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Photoprotection is a critical health prevention strategy to reduce the deleterious effects of ultraviolet radiation (UVR) and visible light (VL). Methods of photoprotection are reviewed in this paper, with an emphasis on sunscreen. The most appropriate sunscreen formulation for personal use depends on several factors. Active sunscreen ingredients vary in their protective effect over the UVR and VL spectrum. There are dermatologic diseases that cause photosensitivity or that are aggravated by a particular action spectrum. In these situations, sunscreen suggestions can address the specific concern. Sunscreen does not represent a single entity. Appropriate personalized sunscreen selection is critical to improve compliance and clinical outcomes. Health care providers can facilitate informed product selection with awareness of evolving sunscreen formulations and counseling patients on appropriate use. This review aims to summarize different forms of photoprotection, discuss absorption of sunscreen ingredients, possible adverse effects, and disease-specific preferences for chemical, physical or oral agents that may decrease UVR and VL harmful effects.

Published MarginProbe (Dune Medical Devices Ltd., Israel) data reports ≥50% reduction in positive lumpectomy margins. We sought to determine whether adjunctive use of MarginProbe would provide value over intraoperative pathologic assessment alone.This is a retrospective chart review of 86 consecutive lumpectomies with MarginProbe from December 2018 to November 2019. Margins were considered positive using 'no ink on tumor' guideline for invasive cancer, and 2 mm or greater for ductal carcinoma in-situ. Significance was measured using Fisher's exact test.Seventy-six patients yielded 86 lumpectomies for inclusion. Mean age was 69.8 and mean tumor size was 1.09 cm. Sixty-eight invasive cancers were assessed using adjunct MarginProbe and gross assessment, while 18 ductal carcinoma in-situ cases utilized MarginProbe only. Among all cases, gross assessment alone reduced positive margins(29.2% relative reduction, p = 0.28). Utilizing both modalities, positive margins decreased from 27.9% to 9.3% (66.7% relative reduction, p 0.01) representing a 46.9% relative reduction versus gross assessment alone. After gross assessment and MarginProbe evaluation, additional excised volume averaged 2.9 cc.Synergistic use of MarginProbe and gross assessment reduces positive margins during breast conserving surgery. Surgeons can weigh its cost against it benefit with the succinct analysis we provide.

Background and objectives Despite a high burden of human papillomavirus (HPV)-attributable cancers, the southern US lags other regions in HPV vaccination coverage. This study sought to characterize and contextualize predictors of HPV vaccination in the southern US. Methods From December 2019 – January 2020, parents of adolescents (ages 9–17 years) living in thirteen southern US states were recruited from a nationally-representative online survey panel and completed a cross-sectional survey. The primary study outcome was initiation of HPV vaccination. Results Of 1105 parents who responded to the survey, most were ≥35 years of age and of female gender. HPV vaccination initiation was reported only among 37.3% of adolescents and was highest at age 12. Cumulative HPV vaccination coverage was highest at age 15 (52%) but lower than coverage for tetanus-diphtheria-acellular pertussis (Tdap, 79.3%) and Meningococcal vaccines (MenACWY, 67.3%). Provider recommendation was strongly associated with higher odds of HPV vaccination (aOR: 49.9, 95 %CI: 23.1–107.5). In alternative predictive models, home/online (vs. public) schooling and parents’ working status were associated with lower odds of vaccination; health care visits in the past 12 months and shorter travel times to adolescents’ usual health care provider were associated with greater odds of vaccination. Conclusions Our findings suggest missed opportunities for HPV vaccination in the southern US and support strengthening provider recommendation for on-time initiation of HPV vaccination among adolescents. Other strategies to increase HPV vaccinations may include encouraging co-administration with other adolescent vaccines, increasing vaccine access, and promoting vaccinations for home/online-school students.

Background: Prurigo pigmentosa (PP) is a rare inflammatory dermatosis characterized by pruritic erythematous papules that coalesce to form a reticulate pattern. PP is often misdiagnosed, and patients are treated with ineffective therapies. Although the majority of reports about PP are from East Asia, patients of all backgrounds can be affected. Objectives: To perform a systematic review of reported PP cases with the purpose of summarizing the clinical presentation and treatment of PP. Methods: MEDLINE and Embase were searched for original articles describing PP. We identified 115 studies from 24 countries representing 369 patients to include in the analysis. Results: Of the 369 patients included in the analysis, the mean age was 25.6 years (range: 13-72 years) with 72.1% (266 of 369) female. Risk factors or aggravating factors were described in 52.3% (193 of 369) of patients and included dietary changes (25.5%, 94 of 369), friction (8.4%, 31 of 369), sweat (7.6%, 28 of 369), and ketonuria (5.1%, 19 of 369). Of those patients who experienced PP following dietary changes, 40.4% (38 of 94) started a ketogenic diet. Minocycline monotherapy was the most frequently prescribed treatment for PP (20.9%, 77 of 369), achieving complete resolution in 48.1% (37 of 77) of patients. Conclusions: PP is sometimes associated with ketogenic diets and can be effectively managed with oral tetracyclines.

The objective of this study was to identify factors at the individual, provider, and systems levels that serve as challenges or opportunities for increasing adolescent vaccination-including Human Papillomavirus (HPV) vaccination-in rural communities in the southern United States (US). As part of a broader study to increase HPV vaccine uptake in the southern US, we conducted in-depth interviews with vaccination stakeholders representing public health and education agencies in North Carolina (NC) and South Carolina (SC). Fourteen key stakeholders were recruited using purposive sampling to obtain insights into challenges and solutions to rural-urban disparities in HPV vaccination coverage. Stakeholders were also queried about their experiences and attitudes toward school-based vaccination promotion programs and campaigns. We used a rapid qualitative approach to analyze the data. Stakeholders identified factors at the individual, provider, and systems levels that serve as challenges to vaccination in rural communities. Similar to previous studies, stakeholders mentioned challenges with healthcare access and vaccine-related misconceptions that pose barriers to HPV vaccination for rural residents. Systems-level challenges identified included limited access to high-speed internet in rural areas that may impact providers' ability to interface with state-level digital systems such as the vaccination registry. Stakeholders identified a number of opportunities to increase HPV vaccination coverage, including through school-based health promotion programs. Stakeholders strongly supported school-based programs and approaches to strengthen confidence and demand for HPV vaccination and to help address persistent social determinants and system level factors that pose challenges to HPV vaccination coverage in many rural areas.

For many secretive species of amphibians and reptiles, observations of reproductive behavior are limited to sparse anecdotes from the field or to animals held in captivity. However, a careful examination of morphological differences between the sexes can help shape hypotheses about behaviors with which they may be correlated. For example, sexual dimorphism in head size and shape are correlated with courtship, territoriality, and mate-defense behaviors in some salamanders. One widespread species with a poorly described reproductive natural history is the Red Salamander (Pseudotriton ruber). Here, we measure head size and employ geometric morphometric methods to evaluate head shape in P. ruber, with the goals of: 1) quantifying and visualizing sexual variation; 2) forming hypotheses about reproductive behavior. We found preliminary evidence for differences in head size and shape that are consistent with mate-guarding behavior, and we remark upon directions for future research.

Research has suggested an interference effect for words taught in semantic clusters due to the semantic links connecting the words. Thematic clustering of vocabulary is an alternative method of presenting new words to second language (L2) learners. However, what is known about the effects of semantic and thematic clustering has been uncovered through the recruitment of adult learners, with little research conducted with very young learners. Moreover, language textbooks and curriculums for very young learners continue to structure vocabulary semantically. Embedded instruction using storybook contexts has been suggested as a suitable context-based vocabulary teaching technique although knowledge of its effects is limited. To investigate this claim, a quasi-experimental within-subjects design was used to investigate whether embedded instruction could differentially affect very young L2 learners’ learning of new vocabulary taught in either semantic or thematic clusters (N = 38) compared to a control (N = 15). The findings suggest that embedded instruction is beneficial for very young L2 learners’ vocabulary learning regardless of the clustering type. Participants gained and retained over time considerable receptive and productive vocabulary knowledge for both semantic and thematic clustered words, indicating that embedding vocabulary in storybook contexts may reduce the potential for interference between target words in semantic clusters.

Review of: Migration and the Media: Debating Chinese Migration to Italy, 1992–2012, Gaoheng Zhang (2019) Toronto: University of Toronto Press, 296 pp., ISBN 978-1-44263-043-7, h/bk, $70.00

Intratumor heterogeneity implies that subpopulations of cancer cells that differ in genetic, phenotypic, or behavioral characteristics coexist in a single tumor (Ma in Breast Cancer Res Treat 162(1):39–48, 2017; Martelotto in Breast Cancer Res 16(3):210, 2014). Tumor heterogeneity drives progression, metastasis and treatment resistance, but its relationship with tumor infiltrating immune cells is a matter of debate, where some argue that tumors with high heterogeneity may generate neoantigens that attract immune cells, and others claim that immune cells provide selection pressure that shapes tumor heterogeneity (McGranahan et al. in Science 351(6280):1463–1469, 2016; McGranahan and Swanton in Cell 168(4):613–628, 2017). We sought to study the association between tumor heterogeneity and immune cells in a real-world cohort utilizing The Cancer Genome Atlas. Mutant allele tumor heterogeneity (MATH) was calculated to estimate intratumoral heterogeneity, and immune cell compositions were estimated using CIBERSORT. Survival analyses were demonstrated using Kaplan–Meir curves. Tumors with high heterogeneity (high MATH) were associated with worse overall survival (p = 0.049), as well as estrogen receptor-positive (p = 0.011) and non-triple-negative tumors (p = 0.01). High MATH tumors were also associated with less infiltration of anti-tumor CD8 (p

Some may think that prediction of metastasis is meaningless since metastatic breast cancer is currently incurable. We argue that effective identification of developing metastasis will enable us to design and conduct clinical trials specifically targeting those patients at high risk. The current study sought to generate the KAM score by 4 genes (BRSK2, EYA1, SIGLEC15, and AGTR1) overexpressed in primary breast cancer that developed metastasis to bone compared with matched controls without metastasis longer than 10 years. A high KAM score was prognostic of poor overall (OS), disease free survival (DFS), and disease specific survival (DSS) in the METABRIC, and OS in the GSE96058 cohorts. A high KAM score was significantly associated with clinical aggressiveness, such as high American Joint Committee Cancer (AJCC) stage, lymph node metastasis, Nottingham pathological grade, and triple negative breast cancer (TNBC). Subgroup analysis revealed that a high KAM score was associated with worse OS in ER-positive/HER2-negative breast cancer in both cohorts. A high KAM breast cancer enriched all 5 cell proliferation-related gene sets of the Hallmark collection and interferon (IFN)-γ response gene sets. Furthermore, a high KAM breast cancer was significantly infiltrated with a high fraction of not only anti-cancer but also pro-cancer immune cells and associated with high level of cytolytic activity. Finally, a high KAM breast cancer was significantly associated with lung metastasis. In conclusion, we developed KAM score using 4 gene expressions that predict lung metastasis and patient survival in breast cancer.

Background:Published MarginProbe (MP) data reports ≥50% reduction in positive lumpectomy margins. Standard of care (SOC) in our facility uses intraoperative pathologic gross assessment for invasive cancer. We sought to determine if adjunctive use of MP would provide incremental value over gross assessment alone. Methods:This is a single-site, single-surgeon retrospective chart review of 86 consecutive lumpectomies with MP from 12/2018–11/2019. Margins were considered positive using SSO/ASTRO “no ink on tumor” consensus guideline for invasive cancer, and SSO/ASTRO/ASCO consensus guideline of 2mm or greater for pure DCIS. Significance was measured using Fisher’s exact two-tailed test.Results:76 patients (7 bilateral, 3 unilateral/multi-focal) yielded 86 lumpectomies for inclusion. Mean age was 69.8 and mean tumor size was 1.09cm. 68 invasive cancers were assessed using adjunct MP and gross assessment while 18 DCIS cases utilized MP only. Among all cases, gross assessment alone reduced positive margins from 27.9% to 19.8% (29.2% relative reduction, p=0.28). Utilizing both modalities in tandem, positive margins decreased from 27.9% to 9.3% (66.7% relative reduction, pConclusion:Adjunctive use of MP with gross assessment maximizes reduction of positive margins during breast conserving surgery while minimizing impact on specimen volumes.

Evaluation of the functional aspects if the tumor immune microenvironment (TIME), such as the recently introduced cytolytic activity score (CYT) index have been under the spotlight in cancer research; however, clinical relevance of immune cell killing activity in breast cancer has never been analyzed in large patient cohorts. We hypothesized that CYT reflects the immune activity of TIME and can predict patient survival. A total of 7533 breast cancer patients were analyzed as both discovery and validation cohorts. We found that high CYT was associated with advanced histological grade and triple-negative breast cancer (TNBC). High CYT in tumors was significantly associated with better survival in TNBC, but unexpectedly, not in other breast cancer subtypes. High CYT TNBC included both favorable immune-related, as well as unfavorable (suppressive) inflammation-related gene sets, and characterized by high infiltration with T cells and B cells. High CYT TNBC was associated with high homologous recombination deficiency and low somatic copy number alteration score and less mutant allele tumor heterogeneity, but not with tumor mutation burden (TMB). Although CYT was not associated with pathological complete response after neoadjuvant chemotherapy, it was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, CYT of TNBC is associated with enhanced anti-cancer immunity, less intra-tumoral heterogeneity, and with better survival.

This chapter examines the way in which general frameworks of law help to structure management practice and create opportunities to demonstrate leadership. Legislation does not make decisions: it simply sets the parameters and provides the framework within which leaders, managers and practitioners make decisions. Laws operate at a high level of abstraction but, in some ways, they are intrinsically linked to ideas about leadership – they provide a framework of rules, codes and conceptual structures that guide social, personal and institutional action. Managers may also need to be familiar with aspects of civil law concerning slander or defamation, for example, and they must remain mindful of the need to express themselves more carefully in their professional capacities than they might on a strictly personal basis. The procedures for deciding how services are provided, who is entitled to them and how they are delivered often involve extensive consultation.

An 82-year-old female presented to her breast surgeon with a hard, painful mass in the left breast. Mammography demonstrated a new hyperdense mass with pleomorphic calcifications of trabeculated appearance. Ultrasound-guided biopsy demonstrated a hypoechoic mass with significantly increased vascularity and tissue stiffness as well as additional irregular, hypoechoic masses in the same area. Together these findings suggested multifocal malignancy. The pathology report from the biopsy demonstrated fragments of solid sheets of epithelioid and focally spindled cells with multinucleated osteoclast giant cells. This was found to be most consistent with metaplastic carcinoma showing osteoblastic differentiation. The patient received a left-sided mastectomy. During follow-up with the patient, adjuvant chemotherapy was not advised given the relatively unknown survival advantage in this elderly patient.

This article began in March 2020, during New Zealand’s Alert Level 4 lockdown, and the writing process has spanned more than five months of the SARS-CoV-2 (COVID-19) pandemic. As at August 2020, COVID-19 continues to rage across the globe, while New Zealanders enjoy a relative freedom of movement. Due to a collective commitment to biosecurity practices such as isolation, quarantine and movement restrictions, along with the government’s strong public health messaging, the ‘team of five million’ had, at the time of writing, eliminated COVID-19 from our communities. This article discusses New Zealand’s biosecurity messaging in light of COVID-19, and argues that biosecurity discussions that link animal management practices with risks to human health are essential for pandemic preparedness. As a global leader in biosecurity, New Zealand is well placed to make the conceptual shift towards treating public health and biosecurity as a shared concern.

Resilience thinking and biosecurity management are both concerned with adaptively governing social-ecological systems to ensure the resilience of socially, culturally, economically and environmenta...

Australia has set a national target of ending HIV by 2020, achieving this will require the inclusion of priority populations (eg, Indigenous Australians) in strategies to reach elimination. To assist in evaluating the target of elimination, we analysed HIV notification data for Indigenous and non-Indigenous Australians.Using the National HIV Registry at The Kirby Institute at UNSW, Sydney, NSW, Australia, we collated and analysed annual HIV notification data for 1996-2015. Patients who were not born in Australia were excluded. We calculated the rates of HIV diagnoses with annual trends in notification rates for Indigenous versus non-Indigenous Australians by demographic characteristics, exposure categories, and stage of HIV at diagnosis. For missing data, assumptions were made and verified through sensitivity analyses. Annual rate ratio (RR) and 4 year summary rate ratio (SRR) trends were calculated to determine patterns of HIV diagnosis in the two populations.Between Jan 1, 1996, and Dec 31, 2015, 11 492 people born in Australia were reported with a diagnosis of HIV, of whom 461 (4%) were recorded as Indigenous Australians and we classified the remaining 11 031 (96%) as non-Indigenous Australians. For exposure to HIV, among Indigenous Australians a higher proportion of diagnoses occurred among women, and through injecting drug use and heterosexual sex than among non-Indigenous Australians (p0·0001). Among Indigenous Australians, we found a significantly higher SRR of HIV diagnoses among men in the period 2012-15 than in previous periods (SRR 1·53, 95% CI 1·28-1·83; p0·0001), and significantly higher diagnosis among Indigenous women (4·92, 4·02-6·02; p0·0001) for the entire study period than among non-Indigenous women. Concurrently, a decrease in HIV diagnoses of 1% per annum (RR 0·99, 95% CI 0·98-0·99; p0·0001) across the study period was seen among non-Indigenous people. Indigenous Australians were more likely to be diagnosed at an advanced stage of HIV infection than non-Indigenous Australians (20·8% vs 15·1%; p=0·0088).Greater efforts should be made to include Indigenous people in prevention strategies, particularly newer biomedical interventions, such as scale up of pre-exposure prophylaxis and treatment as prevention initiatives in Australia. More involvement of Indigenous Australians in these approaches is also required to prevent widening of the gap in HIV diagnosis rates between non-Indigenous and Indigenous Australians.None.

Breast cancer is the most common malignancy in women and a leading cause of morbidity and mortality in them. Breast cancer survival varies by stage at diagnosis. According to Surveillance, Epidemiology, and End Results (SEER) data, the overall 5-year relative survival rate is 99% for localized disease, 85% for regional disease, and 27% for distant-stage disease [1]. Breast cancer screening is used to identify women with asymptomatic cancer so that cases are picked up and treated early leading to better outcomes. Presently, breast cancer detection relies on mammography as the main screening modality, but its role is now declining because of high false-positive rates and limited sensitivity for detection of lesions in dense breast tissues. Biomarkers that can predict early disease are a welcome addition to the imaging methods used for breast cancer screening. Imaging techniques for screening have been discussed in detail in Chap. 27, and the role of clinical examination and biomarkers will be dealt in this chapter.

