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Introduction/Objective NTRK3 gene encodes a transmembrane protein receptor of the tropomyosin receptor kinase (Trk) family. Gene fusions involving NTRK3 result in a constitutive activation or overexpression of Trk receptor, potentially leading to oncogenesis. NTRK targeted therapies show a promising activity in varied cancer types with NTRK fusions. The aim of this case review is to describe the clinical and pathologic findings of thyroid neoplasm with NTRK3 gene fusions. Methods/Case Report The cytology fine needle aspiration (FNA), molecular testing results and pathology of surgical resections are reviewed in 220 cases of total and hemithyroidectomy from January 2018 to May 2021. Results (if a Case Study enter NA) Three cases with NTRK3 gene fusions are identified by Thyroseq or Afirma GSC from FNA of thyroid nodules with later surgical intervention. No other mutations or gene fusions were identified. Each case had total thyroidectomy. Case 1 is a 41-year-old female with FNA diagnosis of suspicious for papillary thyroid carcinoma (PTC) and ETV6/NTRK3 fusion found by Afirma GSC. Pathology diagnosis is PTC classic type, two tumor nodules 1.1cm and 1.0cm, lymphovascular invasion not identified, three lymph nodes not involved by tumor and pathologic stage pT1b(m) pN0. Case 2 is a 49-year-old female with FNA diagnosis of atypia of undetermined significance and ETV6/NTRK3 fusion detected by Thyroseq. Pathology diagnosis is infiltrative PTC follicular variant, 2.0cm, angioinvasion present, no lymph nodes submitted and pathologic stage pT1b(m) pNX. Case 3 is a 28-year-old female with FNA diagnosis of suspicious for follicular derived neoplasm and NTRK3/RBPMS fusion is detected by Afirma GSC. Pathology diagnosis is infiltrative PTC follicular variant, 1.5cm, 9 of 11 lymph nodes positive for metastatic carcinoma and pathologic stage pT1b pN1b. Conclusion Thyroid neoplasm with NTRK3-rearrangement is rare. Cases 1 and 2 with common ETV6-NTRK3 fusion show PTC classic type and infiltrative PTC follicular variant with angioinvasion. Case 3 with less common NTRK3/RBPMS fusion shows infiltrative PTC follicular variant and significant lymph node involvement. Our limited cases of NTRK3-rearranged thyroid carcinoma demonstrate infiltrative growth, diverse phenotypes, one case with angioinvasion and no lymph nodes submitted and one case with multiple lymph node metastasis. This suggests aggressive behavior of thyroid cancer with NTRK3 gene fusion and patients may benefit from targeted NTRK therapy.

Objective To examine exposure to energy drink marketing among youth and young adults, and test perceptions of energy drink advertisements (ads) regarding target audience age and promoting energy drink use during sports. Design A between-group experiment randomly assigned respondents to view one of four energy drink ads (sport-themed or control) and assessed perceptions of the ad. Regression models examined marketing exposure and perceptions. Setting Online survey (2014). Subjects Canadians aged 12–24 years (n 2040) from a commercial panel. Results Overall, 83 % reported ever seeing energy drink ads through at least one channel, including on television (60 %), posters/signs in stores (49 %) and online (44 %). Across experimental conditions, most respondents (70·1 %) thought the ad they viewed targeted people their age or younger, including 42·2 % of those aged 12–14 years. Two sport-themed ads were more likely to be perceived as targeting a younger audience (adjusted OR (95 % CI): ‘X Games’ 36·5 %, 4·16 (3·00, 5·77); ‘snowboard’ 19·2 %, 1·50 (1·06, 2·13)) v. control (13·3 %). Participants were more likely to believe an ad promoted energy drink use during sports if they viewed any sport-themed ad (‘X Games’ 69·9 %, 8·29 (6·24, 11·02); ‘snowboard’ 76·7 %, 11·85 (8·82, 15·92); ‘gym’ 66·8 %, 7·29 (5·52, 9·64)) v. control (22·0 %). Greater reported exposure to energy drink marketing was associated with perceiving study ads as promoting energy drink use during sports. Conclusions Energy drink marketing has a high reach among young people. Ads for energy drinks were perceived as targeting youth and promoting use during sports. Such ads may be perceived as making physical performance claims, counter to Canadian regulations.

