (n = 865 studies) to examine the contexts in which traits may be used for global change prediction. We find that exponential growth in the field over the last decade remains dominated by descriptive studies of terrestrial plant morphology, highlighting significant opportunities to expand trait-based thinking across systems and taxa. Very few studies (less than 3%) focus on predicting ecological effects of global change, mostly in the past 5 years and via singular traits that mediate abiotic limits on species distribution. Beyond organism size (the most examined trait), we identify over 2500 other morphological, physiological, behavioural and life-history traits known to mediate environmental filters of species' range and abundance as candidates for future predictive global change work. Though uncommon, spatially explicit process models-which mechanistically link traits to changes in organism distributions and abundance-are among the most promising frameworks for holistic global change prediction at scales relevant for conservation decision-making. Further progress towards trait-based forecasting requires addressing persistent barriers including (1) matching scales of multivariate trait and environment data to focal processes disrupted by global change, and (2) propagating variation in trait and environmental parameters throughout process model functions using simulation.

Creation of a universal experimental protocol for the investigation of transfer and persistence of trace evidence: Part 2 - Implementation and preliminary data.

This is the second paper on the development and implementation of a universal experimental protocol for transfer and persistence of trace evidence. Here, we present the results of five individual researchers who implemented the universal experimental protocol for the first time. Over 2500 images were collected, computationally analysed and statistically compared. The results were shown to be reliable and consistent under all conditions tested and were used to model the rate of loss of transferred particles over a 7-day timescale. The protocol was additionally extended to include a test of camera settings. The protocol was found to be useable and robust in this preliminary trial paving the way for it to be deployed more widely.

Trait-based vulnerability reveals hotspots of potential impact for a global marine invader.

Predation from the invasive Indo-Pacific lionfish is likely to amplify declines in marine fishes observed in multiple ocean basins. As the invasion intensifies and expands, there is an urgent need to identify species that are most at risk for extirpation-and possible extinction-from this added threat. To address this gap and inform conservation plans, we develop and apply a quantitative framework for classifying the relative vulnerability of fishes based on morphological and behavioural traits known to influence susceptibility to lionfish predation (e.g. body shape, water column position and aggregation behaviour), habitat overlap with lionfish, and degree of geographic range restriction. Applying the framework to fishes across the invaded Caribbean Sea and ahead of the invasion front in the southwestern Atlantic revealed the identity of at least 77 fishes with relatively small ranges that are likely to be most affected by lionfish predation. Trait-based vulnerability scores significantly predict the probability of fishes appearing within the diets of lionfish across the invaded region. Spatial richness analyses reveal hotspots of vulnerable species in the Bahamas, Belize and Curaçao. Crucially, our framework identifies 29 vulnerable fishes endemic to Brazil, which has not yet been colonized by lionfish. Of these, we suggest reefs around offshore island groups occupied by a dozen highly vulnerable and range-restricted species as priorities for intervention should lionfish spread to the region. Observations of the rate of lionfish spread across the invaded range suggest that an average of 5 years (with a median of nearly 2 years) elapses from first sighting to maximum observed densities. This lag may allow managers to mobilize plans to suppress lionfish ahead of an invasion front in priority locations. Our framework also provides a method for assessing the relative vulnerability of cryptobenthic and/or deep-reef fishes, for which population-monitoring data are limited.

Critical review of oncology clinical trial design under non-proportional hazards.

In trials of novel immuno-oncology drugs, the proportional hazards (PH) assumption often does not hold for the primary time-to-event (TTE) efficacy endpoint, likely due to the unique mechanism of action of these drugs. In practice, when it is anticipated that PH may not hold for the TTE endpoint with respect to treatment, the sample size is often still calculated under the PH assumption, and the hazard ratio (HR) from the Cox model is still reported as the primary measure of the treatment effect. Sensitivity analyses of the TTE data using methods that are suitable under non-proportional hazards (non-PH) are commonly pre-planned. In cases where a substantial deviation from the PH assumption is likely, we suggest designing the trial, calculating the sample size and analyzing the data, using a suitable method that accounts for non-PH, after gaining alignment with regulatory authorities. In this comprehensive review article, we describe methods to design a randomized oncology trial, calculate the sample size, analyze the trial data and obtain summary measures of the treatment effect in the presence of non-PH. For each method, we provide examples of its use from the recent oncology trials literature. We also summarize in the Appendix some methods to conduct sensitivity analyses for overall survival (OS) when patients in a randomized trial switch or cross-over to the other treatment arm after disease progression on the initial treatment arm, and obtain an adjusted or weighted HR for OS in the presence of cross-over. This is an example of the treatment itself changing at a specific point in time - this cross-over may lead to a non-PH pattern of diminishing treatment effect.

New insights into patterns and rates of tooth replacement in serrasalmid and characid fishes, with implications for the subsistence fishery of Peru's remote ribereños villages.

