Search

Here, we present a rare case of a patient who developed multiple primary melanomas within the boundaries of two nevi depigmentosa. The melanomas were excised, and as a preventive measure, the remainder of the nevi depigmentosa were removed. We performed whole-exome sequencing on excised tissue from the nevus depigmentosus, adjacent normal skin, and saliva to explain this intriguing phenomenon. We also performed a GeneTrails Comprehensive Solid Tumor Panel analysis on one of the melanoma tissues. Genetic analysis revealed germline MC1R V92M and TYR R402Q polymorphisms and a MET E168D germline mutation that may have increased the risk of melanoma development. This genetic predisposition, combined with a patient-reported history of substantial sun exposure and sunburns, which were more severe within the boundaries of the nevi depigmentosa due to the lack of photoprotective melanin, produced numerous somatic mutations in the melanocytes of the nevi depigmentosa. Fitting with this paradigm for melanoma development in chronically sun-damaged skin, the patient's melanomas harbored somatic mutations in CDKN2A (splice site), NF1, and ATRX and had a tumor mutation burden in the 90-95th percentile for melanoma.

Background Previous work has demonstrated racial/ethnic differences in emergency department (ED) utilization, but less is known about racial/ethnic differences in the experience of care received during an ED visit. Objective To examine differences in self-reported healthcare utilization and experiences with ED care by patients’ race/ethnicity. Design Adult ED patients discharged to community (DTC) were surveyed (response rate: 20.25%) using the Emergency Department Patient Experience of Care (EDPEC) DTC Survey. Linear regression was used to estimate case-mix-adjusted differences in patient experience between racial/ethnic groups. Participants 3122 survey respondents who were discharged from the EDs of 50 hospitals nationwide January–March 2016. Main Measures Six measures: getting timely care, doctor and nurse communication, communication about medications, receipt of sufficient information about test results, whether hospital staff discussed the patient’s ability to receive follow-up care, and willingness to recommend the ED. Key Results Black and Hispanic patients were significantly more likely than White patients to report visiting the ED for an ongoing health condition (40% Black, 30% Hispanic, 28% White, p

Globally, collapse of ecosystems—potentially irreversible change to ecosystem structure, composition and function—imperils biodiversity, human health and well‐being. We examine the current state and recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2, from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic ‘presses’ and/or acute ‘pulses’, drive ecosystem collapse. Ecosystem responses to 5–17 pressures were categorised as four collapse profiles—abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three‐step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.

Objective To examine the association between prior cancer treatments, medical comorbidities, and voluntary childlessness in reproductive-age women who are survivors of cancers diagnosed as adolescents and young adults (AYA survivors). Design Cross-sectional analysis. Setting Participants were recruited from California and Texas cancer registries, fertility preservation programs, and cancer advocacy groups. Patient(s) Women (n = 413) ages 18–40 who were diagnosed with cancer between ages 15 and 35, completed primary cancer treatments, had at least one ovary, and were nulliparous. Intervention(s) Cancer treatment gonadotoxicity and medical comorbidities. Main Outcome Measure(s) Voluntary childlessness. Result(s) The mean age of survivors was 31.8 years (SD, 4.9) with a mean of 6.5 years (SD, 4.4) since cancer diagnosis. Breast (26%), thyroid (19%), and Hodgkin lymphoma (18%) were the most common cancers. Twenty-two percent of the cohort was voluntarily childless. Medical comorbidities, cancer diagnosis, prior surgery, prior chemotherapy, and prior gonadotoxic treatments were not significantly associated with voluntary childlessness. In adjusted analysis, survivors of older reproductive age (adjusted odds ratio = 2.97 [1.71–5.18]) and nonheterosexual participants (adjusted odds ratio = 4.71 [2.15–10.32]) were more likely to report voluntary childlessness. Conclusion(s) A moderate proportion of AYA cancer survivors are voluntarily childless, but reproductive intentions were not related to cancer type or cancer treatments. AYA survivors of older age and nonheterosexual identification were more likely to be voluntarily childless. These data support assessing reproductive intentions and tailoring reproductive care such as fertility and contraception counseling that is appropriate for a survivor’s intentions.

The authors evaluated websites offering therapeutic telehealth services (N = 55) using a 38-item checklist based on the American Psychological Association’s Guidelines for the Practice of Telepsych...

Despite the interest in MXenes in the past decade, MXenes are often highly disordered, which can complicate their study and use. For example, nearly all MXenes have a random mixture of surface term...