As driverless vehicles enter the nation’s roads, engineers will be called on to keep the streets safe and efficient. To do so will require many changes to our transportation infrastructure, affecting everything from the design of intersections and parking facilities to the funding of transportation-related maintenance.

For some engineering firms, a focus on sustainability is not just one of the many services they offer their clients. It’s a critical tool—involving environmental, social, and economic benefits—that they integrate into all aspects of how they run their businesses.

Theoretical and empirical research is challenging long-held assumptions about how culture shapes children’s thinking, emotions, and actions. No longer is ‘culture’ thought to be a family-ba...

When the underwater portions of a bridge or waterfront facility need to be inspected, the right person for the job is often an engineer diver, a specially trained professional who understands load paths in structures and also knows the best ways to avoid contracting “the bends.” Working under conditions that can include zero visibility, strong currents, thick ice, and alligators, engineer divers must confront physical challenges far more daunting than those faced by most civil engineers.

The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees. Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT. For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision making and periodic reevaluation. For bothersome GSM symptoms not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended. This NAMS position statement has been endorsed by Academy of Women's Health, American Association of Clinical Endocrinologists, American Association of Nurse Practitioners, American Medical Women's Association, American Society for Reproductive Medicine, Asociación Mexicana para el Estudio del Climaterio, Association of Reproductive Health Professionals, Australasian Menopause Society, Chinese Menopause Society, Colegio Mexicano de Especialistas en Ginecologia y Obstetricia, Czech Menopause and Andropause Society, Dominican Menopause Society, European Menopause and Andropause Society, German Menopause Society, Groupe d’études de la ménopause et du vieillissement Hormonal, HealthyWomen, Indian Menopause Society, International Menopause Society, International Osteoporosis Foundation, International Society for the Study of Women's Sexual Health, Israeli Menopause Society, Japan Society of Menopause and Women's Health, Korean Society of Menopause, Menopause Research Society of Singapore, National Association of Nurse Practitioners in Women's Health, SOBRAC and FEBRASGO, SIGMA Canadian Menopause Society, Società Italiana della Menopausa, Society of Obstetricians and Gynaecologists of Canada, South African Menopause Society, Taiwanese Menopause Society, and the Thai Menopause Society. The American College of Obstetricians and Gynecologists supports the value of this clinical document as an educational tool, June 2017. The British Menopause Society supports this Position Statement.

The mandate by the Energy Independence and Security Act of 2007 to increase renewable fuel production in the USA has resulted in extensive research into the sustainability of perennial bioenergy crops such as switchgrass (Panicum virgatum) and miscanthus (Miscanthus× giganteus). Perennial grassland crops have been shown to support greater aboveground biodiversity and ecosystem function than annual crops. However, management considerations, such as what crop to plant or whether to use fertilizer, may alter belowground diversity and ecosystem functioning associated with these grasslands as well. In this study, we compared crop type (switchgrass or miscanthus) and nitrogen fertilization effects on arbuscular mycorrhizal fungal (AMF) and soil nematode abundance, activity, and diversity in a long-term experiment. We quantified AMF root colonization, AMF extra-radical hyphal length, soil glomalin concentrations, AMF richness and diversity, plant-parasitic nematode abundance, and nematode family richness and diversity in each treatment. Mycorrhizal activity and diversity were higher with switchgrass than with miscanthus, leading to higher potential soil carbon contributions via increased hyphal growth and glomalin production. Plant-parasitic nematode (PPN) abundance was 2.3 × higher in miscanthus plots compared to switchgrass, mostly due to increases in dagger nematodes (Xiphinema). The higher PPN abundance in miscanthus may be a consequence of lower AMF in this species, as AMF can provide protection against PPN through a variety of mechanisms. Nitrogen fertilization had minor negative effects on AMF and nematode diversity associated with these crops. Overall, we found that crop type and fertilizer application associated with perennial bioenergy cropping systems can have detectable effects on the diversity and composition of soil communities, which may have important consequences for the ecosystem services provided by these systems.

As outlined in compression therapy literature, the performance of a compression textile can be characterized by its stiffness and interface pressure. In this study, an indirect approach for measuring pressure from a set of compression bandages and hosiery was developed, from which rigidity (EI) values were determined, and tension–elongation curves and pressure-elongation data were calculated. The calculated pressure values were compared against PicoPress sensor readings measured on 10 participants. Results showed that the correlation between both approaches varied among bandage and hosiery samples.

While many tourists recognize the necessity of responsible tourism, not all respond to it equally. Thus, this study explores behavioral discrepancies in responsible tourism practices with respect to three types of ethical travel issues (economic, socio-cultural, and environmental). An ethical decision-making process that begins with perceived importance of ethical issues (PIE) was examined using a scenario approach based on responses from tourists in South Korea. Results found that (1) tourists responded to specific responsible issues in different ways, (2) PIE was positively related to ethical decision making, and (3) except for economic issues, tourists with more travel experiences were more likely to make ethically favorable decisions. Such findings provide useful information that can help improve upon the limited understanding of the ethical decisions of tourists. Effective communication and management strategies to raise awareness and facilitate responsible tourist behavior are further discussed.

Often considered the eighth wonder of the world, the Panama Canal now has a third lane with its own set of locks that has doubled the waterway’s capacity and increased the size of vessels that the canal can accommodate. The $5.25-billion expansion project has also sent infrastructure improvement ripples around the globe.

From the modern scientific perspective, Olympia is a ruin at the far end of a fading sense of history that represents little more than the origins from which sport has continuously evolved. Quantitative measurements show continued increases in human performance, equipment efficiency and funding. But some question this athletic evolution. We worry about qualitative issues, such as virtue, meaning and beauty. The source of this contrast is a difference in values: Olympic vs. Efficiency values. Such values establish an ethos in sporting communities that influences how we behave, explain and even conceptualize our activities. I argue from the perspectives of metaphysics, epistemology, aesthetics, ethics and politics, that Olympic Ethos is needed to balance out the modern Efficiency Ethos, which threatens to dehumanize sport.

The growing market for caffeinated energy drinks (CEDs) has caused concern about excessive caffeine intake and potential adverse effects, particularly among young people. The current study examined patterns of CED consumption among youth and young adults in Canada, using data from a national online survey conducted in October 2014. Data from a non-probability sample of 2040 respondents aged 12–24 from a consumer panel was weighted to national proportions; measures of CED consumption were estimated, including prevalence, excessive daily consumption, and context for use (locations and reasons). Separate logistic regression models for two outcomes, past-week consumption and “ever” exceeding two energy drinks in a day (as per common guidance), were conducted to examine associations with demographic variables (sex, age, geographic region, race/ethnicity, and language). Overall, 73.6% of respondents reported “ever” consuming energy drinks; 15.6% had done so in the past week. Any consumption of energy drinks in the past week was more prevalent among males, Aboriginal respondents (vs. white only or mixed/other), and residents of British Columbia. Among “ever-consumers,” 16.0% reported ever consuming more than two energy drinks in a day. Exceeding two in a day was more prevalent among older respondents (young adults aged 18–24), aboriginal respondents (vs. white only), and British Columbia residents. While the majority of youth and young adults had consumed energy drinks, about half were “experimental” consumers (i.e., consumed ≤ 5 drinks in their lifetime). Approximately one in six consumers had exceeded the usual guidance for maximum daily consumption, potentially increasing their risk of experiencing adverse effects., Highlights • Most (73.6%) Canadian youth and young adults (age 12–24) surveyed had consumed CEDs. • Half of ever-consumers (and most youth) had consumed ≤ 5 CEDs in their lifetime. • Past-week CED prevalence was 15.6%, highest among males, Aboriginals, BC residents. • 16.0% of ever-consumers reported exceeding two CEDs in a day (guidance for maximum). • Excess consumption was more prevalent among age 18–24, Aboriginals, BC residents.

Life cycle cost analysis can help engineers make decisions about materials and design that in turn will affect the operating and maintenance costs of infrastructure over the long term. This data-driven approach could also help save hundreds of millions of dollars, which would help close the gap between the funds required and the funds available.

Androgens, both in excessive and depleted states, have been implicated in female reproductive health disorders. As such, serum testosterone measurements are frequently ordered by physicians in cases of sexual dysfunction and in women presenting with hirsutism. Commercially available androgen assays have significant limitations in the female population. Furthermore, the measurements themselves are not always informative in patient diagnosis, treatment, or prognosis. This article reviews the limitations of serum androgen measurements in women suspected to have elevated or reduced androgen action. Finally, we consider when therapeutic use of androgen replacement may be appropriate for women with sexual interest/arousal disorders.

