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Lupinus polyphyllus, known in New Zealand as Russell lupin, is an herbaceous perennial that is invasive in a number of countries outside its natural range in North America. Knowledge of the optimum timeframe and plant development stage for herbicide application is crucial for any effective and cost-efficient weed-control operation. We examined the development and viability ofL. polyphyllusseeds 7 weeks after foliar application of triclopyr ester herbicide at three stages of seed-pod maturity (immature, intermediate and mature). The proportion of seeds in each seed-development class and each seed/seedling viability class from mature pods on treated plants was similar to that in the untreated control. Pods sprayed at immature and intermediate development stages had significantly lower proportions of fully developed seeds (average 82.1% lower) and produced significantly lower proportions of viable seedlings (average 92.7% lower). Our findings indicate thatL. polyphylluscontrol using triclopyr ester can be extended beyond the pre-reproductive stage to include plants bearing up to intermediate-stage seed pods without substantial production of viable seedlings or viable but dormant seed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the present work was to understand why and how RJ Reynolds and other tobacco companies have marketed tobacco products to young adult social trendsetting consumers (termed 'hipsters') to recruit trendsetters and average consumers to smoke. METHODS: Analysis of tobacco industry documents and industry marketing materials. RESULTS: Since 1995, RJ Reynolds developed its marketing campaigns to better suit the lifestyle, image identity and attitudes of hip trendsetters (so-called 'hipsters'), and Camel's brand identity actively shifted to more closely convey the hipster persona. Camel emphasised in-venue events such as promotional music tours to link the brand and smoking to activities and symbols appealing to hipsters and their emulating masses. CONCLUSIONS: To reach this targeted and socially valuable trend-setting population, public health advocates must tap into hipster psychology and expose to the targeted community the tobacco company's efforts to infiltrate the hipster community to turn hipsters into tobacco-using role models. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate youth exposure to smoking in movies in the UK and compare the likely effect with the USA. METHODS: We collected tobacco occurrences data for 572 top-grossing films in the UK screened from 2001 to 2006 and estimated the number of on-screen tobacco impressions delivered to British youths in this time period. RESULTS: 91% of films in our sample that contained smoking were youth-rated films (British Board of Film Classification rating '15' and lower), delivering at least 1.10 billion tobacco impressions to British youths during theatrical release. British youths were exposed to 28% more smoking impressions in UK youth-rated movies than American youth-rated movies, because 79% of movies rated for adults in the USA ('R') are classified as suitable for youths in the UK ('15' or '12A'). CONCLUSION: Because there is a dose-response relation between the amount of on-screen exposure to smoking and the likelihood that adolescents will begin smoking, the fact that there is substantially higher exposure to smoking in youth-rated films in the UK than in the USA suggests that the fraction of all youth smoking because of films in the UK is probably larger than in the USA. Other countries with ratings systems that are less conservative (in terms of language and sexuality) than the USA will also be likely to deliver more on-screen tobacco impressions to youths. Assigning an '18' classification to movies that contain smoking would substantially reduce youth exposure to on-screen smoking and, hence, smoking initiation among British youths. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore viral marketing strategies for Eclipse cigarettes used by the RJ Reynolds Company (Winston-Salem, North Carolina, USA). METHODS: Analysis of previously secret tobacco industry documents and multimedia materials. RESULTS: The failure of RJ Reynolds' (RJR) 1988 'smokeless' cigarette, Premier, was in part due to widespread bad word of mouth about the product's flavour, quality and difficulty of use. In 1994 RJR introduced an updated version of Premier, the ostensibly 'reduced risk' Eclipse cigarette. RJR developed viral marketing channels to promote Eclipse using (1) exploratory interviews to motivate consumers to spread the word about Eclipse prior to market release, (2) promotional videos featuring positive feedback from test group participants to portray majority consensus among triers, (3) 'Tupperware'-like parties for Eclipse where participants received samples to pass around in their social circles and (4) the Eclipse website's bulletin board as a forum for potential users to discuss the brand in their own words. These strategies targeted the brand's likeliest adopters, recruited informal and credible representatives of the product unaffiliated with RJR, and controlled the information spread about the product. CONCLUSIONS: Viral marketing techniques may be particularly useful to promote new tobacco products such as Eclipse that have limited appeal and need a highly motivated audience of early adopters and acceptors. Such techniques help evade the mass rejection that could follow mass promotion, circumvent marketing restrictions, and allow tobacco companies to benefit from health claims made by consumers. Cigarette manufacturers must be held accountable for perceived health benefits encouraged by all promotional activities including viral marketing. [ABSTRACT FROM AUTHOR]

Background: The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone. Methods: 5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830. Findings: Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97.2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98.9% [5072 of 5128]). Only 1.4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65.1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3.9% [515 of 13 171]). The overall accuracy of SLN resection in patients in group 1 was 97.1% (2544 of 2619; 95% CI 96.4-97.7), with a false-negative rate of 9.8% (75 of 766; 95% CI 7.8-12.2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0.7% (37 of 5588) of patients with data on toxic effects. Interpretation: The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of acute ankle injuries present challenges to both primary care physicians and orthopedic specialists. Determining the position of the ankle when the injury occurred may help distinguish sprains from fractures so that unnecessary x-rays can be avoided. Stepwise rehabilitation restores function and diminishes the risk of reinjury. Physicians can stress functional measures of recovery to objectively assess readiness for return to play and balance the risks of incomplete rehabilitation against the desire for an early return to sports. [ABSTRACT FROM AUTHOR]

Two experiments used the distinction between remembering and knowing to investigate the effects of exact and category repetition in recognition memory. In Experiment 1, exact repetition enhanced remember responses but had no reliable effect on know responses. In Experiment 2, category repetition enhanced correct know responses but had no effect on correct remember responses. Category repetition also increased false positive remember and know responses. It is argued that exact repetition influences the recollection component of recognition memory via the creation of multiple episodic traces, each of which is potentially capable of supporting a remember response, whereas category repetition influences the familiarity component of recognition memory by enhancing the fluency with which test items are processed. [ABSTRACT FROM AUTHOR]

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Clinical Relevance: Identifying polarisation-modulated patterns may be an effective method for both detecting and monitoring macular damage., Background: The aim of this work is to determine the effectiveness of polarisation-modulated patterns in identifying macular damage and foveolar involvement using a methodology that involved feature selection, Naïve Bayes supervised machine learning, cross validation, and use of an interpretable nomogram., Methods: A cross-sectional study involving 520 eyes was undertaken, encompassing both normal and abnormal cases, including those with age-related macular disease, diabetic retinopathy or epiretinal membrane. Macular damage and foveolar integrity were assessed using optical coherence tomography. Various polarisation-modulated geometrical and optotype patterns were employed, along with traditional methods for visual function measurement, to complete perceptual detection and identification measures. Other variables assessed included age, sex, eye (right, left) and ocular media (normal, pseudophakic, cataract). Redundant variables were removed using a Fast Correlation-Based Filter. The area under the receiver operating characteristic curve and Matthews correlation coefficient were calculated, following 5-fold stratified cross validation, for Naïve Bayes models describing the relationship between the selected predictors of macular damage and foveolar involvement., Results: Only radially structured polarisation-modulated patterns and age emerged as predictors of macular damage and foveolar involvement. All other variables, including traditional logMAR measures of visual acuity, were identified as redundant. Naïve Bayes, utilising the Fast Correlation-Based Filter selected features, provided a good prediction for macular damage and foveolar involvement, with an area under the receiver operating curve exceeding 0.7. Additionally, Matthews correlation coefficient showed a medium size effect for both conditions., Conclusions: Radially structured polarisation-modulated geometric patterns outperform polarisation-modulated optotypes and standard logMAR acuity measures in predicting macular damage, regardless of foveolar involvement.

We evaluated differences in long-term outcomes of invasive lobular carcinoma (ILC) vs breast cancers of no special type (NST) treated with anthracycline-based adjuvant chemotherapy using 4 National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized phase III trials (B-22, B-25, B-28, B-30). Our cohort included 11,251 patients with NST and 1,231 with ILC. Patients with ILC were older, had larger and more often estrogen receptor-positive tumors, and more positive lymph nodes. During early follow-up (0-5 years), patients with ILC had fewer recurrences (HR: 0.797; 95% confidence interval [CI] 0.685-0.929) and deaths (HR: 0.756; 95% CI 0.623-0.917). After 5 years patients with ILC had more recurrences (HR: 1.30; 95% CI 1.085-1.558) and deaths (HR: 1.044; 95% CI 0.898-1.214). Conditional probability analysis showed significant interactions between time-period and histologic type for recurrences (p < .001) and deaths (p < .001). Patients with ILC have elevated risk of late recurrence and death compared to patients with NST., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Clinical Relevance: The electronic storage of patient records and modern-day search engines present private practitioners with a unique opportunity to extract valuable data for investigative research purposes. However, practitioners seldom harness this resource and consequently a vast repository of clinical data remains largely unexplored., Background: This study, based on real-world data from an optometric practice, stands as an example of how clinicians can actively contribute to research. In doing so it underscores the role played by age in determining the rate of natural myopia progression., Methods: A retrospective data analysis of the refractive status, age and optical correction type of participants, was conducted over six years. Forty-four participants were recruited (25 contact lens and 19 spectacle wearers), with a presenting age varying from 5 to 20 years (median, 11 years). Non-cycloplegic, monocular foveal refractions were completed using a ShinNippon open-field autorefractor, corroborated with subjective refraction. The mean spherical equivalent refractive error was calculated for the participants' initial visit (baseline measure) and for a six-year follow-up visit (progression measure), with myopia progression defined as the difference between these measures. Statistical analyses were computed using Decision Tree Analysis, with a significance level set at 95%., Results: The participant age at first visit exerted a significant influence on natural myopia progression over the assessment period (F 1,42 = 17.11, p  < 0.001). Individuals aged ≤ 10 years had approximately twice the myopic progression (mean, -2.27 D) of those aged > 10 years (mean, -1.13 D). Neither degree of myopia at the initial visit nor optical correction type had a significant effect on progression ( p  > 0.05)., Conclusions: Utilizing the advantage of small real-world data samples, the benefit of research by private practitioners was demonstrated, providing evidence that the age at which a child first presents for an eye examination is highly influential in determining their rate of myopia progression.

Sightseeing air tours have proven to be a challenging management issue for many tourist destinations around the world, especially at locations meant to protect natural and cultural resources and wilderness character. Two of the primary challenges with managing air tours are a lack of information about their travel patterns and how such patterns result in a measurable noise impact to listeners. Recent studies have highlighted the usefulness of newer technology for tracking aircraft travel patterns, particularly over national parks. In this synthesis, we pair aircraft tracks with acoustic data using a quantitative observer-based audibility modelling software toolkit. The findings delimit the long-term geographic scope of audibility for specific aircraft noise sources above landscapes of Hawai'i Volcanoes and Denali National Parks, U.S. and identify practical, 3-dimensional offset distances that can be used to reduce the functional effects of air tour noise in terms of sound level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

As billions of nocturnal avian migrants traverse North America, twice a year they must contend with landscape changes driven by natural and anthropogenic forces, including the rapid growth of the artificial glow of the night sky. While airspaces facilitate migrant passage, terrestrial landscapes serve as essential areas to restore energy reserves and often act as refugia-making it critical to holistically identify stopover locations and understand drivers of use. Here, we leverage over 10 million remote sensing observations to develop seasonal contiguous United States layers of bird migrant stopover density. In over 70% of our models, we identify skyglow as a highly influential and consistently positive predictor of bird migration stopover density across the United States. This finding points to the potential of an expanding threat to avian migrants: peri-urban illuminated areas may act as ecological traps at macroscales that increase the mortality of birds during migration., (© 2023. The Author(s).)

Visual (perceptual) reasoning is a critical skill in many medical specialties, including pathology, diagnostic imaging, and dermatology. However, in an ever-compressed medical curriculum, learning and practicing this skill can be challenging. Previous studies (including work with pigeons) have suggested that using reward-feedback-based activities, novices can gain expert levels of visual diagnostic accuracy in shortened training times. But is this level of diagnostic accuracy a result of image recognition (categorization) or is it the acquisition of diagnostic expertise? To answer this, the authors measured electroencephalographic data (EEG) and two components of the human event-related brain potential (reward positivity and N170) to explore the nature of visual expertise in a novice-expert study in pathology visual diagnosis. It was found that the amplitude of the reward positivity decreased with learning in novices (suggesting a decrease in reliance on feedback, as in other studies). However, this signal remained significantly different from the experts whose reward positivity signal did not change over the course of the experiment. There were no changes in the amplitude of the N170 (a reported neural marker of visual expertise) in novices over time. Novice N170 signals remained statistically and significantly lower in amplitude compared to experts throughout task performance. These data suggest that, while novices gained the ability to recognize (categorize) pathologies through reinforcement learning as quantified by the change in reward positivity, increased accuracy, and decreased time for responses, there was little change in the neural marker associated with visual expertise (N170). This is consistent with the multi-dimensional and complex nature of visual expertise and provides insight into future training programs for novices to bridge the expertise gap., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Prescribing is part of the expanded scope of practice for pharmacists in Alberta, Canada. Given these responsibilities, clinical decision making (the outcome from the diagnostic and therapeutic decision making process) is an essential skill for pharmacists. The current study compared diagnostic and therapeutic decision-making between Additional Prescribing Authority (APA) pharmacists and family physicians using a set of common ambulatory clinical cases that both practitioners could encounter in the community as part of their daily practice., Objectives: To explore clinical decision making performance and behaviors between APA pharmacists and family physicians during the assessment and prescribing of common ambulatory conditions., Methods: Eight written ambulatory clinical cases were developed by a panel of experts in both family medicine and pharmacy that were commonly encountered in both professions' daily practice. Participating APA pharmacists and family physicians reviewed the cases and responded with likely diagnoses, recommended treatments, and reported confidence in therapeutic choices. The responses of 18 APA pharmacists and 9 family physicians in community practices were analyzed., Results: There were no significant differences in diagnostic accuracy, therapeutic accuracy, confidence in diagnostic choices, and confidence in therapeutic choices between APA pharmacists and family physicians to these common ambulatory presentations., Conclusions: This study provides preliminary insights regarding the capabilities of pharmacists in the assessment of common ambulatory community conditions and suggests that APA pharmacists are making similar diagnostic and therapeutic decisions to family physicians. Future research could focus on examining the performance of pharmacists trained in different pharmacy education models, as well as their ability to provide clinical assessment in other specialties, or in more uncommon clinical scenarios., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kent Hecker is also the Chief Assessment Officer for the International Council for Veterinary Assessment., (© 2023 The Authors.)

Light pollution is a global phenomenon where anthropogenic light sources continue to grow unabated, affecting both social and ecological systems. This is leaving parks and protected areas as some of the last vestiges of naturally dark environments for protecting views of the night sky. Yet, even parks and protected areas have outdoor lighting. Alternative lighting practices are needed to reduce or prevent light pollution from within parks. However, making parks darker may not be desirable for some visitors if they believe it will reduce navigability, safety, or restrict how they recreate (e.g., requiring the use of red-light flashlights after dark and before dawn). How visitors will respond to alternative lighting practices that park managers can implement is still unknown. We used an on-site intercept survey at nine state and national park units in Utah, U.S., to investigate nighttime visitors' support or opposition to management actions to protect night sky quality and their interest in learning about topics related to night skies. Further, this study also segmented visitors into two groups: those 'dependent' on the dark sky as a resource and those whose activities did not depend on a dark sky. Defining what a 'dark sky dependent' visitor is, which has yet to be done in the literature, is a fundamental step to furthering night sky research and management efforts. Across nine parks and protected areas, 62% of nighttime visitors participated in dark sky dependent activities. Findings indicate broad support for management actions designed to improve night sky quality, with between 74% and 89% of all visitors supporting seven different management actions. There was stronger support from dark sky dependent visitors for some elements of alternative lighting practices, but there was still strong support for those who do not participate in dark sky dependent outdoor recreation. Additionally, between 57% and 75% of visitors were interested in learning more about topics related to night skies. This research indicates most visitors would welcome actions to preserve the quality of the rapidly dwindling naturally dark experiences offered by parks and protected areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

The microtubule (MT)-stabilizing drug Taxol (paclitaxel) is a commonly used tool to investigate MT dynamics and MT-dependent processes. Here, we present a protocol for using Taxol-sensitized budding yeast to investigate the effect of microtubule stabilization on anaphase onset. We describe steps for establishing a log phase culture, synchronizing cells in G1, arresting in metaphase, and releasing cells into Taxol. We then detail procedures for imaging and scoring anaphase onset. This protocol facilitates maintenance and reproducibility in testing drug-sensitized and Taxol-sensitized yeast strains. For complete details on the use and execution of this protocol, please refer to Proudfoot et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The relationship of macular pigments and foveal anatomy to the perception of Maxwell's spot (MS) and Haidinger's brushes (HB) entoptic phenomena were investigated. Dual-wavelength-autofluorescence and OCT were used to define macular pigment density and foveal anatomy in 52 eyes. MS was generated by alternating unpolarized red/blue and red/green uniform field illumination. HB was generated by alternating the linear polarization axis of a uniform blue field. In Experiment 1, horizontal widths of MS and HB were measured using a micrometer system and compared with macular pigment densities and OCT-defined morphometry. MS radius (mean 1.4°) was significantly less than HB radius (mean 1.6°), with the spatial extent of both phenomena falling between the boundaries of the foveola and foveal pit. Multiple regression showed MS and HB radii to be significantly associated with the macular pigment spatial profile radius. HB radius, but not MS radius, was also significantly associated with foveolar morphometry. Experiment 2 compared perceptual profiles of MS with macular pigment distribution patterns and demonstrated close agreement. The size and appearance of MS is a direct indicator of macular pigment density and distribution. Measures of HB radii are less specific, with dependence on both macular pigment density and foveal structure., Competing Interests: The authors declare no conflicts of interest.

Animal migrations are some of the most ubiquitous and one of the most threatened ecological processes globally. A wide range of migratory behaviours occur in nature, and this behaviour is not uniform among and within species, where even individuals in the same population can exhibit differences. While the environment largely drives migratory behaviour, it is necessary to understand the genetic mechanisms influencing migration to elucidate the potential of migratory species to cope with novel conditions and adapt to environmental change. In this study, we identified genes associated with a migratory trait by undertaking pooled genome-wide scans on a natural population of migrating mule deer. We identified genomic regions associated with variation in migratory direction, including FITM1, a gene linked to the formation of lipids, and DPPA3, a gene linked to epigenetic modifications of the maternal line. Such a genetic basis for a migratory trait contributes to the adaptive potential of the species and might affect the flexibility of individuals to change their behaviour in the face of changes in their environment.

Polygenic models have emerged as promising prediction tools for the prediction of complex traits. Currently, the majority of polygenic models are developed in the context of predicting disease risk, but polygenic models may also prove useful in predicting drug outcomes. This study sought to understand how polygenic models incorporating pharmacogenetic variants are being used in the prediction of drug outcomes. A systematic review was conducted with the aim of gaining insights into the methods used to construct polygenic models, as well as their performance in drug outcome prediction. The search uncovered 89 papers that incorporated pharmacogenetic variants in the development of polygenic models. It was found that the most common polygenic models were constructed for drug dosing predictions in anticoagulant therapies ( n = 27). While nearly all studies found a significant association with their polygenic model and the investigated drug outcome (93.3%), less than half (47.2%) compared the performance of the polygenic model against clinical predictors, and even fewer (40.4%) sought to validate model predictions in an independent cohort. Additionally, the heterogeneity of reported performance measures makes the comparison of models across studies challenging. These findings highlight key considerations for future work in developing polygenic models in pharmacogenomic research.

Appropriate glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells is an essential component of blood glucose homeostasis. Configuration of β-cells as 3D pseudoislets (PI) improves the GSIS response compared to 2D monolayer (ML) culture. The aim of this study was to determine the underlying mechanisms. MIN6 β-cells were grown as ML or PI for 5 days. Human islets were isolated from patients without diabetes. Function was assessed by GSIS and metabolic capacity using the Seahorse bioanalyser. Connexin 36 was downregulated using inducible shRNA. Culturing MIN6 as PI improved GSIS. MIN6 PI showed higher glucose-stimulated oxygen consumption (OCR) and extracellular acidification (ECAR) rates. Further analysis showed the higher ECAR was, at least in part, a consequence of increased glycolysis. Intact human islets also showed glucose-stimulated increases in both OCR and ECAR rates, although the latter was smaller in magnitude compared to MIN6 PI. The higher rates of glucose-stimulated ATP production in MIN6 PI were consistent with increased enzyme activity of key glycolytic and TCA cycle enzymes. There was no impact of connexin 36 knockdown on GSIS or ATP production. Configuration of β-cells as PI improves GSIS by increasing the metabolic capacity of the cells, allowing higher ATP production in response to glucose.

Purpose: Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor fostemsavir in addition to optimized background therapy (OBT) resulted in sustained virologic and immunologic responses in HTE participants throughout 96 weeks in the BRIGHTE trial. In the absence of long-term direct comparative evidence between fostemsavir-based and other antiretroviral regimens, this analysis indirectly compares efficacy and safety across relevant available trials, adjusting for demographic and baseline characteristics., Methods: A systematic literature review was conducted to identify trials with designs and populations comparable to BRIGHTE. Using matching-adjusted indirect comparison analyses, individual participant data from BRIGHTE were reweighted to create balanced populations across trials, and efficacy and safety outcomes were compared., Findings: Three comparator trials were identified, 2 of which reflected an optimized therapy without fostemsavir (OBT alone): TMB-301 (ibalizumab and OBT), BENCHMRK-1/-2 (OBT alone), and VIKING-3 (OBT alone). Compared with ibalizumab and OBT (N = 40), fostemsavir and OBT (unadjusted, N = 347; adjusted, N = 236) were associated with numerically higher nonsignificant odds of virologic suppression (odds ratio [OR] = 1.44; 95% CI, 0.74-2.80; P = 0.284) and a similar increase in CD4 + cell count of approximately 65 cells/mm 3 from baseline through week 24 (mean difference = 7.05 cells/mm 3 ; 95% CI, -60.88 to 74.98 cells/mm 3 ; P = 0.834). Compared with OBT from BENCHMRK-1/-2 (N = 237), fostemsavir and OBT (adjusted, N = 126) were associated with significantly higher odds of virologic suppression (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) and increased CD4 + cell count (135.78 cells/mm 3 ; 95% CI, 91.93-179.63 cells/mm 3 ; P < 0.001) at week 96. Compared with OBT from VIKING-3 (N = 183), fostemsavir and OBT (adjusted, N = 78) were associated with numerically higher odds of virologic suppression (OR = 1.34; 95% CI, 0.78-2.30; P = 0.297) and a modest CD4 + cell count increase (26.86 cells/mm 3 ; 95% CI, -10.79 to 64.52; P = 0.162) through week 48; however, differences were not significant. All-cause discontinuations and safety comparisons varied across studies., Implications: Although matching-adjusted indirect comparison analyses have limitations, these results support the use of fostemsavir and OBT as an important treatment option in HTE people with multidrug-resistant HIV-1., Competing Interests: DECLARATION OF INTEREST S.-J. Anderson is an employee of and owns stock in GlaxoSmithKline. A. van Doornewaard, M. Turner, and I. Jacob were employees of HEOR Ltd at the time of this analysis; HEOR Ltd received fees in relation to the reported analyses. I. Jacob, A. Clark, D. Browning, and M. Schroeder are employees of ViiV Healthcare and own stock in GlaxoSmithKline., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Identifying the genes underlying fitness-related traits such as body size and male ornamentation can provide tools for conservation and management and are often subject to various selective pressures. Here we performed high-depth whole genome re-sequencing of pools of individuals representing the phenotypic extremes for antler and body size in white-tailed deer (Odocoileus virginianus). Samples were selected from a tissue repository containing phenotypic data for 4,466 male white-tailed deer from Anticosti Island, Quebec, with four pools representing the extreme phenotypes for antler and body size after controlling for age. Our results revealed a largely homogenous population but detected highly divergent windows between pools for both traits, with the mean allele frequency difference of 14% for and 13% for antler and body SNPs in outlier windows, respectively. Genes in outlier antler windows were enriched for pathways associated with cell death and protein metabolism and some of the most differentiated windows included genes associated with oncogenic pathways and reproduction, processes consistent with antler evolution and growth. Genes associated with body size were more nuanced, suggestive of a highly complex trait. Overall, this study revealed the complex genomic make-up of both antler morphology and body size in free-ranging white-tailed deer and identified target loci for additional analyses., (© 2022. The Author(s).)

Introduction: Heavily treatment-experienced (HTE) people living with HIV-1 (PLWH) have limited viable antiretroviral regimens available because of multidrug resistance and safety concerns. The first-in-class HIV-1 attachment inhibitor fostemsavir demonstrated efficacy and safety in HTE participants in the ongoing phase III BRIGHTE trial., Objectives: We describe patient-reported outcomes (PROs) through week 48., Methods: Eligible participants for whom their current regimen was failing were assigned to the randomized cohort (RC; one to two fully active agents remaining) or the nonrandomized cohort (NRC; no fully active agents remaining). PRO assessments included the EQ-5D-3L, EQ-VAS, and Functional Assessment of HIV Infection (FAHI) instruments., Results: Both cohorts achieved increases in EQ-5D-3L US- and UK-referenced utility score from baseline at week 24. Mean visual analog scale (VAS) scores in the RC and NRC increased from baseline by 8.7 (95% CI 6.2-11.2) and 5.6 points (95% CI 1.5-9.7) at week 24 and increased from baseline by 9.8 (95% CI 7.0-12.6) and 4.9 points (95% CI 0.6-9.2) at week 48, respectively. Mean increases in FAHI total score from baseline to weeks 24 and 48 in the RC were 6.9 (95% CI 4.2-9.7) and 5.8 (95% CI 2.7-9.0), respectively, whereas mean increases in physical and emotional well-being subscale scores were 2.7 (95% CI 1.9-3.6) and 2.4 (95% CI 1.3-3.4) and 3.2 (95% CI 2.2-4.2) and 2.6 (95% CI 1.6-3.7), respectively, with little to no change in other subscales., Conclusions: Improvements in major domains of the EQ-VAS and FAHI through week 48, combined with efficacy and safety results, support the use of fostemsavir for HTE PLWH., Trial Registration Number and Date: NCT02362503; February 13, 2015., (© 2021. The Author(s).)

