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Melanoma is the most aggressive form of skin cancer and the leading cause of death from cutaneous tumors. Several studies have associated alterations in the TERT promoter region (pTERT) with gene overexpression, aggressiveness and poor prognosis of the disease. The aim of this study was to clarify the role of pTERT molecular status in paired samples of primary melanoma and metastasis using tissue and plasma to establish a correlation with disease progression and survival.A total of 88 FFPE tissue samples from 53 patients with advanced melanoma were analyzed. Of these, 35 had paired samples. We also examined cfDNA samples from plasma of 25 patients. We detected a good correlation between primary tumors and metastases in pTERT mutation and methylation status. We were also able to identify pTERT mutations in plasma samples that correlated with mutational status in tissue samples. Interestingly, the C250T mutation was associated with worse survival and higher TERT mRNA expression, compared to the other most common mutation: C228T. In addition, hyper-methylation of the promoter region seems to be related to the progression of pTERT wild type (WT) patients. These results suggest that TERT gene alterations plays an important role during tumor progression, with the detection of the C250T mutation in tissue and plasma as a potential biomarker of poor prognosis in patients with advanced melanoma.

Background The renal mechanisms involved in the maintenance of human hypertension and resistance to treatment are not well understood. Animal studies suggest that chronic renal inflammation contributes to hypertension. We studied cells shed in first‐morning urine samples from individuals who were hypertensive who exhibited difficult‐to‐control blood pressure (BP). We performed bulk RNA sequencing of these shed cells to develop transcriptome‐wide associations with BP. We also analyzed nephron‐specific genes and used an unbiased bioinformatic approach to find signaling pathways activated in difficult‐to‐control hypertension. Methods and Results Participants who completed the SPRINT (Systolic Blood Pressure Intervention Trial) at a single trial site were recruited, and cells shed in first‐morning urine samples collected. A total of 47 participants were divided into 2 groups based on hypertension control. The BP‐difficult group (n=29) had systolic BP>140 mm Hg, >120 mm Hg after intensive treatment for hypertension, or required more than the median number of antihypertensive drugs used in SPRINT. The easy‐to‐control BP group (n=18) comprised the remainder of the participants. A total of 60 differentially expressed genes were identified with a >2‐fold change in the BP‐difficult group. In BP‐difficult participants, 2 of the most upregulated genes were associated with inflammation: Tumor Necrosis Factor Alpha Induced Protien 6 (fold change, 7.76; P=0.006) and Serpin Family B Member 9 (fold change, 5.10; P=0.007). Biological pathway analysis revealed an overrepresentation of inflammatory networks, including interferon signaling, granulocyte adhesion and diapedesis, and Janus Kinase family kinases in the BP‐difficult group (P

Abstract Long‐range communication between tumor cells and the lymphatic vasculature defines competency for metastasis in different cancer types, particularly in melanoma. Nevertheless, the discovery of selective blockers of lymphovascular niches has been compromised by the paucity of experimental systems for whole‐body analyses of tumor progression. Here, we exploit immunocompetent and immunodeficient mouse models for live imaging of Vegfr3‐driven neolymphangiogenesis, as a versatile platform for drug screening in vivo. Spatiotemporal analyses of autochthonous melanomas and patient‐derived xenografts identified double‐stranded RNA mimics (dsRNA nanoplexes) as potent inhibitors of neolymphangiogenesis, metastasis, and post‐surgical disease relapse. Mechanistically, dsRNA nanoplexes were found to exert a rapid dual action in tumor cells and in their associated lymphatic vasculature, involving the transcriptional repression of the lymphatic drivers Midkine and Vegfr3, respectively. This suppressive function was mediated by a cell‐autonomous type I interferon signaling and was not shared by FDA‐approved antimelanoma treatments. These results reveal an alternative strategy for targeting the tumor cell‐lymphatic crosstalk and underscore the power of Vegfr3‐lymphoreporters for pharmacological testing in otherwise aggressive cancers.

