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Background: Little is known about the heterogeneous nature of financial hardship in younger patients with metastatic disease and the extent to which insurance protects against it. We examine the association between insurance status and multidimensional indicators of financial hardship in a national sample of women with metastatic breast cancer. Methods: We conducted a national, retrospective online survey in partnership with the Metastatic Breast Cancer Network. Eligible participants were =18 years, diagnosed with metastatic breast cancer, and able to respond in English. We estimated multivariate generalized linear models predicting two distinct dimensions of financial hardship--financial insecurity (the ability to afford care and living costs) and financial distress (the extent of emotional/psychological distress experienced due to costs)--as a function of insurance status. Results: Participants responded from 41 states (N = 1054; median age: 44 years). Overall, 30% were uninsured. Financial insecurity was more frequently reported by uninsured respondents. In adjusted analyses, uninsured participants were more likely than insured participants to report contact by debt collectors (adjusted risk ratio [aRR]: 2.38 [2.06, 2.76]) and being unable to meet monthly expenses (aRR: 2.11 [1.68, 2.66]). Financial distress was reported more frequently by insured participants. For example, insured participants were more likely to worry about future financial problems due to cancer and distress about lack of cost transparency. After adjustment, uninsured participants remained about half as likely as insured participants to report financial distress. Conclusions: Young adult women with metastatic cancer reported a high burden of financial toxicity. Importantly, insurance does not protect against financial distress; however, the uninsured are the most materially vulnerable. [ABSTRACT FROM AUTHOR]

Background: Hispanic populations in the United States experience numerous barriers to care access. It is unclear how cancer screening disparities between Hispanic and non‐Hispanic White individuals are explained by access to care, including having a usual source of care and health insurance coverage. Methods: A secondary analysis of the 2019 National Health Interview Survey was conducted and included respondents who were sex‐ and age‐eligible for cervical (n = 8316), breast (n = 6025), or colorectal cancer screening (n = 11,313). The proportion of ever screened and up to date for each screening type was compared. Regression models evaluated whether controlling for reporting a usual source of care and type of health insurance (public, private, none) attenuated disparities between Hispanics and non‐Hispanic White individuals. Results: Hispanic individuals were less likely than non‐Hispanic White individuals to be up to date with cervical cancer screening (71.6% vs. 74.6%) and colorectal cancer screening (52.9% vs. 70.3%), but up‐to‐date screening was similar for breast cancer (78.8% vs. 76.3%). Hispanic individuals (vs. non‐Hispanic White) were less likely to have a usual source of care (77.9% vs. 86.0%) and more likely to be uninsured (23.6% vs. 7.1%). In regressions, insurance fully attenuated cervical cancer disparities. Controlling for both usual source of care and insurance type explained approximately half of the colorectal cancer screening disparities (adjusted risk difference: −8.3 [–11.2 to –4.8]). Conclusion: Addressing the high rate of uninsurance among Hispanic individuals could mitigate cancer screening disparities. Future research should build on the relative successes of breast cancer screening and investigate additional barriers for colorectal cancer screening. Plain language summary: This study uses data from a national survey to compare cancer screening use those who identify as Hispanic with those who identify as non‐Hispanic White.Those who identify as Hispanic are much less likely to be up to date with colorectal cancer screening than those who identify as non‐Hispanic White, slightly less likely to be up to date on cervical cancer screening, and similarly likely to receive breast cancer screening.Improving insurance coverage is important for health equity, as is further exploring what drives higher use of breast cancer screening and lower use of colorectal cancer screening. Hispanic populations in the United States experience numerous barriers to care access. Using a secondary analysis of survey data demonstrated that the magnitude of screening disparities for Hispanic individuals varies by screening type, and that addressing the high rate of uninsurance among Hispanic individuals could help mitigate cancer screening disparities. [ABSTRACT FROM AUTHOR]