Understanding the frequency of and reasons for postpartum revisits, which occur more often for women with delivery complications than for those without, can help identify risk and inform discharge care. The objective of this study was to examine the rate of and reasons for inpatient and emergency department (ED) revisits 7 days and 42 days following deliveries with and without severe maternal morbidity (SMM). Retrospective conveys the intended meaning. cohort study using data from the Agency for Healthcare Research and Quality’s 2016‐2017 Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases from 14 states with de‐identified patient linkage numbers and adequate race/ethnicity coding (AR, FL, GA, IA, MD, MS, MO, NV, OR, SC, SD, TN, VT, and WI). The analysis consisted of delivery hospitalizations and postpartum inpatient and ED revisits for women aged 12‐55 years. SMM conditions at delivery were grouped into eight types: severe cardiac conditions, sickle cell disease with crisis, severe hypertensive disorders, severe respiratory conditions, sepsis, severe hemorrhage, other severe obstetric conditions, and other severe medical conditions. Outcomes included 7‐day and 42‐day inpatient and ED age‐adjusted revisit rates and the reason for the revisit. A total of 9164 index deliveries with an SMM condition and 1 406 582 deliveries without an SMM condition at delivery were included. Of those deliveries with an SMM condition, 35.0% were for black women and 23.1% were for women aged 35 years and older compared with 22.4% and 15.2% of deliveries without an SMM condition, respectively. Overall, 73.2 per 1000 deliveries with an SMM condition had an inpatient or ED revisit within 7 days and one in five women returned within 42 days postpartum (207.0 revisits per 1000 deliveries). These rates were more than twice as high as those for deliveries without an SMM condition (32.1 and 87.7 per 1000, respectively). Among women with only one SMM type at delivery, the 42‐day revisit rate for inpatient or ED care was as high as 445.5 per 1000 deliveries with sickle cell disease with crisis, followed by 250.9 per 1000 deliveries with severe cardiac conditions. An additional 2400 women without an SMM condition diagnosed at delivery had an inpatient readmission within 7 days for an SMM‐related condition. Women with the highest postpartum revisit rates included those with a diagnosis of SMM at delivery overall and specifically those with sickle cell disease with crisis and severe cardiac conditions. A number of women with SMM conditions were diagnosed at a postpartum readmission and not at the delivery. Examining revisits during the postpartum period is an important consideration when studying SMM. This study can help identify women at high risk of postpartum revisits. The data can be used to inform the scheduling and content of coordinated discharge care, assist with resource allocation, and identify research priorities for maternal care. Future research is needed to examine the contributions of clinical factors at delivery, expected payer, and hospital and community characteristics in explaining disparities in the risk of postpartum readmission. Agency for Healthcare Research and Quality.

Objective To examine the sources of vaping products reported by adolescents, and the characteristics of adolescents who reported purchasing a vaping product in the past year in the United States (US), Canada (CA), and England (EN). Methods Data were from the 2017 ITC Youth Tobacco and Vaping Survey, a web-based survey of 12,128 respondents aged 16–19 years recruited from commercial panels in the US, CA, and EN. Respondents who have vaped in the past 12 months were asked whether they had purchased a vaping product, and from where (vape shop, online, retail), as well as whether anyone refused to sell them a vaping product because of their age. Respondents who reported vaping in the past 30 days were asked where they had obtained their vaping product from a social and/or commercial source. Results Only about 7.5% of respondents reported having purchased a vaping product in the past year. Among those who had vaped in the past year, 32.6% reported having purchased a vaping product in the past year. Purchasing prevalence was significantly higher among US respondents compared to those from CA and EN; purchase prevalence was also higher among Canadian adolescents than respondents from England. The most commonly reported purchase location for vaping products in all counties was vape shops. Among past 30-day vapers, 42.5% reported getting their vaping products only from social sources, 41.4% only from commercial sources, and 13.4% from both types of sources. Purchasing a vaping product in the past year was associated with being male, of legal age to buy tobacco and vaping products, and greater frequency of smoking and vaping in the past 30 days. Conclusions Most adolescents have not purchased a vaping product, but among those who had, vape shops were the mostly commonly reported location for buying a vaping product. Purchasing of a vape product was more commonly reported by those who vape more frequently and by those of legal age to buy a vaping product.