Metabolic reprogramming is required to fight infections and thyroid hormones are key regulators of metabolism. We have analyzed in hospitalized COVID-19 patients: 40 euthyroid and 39 levothyroxine (LT4)-treated patients in the ward and 29 euthyroid and 9 LT4-treated patients in the intensive care unit (ICU), the baseline characteristics, laboratory data, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), the FT3/FT4 ratio, 11 antiviral cytokines and 74 metabolomic parameters. No evidence for significant differences between euthyroid and LT4-treated patients were found in the biochemical, metabolomic and cytokines parameters analyzed. Only TSH (p=0.009) and ferritin (p=0.031) showed significant differences between euthyroid and LT4-treated patients in the ward, and TSH (p=0.044) and FT4 (p=0.012) in the ICU. Accordingly, severity and mortality were similar in euthyroid and LT4-treated patients. On the other hand, FT3 was negatively related to age (p=0.012), independently of sex and body mass index in hospitalized COVID-19 patients. Patients with low FT3 and older age showed a worse prognosis and higher levels of the COVID-19 severity markers IL-6 and IL-10 than patients with high FT3. IL-6 negatively correlated with FT3 (p=0.023) independently of age, body mass index and sex, whereas IL-10 positively associated with age (p=0.035) independently of FT3, body mass index and sex. A metabolomic cluster of 6 parameters defined low FT3 ward patients. Two parameters, esterified cholesterol (p=4.1x10-4) and small HDL particles (p=6.0x10-5) correlated with FT3 independently of age, body mass index and sex, whereas 3-hydroxybutyrate (p=0.010), acetone (p=0.076), creatinine (p=0.017) and high-density-lipoprotein (HDL) diameter (p=8.3x10-3) were associated to FT3 and also to age, with p-values of 0.030, 0.026, 0.017 and 8.3x10-3, respectively. In conclusion, no significant differences in FT3, cytokines, and metabolomic profile, or in severity and outcome of COVID-19, were found during hospitalization between euthyroid patients and hypothyroid patients treated with LT4. In addition, FT3 and age negatively correlate in COVID-19 patients and parameters that predict poor prognosis were associated with low FT3, and/or with age. A metabolomic cluster indicative of a high ketogenic profile defines non-critical hospitalized patients with low FT3 levels.

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.

Background. Nonalcoholic fatty liver disease (NAFLD) is a rising indication for liver transplantation (LT). Identification of NAFLD recurrence and those at risk for more progressive disease after LT remains elusive as the diagnosis requires biopsy, which is invasive and impractical for serial monitoring. We therefore aimed to identify metabolites in the blood associated with recurrent NAFLD that could potentially be used for detection and monitoring. Methods. This cross-sectional pilot study included 37 LT recipients who underwent simultaneous liver biopsy and plasma collection for metabolomic analysis. Metabolic profiles were compared between patients with recurrent NAFLD, normal liver (negative control), and acute rejection (rejection control). Results. Univariate analysis revealed 14 metabolites that were significantly altered in patients with recurrence of NAFLD compared with negative controls and 19 compared with rejection controls (P < 0.05). In addition, metabolomic profiling identified 16 metabolites that distinguished nonalcoholic fatty liver versus nonalcoholic steatohepatitis. Metabolite class trends among patients with recurrent NAFLD following LT were consistent with prior metabolomics data in patients with NAFLD in the non-LT setting. Conclusions. In conclusion, we identified candidate metabolites that could be used in the clinical setting to noninvasively identify recurrent NAFLD and differentiate NAFL from the more progressive nonalcoholic steatohepatitis. Further investigation with a larger sample size is warranted to validate these results.

The backfat thickness (BFT) was used to forecast the onset of ovarian activity and predict the calf growth. Eighty Brahman cows with their calves were allocated in two groups of 40 distributed in 4 months according to the month of calving, starting in March and finishing in June. One was synchronized and inseminated at fixed time following by natural mating (TAI+NM); whilst the other only by natural mating (NM). The programs started at 60 ± 5 days postpartum and ended 60 days later. From day 30 postpartum, serial ultrasound examinations and progesterone samples were used to monitor the onset of ovarian activity. The BFT in the rump area was measured by ultrasound from 30 days postpartum and every 15 days thereafter. The weight of the calves was recorded at birth and at weaning on 160 days. The adjusted effect of BFT on ovarian activity and the calves' development was assessed by binomial logistic regression at 30, 60, 75, and 120 days postpartum. The cycling cows averaged higher BFT irrespective of breeding program (P < 0.001). Also, slower changes in BFT were recorded during the follow-up at each time for all cows. However, the former had the higher BFT values from calving to the end of the study (P < 0.001). At 60, 75, and 120 days, the BFT measured, at the preceding time, was the only factor predicting the commencement of cyclicity (P < 0.001). The accumulative pregnancy through time was higher in TAI+NM (P = 0.003). Daily weight gain and weaning weight of the calves born in March was significantly heavier (P < 0.001) than peers born in April, May, or June. The most critical element to forecast the onset of ovarian activity is the monitoring of BFT around calving regardless of the breeding program. BFT to estimate the development of the calves until weaning was unpredictable.

Recientemente, con la institucionalización de VOX en la arena política, se ha puesto fin al llamado “excepcionalismo español”. VOX ha sido rápidamente caracterizado, no solo como miembro de la familia de partidos de la derecha radical, sino también como populista. Esto va en sintonía con buena parte de la literatura, que concibe cualquier manifestación de la derecha radical como intrínsecamente populista. No obstante, existen razones para cuestionar esta visión en ocasiones acrítica y con escaso fundamento empírico. A partir del marco ofrecido por el Discourse-Theoretical Analysis (DTA), se analizan programas y documentos de élites de VOX con objeto de examinar en profundidad su discurso. Los resultados muestran que la oferta de VOX se enmarca en una narrativa netamente nacionalista (basada en un antagonismo endogrupo vs. exogrupo), sin que sea posible identificar un intento por construir discursivamente un sujeto popular. En definitiva, estos hallazgos apuntan a la necesidad de desarrollar una agenda de investigación sobre la derecha radical que conciba el populismo como una expresión contingente más que como un rasgo inherente. Además, este giro deberá avanzar hacia un abordaje más matizado, sistemático y anclado en la evidencia empírica.

In the present work, we introduce the theoretical development and a new approach to validate a novel method to calibrate the efficiency of a gamma radiation detector for point sources, which we have named the “Efficiency Extrapolation Method”. The method consists in the determination of the detector efficiency using a set of monoenergetic gamma sources, which we will refer to as reference efficiencies. From these values, we will extrapolate the detector efficiency to the complete energy range using the first principle physics of gamma radiation detection theory. Therefore the proposed method corresponds to a semi-empirical one. The determination of reference efficiencies must be done experimentally, but in this work, simulations were performed using FLUKA code. The reference energies will be: 59,54 keV, 661,66 keV and 1 274,54 keV associated to the isotopes 241Am, 137Cs and 22Na respectively. The second part of the method, the extrapolation from the reference energies to the gamma range, will be done over the energies emitted by 152Eu and 133Ba. In general, the results are very good. While the obtained results for energies 53,16 keV and greater than 344,3 keV show an excellent agreement, the results obtained for energies in the middle range are only good.

The long-range transport of desert dust over the area of the temperate climate zone is associated with the influx of hot air masses due to the location of the sources of this aerosol in the tropical climate zone. Between 24–26 February 2021, such an aerosol outbreak took place and reached Central Europe. The mean temperature of +11.7 °C was recorded during the event. A comparison of this value to the 20-year (2000–2020) average February temperature for Warsaw (−0.2 °C) indicates the uniqueness of the meteorological conditions. It was the first wintertime inflow of Saharan dust over Warsaw, the presence of which was confirmed by lidar and sun-photometer measurements. The properties of the desert dust layers were obtained; the mean values of the particle depolarization for the fully developed mineral dust layer were 13 ± 3% and 22 ± 4% for 355 and 532 nm, respectively. The aerosol optical thickness was high with average values >0.36 for all wavelengths smaller than 500 nm. The three-modal, aerosol size distribution was dominated by coarse-mode particles, with a visible contribution of accumulation-mode particles. It suggests the possible presence of other aerosol types.