Free Ocean CO2 Enrichment (FOCE) experiments are a relatively recent development in ocean acidification research, designed to address the need for in situ, long-term, community level experiments. FOCE studies have been conducted across different marine benthic habitats and regions, from Antarctica to the tropics. Based on this previous research we have formed some core operating principles that will aid those embarking on future FOCE experiments. FOCE studies have potential to provide important insight into the effects of ocean acidification that can add to or refine conclusions drawn from laboratory or single species studies because they are conducted in situ on intact assemblages. Scaling up from sub-organismal and individual effects to also include indirect impacts on the ecosystem and ecosystem services, make FOCE experiments essential in filling in current knowledge gaps in our understanding of ocean acidification. While FOCE systems are complex, relatively costly, and somewhat difficult to operate, the challenges they pose are tractable and they have proven to be a useful approach in ocean acidification research. The aim of this paper is to draw from the experiences of past FOCE experiments and provide practical advice for designing, building and operating a FOCE experiment. Some of the most important recommendations include: field testing the system design; having a backup power supply; using replicate treatment enclosures; monitoring and maintaining the chemistry appropriately; allowing sufficient time to achieve near CO2 equilibrium conditions; and having a scientific focus with a core set of hypotheses. Future FOCE experiments could focus on longer durations, multiple factors, and testing more intact benthic marine communities and ecosystems. We hope this paper will encourage further FOCE deployments and experiments, as well as provide some guidelines to improve future FOCE studies and advance ocean acidification research.

Author(s): Chen, Peggy G; Tolpadi, Anagha; Elliott, Marc N; Hays, Ron D; Lehrman, William G; Stark, Debra S; Parast, Layla

Benign naevi are closely linked to melanoma, as risk factors, simulators, or sites of melanoma formation. There is a heavy genetic overlap between the two lesions, a shared environmental influence of ultraviolet radiation, and many similar cellular features, yet naevi remain locally situated while melanomas spread from their primary site and may progress systemically to distal organs. Untangling the overlapping contributors and predictors of naevi and melanoma is an ongoing area of research and should eventually lead to more personalized prevention and treatment strategies, through the development of melanoma risk stratification tools and early detection of evolving melanomas. This will be achieved through a range of complementary strategies: risk-adjusted primary prevention counseling; the use of lesion imaging technologies such as sequential 3D total body photography and consumer-performed lesion imaging; artificial intelligence deep phenotyping and clinical assistance; a better understanding of genetic drivers of malignancy, risk variants, clinical genetics, and polygenic effects; and the interplay between genetics, phenotype and the environment.

IMPORTANCE: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. OBJECTIVE: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. EVIDENCE REVIEW: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. FINDINGS: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. CONCLUSIONS AND RELEVANCE: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.

Objectives The major cause of mucosal squamous cell carcinomas of the head and neck (HNSCCs) has been attributed to human papillomavirus (HPV) infection. Here we investigate if microRNA expression in HNSCC can be used as a prognostic tool with or without HPV status. Materials and Methods We performed a discovery miRNA microarray (miRBase v.21) profiling of 52 tonsillar SCCs with TaqMan real-time PCR validation of 228 HNSCCs. Patients had a histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx. Logistic regression models were used to estimate the magnitude of the effect of association with clinical factors and miRNAs associated with HPV status. For recurrence and survival analysis, we used unadjusted and multivariable adjusted Cox proportional hazard regression models. Results Seventeen miRNAs were significantly associated with better prognosis in the discovery phase and were validated in the extended dataset. The best fitting model (AUC = 0.92) for HPV status included age, smoking, and miRNAs: miR-15b, miR-20b, miR-29a, miR-29c, miR-142, miR-146a and miR-205. Using Cox regression model for recurrence, miR-29a was associated with 49% increased risk of recurrence while miR-30e and miR-342 were associated with decreased risk of recurrence with HRs 0.92 (95% CI 0.85–0.99) and 0.84 (95% CI 0.73–0.98), respectively. Our best fitting model for survival included age, gender, alcohol consumption, N stage, recurrence, HPV status, together with miRNAs-20b, 29a, and 342. Conclusion miRNAs show potential to serve as usual biomarkers to predict the clinical course of patients with mucosal HNSCC.

1-5% of individuals with melanoma have a strong family history with a causal gene identified in ~30% of those families, most commonly CDKN2A. Genetic testing and counselling for CDKN2A improves sun-protective and surveillance behaviour without negative psychological sequelae. Given these advantages, dermatologists need to recognise those with a sufficient a priori risk to warrant the offer of genetic testing.

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients’ overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low‐dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.