Photoelectron angular distributions (PADs), ranging up to the maximum 6th order Legendre polynomial term set by the Yang theorem, have been recorded for the (2 + 1) resonance enhanced multiphoton ionization (REMPI) of two terpene isomers, 3-carene and α-pinene, employing femtosecond lasers and electron velocity map imaging detection. PAD measurements made with coincident photoion detection allow ion fragmentation effects to be assessed. Using circular polarization and enantiomerically pure samples the PAD measurements are extended to include chiral (odd) Legendre polynomial terms, and these are analysed and discussed as multiphoton photoelectron circular dichroism (MP-PECD). Comparisons are also made with single photon (synchrotron radiation) PECD of these compounds. Although for a given compound a common final cation state is reached, pronounced differences are observed between PECD and MP-PECD, and between the alternative identified REMPI intermediate states in the case of MP-PECD.

Much of the information in the chemistry, manufacturing, and controls section of regulatory filing is comprised of analytical data. The analytical methods designed for use in development and manufacturing are expected by regulatory authorities to be specific, sensitive, accurate, robust, and suitable and reliable for the specified purpose because data generated by the methods may otherwise be perceived as unreliable. The analytical procedures required for the understanding and control of the manufacturing processes, as well as those required for understanding and quality control of process materials, drug substance, and drug product are essential components of the overall quality control strategy. The development and justification of the specifications are critical to ensure the safety and efficacy of the product. Key methods designed and utilized in a research and development must be sufficiently robust to be transferred to other groups and sites during development and commercialization.

The transfer of an analytical procedure is the documented process that qualifies a laboratory to use the method that originated in another laboratory, therefore ensuring that the receiving unit has the procedural knowledge and ability to perform the procedure as intended. Analytical methods are commonly transferred from the originating (transferring) site to other laboratories during the clinical, scale-up, or commercialization phases of product development. These receiving laboratories could be within the same company, to another company (when a product is sold), or to an external contract laboratory. The methods may be transferred several times to more than one laboratory across the globe over the lifecycle of the product. It is imperative that the knowledge associated with the routine and successful operation of a method be provided to each site. Also, it must be clearly demonstrated and documented that the receiving laboratories are capable of running the methods and obtaining results with the same accuracy and precision as the laboratory that originally developed that method.

The current study examined the efficacy of health warnings on caffeinated energy drinks (CEDs). Participants aged 12–24 years (n = 2040) completed an online survey where they were asked to recall any existing warning statements on CED products and were randomized to one of 29 experimental warning conditions. Regression models were fitted to examine differences between conditions in product appeal, perceived safety and message recall. Overall, fewer than 30% of participants were able to accurately describe an existing CED product warning. Experimental findings indicated that exposure to CEDs with warning labels resulted in greater recall. Warnings on the back of CED cans featuring large font, a border, and a ‘caution’ heading resulted in significantly greater recall (P

The druggability and developability space is rapidly evolving in the post-genomic era. In the past, Lipinski’s rule-of-five (Ro5) emerged and served as a guide for drug-like molecule design for oral delivery in the traditional druggable target space. In contrast, in this new era, a transition is occurring in drug discovery towards novel approaches to bind and modulate challenging biological targets that have led to transformative treatments for patients. Consequently, drugging novel targets using a variety of emerging molecular modalities, namely beyond the Ro5 (bRo5) small molecules (such as protein-protein interaction modulators, protein-targeted chimeras, or PROTACs), peptide/peptidomimetics, and nucleic acid-based modalities, have become a key focus in drug discovery. Herein, the emerging druggability and developability space is discussed side by side to build a general understanding of the potential development challenges of these novel modalities. An overview is provided on the evolving novel targets and molecular modalities, followed by a detailed analysis of the druggability aspects as well as the strategies used to progress drug candidate, and the trending chemistry and formulation strategies used to assess developability.