Urban boundary layer characterization is currently a challenging and relevant issue, because of its role in weather and air quality modelling and forecast. In many cities, the effect of complex topography at local scale makes this modelling even more complicated. This is the case of mid-latitude urban areas located in typical basin topographies, which usually present low winds and high turbulence within the atmospheric boundary layer (ABL). This study focuses on the analysis of the first ever measurements of wind with high temporal and vertical resolution throughout the ABL over a medium-sized city surrounded by mountains in southern Spain. These measurements have been gathered with a scanning Doppler lidar system and analyzed using the Halo lidar toolbox processing chain developed at the Finnish Meteorological Institute. We have used the horizontal wind product and the ABL turbulence classification product to carry out a statistical study using a two-year database. The data availability in terms of maximum analyzed altitudes for statistically significant results was limited to around 1000–1500 m above ground level (a.g.l.) due to the decreasing signal intensity with height that also depends on aerosol load. We have analyzed the differences and similarities in the diurnal evolution of the horizontal wind profiles for different seasons and their modelling with Weibull and von Mises probability distributions, finding a general trend of mean daytime wind from the NW with mean speeds around 3–4 m/s at low altitudes and 6–10 m/s at higher altitudes, and weaker mean nocturnal wind from the SE with similar height dependence. The highest speeds were observed during spring, and the lowest during winter. Finally, we studied the turbulent sources at the ABL with temporal (for each hour of the day) and height resolution. The results show a clear convective activity during daytime at altitudes increasing with time, and a significant wind-shear-driven turbulence during night-time.

La lipomatosis intestinal es un término utilizado para describir una proliferación de tejido graso, histológicamente normal, en el tracto gastrointestinal. Se caracteriza por la presencia de tumores benignos, asintomáticos, de crecimiento lento y de origen subepitelial. En raras ocasiones, estos tumores pueden ser sintomáticos y asociarse a complicaciones importantes como obstrucción y sangrado gastrointestinal. Así, la lipomatosis intestinal es una patología rara, con pocos casos reportados en la literatura y ninguno registrado en Colombia. A continuación, presentamos dos casos evaluados y seguidos en nuestro servicio de Unión de Cirujanos S.A.S de la Universidad de Caldas. El primero es el caso de un hombre de 70 años con historia de episodios de dolor abdominal tipo cólico, asociados a distensión y diarrea posprandial. La endoscopia digestiva alta inicial reportó múltiples lesiones amarillentas, submucosas, en el duodeno, con diagnóstico histológico de lipomas. En este caso, se realizó una videocápsula endoscópica para determinar la distribución y las características de las lesiones presentes en todo el tracto gastrointestinal, así como para valorar la presencia de complicaciones. El otro caso es el de un hombre de 81 años, quien ingresó a la institución por lipotimia y sangrado rectal. Por tanto, se realizó una endoscopia alta y una colonoscopia, cuyos resultados fueron normales. Luego de ello, se efectuó una videocápsula endoscópica que mostró lesiones lipomatosas; una de ellas, con sangrado y angiodisplasia al lado. Estas lesiones se manejaron mediante enteroscopia de doble balón y terapia con argón plasma.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective. In this study, we measured 540 lipids and amino acids in serum samples from biopsy‐proven subjects with normal liver (NL), NAFL, and NASH. Using logistic regression analysis, we identified two panels of triglycerides that could first discriminate between NAFLD and NL and second between NASH and NAFL. These noninvasive tests were compared to blinded histology as a reference standard. We performed these tests in an original cohort of 467 patients with NAFLD (90 NL, 246 NAFL, and 131 NASH) that was subsequently validated in a separate cohort of 192 patients (7 NL, 109 NAFL, 76 NASH). The diagnostic performances of the validated tests showed an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.88 ± 0.05, 0.94, and 0.57, respectively, for the discrimination between NAFLD and NL and 0.79 ± 0.04, 0.70, and 0.81, respectively, for the discrimination between NASH and NAFL. When the analysis was performed excluding patients with glucose levels >136 mg/dL, the area under the receiver operating characteristic curve for the discrimination between NASH and NAFL increased to 0.81 ± 0.04 with sensitivity and specificity of 0.73 and 0.80, respectively. Conclusion: The assessed noninvasive lipidomic serum tests distinguish between NAFLD and NL and between NASH and NAFL with high accuracy. (Hepatology Communications 2018;2:807‐820)

The aim of this study was to assess the seasonal effect of an embryo transfer program in the tropics on the donor response, recipient reproductive performance and calf growth from birth to weaning. This study included five-year records from 145 donors, 1149 embryo transfers (ET) and 609 in calves. The effect of the season (dry or wet) was evaluated at the time of embryo flushing, embryo transfer and birth of the calves. There was a seasonal effect on the yield and quality of the embryos. The number of nonfertilized and transferable good quality embryos increased in the wet season. For the recipients, the probability of pregnancy after an ET decreased by 6% for each year of the dam’s age. However, no seasonal effect was found when comparing ET calves with their control group (natural mating—NM), nevertheless, weaning weight was associated with birth body weight, treatment, sex of the calf, season at birth, year of treatment, and dam’s age. Calves born by NM had lower average daily gain (ADG), and male calves registered higher gains than females. Likewise, calves born during the rainy season had lower ADG compared with calves born during the dry season. In conclusion, this study shows that seasonal effect is more apparent in donor and calf performance than in the recipients.

Abstract Introduction The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease‐modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity. Methods Here, we show a novel, straight‐forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed. Results We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross‐sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aβ42. Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD. Conclusion This biomarker may offer new insights in the early diagnostics for AD.

Keratinocyte infection with high-risk human papillomavirus genotypes has been linked to cancer development. In cervix, the alpha HPV16 and HPV18 have been reported as the mayor causative agents of cervical cancer. Oncogenic progression and chronic inflammation are closely related processes, with IL-6 as one of the main pro-inflammatory cytokines involved. However, there are limited studies about the regulation of IL-6 by low and high risk HPVs and the HPV proteins implicated in this modulation. In this work, we report the overexpression of IL-6 in HPV infected cervical cancer derived cell lines (HeLa and SiHa) compared to non-tumorigenic keratinocytes (HaCaT), and in Cervical Intraepithelial Neoplasia grade 1 HPV16 and HPV18 positive cervical samples compared to HPV negative samples without lesions. Moreover, we generated HaCaT keratinocytes that express E5, E6, and E7 from high risk (16 or 18) or low risk (62 and 84) HPVs. E5 proteins do not modify IL-6 expression, while E7 modestly increase it. Interestingly, E6 proteins in HaCaT cells upregulate IL-6 mRNA expression and protein secretion. Indeed, in HaCaT cells that express high risk HPV16E6 or HPV18E6 proteins, only the truncated E6* isoforms were expressed, showing the stronger IL-6 overexpression, while in HaCaT cells that express low risk HPV62 and HPV84 full length E6 proteins, IL-6 was also upregulated but not so drastically. Since HaCaT cells have a mutated p53 form that is not degraded by the introduction of E6 or E6/E7, it seems that E6/E7 regulate IL-6 by an additional mechanism independent of p53. In addition, basal keratinocytes showed a strong expression of IL-6R using immunohistochemistry, suggesting an autocrine mechanism over proliferative cells. Altogether, IL-6 cytokine expression in keratinocytes is upregulated by E6 and E7 proteins from HPVs 16, 18, 62, and 84, especially by high risk HPV16 and HPV18 E6*, which may contribute to promote a pro-inflammatory and highly proliferative microenvironment that can persist over time and lead to cervical tumorigenesis.

ABSTRACT IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.

The stereoselective addition of Grignard reagents to ketimines is potentially a straightforward route to α-chiral amines. Here the authors report a catalytic, asymmetric Grignard addition to silyl ketimines, givingN-sulfonyl protected α-chiral silyl amines with tetrasubstituted stereocentres.

A set of five new aromatic poly(imide)s (PIs) incorporating pendant acyclic alkyl moieties were synthesized. The difference among them was the length and bulkiness of the pendant group, which comprises of linear alkyl chains from three to six carbon atoms, and a tert-butyl moiety. The effect of the side group length on the physical, thermal, mechanical, and gas transport properties was analyzed. All PIs exhibited low to moderate molecular weights (Mn ranged between 27.930–58.970 Da, and Mw ranged between 41.760–81.310 Da), good solubility in aprotic polar solvents, except for PI-t-4, which had a tert-butyl moiety and was soluble even in chloroform. This behaviour was probably due to the most significant bulkiness of the side group that increased the interchain distance, which was corroborated by the X-ray technique (PI-t-4 showed two d-spacing values: 5.1 and 14.3 Å). Pure gas permeabilities for several gases were reported (PI-3 (Barrer): He(52); H2(46); O2(5.4); N2(1.2); CH4(1.1); CO2(23); PI-t-4 (Barrer): He(139); H2(136); O2(16.7); N2(3.3); CH4(2.3); CO2(75); PI-5 (Barrer): He(44); H2(42); O2(5.9); N2(1.4); CH4(1.2); CO2(27); PI-6 (Barrer): He(45); H2(43); O2(6.7); N2(1.7); CH4(1.7); CO2(32)). Consistent higher volume in the side group was shown to yield the highest gas permeability. All poly(imide)s exhibited high thermal stability with 10% weight loss degradation temperature between 448–468 °C and glass transition temperature between 240–270 °C. The values associated to the tensile strength (45–87 MPa), elongation at break (3.2–11.98%), and tensile modulus (1.43–2.19 GPa) were those expected for aromatic poly(imide)s.