Although the life expectancy for the US population has increased, a high proportion of this population has lived with ≥1 chronic conditions. We have quantified the burden of disease associated with 15 chronic conditions and combinations of conditions by estimating quality-adjusted life years (QALYs) for older US adults.Data were from the Medicare Health Outcomes Survey Cohort 15 (baseline survey in 2012, follow-up survey 2014, with mortality follow-up through January 31, 2015). We included individuals aged 65 years and older (n=96,481). We estimated mean QALY throughout the remainder of the lifetime according to the occurrence of these conditions.The age-adjusted QALY was 5.8 years for men and 7.8 years for women. Over 90% respondents reported at least 1 condition and 72% reported multiple conditions. Respondents with depression and congestive heart failure had the lowest age-adjusted QALY (1.1-1.5 y for men and 1.5-2.2 y for women), whereas those with hypertension, arthritis, and sciatica had higher QALY (4.2-5.4 and 6.4-7.2 y, respectively). Having either depression or congestive heart failure and any 1 or 2 of the other 13 conditions was associated with the lowest QALY among the possible dyads and triads of chronic conditions. Dyads and triads with hypertension or arthritis were more prevalent, but had higher QALY.Understanding the burden of disease for common chronic conditions and for combinations of these conditions is useful for delivering high-quality primary care that could be tailored for individuals with combinations of chronic conditions.

Sewage input and the relationship between chemical markers (linear alkylbenzenes and coprostanol) and fecal indicator bacteria (FIB, Escherichia coli and enterococci), were evaluated in order to establish thresholds values for chemical markers in suspended particulate matter (SPM) as indicators of sewage contamination in two subtropical estuaries in South Atlantic Brazil. Both chemical markers presented no linear relationship with FIB due to high spatial microbiological variability, however, microbiological water quality was related to coprostanol values when analyzed by logistic regression, indicating that linear models may not be the best representation of the relationship between both classes of indicators. Logistic regression was performed with all data and separately for two sampling seasons, using 800 and 100 MPN 100 mL−1 of E. coli and enterococci, respectively, as the microbiological limits of sewage contamination. Threshold values of coprostanol varied depending on the FIB and season, ranging between 1.00 and 2.23 μg g−1 SPM. The range of threshold values of coprostanol for SPM are relatively higher and more variable than those suggested in literature for sediments (0.10–0.50 μg g−1), probably due to higher concentration of coprostanol in SPM than in sediment. Temperature may affect the relationship between microbiological indicators and coprostanol, since the threshold value of coprostanol found here was similar to tropical areas, but lower than those found during winter in temperate areas, reinforcing the idea that threshold values should be calibrated for different climatic conditions.

Context Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown. Objective To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age. Design In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis. Results 763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P Conclusions In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.

Proceedings of the Machining Innovations Conference for Aerospace Industry (MIC) 2021 21. Machining Innovations Conference for Aerospace Industry, MIC, Hannover, Germany, 1 Dec 2021 - 2 Dec 2021; [S.l.] : Social Science Electronic Publ. 78-85 (2020). doi:10.2139/ssrn.3724213, Published by Social Science Electronic Publ., [S.l.]

Melanoma is the most dangerous form of skin cancer: around 15% of cases worldwide are fatal, but with early detection, survival rates are better than 95%. Having many large moles or having red hair increases a person's risk of developing melanoma; having certain versions of the MC1R gene, called R alleles, the main cause of red hair, also increases melanoma risk. This study, from Australia, aimed to find out if having both those risk factors increased melanoma risk more than the two risk levels simply added together. 611 people with melanoma and 656 who had never had melanoma donated a DNA sample, and researchers recorded the number of large moles, their skin and eye colour, and hair colour at age 21. The authors found that people with red hair and 20+ large moles were 10 times more likely to have melanoma than people with 0-4 moles and dark brown hair. Looking specifically at the types of the MC1R gene that people carried, people with 20+ moles and MC1R R/R genotype were 25 times more likely to have melanoma than people with 0-4 moles and MC1R wildtype/wildtype (consensus) genotype. While the R/R genotype, with or without the red hair phenotype, and a high mole count are both strong melanoma risk factors on their own, when combined they result in an extremely high-risk profile for melanoma. The absolute lifetime risk to age 75 of getting melanoma in Australia is 23.3% for men and 19.3% for women who have 20+ moles and MC1R R/R genotype, compared to just 0.8% for men and 0.7% for women with 0-4 moles and MC1R wildtype/wildtype genotype. This is higher than the risk threshold for screening in other cancers, so the authors suggest that people with many moles and red hair should be regularly checked for melanoma by a doctor, and that people with many moles but non-red hair should also be checked to determine if they have an MC1R R/R genotype.

