Scaling-up climate services with users in Latin America

Latin America farmers are highly vulnerable to climate variability, with crop losses observed throughout the region on a virtually annual basis. For instance, as indicated by the United Nations’ Food and Agriculture Organization (FAO) and World Food Program (WFP), the 2014–2017 drought conditions in Central America affected over 3.5 million people in Guatemala, Honduras and El Salvador. At the same time, local stakeholders and farmers generally have limited access to existing climate and forecast information, do not have sufficient capacities to understand the climate information and/or mechanisms to relate this information to the impact that climate variations can generate at a local level. This precludes the translation of information into actionable knowledge, and therefore into action. In this study, we describe a process through which scientists and strategic partners have co-developed, tested and scaled out an approach to assess, co-produce, translate and transfer climate information to enable agricultural decision making –the Local Technical Agroclimatic Committees (LTAC). LTACs allow open and clear dialogues about climate variations at multiple timescales, how these can affect crops, and the design of measures to reduce crop loss, particularly providing agronomic recommendations to farmers. We systematically describe the process of evidence generation, creation, partner engagement, scaling up, and monitoring of the approach throughout Latin America. Currently, 35 LTACs exist in 9 Latin American countries, engaging more than 250 public and private institutions, increasing the resilience and food security of an estimated 330,000 farmers, and potentially transforming how Latin American farmers manage climate risk. The study illustrates changes in institutional and farmers' capacities to co-produce, translate and use climate information and explores how better climate and crop prediction models can effectively underpin this process. We show how strategic alliances with farmer organizations, national public, and private and regional climate outlook forums help deliver improved and accurate climate information to users. Finally, we document how LTACs and their integration with other local-scale processes have led to changes in farmers’ management practices to take better advantage of good climatic conditions or avoid losses

The influence of Online Ratings on Film Choice: Decision Making and Perceived Risk

Online users’ empowerment is an undeniable fact that has brought significant changes to the world of information. Society is becoming increasingly reliant on the online contributions shared by the users of social platforms. This paper focuses on the information provided by peers in movie-based online communities, in the form of numbers (ratings). Given the wide and varied offerings of films, the huge amount of information about each film and the experiential nature of cinema, this study analyses the influence of ratings at the moment of film choice. To test the influence of ratings on a moviegoer’s choice, controlling as they do the subject’s susceptibility to interpersonal influence, we conducted an experiment. A three-way, between-groups design (without rating and film critics/with rating/with rating and film critics) in a decision-controlled setting considers making a decision about what film to watch. Results provide empirical evidence that the addition of ratings simplifies the decision making. Also, ratings exert a significant influence in reducing risk perceptions, either global risk or each specific dimension of risk considered in the study –temporal risk, financial risk, experiential risk. Finally, academic and managerial implications and future research are also discussed

Effect of different types of exercise on health-related quality of life during and after cancer treatment: a protocol for a systematic review and network meta-analysis

INTRODUCTION: Cancer (and survival) is known to affect the quality of life. Strategies as physical activity and exercise during and after cancer may improve health-related qualify of life (HRQOL) outcomes and are, therefore, of clinical and public health importance. To the best of our knowledge, comparative evidence of the effect of the different types of exercise on improving HRQOL in cancer patients has not been synthesised thus far. We aim to conduct a systematic review and network meta-analysis in order to synthesise all available evidence regarding the effect of different types of exercise interventions on HRQOL during and after cancer treatment. METHODS AND ANALYSIS: MEDLINE (via PubMed), Web of Science, Embase, The Cochrane Library and SPORTDiscus will be searched from inception to December 2018 for relevant randomised controlled trials (RCTs) and non-RCTs. Studies assessing physical activity and exercise interventions in cancer patients (during treatment) and survivors (after treatment) will be selected. Two independent reviewers will identify eligible studies. After quality appraisal and data extraction, we will conduct meta-analyses for outcomes of interest, including data from mental and physical dimensions of cancer-specific and/or generic HRQOL questionnaires. Risk of bias assessments will be completed using the Quality Assessment Tool for Quantitative Studies. Study heterogeneity will be measured by the I2 statistic. Bayesian (and traditional approach) network meta-analysis will be performed when possible to determine the comparative effect of the different physical activity or exercise interventions. ETHICS AND DISSEMINATION: This systematic review and network meta-analysis will synthesise evidence on the effect of different types of exercise interventions on HRQOL during and after cancer treatment. The results will be disseminated by publication in a peer-reviewed journal and through scientific conferences and symposia. Ethical approval will not be required because the data used for this work will be exclusively extracted from published studies

Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth.

Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate production) in the tumor microenvironment. Consistent with the idea that glycolytic fibroblasts fuel tumor growth (via L-lactate, a high-energy mitochondrial fuel), MSF fibroblasts significantly increased tumor growth, by up to 4-fold. Mechanistic dissection of the MSF signaling pathway indicated that Cdc42 lies downstream of MSF and fibroblast activation. In accordance with this notion, Cdc42 overexpression in immortalized fibroblasts was sufficient to drive myofibroblast differentiation, to provoke a shift towards glycolytic metabolism and to promote tumor growth by up to 2-fold. In conclusion, the MSF/Cdc42/NFκB signaling cascade may be a critical druggable target in preventing Warburg-like cancer metabolism in tumor-associated fibroblasts. Thus, MSF functions in the metabolic remodeling of the tumor microenvironment by metabolically reprogramming cancer-associated fibroblasts toward glycolytic metabolism

Closure of a large lumbosacral myelomeningocele post operative defect with a human cadaveric split-thickness skin graft: a case report

Spina bifida is the most common birth defect of the central nervous system that is compatible with life, and myelomeningocele represents its most frequent form. Congenital myelomeningocele (CMM) has a worldwide incidence of 0.5 to 0.8 per 1,000 live newborns. CMM is a complex condition resulting from incomplete closure of the neural tube, mainly in the lumbosacral region. The objective of the surgical repair of the CMM is the reconstruction of all the tissue layers of the defect, avoiding possible postoperative complications. The aim of this case review is to present a re-epithelialization closure in a patient with a large CMM defect in who primary hermetic closure was not possible because there was too much tension at the edges of the defect. Therefore, human cadaveric split-thickness skin grafts were placed over the dura mater and the aponeurotic layer, covering the entire defect and an adequate healing and completely closure of the defect were observed in eight weeks. The surgical management of large meningomyelocele defects represents a major challenge and no single protocol exists for its reconstruction. The repair of an MMC defect should be performed during the first 72 hours after birth. After neurosurgical closure of the neural tube and dura, the myelomeningocele defect requires good quality skin and subcutaneous tissue with minimal wound tension for stable coverage. Human cadaveric skin grafts are considered a useful technique for temporary wound coverage because they lead to a more natural healing environment, possess ideal properties, and provide a physiological barrier that reduces microbiological contamination, in addition, it acts as a bridge to adhere to and to seal wound beds

CTGF drives autophagy, glycolysis and senescence in cancer-associated fibroblasts via HIF1 activation, metabolically promoting tumor growth

Previous studies have demonstrated that loss of caveolin-1 (Cav-1) in stromal cells drives the activation of the TGF-β signaling, with increased transcription of TGF-β target genes, such as connective tissue growth factor (CTGF). In addition, loss of stromal Cav-1 results in the metabolic reprogramming of cancer-associated fibroblasts, with the induction of autophagy and glycolysis. However, it remains unknown if activation of the TGF-β / CTGF pathway regulates the metabolism of cancer-associated fibroblasts. Therefore, we investigated whether CTGF modulates metabolism in the tumor microenvironment. For this purpose, CTGF was overexpressed in normal human fibroblasts or MDA-MB-231 breast cancer cells. Overexpression of CTGF induces HIF-1α-dependent metabolic alterations, with the induction of autophagy/mitophagy, senescence, and glycolysis. Here, we show that CTGF exerts compartment-specific effects on tumorigenesis, depending on the cell-type. In a xenograft model, CTGF overexpressing fibroblasts promote the growth of co-injected MDA-MB-231 cells, without any increases in angiogenesis. Conversely, CTGF overexpression in MDA-MB-231 cells dramatically inhibits tumor growth in mice. Intriguingly, increased extracellular matrix deposition was seen in tumors with either fibroblast or MDA-MB-231 overexpression of CTGF. Thus, the effects of CTGF expression on tumor formation are independent of its extracellular matrix function, but rather depend on its ability to activate catabolic metabolism. As such, CTGF-mediated induction of autophagy in fibroblasts supports tumor growth via the generation of recycled nutrients, whereas CTGF-mediated autophagy in breast cancer cells suppresses tumor growth, via tumor cell self-digestion. Our studies shed new light on the compartment-specific role of CTGF in mammary tumorigenesis, and provide novel insights into the mechanism(s) generating a lethal tumor microenvironment in patients lacking stromal Cav-1. As loss of Cav-1 is a stromal marker of poor clinical outcome in women with primary breast cancer, dissecting the downstream signaling effects of Cav-1 are important for understanding disease pathogenesis, and identifying novel therapeutic targets

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

<p>Abstract</p> <p>Background</p> <p>Cutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus <it>Trichophyton rubrum </it>is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of <it>T. rubrum </it>exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST) collection by constructing one cDNA library and nine suppression subtractive hybridization libraries.</p> <p>Results</p> <p>The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS) categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 <it>T. rubrum </it>sequences that had not been previously deposited in public databases.</p> <p>Conclusion</p> <p>In this study, we identified novel <it>T. rubrum </it>genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of <it>T. rubrum </it>to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging <it>T. rubrum </it>with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs.</p

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis