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Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).Methods We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.Results Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.Conclusions We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration number NCT04358302.

Despite growing global attention to the 2015 UN Sustainable Development Goals, we have made limited progress towards achieving them. This article describes an emerging Transformative Learning Journey for Sustainability Leadership being developed for professionals at the University of St. Gallen in Switzerland. The purpose is to help participants achieve the individual transformations needed to enact sustainability-focused interventions in their communities and organizations. From a socio-material lens, we describe four phases of the emerging Learning Journey and identify how they are transformative. The Learning Journey includes spending time in nature, growing an understanding of climate justice, collaborating, and planning action. We draw on reflective data from participants, linking them to Hoggan's (2016a) transformative learning outcomes and other relevant studies, the goal being to contribute to the world's collective knowledge of "how" to facilitate development of the transformative skills identified by the United Nations, the European Commission, and the Inner Developmental Goals.

Introduction Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.Methods Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and dissemination Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration number ClinicalTrials.gov Registry (NCT04358302).

Abstract Background Migratory birds accomplish remarkable feats of long-distance navigation. Vagrants, few individuals who migrate to incorrect locations, reveal conditions where orientation and navigation fail. Studies of vagrancy on a continental scale reveal the importance of external factors such as strong winds driving birds off course, clouds obscuring migratory landmarks, and natural disruptions in the Earth’s magnetic field interfering with migratory orientation. Species may also possess characteristics that make them more prone to vagrancy. The external drivers of vagrancy on a smaller scale are less understood. Methods I used eBird, a community science dataset comprising millions of bird observations, to study land passerines observed over the Pacific Ocean, here termed offshore vagrants. These data present the opportunity to study a particular case of vagrancy: small-scale displacement into highly inhospitable areas. I modeled how season, wind, lack of visibility, interference with magnetoreception, and species differences may predict offshore vagrancy. Then, I modeled how species vagrancy likelihood is predicted by morphological and life history traits. Results Vagrancy was more common in the fall and positively associated with stronger tail winds in the spring. Species with greater preference for understory foraging habitat were less likely to occur as vagrants. Species vagrancy likelihood was higher in birds with a longer migration distance and rounded wings, but the relationship was weaker in birds with a pointed wings. Brown-headed Cowbirds were the most common offshore species in terms of absolute number of records and proportional to onshore frequency. Conclusions Offshore community science records proved revealing of mechanisms for small scale vagrancy in passerines. Offshore vagrancy can be driven by wind drift in the spring, but not in the fall despite higher overall levels of vagrancy. Life history characteristics like foraging habitat preference and migration duration may make some species more vulnerable to the effects of wind drift. Species with longer migrations may have more time to encounter vagrancy causing events, but greater aerodynamic efficiency may counteract this effect.

Despite the significant advances in antibiotic treatments and therapeutics, Staphylococcus aureus (S. aureus) remains a formidable pathogen, primarily due to its rapid acquisition of antibiotic resistance. Known for its array of virulence factors, including surface proteins that promote adhesion to host tissues, enzymes that break down host barriers, and toxins that contribute to immune evasion and tissue destruction, S. aureus poses a serious health threat. Both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) classify S. aureus as an ESKAPE pathogen, recognizing it as a critical threat to global health. The increasing prevalence of drug-resistant S. aureus underscores the need for new therapeutic strategies. This review discusses a promising approach that combines monoclonal antibodies targeting multiple S. aureus epitopes, offering synergistic efficacy in treating infections. Such strategies aim to reduce the capacity of the pathogen to develop resistance, presenting a potent adjunct or alternative to conventional antibiotic treatments.

Purpose: This was an investigation of the dimensionality of oral and written language to test the hypothesis that a two-factor model with sound/word and sentence/discourse language levels would best fit language and literacy data for a population-based sample in the school-age years. Method: A stratified secondary data set of 1,500 participants was drawn randomly from a larger nationally representative U.S. data set (N = 1,853) gathered during standardization of the Test of Integrated Language and Literacy Skills. A sample of 254 students with prior diagnoses of language and literacy disorders (LLD) was drawn from the full data set. Confirmatory factor analysis was used to compare the hypothesized two-factor model with other theoretically possible models. Results: The hypothesized two-factor language-levels model had an acceptable-to-good fit to the full data set, as did the three-factor model, with verbal memory added. High interfactor correlation between verbal memory and sentence/ discourse constructs, as well as a preference for parsimony, led to the acceptance of the two-factor model as best. This language-levels model had a good fit to the data at ages 8-11 years, and an excellent fit at ages 12-18 years, but only a poor fit for ages 6-7 years (yet still better than other two-factor or unitary models). It had a reasonable fit for students with LLD, although the three-factor model fit their data slightly better. Conclusions: Oral and written language abilities during the school-age years are best explained by a two-factor model with sound/word and sentence/ discourse language levels and memory as a contributing factor. Implications for identifying and treating language and literacy disorders as multidimensional rather than categorical are discussed.

Background & Aims: Novel finite therapies for chronic hepatitis B (CHB) are needed, since lifelong treatment is usually required with current available oral antivirals. This phase II study (NCT03615066) evaluated the safety, pharmacodynamics, and antiviral activity of selgantolimod (a Toll-like receptor 8 agonist [TLR8]) with tenofovir alafenamide (TAF). Methods: Viremic patients with CHB not receiving treatment were stratified by HBeAg status and randomized 2:2:1 to TAF 25 mg/day with selgantolimod 3 mg orally once weekly (QW), selgantolimod 1.5 mg QW, or placebo. Combination therapy continued until week (W)24, followed by TAF monotherapy until W48; patients then discontinued TAF and were followed until W96 (treatment-free follow-up [TFFU] period). The primary efficacy endpoint was the proportion with ≥1 log10 IU/ml HBsAg decline at W24. Results: Sixty-seven patients received study drug; 27 were followed during TFFU. Nausea, headache, vomiting, fatigue, and dizziness were the most common adverse events. Most adverse events were grade 1. Alanine aminotransferase flares were not observed up to W48. Four patients experienced alanine aminotransferase and hepatitis flares during TFFU; all had HBV DNA increases. Selgantolimod increased serum cytokines and chemokines and redistributed several circulating immune cell subsets. No patients achieved the primary efficacy endpoint. Mean HBsAg changes were −0.12, −0.16, and −0.12 log10 IU/ml in the selgantolimod 3 mg, selgantolimod 1.5 mg, and placebo groups, respectively, at W48; HBV DNA declined in all groups by ≥2 log10 IU/ml as early as W2, with all groups rebounding to baseline during TFFU. No HBsAg or HBeAg loss or seroconversion was observed throughout TFFU. Conclusions: Selgantolimod up to 3 mg was safe and well tolerated. Pharmacodynamics and antiviral activity in viremic patients support continued study of selgantolimod in combination CHB therapies. Impact and implications: Novel therapeutics for chronic HBV infection are needed to achieve a functional cure. In this study, we confirmed the safety and tolerability of selgantolimod (formerly GS-9688, a TLR8) when administered with tenofovir alafenamide over 24 weeks in viremic patients with chronic HBV infection. Overall, declines in HBsAg levels with selgantolimod treatment were modest; subgroup analysis indicated that patients with alanine aminotransferase levels greater than the upper limit of normal had significantly greater declines compared to those with normal alanine aminotransferase levels (–0.20 vs. –0.03 log10 IU/ml; p

We report the case of a near fatal arterial injury in a patient undergoing an inside-out catheter placement through an occluded central venous system using the Surfacer device (Bluegrass Vascular). The right internal mammary artery was inadvertently lacerated during the procedure, leading to cardiovascular collapse. The patient was rescued by transfusion, placement of a chest tube, and coil embolization of the right internal mammary artery. Postprocedure analysis of intraoperative cone beam computed tomography revealed that this injury was predictable on imaging, underscoring the need for advanced imaging guidance to enhance the safety of this procedure.

Abstract The emergence of COVID-19 virus has led to a pandemic with staggering morbidity and mortality. There is evidence showing that pre-existing conditions and environmental factors are associated with worse COVID-19 outcomes. Among these conditions, altitude is of particular interest. Altitude has been shown to influence the morbidity and mortality of multiple chronic pathologies such as cardiovascular disease, chronic obstructive pulmonary disease and lung cancer. COVID-19 fatality rate has been associated with as altitude as well, but findings are disputed. Therefore, we revisit this assessment with a comprehensive analysis of the relationship between COVID-19 fatality rates and altitude for the Mountain region of the United States while considering the effect of additional comorbidities and sociodemographic factors. A Generalized Additive Model (GAM) approach using one year of county data adjusted by population density was performed to evaluate associations within states and for the whole region. Our analysis revealed a consistent effect where COVID-19 case-fatality rate is decreased with higher altitude, even when controlling for pre-existing conditions and certain demographic variables. In summary, the work presented provides evidence that suggests that the protective effects of high altitude are likely to be influenced by physiologic factors but demographic trends that are associated with life at high altitude must also be considered.

BackgroundThe oral microbiome is incredibly complex, containing a diverse complement of microbiota that has previously been categorized into 6 broad phyla. While techniques such as next-generation sequencing have contributed to a better understanding of the composition of the oral microbiome, the role it plays in human health and disease is still under investigation. Previous studies have identified that a more diverse microbiome is advantageous for health. Therefore, alterations to the physical or mental health that are of interest in this study, such as stress, are the factors that decrease microbial diversity, leading to the potential for dysbiosis and disease disposition. Intensive Surgical Skills Week (ISSW) is a hyper-realistic simulation training week for military medical students that takes place at the Strategic Operations (STOPS) facility in San Diego, CA. This training week puts students through mass causality simulations and requires them to work through distinct roles within the healthcare team, providing an almost ideal environment to assess the impact of acute stress on oral microbiome diversity. Based on the literature on stress and microbiota, we hypothesized that the high stress simulation events at ISSW will impact the composition and diversity of the oral microbiome.MethodsTo investigate this hypothesis, thirty-seven (n = 37) second-or third-year medical students who are enlisted in a branch of the military and who attended ISSW in July of 2021 were included in the study. Student participants were divided into 7 teams to complete the hyper-realistic simulations (SIMs) at ISSW. A pilot of sixty-four buccal samples (n = 64) from three of the seven teams were sent for analysis at the University of Missouri Metagenomic Center.ResultsWe saw an overall increase in species richness at the end of ISSW when looking at all samples (n = 64). Fourteen significantly different bacteria were identified from the beginning to the end of data collection. Additionally, third year medical students appear to have a greater species richness compared to second year medical students. Further, third year medical students had a statically significant difference in their oral microbiome richness from beginning to end of data collection (p = 0.008).ConclusionOur preliminary data indicates that physical and psychological stress can impact the composition of the oral microbiome. The analyses in this study show that using the oral microbiome as an indicator of stress is promising and may provide evidence to support stress management practices.

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed to accomplish intravenous delivery with the potential to target all solid tumors and their metastases in a single dose. This study characterizes CRISPR/Cas9 modified C. novyi-NT to insert the gene for RGD, a tumor targeting peptide, expressed within the promoter region of a spore coat protein. Expression of the RGD peptide on the outer spore coat of C. novyi-NT indicates an increased capacity for tumor localization of C. novyi upon intravenous introduction based on the natural binding of RGD with the αvβ3 integrin commonly overexpressed on the epithelial tissue surrounding a tumor, and lead to immune stimulation.

Oncolytic bacteria are a classification of bacteria with a natural ability to specifically target solid tumors and, in the process, stimulate a potent immune response. Currently, these include species of Klebsiella, Listeria, Mycobacteria, Streptococcus/Serratia (Coley’s Toxin), Proteus, Salmonella, and Clostridium. Advancements in techniques and methodology, including genetic engineering, create opportunities to “hijack” typical host–pathogen interactions and subsequently harness oncolytic capacities. Engineering, sometimes termed “domestication”, of oncolytic bacterial species is especially beneficial when solid tumors are inaccessible or metastasize early in development. This review examines reported oncolytic bacteria–host immune interactions and details the known mechanisms of these interactions to the protein level. A synopsis of the presented membrane surface molecules that elicit particularly promising oncolytic capacities is paired with the stimulated localized and systemic immunogenic effects. In addition, oncolytic bacterial progression toward clinical translation through engineering efforts are discussed, with thorough attention given to strains that have accomplished Phase III clinical trial initiation. In addition to therapeutic mitigation after the tumor has formed, some bacterial species, referred to as “prophylactic”, may even be able to prevent or “derail” tumor formation through anti-inflammatory capabilities. These promising species and their particularly favorable characteristics are summarized as well. A complete understanding of the bacteria–host interaction will likely be necessary to assess anti-cancer capacities and unlock the full cancer therapeutic potential of oncolytic bacteria.

The SARS-CoV-2 epidemic has impacted children's education, with schools required to implement infection control measures that have led to periods of absence and classroom closures. We developed an agent-based epidemiological model of SARS-CoV-2 transmission in a school classroom that allows us to quantify projected infection patterns within primary school classrooms, and related uncertainties. Our approach is based on a contact model constructed using random networks, informed by structured expert judgement. The effectiveness of mitigation strategies in suppressing infection outbreaks and limiting pupil absence are considered. COVID-19 infections in primary schools in England in autumn 2020 were re-examined and the model was then used to estimate infection levels in autumn 2021, as the Delta variant was emerging and it was thought likely that school transmission would play a major role in an incipient new wave of the epidemic. Our results were in good agreement with available data. These findings indicate that testing-based surveillance is more effective than bubble quarantine, both for reducing transmission and avoiding pupil absence, even accounting for insensitivity of self-administered tests. Bubble quarantine entails large numbers of absences, with only modest impact on classroom infections. However, maintaining reduced contact rates within the classroom can have a major benefit for managing COVID-19 in school settings.

The current study explored the associations between relationship stigma, Racial-ethnic Worldview (REW; a construct developed as a comprehensive assessment of individual's perceptions of race and ethnicity), and relationship quality among those in interracial relationships (i. e., participants indicated their race was different than the race of their partner). One type of REW (Color-blind Achieved) was especially susceptible to the negative consequences of stigma from family members. Other significant differences in relationship quality and relationship stigma were found based on REW. Most notable is that individuals who acknowledge institutional racism, have positive intergroup attitudes, and a positive ethnic identity reported better relationship quality than those who denied institutional racism and/or had less positive attitudes toward their own ethnic group. These results demonstrate the utility of REW in contextualizing the experiences of individuals in interracial relationships as it relates to perceived stigma and relationship quality. The study offers a critical account of how individuals understanding of the racial and ethnic social context shapes relationship outcomes for those in interracial relationships in the United States.

Autoimmune (AI) diseases, which present in a multitude of systemic manifestations, have been connected to many underlying factors. These factors include the environment, genetics, individual microbiomes, and diet. An individual’s gut microbiota is an integral aspect of human functioning, as it is intimately integrated into the metabolic, mechanical, immunological, and neurologic pathways of the body. The microbiota dynamically changes throughout our lifetimes and is individually unique. While the gut microbiome is ever-adaptive, gut dysbiosis can exert a significant influence on physical and mental health. Gut dysbiosis is a common factor in various AI, and diets with elevated fat and sugar content have been linked to gut microbiome alterations, contributing to increased systemic inflammation. Additionally, multiple AI’s have increased levels of certain inflammatory markers such as TNF-a, IL-6, and IL-17 that have been shown to contribute to arthropathy and are also linked to increased levels of gut dysbiosis. While chronic inflammation has been shown to affect many physiologic systems, this review explores the connection between gut microbiota, bone metabolism, and the skeletal and joint destruction associated with various AI, including psoriatic arthritis, systemic lupus erythematosus, irritable bowel disease, and rheumatoid arthritis. This review aims to define the mechanisms of microbiome crosstalk between the cells of bone and cartilage, as well as to investigate the potential bidirectional connections between AI, bony and cartilaginous tissue, and the gut microbiome. By doing this, the review also introduces the concept of altering an individual’s specific gut microbiota as a form of regenerative medicine and potential tailored therapy for joint destruction seen in AI. We hope to show multiple, specific ways to target the microbiome through diet changes, rebalancing microbial diversity, or decreasing specific microbes associated with increased gut permeability, leading to reduced systemic inflammation contributing to joint pathology. Additionally, we plan to show that diet alterations can promote beneficial changes in the gut microbiota, supporting the body’s own endogenous processes to decrease inflammation and increase healing. This concept of microbial alteration falls under the definition of regenerative medicine and should be included accordingly. By implementing microbial alterations in regenerative medicine, this current study could lend increasing support to the current research on the associations of the gut microbiota, bone metabolism, and AI-related musculoskeletal pathology.

Abstract The implications of recent discoveries pertaining to immune‐mediated disease and the human gut microbiome are vast. In a symbiotic relationship, the immune system modulates the maintenance of host‐microbe normobiosis, and the gut microbiome plays a critical role in developing and maintaining the host's innate and adaptive immune systems. The cutting edge of microbiome research and personalized medicine targets the clinical application and exploitation of gut microbiota modulation in the setting of specific diseases. For example, prebiotic/probiotic supplementation, microbiome enhancing diets, and fecal microbiota transplant have been studied as potential ameliorative supplemental interventions to combined antiretroviral therapy (cART) in human immunodeficiency virus‐positive (HIV+) individuals. Furthermore, recent evidence shows a positive correlation between improved CD4+ cell counts in HIV+ individuals and improved gut microbiota profile after cART. We supplement this finding with data and supporting evidence from recent studies to aid in the clinical application of these findings in this commentary. Preliminary data support the consideration of the gut microbiota in the proactive management of HIV‐associated comorbidities.

The GEAR UP graduation coach intervention developed by the GEAR UP Learning Centers at Western Michigan University (WMU) addresses the issue of academic failure of at-risk students in high school. This personalized early intervention strategy begins by assessing students' unique circumstances, academic histories, and strengths and weaknesses in 9th grade. Coach and student work together, networking with parents and teachers, to establish a plan that will bolster academic achievement. Intensive graduation coaching identifies internal and external resources to ensure the student's success and closely monitors the student's progress. This intervention has been implemented successfully in two urban school settings and results indicated substantial benefits. This study examines a replication of this model in a rural school setting for one year with an incoming 9th grade class. The process involved several phases: program preparation and staff and student selection; implementing the coaching intervention and monitoring progress for informed, data-driven decision-making; and final summative evaluation. Two general questions were of particular research interest. Could students be identified proactively who are likely to benefit from this program? Did students selected as part of the coaching caseload improve their grades? A longitudinal, retrospective baseline study provided matched comparison groups for examining the effects of the intervention treatment. Results show that these graduation coached at-risk students as a group performed academically in core courses almost an entire letter grade better than would have anticipated based on comparative student results from baseline studies. Well over 50% of the treatment students, all of whom were predicted to fail, actually succeeded well enough to be prepared to progress to the next grade level. In this instance, graduation coaching appears to have significant potential in rural as well as urban school to promote student retention, success, and perseverance to graduation.

Abstract Background School-based physical activity and running programmes, such as The Daily Mile™, are increasing in popularity globally. The aim of this research was to examine the acute impact of such classroom physical activity breaks on cognition and affective wellbeing. Methods A total of 5463 school pupils from 332 schools took part in a citizen science project with a repeated measures design. They completed tasks of cognition (inhibition, verbal, and visuo-spatial working memory) and the Children’s Feeling Scale and Felt Arousal Scale before and after three different outdoor activities: a classroom break of 15 min of self-paced activity, a near maximal exhaustion activity (the bleep test), and a no-exercise control group where pupils sat or stood outside. Wellbeing and fitness were examined as mediators of the relationship between outdoor activity and cognition. Results Fifteen minutes of self-paced outdoor activity was beneficial for pupils’ cognition and wellbeing in comparison to both other activities (Cohen’s d effect sizes ranging from 0.04 to 0.22; small). The relationship with cognition was not mediated by participants’ fitness level and was only partially mediated by wellbeing. Change scores for alertness were higher after the bleep test compared to the control activity but similar for all other outcomes. Conclusions Taking a break from the classroom to complete 15 min of self-paced physical activity should be considered a worthwhile activity by class teachers, school management, and policymakers. Additionally, more intense physical activity should not be considered to be detrimental.

Mountain glaciers and snowfields are rapidly receding because of climate warming. Species living in these habitats remain poorly studied, likely because of the remoteness and ruggedness of their terrain. We leveraged community science data from eBird—an online database of bird observations from around the world—to characterize bird use of mountain glaciers and snowfields. We estimated total bird biodiversity and preference for glaciers and snowfields over nearby, ice-adjacent habitats. We used field notes from eBird users and breeding codes to extend our data set to include insight into habitat usage and behavior. Finally, we compared our community-science approach to previous studies that used traditional (i.e., professional) field survey methods. We identified considerable avian biodiversity in glacier and snowfield habitat (46 species) with four specialists that appeared to prefer glaciers and snowfields over nearby, ice-adjacent habitats. Birds appeared to primarily use the glacier and snowfield habitats for foraging. When community science data was compared to traditional methods, results were similar, but community science resulted in a higher species diversity estimate. Our findings suggest glacier and snowfield retreat threatens specialist species via loss of nutrient resources. Additionally, community science data appears valuable for characterizing difficult to access areas, but traditional surveys are still useful for more rigorous quantification of avian biodiversity.

Cardiac blood pool imaging is currently performed almost exclusively with 99mTc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope 68Ga is used, it can be applied repeatedly on the same day—for example, for the detection of bleeding. Our objective was to prepare and evaluate a long-circulating polymer functionalized with gallium for its biodistribution, toxicity, and dosimetric properties. A 500 kDa hyperbranched polyglycerol was conjugated to the chelator NOTA and radiolabeled rapidly at room temperature with 68Ga. It was then injected intravenously into a rat, and gated imaging allowed us to easily observe wall motion and cardiac contractility, confirming the suitability of this radiopharmaceutical for cardiac blood pool imaging. Internal radiation dose calculations showed that the radiation doses that patients would receive from the PET agent would be 2.5× lower than those from the 99mTc agent. A complete 14-day toxicology study in rats concluded that there were no gross pathology findings, changes in body or organ weights, or histopathological events. This radioactive-metal-functionalized polymer might be a suitable non-toxic agent to advance for clinical application.

Career development is an essential role of the school counselor. This study examined the role of school counselors in assisting middle school and high school students with choosing careers. Special attention is given to school counselors working with students with and without disabilities. Results indicated that school counselors spend more counseling time with students without disabilities. Implications for school counseling practice are discussed. (Contains 4 tables.)

Abstract We thank Daly-Smith et al. for taking the time to read the results of our pilot research study, describing it as an important and welcome contribution. Nonetheless, the authors argue six points against our conclusion. We contend that we addressed three of these points in our original discussion and disagree with their remaining points. Overall, their Commentary adds little to the topic of research into the Daily Mile™ that we had not already raised in our discussion. Additionally, they attribute statements to us that we did not make and ignore the raising of key issues in our original article. Given this, we stand by our original peer-reviewed conclusion that introducing the Daily Mile™ to the primary school day appears to be an effective intervention for increasing levels of moderate to vigorous physical activity, reducing sedentary time, increasing physical fitness and improving body composition, and that these findings have relevance for teachers, policy-makers, public health practitioners and health researchers.

Infection remains one of the largest threats to global health. Among those infections that are especially troublesome, osteomyelitis, or inflammation of the bone, typically due to infection, is a particularly difficult condition to diagnose and treat. This difficulty stems not only from the biological complexities of opportunistic infections designed to avoid the onslaught of both the host immune system as well as exogenous antibiotics, but also from changes in the host vasculature and the heterogeneity of infectious presentations. While several groups have attempted to classify and stage osteomyelitis, controversy remains, often delaying diagnosis and treatment. Despite a host of preclinical treatment advances being incubated in academic and company research and development labs worldwide, clinical treatment strategies remain relatively stagnant, including surgical debridement and lengthy courses of intravenous antibiotics, both of which may compromise the overall health of the bone and the patient. This manuscript reviews the current methods for diagnosing and treating osteomyelitis and then contemplates the role that nanotechnology might play in the advancement of osteomyelitis treatment.