Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/ mTOR axis in metastatic pheochromocytoma/ paraganglioma

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAMPheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients’ liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients’ management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitorsThis work was supported by the Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofounded by FEDER, [grant number PI14/00240, PI17/01796 to M.R., PI15/00783 to A.C], the Paradifference Foundation [no grant number applicable to M.R.], the ANR [ANR-2011-JCJC-00701 MODEOMAPP to AP.G-R], the European Union [FP7/2007-2013 n° 259735, Horizon 2020 n° 633983 to AP.G-R], Epigénétique et Cancer [EPIG201303 METABEPIC to AP.G-R], the the Ligue Nationale contre le Cancer ["Cartes d'Identité des Tumeurs (CIT) program" to AP.G-R], the Institut National du Cancer, the Direction Générale de l’Offre de Soins [PRT-K 2014, COMETE-TACTIC, INCa-DGOS_8663 to AP.G-R], the Deutsche Forschungsgemeinschaft (DFG) [CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease“ to F.B, M.F and G.E], the Rafael del Pino Foundation [Becas de Excelencia Rafael del Pino 2017 to B.C], the Severo Ochoa Excellence Programme [project SEV-2011-0191 to M.C-F], La Caixa Foundation [B004235 to JM.R-R], the Spanish Ministry of Education, Culture and Sport [grant number FPU16/05527 to M.S.], the Site de Recherche Intégré sur le Cancer-SIRIC [CARPEM Project to N.B.] and the AECC Foundation [grant number AIO15152858 to C.M-C

Predictability of Extreme Intensity Pulses in Optically Injected Semiconductor Lasers

The predictability of extreme intensity pulses emitted by an optically injected semiconductor laser is studied numerically, by using a well-known rate equation model. We show that symbolic ordinal time-series analysis allows to identify the patterns of intensity oscillations that are likely to occur before an extreme pulse. The method also gives information about patterns which are unlikely to occur before an extreme pulse. The specific patterns identified capture the topology of the underlying chaotic attractor and depend on the model parameters. The methodology proposed here can be useful for analyzing data recorded from other complex systems that generate extreme fluctuations in their output signals

Agency, Liberation, and Intersectionality among Latina Scholars: Narratives from a Cross-institutional Writing Collective

Among United States residents, the number of doctoral degrees conferred to Latinx students represents a small percentage compared to other groups. For example, from 2009–2010, the percentage of degrees conferred to Latinx students was 5 percent compared to 74 percent for White students, 11 percent for Asian/Pacific Islanders, 7 percent for African Americans, and 0.7 percent for Indian/Alaska Natives. During the same period, the proportion of doctoral degrees conferred to females was 55 percent for Latinas compared to 65 percent for African American students, 56 percent for Asian/Pacific students, 54 percent for American Indian/Alaska Native students, and 51 percent for White female students (National Center for Education Statistics). Historically, underrepresented minority (URM) students encounter a plethora of issues that influence their educational experiences, yet there is a scarcity of scholarship that elucidates the quality of experience of women of color (WOC) pursuing doctorate degrees (Aryan and Guzman). As multi-marginalized, firstgeneration college students, we continuously struggle to find a place within higher education. Our educational pathways to becoming doctoral recipients have occurred primarily within the context of alienation, significantly influencing our need to connect with other WOC who have also felt isolated and disconnected. Consequently, we needed to find each other because knowing that there were other Latinas in doctoral programs, and actually getting to know them, validated our existence within academiaUniversity Writing Cente

A 3-sided Pyramid Wavefront Sensor Controlled by a Neural Network for Adaptive Optics to reach diffraction-limited Imaging of the Retina

In-vivo imaging of the eye's fundus is the basis for the diagnosis of retinal diseases in ophthalmology. However, the resolution of the images is limited - besides the inevitable diffractive limitation by the finite size of the pupil - by the imperfect optical elements of the eye, causing aberrations. In astronomy, first test measurements of atmospheric aberrations with the novel 4-sided pyramid sensor have confirmed the benefits of this sensor compared with conventional wavefront sensors. This work presents a pyramid wavefront sensor for the measurement of aberrations and their compensation on a confocal laser scanning ophthalmoscope. By contrast, a 3-sided pyramid prism is used and it is demonstrated experimentally, that this prism, which is easier to manufacture than the 4-sided prism, reveals to be an equivalent sensor. The control of the deformable mirror which can compensate the aberrations is implemented by an artificial neural network based on the acquired sensor data. With the trained neural network, aberrations of 150nm RMS could already be reduced to half the error. The neural network is composed of a convolutional S_C-net of 2x4 layers, which extracts feature information out of the signal images of the pyramid, and a 3-layer, feed-forward backpropagation net, that determines the required deflection of the mirror in order to compensate for a given aberration

Mexicans' Consumption of Taxed Sugar-Sweetened Beverages and the Psychosocial Determinants of Consumption in the Context of the 2014 Sugar-Sweetened Beverage Tax - A Mixed Methods Study

In Mexico about 73 percent adults and 33 percent children have overweight or obesity; and nearly 14 percent adults are estimated to have Type 2 diabetes, being the principal cause of mortality. Obesity and diabetes rates rose sharply starting in the 1980's and 1990's, coinciding with the globalization processes that Mexico underwent resulting in a higher availability and consumption of energy-dense and nutrient-poor ultra-processed foods. Sugar-sweetened beverages (SSBs), carbonated cola beverages such as Coca-Cola in particular, are widely consumed and well integrated into Mexico's cultural fabric and constitute the major source of added sugars in the Mexican diet. High intake of SSBs is associated with weight gain, type 2 diabetes, coronary heart disease, and metabolic syndrome, In 2014, the Mexican government introduced a 1-peso-per-liter (approx. US 8 cents; about 10 percent of the pre-tax price) on industrialized SSBs along with many other public health measures in an attempt to curb rising obesity rates. Two years into the SSB tax, purchases of sugary beverages in stores decreased by 7.6 percent on average. This decrease in purchases is remarkable, nevertheless, based on the existing cross-sectional data, the change cannot be s attributable solely to the effect of the taxation. Moreover, there are many other concurrent factors that might have affected demand and purchases of SSBs: like an 8 percent ad valorem tax imposed on discretionary energy-dense food in 2014, the regulation of foods and beverages in schools, and the regulation of food and beverage marketing on TV targeted to children. Further, it may be plausible for the SSB tax to have exerted effect via other mechanisms, such as increasing awareness of negative health outcomes. There is evidence from other countries that junk food and SSB taxes imposed with public health goals contribute to enhancing people's awareness about the negative health consequences of unhealthy foods. The purpose of this study was to explore what are Mexicans' beliefs, attitudes, social norms, and behaviors in relation to SSBs in the context of the SSB tax, and why and how behaviors have been modified. This purpose was addressed using a sequential explanatory mixed methods design, starting with a quantitative survey with a nationally representative sample, followed by a qualitative study with parents and construction workers. Quantitative study. The first phase of the study consisted of closed-ended questions (designed to ask about awareness of and opinion about the effectiveness of the tax, psychosocial determinants of SSB consumption, and perception of change in SSB consumption since the year the tax was implemented) that were developed and inserted into a new questionnaire of the 2016 National Health and Nutrition Survey (ENSANUT) carried out by the Mexican INSP. The questionnaire was administered face-to-face to 6,650 Mexican adults 20-59 years old, providing a representative sample at the national, urban and rural, and regional levels. The two principal statistical analysis conducted were: (a) Logistic regression, used to evaluate the probability of a person reporting a decrease in SSB consumption, given their awareness of the tax, opinion about its effectiveness, psychosocial (SSB health-related beliefs, self-efficacy, and liking of SSBs) and environmental (availability of potable water) determinants, after controlling for covariates; (b) Multiple linear regression analysis, utilized to examine the association between the same factors and current consumption of taxed SSBs. Results showed that compared with adults not aware, adults who were aware of the SSB tax were more likely (OR=1.30) to report a decrease in SSB consumption (p=.012). In urban areas, adults aware of the tax drank a significantly lower amount of taxed SSBs (-15.7%; p=.023) than those not aware. Self-efficacy and liking of SSBs were significantly associated with a reported decrease in consumption and with current consumption (p<.001), while health beliefs and availability of potable water were not significantly associated with either reported change in SSB consumption or current consumption of taxed SSBs. We conclude that implementation of an SSB tax accompanied by highly visible campaigns may further influence the impact of taxes on SSBs consumption. Qualitative study. The second phase consisted of a qualitative multi-case study involving interviews and focus groups with parents of children 9 years old or younger and construction workers that assisted in interpreting the findings of the quantitative study. This study also expanded upon the quantitative findings particularly in relation to the ways people modified (or not) their purchasing and consumption behaviors after the imposition of the SSB tax and the reasons why. The analysis was informed by the Reasoned Action Approach and the hyperbolic (future) discounting concept from behavioral economics theory. The main findings of the study with parents are that most reported drinking less soda than in the two-four years prior and that they largely are trying to reduce their children's consumption of SSBs and encourage water consumption. Changes in parents' behaviors and practices were precipitated by health concerns and not necessarily by price increases (although these were of concern). Half of the participants knew about the tax and its purpose; and it seems like the debate around the tax might have contributed to increasing awareness about the detrimental health consequences of taxed beverages. We conclude that for many of these parents the current taxation of SSBs may have had a mild effect on SSB consumption; a higher level of the tax (20 percent) may impose an additional constraint. The main findings of the study with construction workers are that they consume a high amount of both soda and water during their work days (approx. 1.25. liters and 4 liters, respectively). They associate consumption of soda to pause and meal breaks, and consumption of water to the times when they are working. Nevertheless, their identity as construction workers is constructed in relation to their soda consumption. While they are aware of the health consequences that a high soda consumption can entail, it seems like they had never contemplated the need and/or possibility of changing their practices. Construction workers have not (permanently) altered their patterns of soda consumption in the context of the tax. Presence of an illness (i.e., kidney problems) triggered changes in some, but they were only temporary. We conclude that a 1 peso-per-liter (10 percent) tax is not enough to trigger changes in practices in this group, and that the government should consider a higher level of the tax to have an effect on these consumers. In this dissertation, the interpretation of the quantitative and the qualitative results in combination yields a better understanding about the potential influence of the SSB tax on Mexicans SSB-related behaviors and psychosocial factors. The key conclusions of this work are that: 1) A considerable number of the Mexican adult population is aware of the tax on SSBs, but that awareness differs by socio-demographic characteristics; 2) A large majority of the population beliefs that the tax is not reducing consumption of taxed SSBs meaningfully; 3) having been exposed to debates/campaigns in relation the tax, combined withto the price increase, may have contributed to increasing health awareness and/or rethinking beverage choices in some population groups that are more sensitive to diet/nutrition and health (e.g., parents in their role as caregivers) but not of others (e.g., construction workers); 4) the most salient determinants of SSB consumption are: social norms, liking for SSBs, perceived behavioral control, and the beverage environment; 5) Mexican adults are knowledgeable about the health consequences of a high consumption of industrialized SSBs, however, while knowledge is necessary, it might not be sufficient to result in large behavioral changes. This study contributes to the fields of public health and food and nutrition policy by suggesting an alternative pathway through which health taxes may exert an impact on people's behavior. It also highlights the complexity of food choice and behavior change and the need for comprehensive approaches, grounded in research of psychosocial determinants, to have a meaningful impact on changing consumers' behaviors. The findings of this dissertation suggest that in the future, governments could consider accompanying public health taxes with comprehensive and targeted education campaigns in an attempt to create synergy between both approaches. In addition, future nutrition education and public health campaigns might focus more on teaching self-regulation skills, after motivation has been established, and on shifting social norms around SSB drinking

