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Metodos Se incluyeron en el estudio las ciudades con mas de un millon de habitantes que informaron al Carbon Disclosure Project sobre sus acciones de adaptacion entre 2021 y 2023, y que describieron al menos una medida de adaptacion para un peligro climatico en al menos un ano. Se identificaron las ciudades que informaron sobre la existencia de sistemas de alerta temprana conforme al marco Alertas tempranas para todos de las Naciones Unidas, que comprende cuatro pilares: conocimiento del riesgo, monitoreo y prevision de peligros, comunicacion de alertas y preparacion. Asimismo, se analizo la participacion del sector sanitario en estos sistemas. [phrase omitted]

The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant.

: Studies on prognosis of different metastasis sites in patients with lung cancer are limited. The aim of present study was to investigate the prognostic value of metastases sites among patients with metastatic lung cancer. : Between 2010 and 2014, patients diagnosed with metastatic lung cancer were selected using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier methods were adopted and multivariable Cox regression models were built to compare the prognosis of different metastasis sites. : A total of 54,697 eligible patients were identified, including 10,945 (20.0%) patients had isolated bone metastases, 8,294(15.2%) with isolated brain metastases, 5,677(10.4%) with isolated liver metastases, 9,430(17.2%) with isolate lung metastases, and 20,351(37.2%) with multiple organ metastases. The percentage of bone, brain, liver, lung and multisite metastases were 22.3%, 15.4%, 6.1%, 20.1% and 36.1% for non-small cell lung cancer (NSCLC), 12.5%, 14.3%, 24.3%, 7.9%, and 40.9% for small cell lung cancer (SCLC), the difference was statistical(P<0.001). In univariate and multivariable analysis, patients with liver metastases demonstrated a statistically significant disadvantage in cause-specific survival, while those with lung metastases have reduced risk of died of metastases when compared with brain metastases(P<0.001).The difference was consistent when make subgroup analysis in both NSCLC and SCLC(P<0.001). : In patients with distant metastases, those with liver metastases have the poorest survival, whereas those with lung metastases have the best survival. Therefore, we should take into consideration of such discrepancy when making treatment strategies.

Human‐induced changes in the climate and environment that occur at an unprecedented speed are challenging the existence of migratory species. Faced with these new challenges, species with diverse and flexible migratory behaviors may suffer less from population decline, as they may be better at responding to these changes by altering their migratory behavior. At the individual level, variations in migratory behavior may lead to differences in fitness and subsequently influence the population's demographic dynamics. Using lifetime GPS bio‐logging data from 169 white storks (Ciconia ciconia), we explore whether the recently shortened migration distance of storks affects their survival during different stages of their juvenile life. We also explore how other variations in migratory decisions (i.e., time, destination), movement activity (measured using overall body dynamic acceleration), and early life conditions influence juvenile survival. We observed that their first autumn migration was the riskiest period for juvenile white storks. Individuals that migrated shorter distances and fledged earlier experienced lower mortality risks. In addition, higher movement activity and overwintering “closer‐to‐home” (with 84.21% of the tracked individuals stayed Europe or North Africa) were associated with higher survival. Our study shows how avian migrants can change life history decisions over only a few decades, and thus it helps us to understand and predict how migrants respond to the rapidly changing world. Using bio‐logging data from a long‐distance migratory species, the white stork (Ciconia ciconia), we found that the individuals with shortened migration distance and those that overwintered in Europe and North Africa had higher survival probability during the juvenile stage, the riskiest life period for many migrants. In addition, higher movement activity and early fledging were associated with higher survival. Our study shows how avian migrants can adjust life history decisions linked to fitness over few decades.