Cervical cancer is a major source of morbidity and mortality in Uganda. In addition to prophylactic HPV vaccination, secondary prevention strategies are needed to reduce cancer burden. We evaluated the potential cancer reductions associated with a hypothetical single‐contact therapeutic HPV intervention—with 70% coverage and variable efficacy [30%‐100%]—using a three‐stage HPV modeling framework reflecting HPV and cervical cancer burden in Uganda. In the reference case, we assumed prophylactic preadolescent HPV vaccination starting in 2020 with 70% coverage. A one‐time therapeutic intervention targeting 35‐year‐old women in 2025 (not age‐eligible for prophylactic vaccination) averted 1801 cervical cancers per 100 000 women over their lifetime (100% efficacy) or 533 cancers per 100 000 (30% efficacy). Benefits were considerably smaller in birth cohorts eligible for prophylactic HPV vaccination (768 cases averted per 100 000 at 100% efficacy). Evaluating the population‐level impact over 40 years, we found introduction of a therapeutic intervention in 2025 with 100% efficacy targeted annually to 30‐year‐old women averted 139 000 incident cervical cancers in Uganda. This benefit was greatly reduced if efficacy was lower (30% efficacy; 41 000 cases averted), introduction was delayed (2040 introduction; 72 000 cases averted) or both (22 000 cases averted). We demonstrate the potential benefits of a single‐contact HPV therapeutic intervention in a low‐income setting, but show the importance of high therapeutic efficacy and early introduction timing relative to existing prophylactic programs. Reduced benefits from a less efficacious intervention may be somewhat offset if available within a shorter time frame. [ABSTRACT FROM AUTHOR]

Background: For women with hormone receptor positive breast cancer, long-term endocrine therapy (ET) can greatly reduce the risk of recurrence, yet adherence is low- particularly among traditionally underserved populations.Methods: The Carolina Breast Cancer Study oversampled Black and young women (<50 years of age). Participants answered an ET-specific medication adherence questionnaire assessing reasons for non-adherence. We used principal factor analysis to identify latent factors describing ET non-adherence. We then performed multivariable regression to determine clinical and demographic characteristics associated with each ET non-adherence factor.Results: 1,231 women were included in analysis, 59% reported at least one barrier to ET adherence. We identified three latent factors which we defined as: habit - challenges developing medication-taking behavior; tradeoffs - high perceived side effect burden and medication safety concerns; and resource barriers - challenges related to cost or accessibility. Older age (50+) was associated with less reporting of habit (Adjusted Risk Ratio (aRR) 0.54[95% CI: 0.43-0.69] and resource barriers (aRR 0.66[0.43-0.997]), but was not associated with tradeoff barriers. Medicaid-insured women were more likely than privately-insured to report tradeoff (aRR:1.53 [1.10-2.13]) or resource barriers (aRR:4.43[2.49-6.57]). Black race was associated with increased reporting of all factors (habit: aRR 1.29[1.09-1.53]; tradeoffs: 1.32[1.09-1.60], resources: 1.65[1.18-2.30]).Conclusion: Barriers to ET adherence were described by three distinct factors, and strongly associated with sociodemographic characteristics. Barriers to ET adherence appear inadequately addressed for younger, Black, and publicly-insured breast cancer survivors. These findings underscore the importance of developing multi-faceted, patient-centered interventions that address a diverse range of barriers to ET adherence. [ABSTRACT FROM AUTHOR]

This paper explores the relationship between firms' strategies to share knowledge with their innovation system and innovative performance. The empirical analysis showed that many firms designed strategies to share technological knowledge with competitors, and those firms that shared knowledge with their innovation system earned higher innovative performance than firms that did not share knowledge. In addition, firms that interacted with their global innovation system earned higher innovative performance than firms that interacted with only their national innovation system. These results should help managers and researchers understand how to devise technology strategies in globally integrated industries. [ABSTRACT FROM AUTHOR]

The article explores the implications of high medical care costs for cancer patients and their family. Topics mentioned include association of self-reported well-being of the patients and the advancement of the disease, differences in cost exposure by insurance type and disease burden, and the out-of-pocket (OOP) costs in managing and treating cancer.