Mejora integral del cultivo del azafrán del Jiloca

Proyecto INIA PET 2007-14-C05-0

Digital Automated Motor Current Analyzing Test System

Bison Gear and Engineering Corporation is a motor manufacturing company. To ensure quality, Bison must test the current through its manufactured motors to verify that they are in proper operating conditions. The designed product provides an automated solution to measuring motor current of the 560 and 562 series Hollow Shaft Offset Gear motors under emergency power conditions. The product is user friendly and efficient. It requires minimal operator input and automatically tests the motor in the clockwise and counter-clockwise directions. The system delivers a pass or fail to the operator, and archives serialized motor current data at the end of each test. The product also includes a user interface which allows the operator to observe the maximum current, current range, and the time remaining before a pass or fail result is delivered. The supervisor interface allows the client to access previously tested motor data. The client supervisor has the ability to generate a query based on the following parameters: pass, fail, date or motor id. The report will provide the client with the date the motor was tested, the maximum current in both clockwise and counter-clockwise directions, the current range in both clockwise and counter-clockwise directions, and the pass or fail status of the motor. Accuracy of the current sensing circuitry is essential to ensuring the overall reliability of the final product as determined by the Failure Mode Effect Analysis. In product testing, it was found that the current sensing circuity was highly accurate, and the device functioned properly.B.A. (Bachelor of Arts

Validation of the Standardized Swallowing Assessment – Svenska (SSA-S) for screening of dysphagia in acute stroke

Dysphagia is common in acute stroke patients. A screening tool with high predictive validity can improve the identification of dysphagia. The aim of this study was to validate the Swedish version of The Standardized Swallowing Assessment (SSA-S). 22 patients with acute stroke participated in the study. The results of SSA-S were compared with the clinical swallowing assessments. The results (sensitivity, 86%; specificity, 93%; positive predictive value, 86%; negative predictive value, 93%) indicated good validity for SSA-S. Testing with the complete SSA-S (k = 0.79) demonstrates a higher agreement with clinical swallowing assessment than testing with only part 2 (k = 0.67) or part 3 (k = 0.7). The study found that part 2 could be shortened without decreasing the validity. Further research is needed to determine this matter. In conclusion, this study shows that SSA-S is a tool with good validity for screening dysphagia in individuals with acute stroke.Dysfagi är vanligt förekommande hos akutstrokepatienter. Ett screeningtest med god prediktiv träffsäkerhet kan effektivisera identifieringen av dysfagi. Syftet med denna studie var att validera screeningtestet The Standardized Swallowing Assessment - Svenska (SSA-S). Totalt deltog 22 akutstrokepatienter. Utfallen från SSA-S, utförd av sjuksköterskor, jämfördes med resultaten från den kliniska sväljundersökningen, utförd av studieledarna. Resultaten (sensitivitet, 86 %; specificitet, 93 %; positivt prediktivt värde, 86 %; negativt prediktivt värde, 93 %) visade att SSA-S har god träffsäkerhet. Testning med hela SSA-S överensstämde bättre (k = 0,79) med den kliniska sväljundersökningen än testning med enbart del 2 (k = 0,67) eller del 3 (k = 0,77). Vidare fann studien att del 2 kan kortas ned utan att försämra SSA-S träffsäkerhet. Vidare forskning behövs för att med säkerhet fastställa om del 2 kan förkortas. Slutsatsen är att SSA-S är ett träffsäkert instrument för screening av dysfagi hos strokepatienter i akutskedet