BackgroundDifferences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described.MethodsA retrospective cohort study, 1990–2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distant metastatic recurrence (stage I–III initial diagnosis) [dnMBC = 247, rMBC = 911)]. Analysis included Chi squared tests of categorical variables, Kaplan–Meier survival estimates, and Cox proportional adjusted hazard ratios (HzR) and 95% confidence intervals (CI). Disease specific survival (DSS) was time from diagnosis or distant recurrence to BC death.ResultsOver time, 1990–1998, 1999–2004, and 2005–2010, dnMBC incidence was constant (3%) and rMBC incidence decreased [18% to 7% (p < 0.001)] with no change in dnMBC hormone receptor (HR) or her2-neu (HER2) status but a decrease in rMBC HER2-positive cases and increase in triple negative breast cancer (HR-negative/HER2-negative) (p = 0.049). Five-year dnMBC DSS was 44% vs. 21% for rMBC (p < 0.001). Five-year dnMBC DSS improved over time [28% to 55% (p = 0.008)] and rMBC worsened [23% to 13%, p = 0.065)]. Worse DSS was associated with HR-negative status (HzR = 1.63; 1.41, 1.89), rMBC (HzR = 1.88; 1.58, 2.23), older age (70 +) (HzR = 1.88; 1.58, 2.24), > 1 distant metastases (HzR 1.39; 1.20, 1.62), and visceral dominant disease (HzR 1.22; 1.05, 1.43). After 1998, HER2-positive disease was associated with better DSS (HzR = 0.72, 95% CI 0.56, 0.93).ConclusionsFactors associated with the widening survival gap and non-equivalence between dnMBC and rMBC and decreased rMBC incidence warrant further study.

The tumor microenvironment (TME) is being increasingly recognized as a key factor in multiple stages of disease progression, particularly local resistance, immune-escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. An appropriate understanding of the TME promotes evaluation and selection of candidate agents to control malignancies at both the primary sites as well as the metastatic settings. This review presents a timely outline of research advances in TME biology and highlights the prospect of targeting the TME as a critical strategy to overcome acquired resistance, prevent metastasis, and improve therapeutic efficacy. As benign cells in TME niches actively modulate response of cancer cells to a broad range of standard chemotherapies and targeted agents, cancer-oriented therapeutics should be combined with TME-targeting treatments to achieve optimal clinical outcomes. Overall, a body of updated information is delivered to summarize recently emerging and rapidly progressing aspects of TME studies, and to provide a significant guideline for prospective development of personalized medicine, with the long term aim of providing a cure for cancer patients.

BackgroundIn patients with breast cancer, increasing tumour size at diagnosis is associated with an increased likelihood of axillary lymph node involvement and increased breast cancer-specific mortality. However, this relation is based on studies which combine all tumours smaller than 1.0 cm in a single category and all tumours larger than 5.0 cm in another category. This coarse classification may obscure a nuanced description of the effects of tumour size across the full range of possible sizes.MethodsWe examined the relationship between primary tumour size, lymph node status and distant metastases in a cohort of 819,647 women diagnosed with first primary invasive breast cancer from 1990 to 2014 in the Surveillance, Epidemiology and End Results (SEER) registries database. All patients in the cohort had a known primary tumour size between 1 and 150 mm in greatest dimension. Primary tumour size was examined as a continuous (1–150 mm) and categorical variable (15 size groups; 10-mm intervals). For each 1- or 10-mm size group, we determined the proportion of patients with positive lymph nodes at diagnosis, the proportion of patients with distant metastases at diagnosis and the actuarial cumulative risk of breast cancer-specific mortality at 15 years from diagnosis.ResultsAmong 819,647 patients with invasive breast tumours between 1 and 150 mm in size, there was a non-linear correlation between increasing tumour size and the prevalence of lymph node metastases at diagnosis (% node-positive), the prevalence of distant metastases at diagnosis (% stage IV) and the 15-year rate of breast cancer-specific mortality across the entire size spectrum. For very small tumours (under 10 mm) and for very large tumours (larger than 60–90 mm) there was little correlation between tumour size and metastasis risk.ConclusionsThe relationship between tumour size, lymph node status and distant metastases in patients with invasive breast cancer is not linear. This calls into question the conventional model that the capacity for a primary breast tumour to metastasize increases as the tumour enlarges.

