Fortalecimiento de las contrataciones públicas en los servicios de consultoría para supervisiones de obra en el marco de la reconstrucción con cambios del Ministerio de Transportes y Comunicaciones. Período 2021-2022

La presente investigación propone mejorar el procedimiento de contratación de las supervisiones de obras de Reconstrucción con Cambios, en el Ministerio de Transportes y Comunicaciones, empleando productos, el desarrollo de un instructivo conteniendo un catálogo o ficha de Acuerdo Marco para que sea utilizado en el portal Perú Compras y el desarrollo de un Plan de Capacitación, los cuales conllevarían a que se agilicen las contrataciones en beneficio de la población afectada por el fenómeno del Niño Costero. Es de señalar que también esta modalidad podría ser usada para procedimientos que no estén vinculados al Fenómeno del Niño Costero. La presente investigación se encuentra enmarcada en el Programa Presupuestal N° 149, el cual espera como resultado específico la Mejora del desempeño en las Contrataciones Públicas. En ese sentido, la propuesta presentada aborda la causa “Insuficiente e inadecuada información para la gestión del proceso de contratación pública” y se presentan alternativas para solucionar dicho problema

Next-generation sequencing identifies rare variants associated with Noonan syndrome

Noonan syndrome (NS) is a relatively common genetic disorder, characterized by typical facies, short stature, developmental delay, and cardiac abnormalities. Known causative genes account for 70-80% of clinically diagnosed NS patients, but the genetic basis for the remaining 20-30% of cases is unknown. We performed next-generation sequencing on germ-line DNA from 27 NS patients lacking a mutation in the known NS genes. We identified gain-of-function alleles in Ras-like without CAAX 1 (RIT1) and mitogen-activated protein kinase kinase 1 (MAP2K1) and previously unseen loss-of-function variants in RAS p21 protein activator 2 (RASA2) that are likely to cause NS in these patients. Expression of the mutant RASA2, MAP2K1, or RIT1 alleles in heterologous cells increased RAS-ERK pathway activation, supporting a causative role in NS pathogenesis. Two patients had more than one disease-associated variant. Moreover, the diagnosis of an individual initially thought to have NS was revised to neurofibromatosis type 1 based on an NF1 nonsense mutation detected in this patient. Another patient harbored a missense mutation in NF1 that resulted in decreased protein stability and impaired ability to suppress RAS-ERK activation; however, this patient continues to exhibit a NS-like phenotype. In addition, a nonsense mutation in RPS6KA3 was found in one patient initially diagnosed with NS whose diagnosis was later revised to Coffin-Lowry syndrome. Finally, we identified other potential candidates for new NS genes, as well as potential carrier alleles for unrelated syndromes. Taken together, our data suggest that next-generation sequencing can provide a useful adjunct to RASopathy diagnosis and emphasize that the standard clinical categories for RASopathies might not be adequate to describe all patients

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Experimental study of different coatings on silica sand in a directly irradiated fluidised bed: Thermal behaviour and cycling analysis

The present work shows the experimental results obtained with sand particles, which where coated to increase the thermal absorptivity for CSP applications. The particles were tested in a lab-scale fluidised bed with concentrated irradiation on the top. The experimental results indicates that two of the three coatings tested, based on graphite and carbon black, worked properly and absorbed between 30 and 40% more energy than raw sand due to the higher thermal absorptivity. Both coatings were also experimentally tested during 10 cycles of charging/discharging without apparent deterioration of their thermal properties. Sand coated with graphite exhibited colour change, from an initial dark black to a greyish tone that did not have an impact on the particles thermal response. The extrapolation of the results observed at lab-scale, to the maximum expected temperatures in new generation of CSP plants with solid particles, up to 1250 K, shows that coated particles may enhance the energy effectively stored in the bed by 60–80% compared to raw sand.This work was partially funded by the Ministerio de Economía y Competitividad (Projects RTI2018-093849-B-C32 MCIU/AEI/FEDER,UE and ENE2016-78908-R) of the Spanish Government, the Regional Government of Castilla-La Mancha (project SBPLY/17/180501/000412), Generalitat Valenciana (PROMETEO/2020/029), the Universitat Jaume I (UJI-B2020-32) and the Ministerio de Ciencia, Innovación y Universidades - Agencia Estatal de Investigación (AEI) (RED2018-102431-T). The authors would like to thank the Catalan Government for the quality accreditation given to their research group (DIOPMA 2017 SGR 0118). DIOPMA is certified agent TECNIO in the category of technology developers from the Government of Catalonia. We also acknowledge financial support of the UCLM through the “Ayudas a Grupos de Investigación-Plan Propio” (ref. 2021-GRIN-31341 and 2021-GRIN-30978). Minerva Díaz-Heras is also a postdoctoral researcher Margarita Salas, with a contract within the framework of the call for grants for the requalification of the Spanish University system, funded by the European Union Recovery Instrument NextGenerationEU and obtained through the Universidad de Castilla-La Mancha (UCLM)

Evaluating Pain Management Practices for Cancer Patients among Health Professionals: A Global Survey