Objective: To understand the role of county characteristics in the growing divide between rural and urban mortality from 1980 to 2010.Data Source: Age-adjusted mortality rates for all U.S. counties from 1980 to 2010 were obtained from the CDC Compressed Mortality File and combined with county characteristics from the U.S. Census Bureau, the Area Health Resources File, and the Inter-University Consortium for Political and Social research.Study Design: We used Oaxaca-Blinder decomposition to assess the extent to which rural-urban mortality disparities are explained by observed county characteristics at each decade.Principal Findings: Decomposition shows that, at each decade, differences in rural/urban characteristics are sufficient to explain differences in mortality. Furthermore, starting in 1990, rural counties have significantly lower predicted mortality than urban counties when given identical county characteristics. We find changes in the effect of characteristics on mortality, not the characteristics themselves, drive the growing mortality divide.Conclusions: Differences in economic and demographic characteristics between rural and urban counties largely explain the differences in age-adjusted mortality in any given year. Over time, the role these characteristics play in improving mortality has increased differentially for urban counties. As characteristics continue changing in importance as determinants of health, this divide may continue to widen. [ABSTRACT FROM AUTHOR]

Abstract: Ecological networks are a cornerstone of ecological theory, offering an integrated approach to understanding food webs and ecosystem dynamics required for restoration and conservation ecology. We investigated ecological network dynamics in a large floodplain undergoing extreme variation in water availability, with drought and subsequent flooding representing a resource pulse. We used structural equation models to quantify ecological network dynamics for the Lowbidgee floodplain (Australia), based on surveys over 5 years while the floodplain transitioned from extremely dry (2009, 2010) to wet (2011) and post‐wet (2013, 2014) conditions. We identified significant associations of species and trophic guilds with inundation at the site and floodplain scale, which allowed us to quantify the strength of biotic interactions within the network and the stability of interactions under differing patterns of resource availability. At the floodplain scale, most taxa responded strongly in distribution and abundance to the 2011 resource pulse, a widespread flood, but this response did not persist during subsequent years of moderate floods. In contrast, fish species, both native and exotic, responded strongly only in the post‐wet period. At the fine spatial scale (i.e., sites), complex responses were observed, with only waterbirds, frogs and tadpoles positively associated with inundation, while fish species showed a range of associations with fine‐scale inundation. Biotic interactions within sites, across all trophic guilds, were predominately overridden by inundation and water temperature, mediated by strong associations with aquatic vegetation. Stratifying the ecological network to dry, wet and post‐wet periods highlighted varying associations of taxa with fine‐scale inundation, generally responding synchronously to resource pulses, with relatively weak biotic interactions. Associations with site‐scale inundation were strongest during the post‐wet period for fishes and frogs. Only Litoria spp. (Hylidae) tadpoles, waterbirds and aquatic vegetation had positive associations with site‐scale inundation during the dry period. We conclude that responses of trophic guilds are largely dependent on the way they interact with their environment at particular spatial and temporal scales. Our investigation of this ecological network reinforced the importance of hydrological drivers over biotic interactions, with clear implications for the management of environmental flows, particularly in systems recovering from long‐term flow alteration. Management efforts should focus environmental flows to promote specialist species (e.g., southern bell frog, Litoria raniformis) and Murray hardyhead (Craterocephalus fluviatilis: Atherinidae), waterbirds and aquatic vegetation over the more generalist fish species that have established because of the loss of the natural flow regime. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the relative risks and benefits of common treatment options for abnormal uterine bleeding (AUB) can help providers and patients to make balanced, evidence-based decisions.Objectives: To provide comparative estimates of clinical outcomes after placement of levonorgestrel-releasing intrauterine system (LNG-IUS), ablation, or hysterectomy for AUB.Search Strategy: A PubMED search was done using combinations of search terms related to abnormal uterine bleeding, LNG-IUS, hysterectomy, endometrial ablation, cost-benefit analysis, cost-effectiveness, and quality-adjusted life years.Selection Criteria: Full articles published in 2006-2016 available in English comparing at least two treatment modalities of interest among women of reproductive age with AUB were included.Data Collection and Analysis: A decision tree was generated to compare clinical outcomes in a hypothetical cohort of 100 000 premenopausal women with nonmalignant AUB. We evaluated complications, mortality, and treatment outcomes over a 5-year period, calculated cumulative quality-adjusted life years (QALYs), and conducted probabilistic sensitivity analysis.Main Results: Levonorgestrel-releasing intrauterine system had the highest number of QALYs (406 920), followed by hysterectomy (403 466), non-resectoscopic ablation (399 244), and resectoscopic ablation (395 827). Ablation had more treatment failures and complications than LNG-IUS and hysterectomy. Findings were robust in probabilistic sensitivity analysis.Conclusions: Levonorgestrel-releasing intrauterine system and hysterectomy outperformed endometrial ablation for treatment of AUB. [ABSTRACT FROM AUTHOR]