Crowds can be very effective, but that is not always the case. To actually render the usage of crowds effective, several factors need to be aligned: crowd composition, the right question at the right time, and the right analytic method applied to the responses. Specific skills are mandatory to tap into the creativity of a crowd, harness it effectively and transform it into offers that markets value. The “DBAS” framework is recommended to successfully implement a crowd project. It consists of four stages, and in each phase some key questions need to be addressed. Each decision along the DBAS pathway matters and how you navigate each stage can either reinforce or undermine decisions made at the other stages. The right degree of innovativeness, listening to contributors and informing participants openly about the fate of rejected ideas are key success factors that require special attention. To continually improve the odds of success, crowdsourcing should best be treated as a continual iterative churn.

Human-nature interactions are complex and have important implications for achieving sustainable development goals and addressing other global challenges. Although numerous studies have explored human-nature (or human-environment) interactions and generated useful insights, they are largely disintegrated. Because conceptual frameworks are the foundation of quantitative and qualitative integration, many have been proposed but focus mainly on human-nature interactions within a specific system. To reflect human-nature interactions between distant coupled systems, the framework of telecoupling (socioeconomic and environmental interactions over distances) has been developed. However, no framework has explicitly integrated human-nature interactions between adjacent coupled systems, let alone within a coupled system as well as between adjacent and distant coupled systems simultaneously. To fill such an important gap, in this paper I present an integrated framework of metacoupling: human-nature interactions within a system (intracoupling), between distant systems (telecoupling), and between adjacent systems (pericoupling). A metacoupled system is a set of two or more coupled systems that interact internally as well as nearby and far away, facilitated by agents affected by various causes with various effects. By differentiating and integrating intracoupling, pericoupling, and telecoupling, the metacoupling framework advances a systems perspective on global sustainability and human well-being. The framework can help uncover hidden systemic connections such as spillovers and feedbacks that may not be apparent when focusing on a particular system. To demonstrate the utility of the metacoupling framework, I illustrate its application to human-nature interactions within a global flagship nature reserve as well as between the reserve and the rest of the world. The illustration suggests that the framework has the potential to help holistically understand and integrate human-nature interactions from local to global scales, over time, and among organizational levels. Finally, I offer suggestions for operationalizing the metacoupling framework and discuss the need for new policy, governance, and management for a sustainable future across the metacoupled world.

Abstract Context Patients with differentiated thyroid cancer (DTC) with distant metastasis (DM) are usually not recognized as radioactive iodine (RAI)-refractory DTC in a timely manner. The elucidation of genetic features related to RAI uptake patterns may shed light on the early recognition of RAI-refractory DTC. Objective This work aimed to elucidate the underlying molecular features behind different RAI uptake patterns. Methods A total of 214 patients with DM-DTC were retrospectively included in the analysis. RAI uptake patterns were defined as initially RAI refractory (I-RAIR) and initially RAI avid (I-RAIA) according to the first post-treatment scan, then I-RAIA was further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR) according to subsequent scans. The molecular subtype groups—BRAFV600E mutated, RAS mutated, fusions, and others—were classified according to main driver genes status. Results BRAF, TERT promoter, and TP53 mutations are more frequently detected in the I-RAIR pattern while RET fusions and RAS mutations are more frequent in the I-RAIA pattern. A late-hit mutation including TERT, TP53, or PIK3CA is more common in I-RAIR than that in I-RAIA (50.0% vs 26.9%, P = .001), particularly for those with RAS mutations in the I-RAIR group, always accompanied by TERT promoter. Isolated RET fusions accounts for 10% of I-RAIR. When compared among driver gene groups, BRAFV600E-mutated tumors have a higher rate of the I-RAIR pattern (64.4%) than RAS-mutated (4.5%, P < .001) and fusion-positive (20.7%, P < .001) tumors. In I-RAIA subgroups, BRAFV600E-mutated tumors have lower prevalence of the C-RAIA pattern than those with RAS mutation or fusions. Conclusion Patients with the I-RAIR pattern predominantly featured mutations of the BRAF and/or TERT promoter, of which RAS mutations were usually accompanied by late-hit mutations, while fusions mostly occurred alone.