PurposeBreast cancer survivorship care plans (SCP) have limited content addressing women's health issues. This trial tested if young breast cancer survivors who receive a web-based, women's health SCP were more likely to improve on at least one of the four targeted issues (hot flashes, fertility-related concerns, contraception, and vaginal symptoms) compared to attention controls.MethodsA randomized controlled trial recruited female survivors ages 18-45 at diagnosis, 18-50 at enrollment, completed primary cancer treatment, and had a significant women's health issue: moderate or higherfertility-related concerns; ≥ 4 hot flashes/day with ≥ 1 of moderate severity; ≥ 1 moderate vaginal atrophy symptoms; or not contracepting/using less effective methods. Survivors underwent stratified, block randomization with equal allocation to intervention and control groups. The intervention group accessed the online SCP; controls accessed curated resource lists. In intention-to-treat analysis, the primary outcome of improvement in at least one issue by 24weeks was compared by group.Results182 participants (86 intervention, 96 control), mean age 40.0 ± 5.9 and 4.4 ± 3.2years since diagnosis, were randomized. 61 intervention group participants (70.9%) improved, compared to 55 controls (57.3%) (OR 1.82, 95% CI 0.99-3.4, p = 0.057). The following issue-specific improvements were observed in the intervention versus control arms: fertility-related concerns (27.9% vs. 14.6%, OR 2.3, 95% CI 1.1-4.8); hot flashes (58.5% vs. 55.8%, OR 1.1, 95% CI 0.57-2.2); vaginal symptoms (42.5% vs. 40.7%, OR 1.1, 95% CI 0.6-2.0); contraception (50% vs. 42.6%, OR 1.4, 95% CI 0.74-2.5).ConclusionsIn young breast cancer survivors, a novel, web-based SCP did not result in more change in the primary outcome of improvement in at least one of the four targeted women's health issues, than the attention control condition. The intervention was associated with improved infertility concerns, supporting efficacy of disseminating accessible, evidence-based women's health information to this population.

Objective To estimate the association between perceived fertility potential and contraception use and to characterize factors important in contraceptive decision making in reproductive-age, female cancer survivors. Design Cross-sectional study. Setting Participants were from two state cancer registries, physician referrals, and cancer survivor advocacy groups in the United States. Patient(s) A total of 483 female survivors aged 18–40 years. Intervention(s) Online questionnaire. Main Outcome Measure(s) Contraception use. Result(s) Eighty-four percent of participants used contraception; 49.7% used highly effective, World Health Organization tiers I and II methods (surgical sterilization, intrauterine devices, contraceptive implant, combined hormonal contraceptives, medroxyprogesterone acetate, progestin-only pills, contraceptive diaphragm). Contraception non-use was more common among survivors who perceived themselves to be infertile, compared with survivors who perceived themselves to be as or more fertile than similarly aged peers (prevalence ratio 4.0, 95% confidence interval 2.5–7.4). In mediation analysis that adjusted for clinical infertility, 59% of the association between prior chemotherapy and contraception non-use was explained by perceived infertility. Contraception efficacy (n = 62, 25.8%) and ease of use (n = 50, 20.8%) were the most cited reasons for using tier I/II methods; compared with lack of hormones (n = 81, 49.7%) as the predominant reason for using less-effective, tier III/IV methods. Conclusion(s) Although female, reproductive-age cancer survivors had high uptake of contraception, those who perceived themselves to be infertile were less likely to use contraception. Throughout survivorship, clinicians should counsel survivors on fertility potential in the context of their prior cancer treatments and on factors, including contraceptive efficacy and hormone-free contraception, that inform reproductive decision making in this population.

A high total body naevus count is the highest risk factor for melanoma; the phenotype of red hair colour, freckling and pale skin that burns easily, produced by MC1R R alleles, also predisposes to melanoma.To determine whether the known melanoma risk factors of high naevus count and red hair or MC1R R alleles act synergistically to increase melanoma risk.The Brisbane Naevus Morphology Study involved 1267 participants from volunteers presenting at a melanoma unit, dermatology outpatient clinic, private dermatology clinics, the Brisbane Longitudinal Twin Study and the QSkin Study. We examined pigmentation characteristics, total body naevus ≥ 5 mm count, and MC1R, ASIP and CDKN2A genotype in participants with and without a personal history of melanoma, living in Queensland, Australia, which is an area of high ultraviolet radiation.Cases were older than controls (median 57 vs. 33 years). Compared with individuals with dark brown hair and zero to four naevi, individuals with red hair and ≥ 20 naevi had a melanoma odds ratio of 10·0 (95% confidence interval 4·2-24·3). Individuals with MC1R R/R genotype and ≥ 20 naevi (≥ 5 mm diameter) had a melanoma odds ratio of 25·1 (95% confidence interval 8·4-82·7) compared with wild-type (WT)/WT individuals with zero to four naevi. The highest risk group is Australian men with the MC1R R/R genotype and ≥ 20 moles, who have an absolute risk of melanoma to age 75 years of 23·3%, compared with 0·8% for men with the WT/WT genotype and zero to four naevi.Patients who live in areas of high ultraviolet radiation, and have many large naevi and the red hair colour phenotype, particularly those with the MC1R R/R genotype, have a high risk of melanoma above the threshold recommended for screening in other cancers. Therefore, they should undergo intensive physician-led surveillance. What's already known about this topic? A high number of acquired melanocytic naevi, the red hair phenotype and MC1R R alleles all independently increase melanoma risk. Women with atypical naevi have an increasing melanoma risk gradient from darker hair to lighter hair. Women with many naevi have an increasing melanoma risk gradient from those with no elements of the red hair phenotype, to those with freckles but not red hair, to those with red hair. What does this study add? In Queensland, Australia, people with ≥ 20 naevi (≥ 5 mm diameter) and MC1R R/R genotype have a 25-fold increased melanoma risk, relative to people with zero to four naevi and the MC1R WT/WT genotype. In Queensland, individuals with ≥ 20 naevi and the MC1R R/R genotype have an absolute melanoma risk to age 75 years of 23·3% for men and 19·3% for women. This effect is independent of CDKN2A genotype. Further research is required to determine the effect of areas of lower ultraviolet radiation, as this study took place in the Queensland, Australia, which is an area of high ultraviolet radiation. MC1R R/r genotype is associated with increased total body naevus count but this is not the case for R/R. What is the translational message? Patients with many large naevi and the red hair colour phenotype, particularly those with an MC1R R/R genotype, have an unusually high risk of melanoma. In a high ultraviolet environment, this risk exceeds the threshold recommended for screening in other cancers, and such individuals should undergo intensive, regular, physician-led surveillance. Patients with many large naevi but with non-red colour hair may benefit further from clinical MC1R genotyping.