Short-term study-abroad (STSA) programs provide a more accessible alternative for students who would otherwise not consider engaging in academic activities overseas. Though improvements in the levels of intercultural sensitivity and general academic aspects attained by STSA programs have been previously examined, much less is known regarding the impact such programs have in the mood of students. Here, we examined changes in mood state associated with participation in an STSA program in a group of Japanese university students. Mood states were assessed using the Profile of Mood States (POMS), the Satisfaction With Life Scale (SWLS), and the Gratitude Questionnaire (GQ-6). Results indicated that the POMS mean scores of Vigor-Activity and SWLS peaked at the time immediately following participation in the STSA program; moreover, the same scores were found to be at comparable levels even one month after the end of the program. These results indicate that participation in STSA programs can positively influence the mood state of university students, suggesting that the benefits associated with participation in such programs extend beyond typically reported improvements in the academic domain., Competing Interests: NO authors have competing interests.

Background: The experimental therapeutics approach that combines a placebo-controlled clinical trial with translational neuroscience methods can provide a better understanding of both the clinical and physiological effects of pharmacotherapy. We aimed to test the efficacy and tolerability of low-dose augmentation with buprenorphine (BPN) for treatment-resistant depression, combined with multimodal assessment of target engagement., Methods: In this multisite randomized clinical trial, 85 participants ≥50 years of age with a major depressive episode that had not responded to venlafaxine extended release were randomized to augmentation with BPN or placebo for 8 weeks. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale. In addition, three linked experiments were conducted to test target engagement: 1) functional magnetic resonance imaging using the monetary incentive delay task, 2) brain positron emission tomography of healthy participants using a novel kappa opioid receptor antagonist tracer [ 11 C]LY2795050, and 3) transcranial magnetic stimulation measure of cortical transmission after daily BPN administration., Results: The mean ± SD dosage of BPN was 0.59 ± 0.33 mg/day. There were no significant differences between the BPN and placebo groups in Montgomery-Åsberg Depression Rating Scale changes over time or adverse effects. BPN administration had minimal effects on functional magnetic resonance imaging blood oxygen level-dependent responses in regions involved in reward anticipation and response, no significant displacement of kappa opioid receptor radioligand in positron emission tomography imaging, and no significant changes in transcranial magnetic stimulation measures of inhibitory and excitatory cortical transmission., Conclusions: Our findings suggest a lack of clinical effect of low-dose BPN augmentation and lack of target engagement with this dosage and physiological probes., (© 2021 The Authors.)

Indirect fundoscopy is challenging for novice learners, as patients are often intolerant of the procedure, impeding development of proficiency. To address this, we developed a canine ocular simulator that we hypothesized would improve student learning compared to live dogs. Six board-certified veterinary ophthalmologists and 19 second-year veterinary students (novices) performed an indirect fundic examination on the model and live dog. Prior to assessment, novices were introduced to the skill with a standardized teaching protocol and practiced (without feedback) with either the model ( n = 10) or live dog ( n = 9) for 30 minutes. All participants evaluated realism and usefulness of the model using a Likert-type scale. Performance on the live dog and model was evaluated in all participants using time to completion of task, performance of fundic examination using a checklist and global score, identification of objects in the fundus of the model, and evaluation of time spent looking at the fundus of the model using eye tracking. Novices (trained on simulator or live dogs) were compared in fundic examination performance on the live dog and identification of shapes in the model. In general, experts performed the fundic examination faster ( p ≤ .0003) and more proficiently than the novices, although there were no differences in eye tracking behavior between groups ( p ≥ .06). No differences were detected between training on simulator versus live dog in development of fundoscopy skills in novices ( p ≥ .20). These findings suggest that this canine model may be an effective tool to train students to perform fundoscopy.

