ABSTRACT Solar flares produce radiation that can have an almost immediate effect on the near-Earth environment, making it crucial to forecast flares in order to mitigate their negative effects. The ...number of published approaches to flare forecasting using photospheric magnetic field observations has proliferated, with varying claims about how well each works. Because of the different analysis techniques and data sets used, it is essentially impossible to compare the results from the literature. This problem is exacerbated by the low event rates of large solar flares. The challenges of forecasting rare events have long been recognized in the meteorology community, but have yet to be fully acknowledged by the space weather community. During the interagency workshop on "all clear" forecasts held in Boulder, CO in 2009, the performance of a number of existing algorithms was compared on common data sets, specifically line-of-sight magnetic field and continuum intensity images from the Michelson Doppler Imager, with consistent definitions of what constitutes an event. We demonstrate the importance of making such systematic comparisons, and of using standard verification statistics to determine what constitutes a good prediction scheme. When a comparison was made in this fashion, no one method clearly outperformed all others, which may in part be due to the strong correlations among the parameters used by different methods to characterize an active region. For M-class flares and above, the set of methods tends toward a weakly positive skill score (as measured with several distinct metrics), with no participating method proving substantially better than climatological forecasts.
Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits ...tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in the absence of these miRNAs, epithelial regeneration after injury was dramatically impaired. Surprisingly, we found that miR-143/145 are expressed and function exclusively within the mesenchymal compartment of intestine. Defective epithelial regeneration in miR-143/145-deficient mice resulted from the dysfunction of smooth muscle and myofibroblasts and was associated with derepression of the miR-143 target Igfbp5, which impaired IGF signaling after epithelial injury. These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer.
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•miR-143/145 are essential for mouse intestinal epithelial regeneration after injury•miR-143/145 expression and function are restricted to the intestinal mesenchyme•Upregulated IGFBP5 and reduced IGF signaling correlate with regenerative failure•Results challenge a cell-autonomous tumor suppressor role for miR-143/145 in colon
miR-143/145 are expressed and function exclusively within the mesenchyme of intestine to regulate proregenerative signaling and wound healing, challenging a long-presumed role for these microRNAs as cell-autonomous tumor suppressors in colon cancer.
We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would ...differ from primary mucosal melanomas at different anatomical sites.
Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites.
The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%,P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%,P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively.
The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.
This paper is the primary deliverable of the very first NASA Living With a Star Institute Working Group, Geomagnetically Induced Currents (GIC) Working Group. The paper provides a broad overview of ...the current status and future challenges pertaining to the science, engineering, and applications of the GIC problem. Science is understood here as the basic space and Earth sciences research that allows improved understanding and physics-based modeling of the physical processes behind GIC. Engineering, in turn, is understood here as the ''impact'' aspect of GIC. Applications are understood as the models, tools, and activities that can provide actionable information to entities such as power systems operators for mitigating the effects of GIC and government agencies for managing any potential consequences from GIC impact to critical infrastructure. Applications can be considered the ultimate goal of our GIC work. In assessing the status of the field, we quantify the readiness of various applications in the mitigation context. We use the Applications Readiness Level (ARL) concept to carry out the quantification.
We present a novel algorithm that predicts the probability that the time derivative of the horizontal component of the ground magnetic field dB/dt exceeds a specified threshold at a given location. ...This quantity provides important information that is physically relevant to geomagnetically induced currents (GICs), which are electric currents associated with sudden changes in the Earth's magnetic field due to space weather events. The model follows a “gray‐box” approach by combining the output of a physics‐based model with machine learning. Specifically, we combine the University of Michigan's Geospace model that is operational at the National Oceanic and Atmospheric Administration (NOAA) Space Weather Prediction Center, with a boosted ensemble of classification trees. We discuss the problem of recalibrating the output of the decision tree to obtain reliable probabilities. The performance of the model is assessed by typical metrics for probabilistic forecasts: Probability of Detection and False Detection, True Skill Statistic, Heidke Skill Score, and Receiver Operating Characteristic curve. We show that the ML‐enhanced algorithm consistently improves all the metrics considered.
Key Points
We present a new model to forecast the maximum value of dB/dt over 20‐min intervals at specific locations
The model enhances the output of the physics‐based Geospace model with a machine learning technique
The model provides a probabilistic forecast of exceeding a predefined threshold at a given location
Background
Postoperative complications (POCs) are associated with worse oncologic outcomes in several cancer types. The implications of complications after rectal cancer surgery are not well studied.
...Methods
The United States Rectal Cancer Consortium (2007–2017) was reviewed for primary rectal adenocarcinoma patients who underwent R0/R1 resection. Ninety-day POCs were categorized as major or minor and were grouped into infectious, cardiopulmonary, thromboembolic, renal, or intestinal dysmotility. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS).
Results
Among 1136 patients, the POC rate was 46% (
n
= 527), with 63% classified as minor and 32% classified as major. Of all POCs, infectious complications comprised 20%, cardiopulmonary 3%, thromboembolic 5%, renal 9%, and intestinal dysmotility 19%. Compared with minor or no POCs, major POCs were associated with both worse RFS and worse OS (both
p
< 0.01). Compared with no POCs, a single POC was associated with worse RFS (
p
< 0.01), while multiple POCs were associated with worse OS (
p
= 0.02). Regardless of complication grade, infectious POCs were associated with worse RFS (
p
< 0.01), while cardiopulmonary and thromboembolic POCs were associated with worse OS (both
p
< 0.01). Renal POCs were associated with both worse RFS (
p
< 0.001) and worse OS (
p
= 0.01). After accounting for pathologic stage, neoadjuvant therapy, and final margin status, Multivariable analysis (MVA) demonstrated worse outcomes with cardiopulmonary, thromboembolic, and renal POCs for OS (cardiopulmonary: hazard ratio HR 3.6,
p
= 0.01; thromboembolic: HR 19.4,
p
< 0.01; renal: HR 2.4,
p
= 0.01), and renal and infectious POCs for RFS (infectious: HR 2.1,
p
< 0.01; renal: HR 3.2,
p
< 0.01).