Author(s): Stark, Shaylyn S; Natarajan, Loki; Chingos, Diana; Ehren, Jennifer; Gorman, Jessica R; Krychman, Michael; Kwan, Brian; Mao, Jun J; Myers, Emily; Walpole, Tom; Pierce, John P; Su, H Irene | Abstract: BACKGROUND:Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE:Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS:SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. RESULTS:Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5-90.7%) and confidence (50.0-74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. CONCLUSION:Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management.

Discharge of untreated sewage into Antarctic environments presents a risk of introducing non-native microorganisms, but until now, adverse consequences have not been conclusively identified. Here we show that sewage disposal introduces human derived Escherichia coli carrying mobile genetic elements and virulence traits with the potential to affect the diversity and evolution of native Antarctic microbial communities. We compared E. coli recovered from environmental and animal sources in Antarctica to a reference collection of E. coli from humans and non-Antarctic animals. The distribution of phylogenetic groups and frequency of 11 virulence factors amongst the Antarctic isolates were characteristic of E. coli strains more commonly associated with humans. The rapidly emerging E. coli ST131 and ST95 clones were found amongst the Antarctic isolates, and ST95 was the predominant E. coli recovered from Weddell seals. Class 1 integrons were found in 15% of the Antarctic E. coli with 4 of 5 identified gene cassette arrays containing antibiotic resistance genes matching those common in clinical contexts. Disposing untreated sewage into the Antarctic environment does disseminate non-native microorganisms, but the extent of this impact and implications for Antarctic ecosystem health are, as yet, poorly understood.

Engineering electrode materials for optoelectronic and energy storage applications requires a fundamental understanding of intercalation using spatially-resolved techniques. However, spectroscopic methods can have limited spatial resolution and low intensity since the signal passes through electrolyte. Here, a device geometry is presented in which the electrolyte is laterally separated from the area probed spectroscopically, so that the signal does not pass through the electrolyte. This geometry enables us to visualize ion transport with optical microscopy and monitor charge transfer with Raman and visible reflectance spectroscopies. In addition, vibrational changes are probed in the mid-IR, a region previously difficult to access due to electrolyte absorption. This geometry will allow many layered electrodes to be probed in situ using time- and spatially-resolved techniques, including photon and electron spectroscopies.

Amelanotic/hypomelanotic melanoma is a clinicopathologic subtype with absent or minimal melanin. This study assessed previously reported coding variants in albinism genes (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, LRMDA) and common intronic, regulatory variants of OCA2 in individuals with amelanotic/hypomelanotic melanoma, pigmented melanoma cases and controls. Exome sequencing was available for 28 individuals with amelanotic/hypomelanotic melanoma and 303 individuals with pigmented melanoma, which were compared to whole exome data from 1144 Australian controls. Microarray genotyping was available for a further 17 amelanotic/hypomelanotic melanoma, 86 pigmented melanoma, 147 melanoma cases (pigmentation unknown) and 652 unaffected controls. Rare deleterious variants in TYR/OCA1 were more common in amelanotic/hypomelanotic melanoma cases than pigmented melanoma cases (set mixed model association tests P = 0.0088). The OCA2 hypomorphic allele p.V443I was more common in melanoma cases (1.8%) than controls (1.0%, X2 P = 0.02), and more so in amelanotic/hypomelanotic melanoma (4.4%, X2 P = 0.007). No amelanotic/hypomelanotic melanoma cases carried an eye and skin darkening haplotype of OCA2 (including rs7174027), present in 7.1% of pigmented melanoma cases (P = 0.0005) and 9.4% controls. Variants in TYR and OCA2 may play a role in amelanotic/hypomelanotic melanoma susceptibility. We suggest that somatic loss of function at these loci could contribute to the loss of tumor pigmentation, consistent with this we found a higher rate of somatic mutation in TYR/OCA2 in amelanotic/hypomelanotic melanoma vs pigmented melanoma samples (28.6% vs 3.0%; P = 0.021) from The Cancer Genome Atlas Skin Cutaneous Melanoma collection.