We explored patterns, rates and unexpected socio-ecological consequences of tooth replacement in serrasalmids and characids of the Peruvian Amazon using microcomputed tomography. Of 24 specimens collected in February 2019, representing a mix of red-bellied piranha Pygocentrus nattereri, redeye piranha Serrasalmus rhombeus, silver dollar fish Ctenobrycon hauxwellianus and mojara Astyanax abramis, six individuals possessed edentulous jaw quadrants. On average, 22.9% of fish collected per day from these species featured incomplete dentition, a value three to five times higher than anticipated based on replacement rates estimated from captive fish, differences that may be driven by ontogeny, seasonality or environmental quality.

The roles of jim lovell and uninflatable in different endopolyploid larval tissues of Drosophila melanogaster.

The larvae of Drosophila melanogaster grow rapidly through use of a highly truncated cell cycle in which mitosis is entirely eliminated. The Drosophila homolog of the protooncogene transcription factor Myc plays a major role in promoting this endopolyploid (EP) growth. We have previously determined that the gene jim lovell (lov), which encodes a member of the BTB/POZ (Bric-a-brac, Tramtrack, Broad/Pox virus zinc finger) domain family of transcription factors, is also required for EP growth in one larval tissue, the trachea. Here we show that lov promotes EP growth in three further tissues indicating a fundamental role in this process. However, epistasis experiments revealed heterogeneity in lov's action in these tissues. Whereas in the tracheae and salivary glands lov acts downstream of Myc, in the fat body, reduced expression of lov does not impede the action of Myc, indicating an upstream action for the gene. We show here that lov's regulation of the gene uninflatable (uif) in the tracheae is a component of this difference. uif is required for tracheal EP growth downstream of Myc and lov but has no equivalent role in the fat body. Although Uif is a transmembrane component of the plasma membrane in the tracheae, its action downstream of Myc suggests an intracellular role for the protein in the tracheae. In addition to regulating uif expression in some tissues we also show that lov locates to the nucleolus, indicating it can function in both polymerase I and polymerase II transcriptional events. Our major finding is that tissue-specific mechanisms can interact with universal growth promotion by Myc to generate the individual endopolyploid organs of the larvae.

2D (2 Dimensional) TEQR design for Determining the optimal Dose for safety and efficacy.

Designs, such as the Eff-Tox, OBD (optimal biological dose), STEIN (simple efficacy toxicity interval), and TEPI (toxicity efficacy probability interval) designs, have been proposed to determine the optimal dose of a new oncology drug using both efficacy and toxicity. The goal of these designs is to select the optimal drug dose for further phase trials more accurately than dose finding designs that only consider toxicity, such as the 3 + 3, TEQR (toxicity equivalence range), mTPI (modified toxicity probability interval), and EWOC (escalation with overdose control) designs. We propose a new frequentist design for optimal dose selection, the 2D TEQR design, that is easier to understand and simpler to implement than the TEPI, Eff-Tox, STEIN and OBD designs, as it is based on the empirical or observed toxicity and efficacy rates and does not require specialized computations. We compare the performance of this new design with those of the TEPI, STEIN, Eff-Tox and OBD Isotonic designs. Although for the same sample size and cohort size, the frequentist 2D TEQR design is less accurate than the Bayesian TEPI design and also the STEIN design in selecting the optimal dose, the accuracy of optimal dose selection of the 2D TEQR design can be increased, in many cases, with a moderate increase in cohort size. The 2D TEQR design is as accurate as or more accurate than the Eff-Tox design in optimal dose selection, and better than the OBD Isotonic design, unless there is a clear peak in the true response rates, in which case the OBD Isotonic design performs better than the other designs.

Extensions of the mTPI and TEQR designs to include non-monotone efficacy in addition to toxicity for optimal dose determination for early phase immunotherapy oncology trials.

With the emergence of immunotherapy and other novel therapies, the traditional assumption that the efficacy of the study drug increases monotonically with dose levels is not always true. Therefore, dose-finding methods evaluating only toxicity data may not be adequate. In this paper, we have first compared the Modified Toxicity Probability Interval (mTPI) and Toxicity Equivalence Range (TEQR) dose-finding oncology designs for safety with identical stopping rules; we have then extended both designs to include efficacy in addition to safety - we determine the optimal dose for safety and efficacy using these designs by applying isotonic regression to the observed toxicity and efficacy rates, once the early phase trial is completed. We consider multiple types of underlying dose response curves, i.e., monotonically increasing, plateau, or umbrella-shaped. We conduct simulation studies to investigate the operating characteristics of the two proposed designs and compare them to existing designs. We found that the extended mTPI design selects the optimal dose for safety and efficacy more accurately than the other designs for most of the scenarios considered.

Changes in working memory performance in youth following concussion.