Background PD‐1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD‐L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab. Methods Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6–12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD‐L1. Results CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD‐L1+ CTCs (14/25, 64%) had significantly longer progression‐free survival (PFS) compared with patients with PD‐L1− CTCs (26.6 months vs. 5.5 months; p = .018). The 12‐month PFS rates were 76% versus 22% in the PD‐L1+ versus PD‐L1− CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD‐L1+ CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052–1.012; p = .026). Conclusion Our results reveal the potential of CTCs as a noninvasive real‐time biopsy to evaluate PD‐L1 expression in patients with melanoma. PD‐L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS. Implications for Practice The present data suggest that PD‐L1 expression on circulating tumor cells may predict response to pembrolizumab in advanced melanoma. This needs further validation in a larger trial and, if proven, might be a useful liquid biopsy tool that could be used to stratify patients into groups more likely to respond to immunotherapy, hence leading to health cost savings., The objective of this study was to determine whether PD‐L1 expression on circulating tumor cells can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab.

Current regulations in Canada prohibit the marketing of caffeinated energy drinks (CEDs) for use during sports, with alcohol, and by children. The study examined perceptions of CED ads in association with sports and alcohol use, as well as target age groups. An online survey was conducted in 2015 with youth and young adults aged 12–24 years (n = 2010). Participants completed three experiments in which they were randomized to view CED advertisements: 1) sports/party-themed ads, 2) sports-themed ad, and 3) party-themed ad, vs. control ‘product information’ ads. For each ad, participants were asked about perceived target age group, and if the ad promoted using CEDs during sports and with alcohol. Logistic regression models were fitted to test differences in outcomes between conditions. The majority of respondents reported that the ads, across all themes, targeted people their age. In experiment 1, both sports/party-themed ads were more likely to be perceived as promoting use of CEDs during sports (AOR = 13.32; 95% CI 9.90, 17.91, and AOR = 9.73; 95% CI 7.38, 12.81, respectively), and with alcohol (AOR = 8.55; 95% CI 6.37, 11.48, and AOR = 2.81; 95% CI 2.08, 3.78, respectively), compared to the control ad. In experiment 2, the sports-themed ad was more likely to be perceived as promoting use of CEDs during sports (AOR = 15.02; 95% CI 11.83, 19.08), but not with alcohol, compared to the control ad. In experiment 3, the party-themed ad was more likely to be perceived as promoting use of CEDs with alcohol (AOR = 13.79; 95% CI 10.69, 17.78), but not during sports, compared to the control ad. Ads from leading energy drink brands are perceived as targeting young people and encouraging energy drink use during sports and with alcohol, despite Canadian regulations prohibiting these marketing practices.

Management of acute pain in children is fundamental to our practice. Its myriad benefits include reduced suffering, improved patient satisfaction, more rapid recovery, and a reduced risk of developing postsurgical chronic pain. Although a multimodal analgesic approach is now routinely used, informed and judicious use of opioid receptor agonists remains crucial in this treatment paradigm, as long as the benefits and risks are fully understood. Further, an ongoing public health response to the current opioid crisis is required to help prevent new cases of opioid addiction, identify opioid-addicted individuals, and ensure access to effective opioid addiction treatment, while at the same time continuing to safely meet the needs of patients experiencing pain.

Agrobacterium vitis was isolated from roots of 41 of 66 feral Vitis riparia vines collected in three different regions of New York State. Two of the regions were more than 150 km from commercial vineyards. The strains were highly diverse as determined by DNA fingerprinting of the chromosomal region lying between the 16S and 23S rRNA genes. Of 24 strains examined, 15 different fingerprints were generated, and none was identical to fingerprints generated by previously identified groups of tumorigenic A. vitis strains. Results of physiological tests that were done to characterize strains from V. riparia conformed closely to those expected for A. vitis, except that 23 of 26 strains did not utilize tartrate. All strains were nontumorigenic, did not hybridize with a probe consisting of T-DNA genes, did not utilize octopine or nopaline, and carried zero to three plasmids. Of 26 strains, 7 inhibited A. vitis strain K306 from causing galls at wound sites on grape as well as or better than a previously studied nontumorigenic A. vitis strain, F2/5, that is known to have biological control activity.

Limb malalignment and length discrepancy are common problems treated by pediatric orthopaedic surgeons. These deformities may increase the rate of degenerative disease of the knee, hip, and spine. Previous teaching suggested that there were no long term consequences of mild deformity, however, newer studies suggest that there may be morbidity associated with as little at 5 mm of leg length discrepancy. There are many etiologies that can contribute to limb deformity, and so a thorough history and physical is key to management. Pediatric patients present the unique opportunity to utilize the growth of the physis to correct these deformities with adequate planning. Alternatively, lengthening techniques have become safer and are associated with excellent patient satisfaction. The mounting evidence of the long term consequences of leg deformity, coupled with more sophisticated correction techniques, brings traditional indications for deformity correction into question.

The economic valuation of ecosystem services in part reflects the desire to use conventional economic tools (markets and economic instruments) to conserve ecosystem services. However, for regulating and supporting ecosystem services that depend on ecosystem structure and function, estimation of economic value requires estimates of the current level of underlying ecological functions first. This primary step is in principle, the job of environmental scientists, not economists. Here, we provide a coarse-level quantitative assessment of the relationship between the research effort expended by environmental scientists (on the biophysical values) and economists (on the monetary values) on 15 different regulating and supporting services in 32 ecosystem types using peer-reviewed article hits retrieved from bibliographic databases as a measure of research effort. We find a positive, moderately strong (r = 0.69) correlation between research efforts in the two domains, a result that, while encouraging, is likely to reflect serendipity rather than the deliberate design of integrated environmental science-economics research programs. Our results suggest that compared to environmental science research effort economic valuation is devoted to a smaller, less diverse set of ecosystem services but a broader, more diverse, set of ecosystem types. The two domains differed more with respect to the ecosystem services that are the major focus of research effort than they did with respect to the ecosystem types of principal research interest. For example, carbon sequestration, erosion regulation, and nutrient cycling receive more relative research effort in the environmental sciences; air quality regulation in economic valuations. For both domains, cultivated areas, wetlands, and urban/semi-urban ecosystem types received relatively large research effort, while arctic and mountain tundra, cave and subterranean, cryosphere, intertidal/littoral zone, and kelp forest ecosystem types received negligible research effort. We suggest ways and means by which the field of sustainability science may be improved by the design and implementation of a searchable database of environmental science and economic valuation literature as well as a global ecosystem service research network and repository that explicitly links research on the estimation and prediction of biophysical ecosystem functions with that of the social sciences and other knowledge systems. These suggestions would, at least in principle, facilitate a more efficient research agenda between economists and environmental scientists and aid management, regulatory and judicial decision-makers.

e21512 Background: Anti-PD-1 therapy has improved the outcome of advanced melanoma patients with a 5-year survival rate of about 40-45%. However, biomarkers predictive of response to immune checkpoint blockade therapy are lacking. There is limited data on the utility of host germline human leucocyte antigen (HLA) genotype as a predictor of response to anti-PD-1 therapy in advanced melanoma. Here, we investigate the prognostic value of HLA in predicting survival outcomes of patients with unresectable locally advanced, metastatic melanoma on anti-PD-1 therapy. Methods: Blood was collected from 113 metastatic melanoma patients who were treated with anti-PD-1 therapy at two major oncology centres in Western Australia. High quality DNA was extracted from white blood cells and subsequently HLA-I and HLA-II typed using clinically validated assay. Univariate analyses were conducted using Cox regression model correlating homozygosity at HLA-I and HLA-II loci with overall survival (OS). HLA-A and HLA-B were classified into 12 supertypes and correlated with OS. Multivariate analyses were performed while controlling for age, gender, prior therapy, BRAF mutation status, ECOG performance status and presence of liver and brain metastases. Results: Homozygosity at HLA-I or HLA-II loci was not associated with OS. However, the absence of HLA-B62 supertype was associated with a trend towards improved OS (HR: 0.53 [95% CI:0.25-1.10]; P = 0.09) as reported previously. Notably, the absence of HLA-B27 supertype was associated with improved OS which was statistically significant (HR: 0.45 [95% CI:0.24-0.85]; P = 0.01). In multivariate analyses, the prognostic value of HLA-B27 supertype (HR: 0.38 [95% CI:0.19-0.76]; P = 0.006) was maintained, whereas the prognostic value of HLA-B62 supertype significantly improved (HR: 0.42 [95% CI:0.19-0.94]; P = 0.03). Conclusions: Our results suggest a limited role of HLA homozygosity in predicting survival of melanoma patients treated with anti-PD-1 therapy. However, we identified that the absence of HLA-B62 and HLA-B27 supertype is associated with improved survival benefit. Therefore, HLA-B27 and HLA-B62 supertype may be used as adjunct biomarkers of response to anti-PD-1 therapy in patients with melanoma in addition to PD-L1 status, pending validation in prospective randomised clinical trials.