The use of renewable resources for plastic production is an imperious need for the reduction of the carbon footprint and the transition towards a circular economy. With that goal in mind, fully biobased epoxy resins have been designed and prepared by combining epoxidized linseed oil, lignin, and a biobased diamine derived from fatty acid dimers. The aromatic structures in lignin provide hardness and strength to an otherwise flexible and breakable epoxy resin. The curing of the system was investigated by infrared spectroscopy and differential scanning calorimetry (DSC). The influence of the different components on the thermo-mechanical properties of the epoxy resins was analyzed by DSC, thermal gravimetric analysis (TGA), and tensile tests. As the content of lignin in the resin increases, so does the glass transition, the Young’s modulus, and the onset of thermal degradation. This correlation is non-linear, and the higher the percentage of lignin, the more pronounced the effect. All the components of the epoxy resin being commodity chemicals, the present system provides a realistic opportunity for the preparation of fully biorenewable resins at an industrial scale.

In this paper a parallel iterative solver based on the Generalized Minimum Residual Method (GMRES) with complex-valued coefficients is explored, with applications to the Boundary Element Method (BEM). The solver is designed to be executed in a GPU (Graphic Processing Unit) device, exploiting its massively parallel capabilities. The BEM is a competitive method in terms of reduction in the number of degrees of freedom. Nonetheless, the BEM shows disadvantages when the dimension of the system grows, due to the particular structure of the system matrix. With difference to other acceleration techniques, the main objective of the proposed solver is the direct acceleration of existing standard BEM codes, by transfering to the GPU the solver task. The CUDA programming language is used, exploiting the particular architecture of the GPU device for complex-valued systems. To explore the performances of the solver, two linear water wave problems have been tested: the frequency-dependent added mass and damping matrices of a 3D floating body, and the Helmholtz equation in a 2D domain. A NVidia GeForce GTX 1080 graphic card has been used. The parallelized GMRES solver shows reductions in computing times when compared with its CPU implementation.

Roleplaying has a history of serving diverse aims, including art, entertainment, therapeutic purposes, and political action (Piper 1973; Gygax 1978; Boal 1993; Matthews et al. 2014). This paper presents an interactive narrative called Grayscale that uses roleplaying to provoke critical reflection through modeling workplace gender discrimination. Grayscale's interface resembles a streamlined email system, constituting what Henry Jenkins has termed an “embedded narrative” since the narration is distributed across elements in the space (e.g. emails, notes, draft messages).

Oxymycterus wayku Jayat, D’Elía, Pardinãs, Miotti & Ortiz, 2008, a rodent species recently described, is known in only four localities within the Subtropical Mountain Forests of the Yungas eco-region in Tucumán, northwestern Argentina. Specimens were recorded in an owl pellet sample during a recent survey. This record represents the first for Oxymycterus in Catamarca Province, extending approximately 60 km south its southern distribution in the region. Sixteen other small non-volant mammal species were recorded there, turning this area into one of the most diverse for this understudied group in Argentina.

Se presenta la investigación en aula titulada “Aproximación al concepto de Biodiversidad: Una experiencia desde el enfoque de la Enseñanza para la Comprensión”, la cual fue desarrollada en el Colegio Manuela Ayala de Gaitán, con estudiantes de noveno grado, en el espacio académico de la Licenciatura en Biología de la Universidad Distrital Francisco José de Caldas. Centra la mirada en la implementación de una estrategia que busca reconocer la comprensión de los estudiantes en relación al concepto de Biodiversidad y el avance que presentan en correspondencia a los desempeños de comprensión, evidenciados a través de el seguimiento a la dimensión de contenidos en los niveles de comprensión (Ingenuo, Principiante, Aprendiz, Maestría).