Conclusions
Major complications after proctectomy for cancer are associated with decreased RFS and OS. Given the association of infectious complications and postoperative renal dysfunction with earlier recurrence of disease, efforts must be directed towards defining best practices and standardizing care.
To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC).
The prognostic factors analysis described in the companion publication (this ...issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system.
Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.
This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.
Preoperative staging of clinical stage I rectal cancer can fail to diagnose T3 or nodal disease. Adjuvant treatment of these upstaged patients remains controversial.
The objective was to identify ...predictors of clinical stage I rectal cancer upstaging and quantify rates of local and systemic recurrence.
This was a retrospective cohort study.
The study was conducted using data from the United States Rectal Cancer Consortium, a registry of 1881 rectal cancer resections performed at 6 academic medical centers.
There were a total of 94 clinical stage I rectal cancer patients who underwent proctectomy without preoperative therapy.
The primary measures were incidence of pathologic upstaging, recurrence (local and systemic), and overall survival.
Among 94 clinical stage I patients who underwent proctectomy without preoperative therapy, 23 (24.5%) were upstaged by surgical pathology. There were 6 pT3N0 patients, 8 pT1-2N+ patients, and 9 pT3N+ patients. There were no significant differences in demographic or clinical characteristics between upstaged and nonupstaged patients. Of the 6 patients who were upstaged to T3N0 disease, none received adjuvant therapy and none developed recurrence. Of the 17 patients who were upstaged to N+ disease, 14 (82%) received adjuvant chemotherapy and 6 (35%) received adjuvant chemoradiation. None developed a local recurrence, but 4 (24%) developed systemic recurrence, and 2 (12%) died of disease over a mean of 36 months of follow-up. Among the 9 pT3N+ patients, the systemic recurrence rate was 33%, despite 8 of 9 patients receiving adjuvant fluorouracil, leucovorin, and oxaliplatin.
Small sample size hinders the ability to draw significant conclusions.
One in 4 patients with stage I rectal cancer had unrecognized T3 or nodal disease found on operative pathology. Occult nodal disease was associated with worse outcomes, despite receiving adjuvant therapy. Systemic recurrence was more common than local recurrence. See Video Abstract at http://links.lww.com/DCR/B885 .
ANTECEDENTES:El estadiaje pre-operatorio del cáncer de recto en fase clínica I puede ser erróneo en el diagnóstico T3 o en la diseminación ganglionar. El tratamiento adyuvante de estos pacientes sobre-estadificados sigue siendo controvertido.OBJETIVO:El identificar los factores predictivos en fase clínica I del cáncer de recto y cuantificar las tasas de recurrencia local y sistémica.DISEÑO:Estudio de cohortes retrospectivo.AJUSTE:El estudio se realizó utilizando los datos del Consorcio del Cáncer de Recto de los Estados Unidos, con un registro de 1.881 resecciones oncológicas rectales realizadas en seis centros médicos académicos.PACIENTES:Un total de 94 pacientes con cáncer de recto en fase clínica I fueron sometidos a proctectomía sin terapia preoperatoria.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la incidencia del sobre-estadiaje histopatológico, la recurrencia (local y sistémica) y la sobrevida general.RESULTADOS:De 94 pacientes en fase clínica I que se sometieron a una proctectomía sin terapia preoperatoria, 23 (24,5%) fueron sobre-estadiados por la histopatología quirúrgica. Hubieron 6 pacientes pT3N0, 8 pT1-2N + y 9 pT3N +. No hubo diferencias significativas en las características demográficas o clínicas entre los pacientes sobre-estadiados y los no sobre-estadiados. De los 6 pacientes que fueron sobre-estadiados en la enfermedad T3N0, ninguno de ellos recibió terapia adyuvante y ninguno recidivó. De los 17 pacientes que fueron sobre-estadiados a la enfermedad N +, 14 (82%) recibieron quimioterapia adyuvante y 6 (35%) recibieron quimio-radioterapia adyuvante. Ninguno desarrolló recidiva local, pero 4 (24%) desarrollaron recidiva sistémica y 2 (12%) murieron a causa de la enfermedad durante el seguimiento medio de 36 meses. Entre los 9 pacientes con pT3N +, la tasa de recidiva sistémica fue del 33%, a pesar de que 8 de 9 pacientes recibieron fluorouracilo, leucovorina y oxaliplatino como quimio-adyuvantes.LIMITACIONES:El tamaño pequeño de la muestra dificulta la capacidad de obtener conclusiones significativas.CONCLUSIONES:Uno de cada cuatro pacientes con cáncer de recto en estadío I presentaba enfermedad ganglionar o T3 no descrita en la histopatología operatoria. La enfermedad ganglionar oculta se asoció con peores resultados, a pesar de recibir terapia adyuvante. La recidiva sistémica fue más común que la recidiva local. Consulte Video Resumen en http://links.lww.com/DCR/B885 . (Traducción-Dr. Xavier Delgadillo ).
Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes ...tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apc(min/+) mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type.
The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and ...cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal.
There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients.
This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients.
The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.
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