As the provision of publicly funded pre-kindergarten has expanded in recent years, public programs for infants and toddlers have received relatively little policy attention. However, federal, state, and local governments are now trying to promote quality in family child care and center-based programs that serve infants and toddlers, often with an emphasis on workforce development. Despite the developmental importance of the first years in a child’s life, infant and toddler teachers in family child care and centers remain greatly under-studied in the research literature. This descriptive study seeks to help fill that gap by comparing the characteristics and views of family child care and center-based infant and toddler teachers in the context of New York City, where ambitious policies to promote the quality of infant and toddler programs have focused on workforce development in both settings. Quantitative and qualitative data were collected in 2019 via online surveys of 32 center-based and 30 family child care teachers, and then analyzed quantitatively to identify similarities and differences between the two groups. The results can inform the design of policies in New York City, other cities, and states that seek to promote the quality of infant and toddler care in different settings.

The Detroit Zoo’s Polk Penguin Conservation Center has created a habitat for Antarctic and subantarctic penguins designed to match their natural environment to the fullest extent possible. In addition to a 326,000 gal pool with depths that reach 25 ft and special channels for extensive swimming, the habitat includes sculpted rock and ice features below and above the water. Temperatures and water quality are carefully controlled, and there is even a system to make it snow indoors. For zoo visitors, the center provides underwater viewing tunnels and galleries, as well as a so-called 4-D system designed to create a truly immersive experience.

Agrobacterium vitis, the primary cause of grape crown gall disease, is known to survive internally in grapevines and to spread in propagation material. In this study, we showed that the bacterium can be detected in dormant grape buds and on surfaces of leaves collected from commercial vineyards. Using a highly selective and sensitive method based on magnetic capture hybridization (MCH) together with real-time PCR, we detected A. vitis in as much as 90% of dormant bud samples and in up to 40% of leaf samples from individual vineyards. The highest percentages of detection occurred in samples collected from vineyards with high incidences of crown gall. A. vitis was also detected in 22% of wild grapevines (Vitis riparia) collected in New York and in 25% of feral grapevines that included V. californica in California. Several of these vines were growing more than 2 km from commercial vineyards, demonstrating that wild grapevines can serve as a significant inoculum reservoir. The specificity of the MCH and real-time PCR assay used to detect tumorigenic A. vitis in the environment was further demonstrated by the finding that 69 nontumorigenic strains from regions across the United States did not amplify a virD2 PCR product.

Venous thromboembolism (VTE) is a known risk with some forms of hormonal contraception, and should be considered by health care providers when counselling patients about their contraceptive options. Various other risk factors exist for VTE, including family history of VTE and a personal history of VTE or thrombophilia. This article will summarize various known risk factors for VTE, as well as what is known about the VTE risk imparted by the use of different contraceptives.

Despite the introduction of promising products into the contraceptive market, the rate of unintended pregnancies remains high. Women with underlying medical conditions should have access to safe and effective contraceptive methods for various reasons, including the potential deleterious effect of the disease on the pregnancy or the effect of the pregnancy on the disease process. Healthcare providers are often confronted with cases in which contraception counseling is problematic due to controversial evidence and persistent myths. This review will examine a number of medical conditions that often create contraception counseling challenges. It should in no way be considered as an extensive review of all contraceptive options for a given medical condition. The following topics will be explored: depression, immunosuppression, inflammatory bowel diseases, past bariatric surgery, liver diseases, family history of breast cancer, migraines, polycystic ovarian syndrome, perimenopausal state, and sickle cell disease. We advocate for improved information and accessibility to contraception as a means of decreasing the rate of unintended pregnancies.

Rising from a beach on the southeast coast of the United Kingdom is the 162 m tall British Airways i360, considered the tallest observation tower in the world to feature a movable level as well as the world’s slenderest tower. Constructed near the site of a famous 19th-century pier on which visitors could “walk on water,” the i360 offers modern tourists the opportunity to “walk on air.”

A common argument for the social value of sport is that athletes serve as heroes who inspire people – especially young people – to strive for excellence. This argument has been questioned by sport ...