Background: Cancer incidence in the world is predicted to increase in the next decade. While progress has been in diagnosis and treatment, much still remains to be done to improve cancer pain therapy, mainly in underserved communities in low-income countries. Objective: To determine knowledge, beliefs, and barriers regarding pain management in both high- and low-income countries (according to the WHO classification); and to learn about ways to improve the current state of affairs. Design: Descriptive survey. Setting/Subjects: Fifty-six countries worldwide; convenience sample of 1639 consisted of 36.8% physicians; 45.1% nurses, and 4.5% pharmacists employed in varied settings. Results: Improved pain management services are key elements. Top barriers include religion factors, lack of appropriate education and training at all levels, nonadherence to guidelines, patients\u27 reluctance to report on pains, over regulation associated with prescribing and access to opioid analgesics, fear of addiction to opioids, and lack of discussions around prognosis and treatment planning. Conclusion: The majority of patients with cancer in low-income countries are undertreated for their pain. Promoting cancer pain accredited program of training and education on pain management for physicians and nurses is crucial, as well as advocating policymakers and the public at large

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: Among 862 patients (640 female, mean age 54.2 years), 1010 nodules (median size 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4 and 5 in 3%, 34%, 42% and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V and VI in 8%, 48%, 17%, 17%, 3% and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68% and 21% of patients with Bethesda III, IV and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.</p

Effects of phytoestrogens on mammalian reproductive physiology

Global consumption of phytoestrogens and their effects have increased both in animals and humans due to the augmented use of legumes in animal diets as well as the increase in vegetarian diets in some human populations. Even though the general opinion and that of clinicians toward phytoestrogens is generally positive, many phytoestrogens are now recognized as endocrine disruptor compounds, capable of interfering with the synthesis, secretion, transport, binding, action or elimination of natural hormones in the body that are responsible for reproduction. The effects of phytoestrogens mainly depend on the type, amount and plant species ingested. These compounds are found widely in a variety of plants and fodder, and can have adverse effects mainly on the reproductive tract in most animal species. Many phytoestrogens can act as estrogenic agonists or antagonists, and their effects can vary from infertility to an estrogenic over-response, thus increasing secretions in the reproductive tract and disrupting animal behavior. Presently, there is still a lack of knowledge on this subject, and the effects on reproductive parameters of estrogenic forage in animal production systems are unknown. Therefore, it is necessary to continue research in order to elucidate the effects of phytoestrogens, the doses at which effects are seen, the species, the disruptive or beneficial effects, as well as the mechanisms of action involved. This review focuses on the effects of phytoestrogens in the reproductive physiology of livestock and human, as well as the knowledge obtained from research in animal models.El consumo de dietas a base de leguminosas en los animales de granja, así como así como las dietas vegetarianas y el consumo de suplementos alimenticios con alto contenido de fitoestrógenos en los humanos se han incrementado en los últimos años. Los fitoestrógenos están ampliamente contenidos en gran variedad de leguminosas, pastos, ensilajes y hierbas, y pueden causar efectos adversos principalmente en el tracto reproductivo de la mayoría de las especies animales. Muchos fitoestrógenos pueden actuar como agonistas o antagonistas estrogénicos, por lo que sus efectos varían desde la sobre-respuesta estrogénica, aumentando las secreciones del tracto reproductivo, hasta la infertilidad, alterando además el comportamiento animal. Por lo tanto, se ha considerado a los fitoestrógenos como disruptores o desorganizadores endocrinos, capaces de interferir con la síntesis, la secreción, el transporte, la unión, la acción y eliminación de las hormonas que produce el organismo de forma natural y que son responsables de la reproducción. El efecto de los fitoestrógenos en la reproducción depende básicamente del tipo y la cantidad presente en la especie vegetal que se consuma. A pesar de la abundante literatura que muestra los efectos de los fitoestrógenos en los humanos y en los modelos animales de laboratorio, en la actualidad aún se desconoce el grado en que los parámetros reproductivos en los sistemas de producción animal se han visto afectados por el consumo de forrajes fitoestrogénicos. Por lo tanto, es necesario continuar con investigaciones que permitan dilucidar los efectos de estos compuestos con respecto a las dosis utilizadas, las especies, los efectos nocivos o benéficos, así como los mecanismos de acción involucrados. Esta revisión se centra en los efectos de los fitoestrógenos en diversas especies de ganado y en los humanos, así como en los hallazgos obtenidos de la investigación en modelos animales de laboratorio

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients

COSMOS is sponsored by the Bone and Mineral Research Unit (Hospital Universitario Central de Asturias), SAFIM (Sociedad Asturiana Fomento Investigaciones Óseas), the European Renal Association. This study has been funded by Instituto de Salud Carlos III (ISCIII), the ISCIII Retic REDinREN (RD06/0016/1013, RD12/0021/0023 and RD16/0009/0017), the ISCIII Red de Investigación Cooperativa Orientada a Resultados en Salud RICORS2040 (RD21/0005/0001 and RD21/0005/0019, Next Generation EU; Recovery, Transformation and Resilience Plan), the ISCIII (ICI14/00107, PI17/00384 and PI20/00633, co-funded by the European Union), Plan Estatal de I + D + I 2013-2016, Plan de Ciencia, Tecnología e Innovación 2013-2017 y 2018-2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152, IDI/2021/000080), Fundación Renal Íñigo Álvarez de Toledo (FRIAT) and the Spanish Society of Nephrology (Estudio Estratégico de la SEN). Logistics (meetings, secretarial help, printing of materials, development of website for data entry, etc.) have been financially supported by an unrestricted grant from AMGEN Europe and Fundación Renal Íñigo Álvarez de Toledo (FRIAT).BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.publishersversionepub_ahead_of_prin