BackgroundTreatment as prevention approaches for HIV require optimal HIV testing strategies to reduce undiagnosed HIV infections. In most settings, HIV testing strategies still result in unacceptably high rates of missed and late diagnoses. This study aimed to identify clinical opportunities for targeted HIV testing in persons at risk to facilitate earlier HIV diagnosis in New South Wales, Australia; and to assess the duration between the diagnosis of specific conditions and HIV diagnosis.MethodsThe Australian National HIV registry was linked to cancer diagnoses, notifiable condition diagnoses, emergency department presentations and hospital admissions for all HIV diagnoses between 1993 and 2012 in NSW. Date of HIV acquisition was estimated from back-projection models and people with a likely duration from infection to diagnosis of less than 180 days were excluded. Risk factors associated with clinical opportunities for the earlier diagnosis of HIV were identified.ResultsSexually transmitted infection diagnoses (particularly gonorrhoea and syphilis) and some hospital admissions (mental health and drug-related diagnoses, and non-infective digestive disorder diagnoses) were prominent among people estimated to be living with undiagnosed HIV. The length of time between a clinical opportunity for the earlier HIV diagnosis and actual HIV diagnosis was 13.3 months for notifiable conditions, and 15.2 months for hospital admissions. People with lower CD4+ cell count at diagnosis, and older people were significantly less likely to have a missed opportunity for earlier HIV diagnosis.ConclusionsAdditional targeted clinical HIV testing strategies are warranted for people with gonorrhoea and syphilis; and hospital presentations or admissions for mental health, drug-related and gastrointestinal diagnoses.

Precision medicine can be defined as the customization of medical treatment based on the individual genetic profile, which enables one to identify patients who respond to therapies while sparing side effects for those who do not. Breast cancer patients have been treated based on subtyping, which is considered a prototype of precision medicine. Furthermore, the development of multigene panel testing has resulted in a paradigm shift in the treatment of breast cancer. The knowledge generated from the Human Genome Project, and subsequently The Cancer Genome Atlas, has provided the concept of precision medicine, in which cancer patients can be sub-classified based on actionable driver mutations that can be selectively targeted by molecular targeted drugs and treated by appropriate molecular targeted therapies. Development of next-generation sequencing has both dramatically advanced genomic sequencing technology and revealed actionable driver mutations for individual cancer patients when applied to a clinical setting. Clinical target sequencing by next-generation sequencing enables one to formulate treatment strategies, not only by selecting a subgroup of patients who are expected to experience more effectiveness of each drug, but also by revealing patients with drug resistance based on their actionable driver mutations.

Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in several types of cancer. However, the role of the lipid mediator in BTC has never been examined. Here we found that S1P is elevated in BTC with the activation of ceramide-synthetic pathways, suggesting that BTC utilizes SPHK1 to promote lymphatic metastasis. We found that S1P, sphingosine and ceramide precursors such as monohexosyl-ceramide and sphingomyelin, but not ceramide, were significantly increased in BTC compared to normal biliary tract tissue using LC-ESI-MS/MS. Utilizing The Cancer Genome Atlas cohort, we demonstrated that S1P in BTC is generated via de novo pathway and exported via ABCC1. Further, we found that SPHK1 expression positively correlated with factors related to lymphatic metastasis in BTC. Finally, immunohistochemical examination revealed that gallbladder cancer with lymph node metastasis had significantly higher expression of phospho-SPHK1 than that without. Taken together, our data suggest that S1P generated in BTC contributes to lymphatic metastasis.

BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care.METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366.FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

Overdoses (ODs) of prescription opioids (RxOs) have become a major public health issue in the United States. Objective: To determine the root causes of accidental prescription opioid overdoses (RxO-OD). Design/setting/participants/intervention: The authors conducted a root cause analysis using the Antecedent Target-Measurement method, interviewing three types of key informants: survivors of RxO-ODs, family members, and clinical experts. Results: Ten survivors, five family members, and three experts were interviewed. Proximal causes of RxO-ODs described by survivors and family members were recent RxO dose escalation (n = 9), polysubstance use (n = 5), and polypharmacy use (n = 3). Proximal causes were elicited by the following six antecedent causes: wanting to feel good/high (n = 9), perceived tolerance to RxO (n = 6), didn't know/believe it was dangerous (n = 5), wanting to reduce psychosocial pain (n = 5), wanting to reduce physical pain (n = 4), and wanting to avoid discomfort due to withdrawal symptoms (n = 4). RxOs involved in the OD were either prescribed by a doctor (n = 7), purchased from a dealer (n = 6), given/purchased from family/friends (n = 3), or stolen from family (n = 1). Psychosocial stressors (n = 9), chronic recurrent depression (n = 3), and chronic substance abuse/addiction (n = 4) were also distal and proximal causes of OD. Experts cited similar causes but added prescriberrelated causes (eg, inadequate training) and healthcare system and culture. Conclusions: Patients at risk for OD can be identified and ODs potentially prevented. Opportunities for intervention include routine screening of patients using RxOs for psychosocial distress and coping, flagging of high-risk patients, care pathways for high-risk patients, clinician and patient training on OD prevention, and developing abuse-deterrent formulations of RxOs .

As Barbara Alfano cogently points out in The Mirage of America in Contemporary Italian Literature and Film, America continues to hold a privileged place in the Italian cultural imagination. Italy h...

Focusing on southern Alberta, my paper discusses the power of settler life writing to replace Indigenous conceptions of the prairies with colonial visions. Pioneer memoirs promote myths of the prairie as a fertile utopian environment or as a hostile frontier. By accentuating their labour and their social status, pioneer life writers support their claims of entitlement to colonize land.

Solute carrier organic anion (SLCO) gene families encode organic anion transport proteins, which are transporters that up-take a number of substrates including androgens. Among them, high expression of SLCO2B1 is known to associate with the resistance to androgen deprivation therapy in prostate cancer (PCa). We hypothesized that high expression of SLCO genes enhances PCa progression by promoting the influx of androgen. Here, we demonstrated the impact of the expression levels of SLCO2B1 on prognosis in localized PCa after radical prostatectomy (RP) utilizing 494 PCa cases in The Cancer Genome Atlas (TCGA). SLCO2B1 high expression group showed significantly worse Disease-free survival (DFS) after RP (p = 0.001). The expression level of SLCO2B1 was significantly higher in advanced characteristics including Gleason Score (GS ≤ 6 vs GS = 7; p = 0.047, GS = 7 vs GS ≥ 8; p = 0.002), pathological primary tumor (pT2 vs pT3/4; p < 0.001), and surgical margin status (positive vs negative; p = 0.013), respectively. There was a significant difference in DFS between these two groups only in GS ≥ 8 patients (p = 0.006). Multivariate analysis demonstrated that only SLCO2B1 expression level was an independent predictor for DFS after RP in GS ≥ 8. SLCO2B1 high expressed tumors in GS ≥ 8 not only enriched epithelial mesenchymal transition (EMT) related gene set, (p = 0.027), as well as Hedgehog (p < 0.001), IL-6/JAK/STAT3 (p < 0.001), and K-ras signaling gene sets (p < 0.001), which are known to promote EMT, but also showed higher expression of EMT related genes, including N-cadherin (p = 0.024), SNAIL (p = 0.001), SLUG (p = 0.001), ZEB-1 (p < 0.001) and Vimentin (p < 0.001). In conclusion, PCa with high expression of SLCO2B1 demonstrated worse DFS, which might be due to accelerated EMT.