Abrothrix jelskii is one of the lesser-known species in the genus Abrothrix, and it has only been recorded in a few localities in highland environments along the central Andean range. In Argentina, existing records are restricted to just one locality in Jujuy province. We have recently recorded this species in Salta Province, extending its known distribution 150 km northward in northwestern Argentina and 175 km further to the southeast compared to existing records from localities in southern Bolivia. Ten other rodent species were also recorded in the same area, with some of these records, such as those for Auliscomys sublimis, Akodon boliviensis, and Phyllotis sp., being noteworthy as well.

Introducción: Las complicaciones asociadas al proceso fisiopatológico crónico de la diabetes mellitus tipo 2 (DM2) inciden enormemente en la población que la padece. El Diabetes Knowledge Questionnaire (DKQ-24), determina el nivel de conocimientos sobre diabetes, proporcionando información a los profesionales de la salud, para realizar intervenciones educativas útiles y prevenir complicaciones agudas y crónicas de la enfermedad. Objetivo: Evaluar el efecto de la aplicación de un modelo de educación terapéutica diabetológica hospitalario (autocuidado y conocimiento) a largo plazo en pacientes con diabetes mellitus tipo 2 (DM2) en una población del sur de Colombia. Materiales y métodos: Estudio longitudinal prospectivo, realizado en 60 pacientes con DM2 hospitalizados. Se utilizó el cuestionario DKQ-24 como evaluación previa y posterior a 90 días se aplicó de nuevo junto con la toma de las variables biométricas. Se realizo la intervención en 5 sesiones educativas de educación terapéutica diabetológica en ámbitos hospitalarios. Resultados: Los resultados promedios según el cuestionario DKQ-2 pre (10,13±3,28) y posintervención (20,13±2,77) presentaron diferencias significativas (p

Sigmodontine rodents are well represented in northwestern Argentina, but information regarding their distribution in La Rioja is scarce. We add new information for seven species from seven localities in the Famatina range. These new records were obtained using both captures and owl pellet analysis. We cite the first record of Neotomys ebriosus in La Rioja. The collection locality is unusual for this species because of its low altitude and xeric conditions. Other notable results include the second record of Abrothrix andinus and of the genus Oligoryzomys at the province.

La conflictividad entre la lógica estatal de uso y explotación de la naturaleza, y la necesidad del propio Estadode generar excedentes o ganancias económicas que le permita satisfacer las demandas de la población es creciente.Por otro lado, persisten las tensiones entre la razón de Estado y los derechos económicos, sociales ypolíticos de las comunidades locales. Aquella conflictividad y tensión demanda la búsqueda de varios equilibriosy acuerdos, que en la historia reciente ecuatoriana parecen estar lejanos. El texto, a lo largo de tresbreves acápites, intenta esbozar algunos elementos a fin de contribuir a la reflexión colectiva, crítica y urgentede este tema.

Cuando se aprobó la Constitución de 1998, la sensación incierta de haber logrado algo invadió los círculos intelectuales y políticos cercanos a algunos movimientos sociales, en particular, al movimiento indígena. Los derechos colectivos junto a ciertos principios, insertos en la parte dogmática,constituyeron sin duda un avance, peroquedó la duda cuando otras disposiciones, incluyendo transitorias, posibilitaron varias reformas legales e institucionales acordes a las prioridades de las políticas de ajuste neo-liberal.