The US National Park Service (NPS) Night Skies Program measured changes in sky brightness resulting from a countywide lighting retrofit project. The retrofit took place in Chelan County, a gateway community to North Cascades National Park and Lake Chelan National Recreation Area in Washington State. The county retrofitted all 3693 county-owned high pressure sodium (HPS) street lamps to full cutoff LEDs. This number is about 60% of the County's total outdoor street and area lights. About 80% of the newly installed lights were 3000 K in color temperature and 20% were 4000 K. The 4000 K LEDs were used to meet Washington State Department of Transportation guidelines. To measure sky brightness, we used the NPS night sky camera system before the retrofit started in 2018 and after its completion in 2019. These images were photometrically calibrated and mosaicked together to provide hemispherical images in V band. For comparison with our ground-based measurement, we obtained the satellite imagery taken by Visible Infrared Imaging Radiometer Suite (VIIRS) onboard the Suomi National Polar-orbiting Partnership satellite. Our measurements show that the post-retrofit skyglow became brighter and extended higher in the sky, but upward radiance, as measured by the day-night band radiometer, decreased. These divergent results are likely explained by a substantial increase in light emitted at wavelengths shorter than 500 nm, and a relative decrease in upward light emission due to better shielded luminaires. These results also demonstrate that earlier models relating VIIRS day-night band data to skyglow will - at a minimum - require substantial revision to account for the different characteristics of solid state luminaires., (Published by Elsevier Ltd.)

Purpose: The purpose of this study was to determine if a battery of polarization-modulated stimuli, quantified as a single metric, is effective in identifying macular disease in the presence/absence of cataract or pseudophakia., Methods: Using a modified liquid crystal display, polarization pattern perception (PPP) for a formulated battery of geometric and logMAR stimuli was evaluated in participants that had either no eye pathology (healthy participants) or were grouped according to the presence of cataract, pseudophakia, and/or age-related macular degeneration (AMD). PPP was quantified as response frequencies to individual stimuli, and as a novel monocular polarization sensitivity score (Ps) based on perception of the stimulus battery set., Results: Stimulus response frequencies were pattern-dependent and, compared with healthy participants, reduced for cataract and AMD groups but not for subjects with pseudophakia. Compared with healthy eyes (n = 47, median Ps = 17), Ps was significantly reduced by AMD (n = 59, median Ps = 1, P < 0.001) and, to a lesser extent, by cataracts (n = 80, median Ps = 6, P < 0.001). There was no significant difference between Ps for healthy and pseudophakic eyes (n = 47, median Ps = 13, P = 0.323). There was no significant correlation between Ps and logMAR visual acuity., Conclusions: In the absence of significant cataract, or in pseudophakia, a set of polarization-modulated visual stimuli, quantified as the Ps score, distinguishes AMD from healthy maculae., Translational Relevance: Perception of polarization-modulated stimuli, previously shown to be macula-dependent in a laboratory setting, is effective as a test of macular function in health and disease in a clinic setting.

Purpose: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS)., Patients and Methods: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years., Results: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years., Conclusion: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy., Competing Interests: Melody A. CobleighConsulting or Advisory Role: Roche/Genentech, Immunomedics, Genomic Health, Puma Biotechnology, Seattle GeneticsResearch Funding: Macrogenics, Radius Health, Genentech/Roche, Seattle Genetics, Zymeworks, SynthonPatents, Royalties, Other Intellectual Property: Genomic HealthTravel, Accommodations, Expenses: Genentech, Immunomedics, Puma Biotechnology, Seattle Genetics Stewart J. AndersonConsulting or Advisory Role: Jazz Pharmaceuticals Kalliopi P. SiziopikouHonoraria: Ventana Medical Systems, Lilly, Merck Douglas W. ArthurStock and Other Ownership Interests: Advanced Radiation Therapy Rachel RabinovitchStock and Other Ownership Interests: Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, IDEXX LaboratoriesResearch Funding: Prelude Therapeutics Dennis L. CarterEmployment: Rocky Mountain Cancer Centers Melissa S. DillmonStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Puma Biotechnology Vivek S. KavadiEmployment: US Oncology Network Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava Sciences Sushil BeriwalHonoraria: Varian Medical Systems, XOFT Eleftherios P. MamounaHonoraria: Genentech/Roche, Genomic Health, PreciscaConsulting or Advisory Role: Genomic Health, BioTheranostics, Roche/Genentech, Merck, Daiichi Sankyo, Puma Biotechnology, PreciscaSpeakers' Bureau: Genomic Health, Genentech/RocheTravel, Accommodations, Expenses: Genomic Health, Genentech/RocheNo other potential conflicts of interest were reported.