This study assesses the prevalence of falls, factors predicting future falls, and health impacts of falls and balance or walking problems for U.S. older adults. Data were from participants ≥65 years in the Medicare Health Outcomes Survey Cohort 15 (baseline survey in 2012; follow-up survey in 2014; n = 164,597). We examined baseline factors predicting falls at follow-up and estimated the impact of falls and balance/walking problems on health-related quality of life (HRQOL), mortality, and quality-adjusted life years (QALYs). About 23% reported falls and 34% reported balance/walking problems in the past 12 months. The strongest predictors of falls were previous falls [adjusted odds ratio (OR) = 2.9] and balance/walking problems (OR = 1.7). Many self-reported chronic conditions (e.g., depression, stroke, and diabetes), geriatric symptoms (e.g., urine leakage), and limitations of activities of daily living (e.g., transferring and walking) also predicted falls, but at a smaller magnitude (ORs = 1.1–1.3). Having balance/walking problems was associated with a greater decrease in HRQOL scores (0.195 points) than falls (0.077 points), while falls were associated with a greater increase in mortality [adjusted hazard ratio (HR) = 1.5] than balance/walking problems (HR = 1.1). Falls were associated with a 4.6-year (48%) decrease in QALYs, while balance/walking problems was associated with a 7.3-year (62%) decrease in QALYs. Falls are a major problem for U.S. elderly and will continue to have an even greater impact as the population ages. The nearly 50% decrease in QALYs for falls and >60% decrease for balance or walking problems demonstrates the substantial burden associated with these problems among older Americans.

The continuous increase of (volatile) renewable energy production and the coupling of different energy sectors such as heating, cooling and electricity have significantly increased the complexity of urban energy systems. Such multi-energy systems (MES) can be operated more efficiently with the aid of optimization-based energy management systems (EMS). However, most existing EMS are tailor-made for one specific system or class of systems, i.e. are not generally applicable. Furthermore, only limited information on the actual savings potential of the usage of an EMS under realistic conditions is available. Therefore, this paper presents a novel modular modeling approach for an EMS for urban MES, which also enables the modeling of complex system configurations. To assess the actual savings potential of the proposed EMS, a comprehensive case study was carried out. In the course of this the influence of different user behavior, changing climatic conditions and forecast errors on the savings potential was analyzed by comparing it with a conventional control strategy. The results showed that using the proposed EMS in conjunction with supplementary system components (thermal energy storage and battery) an annual cost savings potential of between 3 and 6% could be achieved.

Background. The Medicare Health Outcomes Survey (HOS), a nationwide annual survey of Medicare beneficiaries, includes the Centers for Disease Control and Prevention’s HRQOL-4 questionnaire and Veterans RAND 12-item Health Survey (VR-12). This study compared EQ-5D scores derived from the HRQOL-4 (dEQ-5D) to SF-6D scores derived from VR-12. Methods. Data were from Medicare HOS Cohort 15 (2012 baseline; 2014 follow-up). We included participants aged 65+ ( n = 105,473). We compared score distributions, evaluated known-groups validity, assessed each index as a predictor for mortality, and estimated quality-adjusted life years (QALYs) using the dEQ-5D and SF-6D. Results. Compared to the SF-6D, the dEQ-5D had a higher mean score (0.787 v. 0.691) and larger standard deviation (0.310 v. 0.101). The decreases in estimated scores associated with chronic conditions were greater for the dEQ-5D than for the SF-6D. For example, dEQ-5D scores for persons with depression decreased 0.456 points compared to 0.141 points for the SF-6D. The dEQ-5D strongly predicted mortality, as adjusted hazard ratios for the first to fourth quintiles, relative to the fifth quintile, were 2.2, 1.7, 1.8, and 1.5, respectively, while the association between SF-6D and mortality was weaker or nonexistent (adjusted hazard ratios were 1.3, 1.1, 1.0, and 0.6, respectively). Compared to the SF-6D, QALYs estimated using the dEQ-5D were higher overall (5.6 v. 4.9 years), higher for persons with less debilitating conditions (e.g., hypertension, 5.0 v. 4.4 years), and lower for more debilitating conditions (e.g. depression, 2.5 v. 2.8 years). Conclusions. Compared to the SF-6D, the dEQ-5D was better able to measure individuals’ overall health; detect the differential impact of chronic conditions, particularly among persons in poorer health; and predict mortality. The HRQOL-4 questionnaire may be valuable for monitoring and improving health outcomes for the Medical HOS data set.

Background The staging method for activities of daily living (ADLs) limitations developed by Stineman and colleagues that classifies people into five stages can reflect severity of activity limitations. Objective To assess the impact of stages of limitations in ADLs on quality-adjusted life years (QALYs) and the relative severity of each ADL limitation for a large, nationally-representative sample of the U.S. community-dwelling older population. Methods Data were obtained from the Limited Dataset of the Medicare Health Outcomes Survey Cohort 15 (2012 baseline survey, 2014 follow-up survey). We included respondents aged ≥65 years (n = 105,473). We estimated expected QALYs throughout the remaining lifetime of participants stratified by the ADL limitation status and stages of ADL limitations. Results Overall, the expected QALYs was 5.6 years. QALYs decreased with increasing stages of ADL limitations. The adjusted QALYs for Stage 0 (no limitation) participants were 6.8; for Stage I (mild) participants, 3.9; for Stage II (moderate) participants, 2.2; for Stage III (severe) participants, 1.8; and for Stage IV (complete limitations) participants, 1.5. Differences in QALYs occurred between individual ADL items within an ADL stage. In Stage I, for example, participants who reported only problems with getting in or out of chairs had 6.7 QALYs which was markedly higher than participants who reported only problems with walking (3.8 QALYs). Conclusions Our findings provide additional evidence that Stineman's ADL stages serve as valid estimates of the overall health of elderly Americans. Self-reported ADL status should be routinely collected as a patient-reported outcome in the elderly population.

Objective To test whether emergency contraception use in reproductive-aged cancer survivors is higher than in the general U.S. population and evaluate factors associated with use among survivors. Design A retrospective cohort study compared emergency contraception use between cancer survivors in the Reproductive Window Study on ovarian function after cancer and in the general population in the 2006–2010 National Survey for Family Growth. In a cross-sectional analysis of survivors, multivariable models were used to test associations between participant characteristics and emergency contraception use. Setting Not applicable. Patient(s) A total of 616 female cancer survivors aged 18–40. Intervention(s) None. Main Outcome Measure(s) Self-reported emergency contraception use. Result(s) The mean age of survivors was 33.4 ± 4.7, at a mean 7.5 years since diagnosis. Breast cancer (22%), Hodgkin lymphoma (18%), and leukemia (8%) were the most common cancers. Since diagnosis, 156 (25.3%) used emergency contraception, 60% because of not otherwise using contraception. Age-adjusted prevalence of use was higher in survivors than in the general population (28.3% [95% confidence interval (CI) 24.7–31.9] vs. 12.0% [95% CI 11.1–12.9]). In multivariable analysis among survivors, nonwhite race (prevalence ratio [PR] 1.3, 95% CI 1.0–1.8), breast cancer (PR 0.6, 95% CI 0.4–1.0), partnered relationship (PR 0.6, 95% CI 0.5–0.9), and older age (age 36–40 vs. 31–35; PR 0.7, 95% CI 0.5–1.0) were associated with emergency contraception. Conclusion(s) Female young adult cancer survivors were significantly more likely to use emergency contraception compared with the general population. Populations including nonwhite survivors have a higher risk, suggesting differences in family planning care. Strategies to improve contraception and decrease the need for emergency contraception are needed.

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are, Highlights • A seven-miRNA panel (MELmiR-7) detected the presence of melanoma with high sensitivity (93%) and specificity (≥ 82%). • In serially collected stage IV specimens, members of the ‘MELmiR-7’ panel confirmed tumour progression in 100% of cases. • The ‘MELmiR-7’ panel is superior to currently used serological markers for melanoma progression, recurrence, and survival.

The melanoma transformation rate of an individual nevus is very low despite the detection of oncogenic BRAF or NRAS mutations in 100% of nevi. Acquired melanocytic nevi do, however, mimic melanoma, and approximately 30% of all melanomas arise within pre-existing nevi. Using whole-exome sequencing of 30 matched nevi, adjacent normal skin, and saliva we sought to identify the underlying genetic mechanisms for nevus development. All nevi were clinically, dermoscopically, and histopathologically documented. In addition to identifying somatic mutations, we found mutational signatures relating to UVR mirroring those found in cutaneous melanoma. In nevi we frequently observed the presence of the UVR mutation signature compared with adjacent normal skin (97% vs. 10%, respectively). Copy number aberration analysis showed that for nevi with copy number loss of tumor suppressor genes, this loss was balanced by loss of potent oncogenes. Moreover, reticular and nonspecific patterned nevi showed an increased (P0.0001) number of copy number aberrations compared with globular nevi. The mutation signature data generated in this study confirms that UVR strongly contributes to nevogenesis. Copy number changes reflect at a genomic level the dermoscopic differences of acquired melanocytic nevi. Finally, we propose that the balanced loss of tumor suppressor genes and oncogenes is a protective mechanism of acquired melanocytic nevi.