Cholesterol is important for membrane stability and is the key substrate for the synthesis of steroid hormones and vitamin D. Furthermore, it is a major component of the lipid barrier in the stratum corneum of the human epidermis. Considering that steroid hormone synthesis is taking place in epidermal melanocytes, we tested whether downstream oestrogen receptor/cAMP signalling via MITF/tyrosine hydroxylase/tyrosinase/pigmentation could be possibly modulated by cholesterol. For this purpose, we utilized human primary melanocyte cell cultures and human melanoma cells with different pigmentation capacity applying immunofluorescence, RT-PCR, Western blotting and determination of melanin content. Our in situ and in vitro results demonstrated that melanocytes can synthesize cholesterol via HMG-CoA reductase and transport cholesterol via LDL/Apo-B100/LDLR. Moreover, we show that cholesterol increases melanogenesis in these cells and in human melanoma cells of intermediate pigmentation (FM55) in a time- and dose-dependent manner. Cellular cholesterol levels in melanoma cells with different pigmentation patterns, epidermal melanocytes and keratinocytes do not differ except in the amelanotic (FM3) melanoma cell line. This result is in agreement with decreasing cholesterol content versus increasing pigmentation in melanosomes. Cholesterol induces cAMP in a biphasic manner i.e. after 30 min and later after 6 and 24 h, meanwhile protein expression of oestrogen receptor β, CREB, MITF, tyrosine hydroxylase and tyrosinase is induced after 72 h. Taken together, we show that human epidermal melanocytes have the capacity of cholesterol signalling via LDL/Apo-B100/LDL receptor and that cholesterol under in vitro conditions increases melanogenesis. [ABSTRACT FROM AUTHOR]

Despite many efforts, regulation of skin and hair pigmentation is still not fully understood. This article focuses mainly on controversial aspects in pigment cell biology which have emerged over the last decade. The central role of tyrosinase as the key enzyme in initiation of melanogenesis has been closely associated with the 6BH4 dependent phenylalanine hydroxylase (PAH) and tyrosine hydroxylase isoform I (THI) providing evidence for an old concept of the three enzyme theory in the initiation of the pigmentation process. In this context, it is noteworthy that intracellular L-phenylalanine uptake and turnover to L-tyrosine via PAH is vital for substrate supply of THI and tyrosinase. While PAH acts in the cytosol of melanocytes, THI and tyrosinase are sitting side by side in the melanosomal membrane. THI at low pH provides L-3,4-hydroxyphenylalanine L-DOPA which in turn is required for activation of met-tyrosinase. After an intramelanosomal pH change, possibly by the p-protein, has taken place, tyrosinase is subject to control by 6/7BH4 and the proopiomelanocortin (POMC) peptides α-MSH melanocyte stimulating hormone and β-MSH in a receptor independent manner. cAMP is required for the activation of microphthalmia-associated transcription factor to induce expression of tyrosinase, for transcription of THI and for activation of PAH. The redundancy of the cAMP signal is discussed. Finally, we propose a novel mechanism involving H2O2 in the regulation of tyrosinase via p53 through transcription of hepatocyte nuclear factor 1α which in turn can also affect the POMC response. [ABSTRACT FROM AUTHOR]

Nine hunting dogs were bled pre and post vaccination with modified-live virus vaccine. Their antibody responses to canine adenovirus type 1 was measured by an indirect immunofluorescent antibody test. The vaccine proved to be both effective and safe. [ABSTRACT FROM AUTHOR]