Objectives: Age is an understudied factor when considering treatment options for melanoma. Here, we examine the impact of age on primary melanoma treatment in a prospective cohort of patients. Methods: We used logistic regression models to examine the associations between age and initial treatment, using recurrence and melanoma-specific survival as endpoints. Results: 444 primary melanoma patients were categorized into three groups by age at diagnosis: 19-45 years (24.3%), 46-70 (50.2%), and 71-95 (25.5%). In multivariate models, older patients experienced a higher risk of recurrence (hazard ratio 3.34, 95% confidence interval, CI, 1.53-7.25; p < 0.01). No significant differences were observed in positive biopsy margin rates or extent of surgical margins across age groups. Patients in the middle age group were more likely to receive adjuvant therapy than those in the older group (odds ratio 2.78, 95% CI 1.19-6.45; p = 0.02) and showed a trend to longer disease-free survival when receiving adjuvant therapy (p = 0.09). Conclusion: Our data support age as an independent negative prognostic factor in melanoma. Our data suggest that age does not affect primary surgical treatment but may affect decisions of whether or not patients receive postoperative treatment(s). Further work is needed to better understand the biological variables affecting treatment decisions and efficacy in older patients.

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Tetracycline (TC) abuse has caused a serious threat to human health and the ecological environment, so it is very important to develop the materials that can simultaneously detect and remove TC in animal feed and environmental water. In this present work, at first, an original oxygen-rich 2D nanoporous covalent organic framework (BrPz-COF) was synthesized by an irreversible condensation reaction of tetrabromo-1,4-benzoquinone and piperazine and then a rare-earth covalent organic framework (Ln@COF) was successfully obtained for the detection and removal of tetracycline by post-synthesis modification. The carbonyl group contained in BrPz-COF provides a large number of active sites for the binding of Eu 3+ ions by post-synthetic modifications so that the resulting Eu 3+ @BrPz-COF hybrid shows a good chemical stability under harsh chemical conditions such as strong acid, strong base, and various organic solvents. The resulting Eu 3+ @BrPz-COF exhibited a turn-on response toward tetracycline, which allowed this interesting material to be applied as a fluorescence sensor. It is worth mentioning that the reusable sensor had a high sensitivity and excellent selectivity to TC, and the detection limit was 7 nM, which can be applied to detect TC in animal feed. In addition, Eu 3+ @BrPz-COF also showed a good performance in the removal of TC with the maximum adsorption amount of 205.34 mg•g −1 . Metal-COF-based hybrid materials with the performances of simultaneous detection and removal of TC are rare, so this work is very significant for developing a material to solve this matter.

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The security of farmland property rights is an important factor that affects farmland investment and succession, and farm succession is highly significant for achieving sustainable agricultural development. In this study, based on survey data obtained from 1012 apple growers in Shandong and Shaanxi Provinces, we analyzed the impact of land tenure security on the farm succession willingness of farmers and related paths by constructing binary logistic regression and mediating effect models. The results showed that: (1) land tenure security plays a significant role in promoting the farm succession willingness of farmers; and that (2) land tenure security promotes farm succession willingness by improving the farmland investment intentions of farmers. In the future, reforms of the farmland property rights system need to ensure the security of farmland property rights. In addition, with the influence of climate change, it is necessary to encourage farmers with advantageous agricultural resource endowments to invest in farmland and intergenerational transfers, as well as inducing farmers who lack advantageous agricultural resource endowments to conduct non-agricultural transfers, thereby providing more opportunities and a greater development area for agricultural land transfers and agricultural-scale operations.

No abstract

9067 Background: PP6C binds to regulatory units to affect a number of important pathways including cell proliferation and DNA repair. Recently two independent groups reported for the first time the presence of somatic mutations in the PPP6C gene in ~10% of short term cultures and limited number of human melanoma tissues. However, the clinical or biological relevance of PPP6C mutations in melanoma patients is unknown. Our objectives were to examine the clinical relevance of PPP6C mutations in a well characterized cohort of melanoma specimens linked to extensive, prospectively-collected clinical information and to explore the functional consequence of different categories of mutations. Methods: Sanger dideoxy sequencing was performed on PCR-amplified DNA from macro-dissected FFPE tumors. Associations between PPP6C mutations and baseline characteristics, recurrence, survival, and BRAF/ NRAS mutational status were examined. The impact of mutations on binding PP6C regulatory units was assessed as well as the effect on additional downstream pathways. Results: 308 primary melanoma patients (118 Stage I, 92 Stage II, and 98 Stage III) were examined (median follow up: 5.3 years). 50 PPP6C mutations in 33 patients (10.7%) were identified with 11 tumors harboring more than one mutation. One mutation (R301C) was identified in 6 patients. PPP6C mutations occurred with similar frequencies across stages and showed no association with BRAF or NRAS mutations. Mutations were categorized into 3 groups: Mutations resulting in premature stop codon (n=9), those occurring in the active site (n=16) and others (n=8). 8/9 (89%) patients with stop mutations recurred and developed visceral metastases. Functional studies revealed that PPP6C mutants also behaved differently; some PPP6C mutations led to decreased binding to regulatory subunits, others, including the R301C mutation did not. Conclusions: Our data suggest that PPP6C mutation is an early event in melanoma progression and independent of BRAF or NRAS mutations. Data also suggest different biologic and clinical impact of PPP6C mutations, with stop mutations showing association with development of visceral metastases that requires further clinical and functional study.

9054 Background: Although patient age at diagnosis is not currently included in guidelines for treatment of primary melanoma, several lines of evidence suggest that patient age is an important, yet understudied, factor when considering treatment options. Here, we attempt to address the limited knowledge of the impact of age on primary melanoma treatment. Methods: In a prospectively enrolled and followed-up cohort of melanoma patients at NYU, we used logistic regression models to evaluate the association between patient age at diagnosis, tumor baseline characteristics, including BRAF and NRAS mutation status, and likelihood of receiving and responding to adjuvant therapy. We examined adjuvant therapy effectiveness using recurrence and melanoma-specific survival as endpoints. Results: 444 primary melanoma patients were included in the study (median follow-up: 6.3 years; age range: 19-95 years). Age was categorized into three groups spanning the range of age at presentation: younger (19-45 years; 24%), middle (46-70 years; 50%), and older (71-95 years; 26%). Older patients were significantly more likely to have advanced stage, nodular subtype (P < 0.01, both variables), and BRAF wildtype tumors (P = 0.04). Controlling for these factors as well as gender, older patients experienced a higher risk of recurrence (HR older vs. younger 3.34, 95% CI 1.53-7.25; P < 0.01). Of the 128/444 (29%) patients who were eligible for adjuvant treatment (clinical stage ≥ IIB), only 67/128 (52%) received treatment. Using a propensity score that accounts for stage at presentation, patients in the middle age group were more likely to receive adjuvant therapy than those in the older group (OR 2.61, 95% CI 1.12-6.08; P = 0.03). In addition, a trend suggesting benefit from adjuvant therapy (defined as longer melanoma-specific survival) was observed only in the middle age group (P = 0.07). Conclusions: Our data suggest that older melanoma patients, despite having a significantly worse prognosis, are less likely to receive and benefit from adjuvant therapy. Further work is needed to understand the biological variables contributing to the limited response to treatment in elderly primary melanoma.