Mouse embryos lacking the polycomb group gene member Yin-Yang1 (YY1) die during the peri-implantation stage. To assess the post-gastrulation role of YY1, a conditional knock-out (cKO) strategy was used to delete YY1 from the visceral endoderm of the yolk sac and the definitive endoderm of the embryo. cKO embryos display profound yolk sac defects at 9.5 days post coitum (dpc), including disrupted angiogenesis in mesoderm derivatives and altered epithelial characteristics in the visceral endoderm. Significant changes in both cell death and proliferation were confined to the YY1-expressing yolk sac mesoderm indicating that loss of YY1 in the visceral endoderm causes defects in the adjacent yolk sac mesoderm. Production of Vascular Endothelial Growth Factor A (VEGFA) by the visceral endoderm is essential for normal growth and development of the yolk sac vasculature. Reduced levels of VEGFA are observed in the cKO yolk sac, suggesting a cause for the angiogenesis defects. Ex vivo culture with exogenous VEGF not only rescued angiogenesis and apoptosis in the cKO yolk sac mesoderm, but also restored the epithelial defects observed in the cKO visceral endoderm. Intriguingly, blocking the activity of the mesoderm-localized VEGF receptor, FLK1, recapitulates both the mesoderm and visceral endoderm defects observed in the cKO yolk sac. Taken together, these results demonstrate that YY1 is responsible for maintaining VEGF in the developing visceral endoderm and that a VEGF-responsive paracrine signal, originating in the yolk sac mesoderm, is required to promote normal visceral endoderm development.

Un análisis del conocimiento ancestral sobre la pesca se realizó en las comunidades Shuar asentadas a lo largo del corredor fluvial Zamora – Nangaritza. El objetivo del estudio fue recuperar, valorar, difundir y potenciar sus saberes y costumbres con el fin de mantener activa su cultura. Un enfoque basado en entrevistas estructuradas o semi-estructuradas fue utilizado en 32 comunidades (404 encuestas). Una gran diversidad de peces caracterizó el área de estudio, siendo las principales especies de captura el corroncho (Dekeyseria sp.), el corronchillo (Dekeyseria sp.), la anguilla (Henonemus sp.), el blanco (Brycon sp.) y el bocachico (Prochilodus sp.). Estas especies habitan distintos ecosistemas fluviales (ríos, quebradas, lagos y lagunas). En la captura se emplean aún instrumentos autóctonos, pero la influencia de la colonización ha permitido el uso de otros instrumentos y artefactos. Como cebo o carnada emplean insectos de origen acuático y terrestre, así como desperdicios y víseras de animales. La actividad de pesca en ríos y quebradas se realiza, durante todo el año. La gastronomía de esta zona se ve influenciada por el empleo de estas especies en una variedad de platos en diferentes preparaciones. La conservación y almacenamiento de la carne se realiza principalmente con la técnica del secosalado. El consumo de pescado ha disminuido considerablemente en los últimos años, a niveles críticos, debido a la disminución de los bancos de peces y la alteración del hábitat.

Cuando se aprobó la Constitución de 1998, la sensación incierta de haber logrado algo invadió los círculos intelectuales y políticos cercanos a algunos movimientos sociales, en particular, al movimiento indígena. Los derechos colectivos junto a ciertos principios, insertos en la parte dogmática, constituyeron sin duda un avance, pero quedó la duda cuando otras disposiciones, incluyendo transitorias, posibilitaron varias reformas legales e institucionales acordes a las prioridades de las políticas de ajuste neoliberal.

We report the first record of the genus Cavia and the species Cavia tschudii (Rodentia, Caviidae) in Catamarca province, northwestern Argentina, which represents a range extension of about 110 km southward for the species. The cranial and dental remains were recovered from an owl pellet sample found in eastern slopes of the Ambato range, at 1600 m elevation, in a highland grasslands-Chaco Serrano ecotone. According to the environmental continuity along the Ambato range, we suggest that the presence of C. tschudii in southernmost Catamarca and northern La Rioja province is likely.

Poor management of either type 1 diabetes or haemophilia A can lead to complications such as organ dysfunction and haemarthropathy. Here, we describe the case of an 8-year-old boy diagnosed with severe haemophilia A shortly after birth. At 2 years old, he was also diagnosed with type 1 diabetes. After six years, the haemophilia treatment was changed from a plasma-derived factor VIII (FVIII) concentrate (octanate®, Octapharma, Lachen, Switzerland) to Nuwiq® (simocotocog alfa, Octapharma, Lachen, Switzerland), a recombinant FVIII (rFVIII) product from a human cell line, which allowed for a personalised treatment schedule that supported good adherence. The dosing regimen could be reduced to two weekly rFVIII infusions. The patient has experienced no spontaneous bleeds since switching to rFVIII and shows no signs of joint damage after over seven years of FVIII prophylaxis. rFVIII was well tolerated, with no treatment-related adverse events observed. This case illustrates the importance of treatment personalisation for young patients and their families managing concomitant diseases.