a b s t r a c t Introduction: Despite burns being common in children, research into the psychological experience and trauma remains limited. Improvements in the professional understanding of children's experiences will assist in improving holistic care. Purpose: This study uses phenomenology, a qualitative methodology to explore the psy- chological experiences following a burn injury in children. Methods: In-depth interviews were conducted six months after burn with 12 (six girls and six boys) children who underwent surgery for a burn. The children were aged eight to 15 years. The interview examined the overall experience of children and included probing questions exploring participants' perceptions, thoughts and feelings. Transcripts were analysed according to the seven-step Coliazzi method. Relationships between themes were explored to identify core concepts. Results: The findings demonstrated that trauma was central to the burn experience and comprised two phases: the burn trauma and the recovery trauma. Six themes emerged as a result of this experience: ongoing recurrent trauma; returning to normal activities; beha- vioural changes; scarring-the permanent reminder; family and adaptation. Conclusion: This research has clinical implications as its findings can be used to inform clinical care at all stages of the burn journey. These research conclusions could be used to develop comprehensive information and support management plans for children. This would complement and support the surgical and medical treatment plan, providing direction for comprehensive service delivery and improved psychosocial outcomes in children.

In Australia, unlike much of the rest of the world, HIV transmission through heterosexual contact remains a relatively rare occurrence. In consequence, HIV-prevention efforts have been firmly focused on male-to-male sex as the most frequent source of HIV transmission. There are emerging signs that this epidemiological landscape may be shifting, which raises questions about current and future HIV prevention strategies. Over the past decade, national surveillance data have shown an increase in HIV notifications for which exposure to HIV was attributed to heterosexual contact. This paper offers an epidemiological and sociocultural picture of heterosexual HIV transmission in Australia. We outline recent trends in heterosexually acquired HIV and discuss specific factors that shape transmission and prevention among people at risk of HIV infection through heterosexual contact. To illustrate the contextual dynamics surrounding HIV in this diverse population, we detail two key examples: HIV among people from minority ethnic backgrounds in New South Wales; and overseas-acquired HIV among men in Western Australia. We argue that, despite their differences, there are significant commonalities across groups at risk of HIV infection through heterosexual contact, which not only provide opportunities for HIV prevention, but also call for a rethink of the dominant HIV response in Australia.

Background Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. Study Design and Methods An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. Results Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. Conclusion The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.

Nanni Moretti’s La stanza del figlio/The Son’s Room (2001) reveals the effects of a child’s death on the protagonist Giovanni (a psycoanalyst played by Moretti) and his family. This film appears after Aprile/April (1998), which narrates both the birth of the director’s son Pietro as well as the Italian electoral campaign in 1996 in the month of the title. The arrival of a biological son followed by the death of a fictional one in Moretti’s oeuvre suggests greater implications for the parent-child relationship in Italy. This phenomenon also comments on the relationship between generations of Italian directors. An examination of Moretti’s earlier autobiographical film Caro diario/Dear Diary (1994) gives insight into this director’s relationship to other artists and also suggests implications for the future of Italian filmmaking.

Toll-like receptor 4 (TLR4) is ubiquitously expressed on parenchymal and immune cells of the liver and is the most studied TLR responsible for the activation of proinflammatory signaling cascades in liver ischemia and reperfusion (I/R). Since pharmacological inhibition of TLR4 during the sterile inflammatory response of I/R has not been studied, we sought to determine whether eritoran, a TLR4 antagonist trialed in sepsis, could block hepatic TLR4-mediated inflammation and end organ damage. When C57BL/6 mice were pretreated with eritoran and subjected to warm liver I/R, there was significantly less hepatocellular injury compared to control counterparts. Additionally, we found that eritoran is protective in liver I/R through inhibition of high-mobility group box protein B1 (HMGB1)-mediated inflammatory signaling. When eritoran was administered in conjunction with recombinant HMGB1 during liver I/R, there was significantly less injury, suggesting that eritoran blocks the HMGB1-TLR4 interaction. Not only does eritoran attenuate TLR4-dependent HMGB1 release in vivo, but this TLR4 antagonist also dampened HMGB1's release from hypoxic hepatocytes in vitro and thereby weakened HMGB1's activation of innate immune cells. HMGB1 signaling through TLR4 makes an important contribution to the inflammatory response seen after liver I/R. This study demonstrates that novel blockade of HMGB1 by the TLR4 antagonist eritoran leads to the amelioration of liver injury.