During the 2009/2010 summer, a comprehensive environmental impact assessment (EIA) of the wastewater discharge at Davis Station, East Antarctica was completed. As part of this, histological alteration of gill and liver tissue in Antarctic Rock-cod (Trematomus bernacchii) from four sites along a spatial gradient from the wastewater outfall were assessed. All fish within 800 m of the outfall exhibited significant histological changes in both tissues. Common pathologies observed in fish closest to the outfall include proliferation of epithelial cells with associated secondary lamellar fusion in the gills and multifocal granulomata with inflammation and necrosis as well as cysts in the liver. Fish from sites >800 m from the outfall also exhibited alterations but to a lesser degree, with prevalence and severity decreasing with increasing distance from the outfall. This study highlights the value of histopathological investigations as part of EIAs and provides the first evidence of sub-lethal alteration associated with wastewater discharge in East Antarctica.

Wastewater containing human sewage is often discharged with little or no treatment into the Antarctic marine environment. Faecal sterols (primarily coprostanol) in sediments have been used for assessment of human sewage contamination in this environment, butin situproduction and indigenous faunal inputs can confound such determinations. Using gas chromatography with mass spectral detection profiles of both C27and C29sterols, potential sources of faecal sterols were examined in nearshore marine sediments, encompassing sites proximal and distal to the wastewater outfall at Davis Station. Faeces from indigenous seals and penguins were also examined. Faeces from several indigenous species contained significant quantities of coprostanol but not 24-ethylcoprostanol, which is present in human faeces.In situcoprostanol and 24-ethylcoprostanol production was identified by co-production of their respectiveepi-isomers at sites remote from the wastewater source and in high total organic matter sediments. A C29sterols-based polyphasic likelihood assessment matrix for human sewage contamination is presented, which distinguishes human from local fauna faecal inputs andin situproduction in the Antarctic environment. Sewage contamination was detected up to 1.5 km from Davis Station.

Until April 2007 the MAGIC telescope used a 300 MSamples/s FADC system to sample the shaped PMT signals produced by the captured Cherenkov photons of air showers. Different algorithms to reconstruct the signal from the read-out samples (extractors) have been implemented and are described and compared. Criteria based on the obtained charge and time resolution/bias are defined and used to judge the different extractors, by applying them to calibration, cosmic and pedestal signals. The achievable charge and time resolution have been derived as functions of the incident number of photo-electrons., Accepted for publication in NIM A

Purpose To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi. Methods We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (n = 10), localized uveal melanoma (n = 50), or metastatic uveal melanoma (n = 5). Levels of 17 miRNAs were measured in blood samples of study participants using a sensitive real-time PCR system. Results A panel of six miRNAs (miR-16, miR-145, miR-146a, miR-204, miR-211, and miR-363-3p) showed significant differences between participants with uveal nevi compared with patients with localized and metastatic uveal melanoma. Importantly, miR-211 was able to accurately distinguish metastatic disease from localized uveal melanoma (P < 0.0001; area under the curve = 0.96). When the six-miRNA panel was evaluated as a group it had the ability to identify uveal melanoma when four or more miRNAs (93% sensitivity and 100% specificity) reached or exceeded their cut-point. Conclusions This miRNA panel, in tandem with clinical findings, may be suited to confirm benign lesions. In addition, due to the panel's high precision in identifying malignancy, it has the potential to augment melanoma detection in subsequent clinical follow-up of lesions with atypical clinical features. Translational Relevance Uveal nevi mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. This panel is most relevant at the nevus stage and in lesions with uncertain malignant potential as a companion diagnostic tool to assist in clinical decision-making.

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses., Comment: Submitted to NIM A

We present a comprehensive scientific assessment of the environmental impacts of an Antarctic wastewater ocean outfall, at Davis station in East Antarctica. We assessed the effectiveness of current wastewater treatment and disposal requirements under the Protocol on Environmental Protection to the Antarctic Treaty. Macerated wastewater has been discharged from an outfall at Davis since the failure of the secondary treatment plant in 2005. Water, sediment and wildlife were tested for presence of human enteric bacteria and antibiotic resistance mechanisms. Epibiotic and sediment macrofaunal communities were tested for differences between sites near the outfall and controls. Local fish were examined for evidence of histopathological abnormalities. Sediments, fish and gastropods were tested for uptake of sewage as measured by stable isotopes of N and C. Escherichia coli carrying antibiotic resistance determinants were found in water, sediments and wildlife (the filter feeding bivalve Laternula eliptica). Fish (Trematomus bernacchii) within close proximity to the outfall had significantly more severe and greater occurrences of histopathological abnormalities than at controls, consistent with exposure to sewage. There was significant enrichment of 15N in T. bernacchii and the predatory gastropod Neobuccinum eatoni around the outfall, providing evidence of uptake of sewage. There were significant differences between epibiotic and sediment macrofaunal communities at control and outfall sites (