OBJECTIVE: The purpose of this study was to compare the working memory (WM) performance pre- and post-concussion, and investigate the relationships between performance changes and characteristics such as self-reported symptom scores, number of days post-injury and age at injury in 10-14-year-old youth. METHODS: Twenty-one youth (17 males) aged 10-14 years recruited from the community completed verbal and non-verbal WM tasks pre- and post-concussion. Performance was measured using accuracy and performance errors (false alarms and misses). Pre- and post-tests were compared using a Wilcoxon signed rank test, and effect size was determined using matched-pairs rank biserial correlation. RESULTS: Comparisons showed lower verbal WM accuracy at post-test, greater verbal and non-verbal WM false alarm errors at post-test, and greater verbal WM miss errors at post-test (all r ≥ 0.30). Correlations between performance and characteristics revealed associations between younger youth and lower non-verbal WM accuracy and more false alarms at post-test, as well as an association among non-verbal WM miss errors, higher PCS scores and fewer days since injury at post-test. CONCLUSIONS: The current study found lower WM performance in youth following concussion. Furthermore, the findings suggest that false alarm errors may be a useful screening measure acutely post-concussion when assessing WM performance in youth.

Systematic comparison of the statistical operating characteristics of various Phase I oncology designs.

Dose finding Phase I oncology designs can be broadly categorized as rule based, such as the 3 + 3 and the accelerated titration designs, or model based, such as the CRM and Eff-Tox designs. This paper systematically reviews and compares through simulations several statistical operating characteristics, including the accuracy of maximum tolerated dose (MTD) selection, the percentage of patients assigned to the MTD, over-dosing, under-dosing, and the trial dose-limiting toxicity (DLT) rate, of eleven rule-based and model-based Phase I oncology designs that target or pre-specify a DLT rate of ∼0.2, for three sets of true DLT probabilities. These DLT probabilities are generated at common dosages from specific linear, logistic, and log-logistic dose-toxicity curves. We find that all the designs examined select the MTD much more accurately when there is a clear separation between the true DLT rate at the MTD and the rates at the dose level immediately above and below it, such as for the DLT rates generated using the chosen logistic dose-toxicity curve; the separations in these true DLT rates depend, in turn, not only on the functional form of the dose-toxicity curve but also on the investigated dose levels and the parameter set-up. The model based mTPI, TEQR, BOIN, CRM and EWOC designs perform well and assign the greatest percentages of patients to the MTD, and also have a reasonably high probability of picking the true MTD across the three dose-toxicity curves examined. Among the rule-based designs studied, the 5 + 5 a design picks the MTD as accurately as the model based designs for the true DLT rates generated using the chosen log-logistic and linear dose-toxicity curves, but requires enrolling a higher number of patients than the other designs. We also find that it is critical to pick a design that is aligned with the true DLT rate of interest. Further, we note that Phase I trials are very small in general and hence may not provide accurate estimates of the MTD. Thus our work provides a map for planning Phase I oncology trials or developing new ones.

Trait-based diet selection: prey behaviour and morphology predict vulnerability to predation in reef fish communities.

Understanding how predators select their prey can provide important insights into community structure and dynamics. However, the suite of prey species available to a predator is often spatially and temporally variable. As a result, species-specific selectivity data are of limited use for predicting novel predator-prey interactions because they are assemblage specific. We present a method for predicting diet selection that is applicable across prey assemblages, based on identifying general morphological and behavioural traits of prey that confer vulnerability to predation independent of species identity. We apply this trait-based approach to examining prey selection by Indo-Pacific lionfish (Pterois volitans and Pterois miles), invasive predators that prey upon species-rich reef fish communities and are rapidly spreading across the western Atlantic. We first generate hypotheses about morphological and behavioural traits recurring across fish species that could facilitate or deter predation by lionfish. Constructing generalized linear mixed-effects models that account for relatedness among prey taxa, we test whether these traits predict patterns of diet selection by lionfish within two independent data sets collected at different spatial scales: (i) in situ visual observations of prey consumption and availability for individual lionfish and (ii) comparisons of prey abundance in lionfish stomach contents to availability on invaded reefs at large. Both analyses reveal that a number of traits predicted to affect vulnerability to predation, including body size, body shape, position in the water column and aggregation behaviour, are important determinants of diet selection by lionfish. Small, shallow-bodied, solitary fishes found resting on or just above reefs are the most vulnerable. Fishes that exhibit parasite cleaning behaviour experience a significantly lower risk of predation than non-cleaning fishes, and fishes that are nocturnally active are at significantly greater risk. Together, vulnerable traits heighten the risk of predation by a factor of nearly 200. Our study reveals that a trait-based approach yields insights into predator-prey interactions that are robust across prey assemblages. Importantly, in situ observations of selection yield similar results to broadscale comparisons of prey use and availability, which are more typically gathered for predator species. A trait-based approach could therefore be of use across predator species and ecosystems to predict the outcomes of changing predator-prey interactions on community dynamics.