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Post-silicon electrical validation of high-speed input/output (HSIO) links is a critical process for product qualification schedules of high-performance computer platforms under current aggressive time-to-market commitments. Improvements in signaling methods, circuits, and process technologies have allowed HSIO data rates to scale well beyond 10 Gb/s. Noise and EM effects can create multiple signal integrity problems, which are aggravated by continuously faster bus technologies. The goal of post-silicon validation for HSIO links is to ensure design robustness of both receiver (Rx) and transmitter circuitry in real system environments. One of the most common ways to evaluate the performance of an HSIO link is to characterize the Rx jitter tolerance (JTOL) performance by measuring the bit error rate (BER) of the link under worst stressing conditions. However, JTOL testing is extremely time-consuming when executed at specification BER considering manufacturing process, voltage, and temperature test coverage. In order to significantly accelerate this process, we propose a novel approach for JTOL testing based on an efficient direct search optimization methodology. Our approach exploits the fast execution of a modified golden section search with a high BER, while overcoming the lack of correlation between different BERs by performing a downward linear search at the actual target BER until no errors are found. Our proposed methodology is validated in a realistic industrial server post-silicon validation platform for three different computer HSIO links: SATA, USB3, and PCIe3.

OBJECTIVE Visualization of subcortical language pathways by means of diffusion tensor imaging–fiber tracking (DTI-FT) is evolving as an important tool for surgical planning and decision making in patients with language-suspect brain tumors. Repetitive navigated transcranial magnetic stimulation (rTMS) cortical language mapping noninvasively provides additional functional information. Efforts to incorporate rTMS data into DTI-FT are promising, but the lack of established protocols makes it hard to assess clinical utility. The authors performed DTI-FT of important language pathways by using five distinct approaches in an effort to evaluate the respective clinical usefulness of each approach. METHODS Thirty patients with left-hemispheric perisylvian lesions underwent preoperative rTMS language mapping and DTI. FT of the principal language tracts was conducted according to different strategies: Ia, anatomical landmark based; Ib, lesion-focused landmark based; IIa, rTMS based; IIb, rTMS based with postprocessing; and III, rTMS enhanced (based on a combination of structural and functional data). The authors analyzed the respective success of each method in revealing streamlines and conducted a multinational survey with expert clinicians to evaluate aspects of clinical utility. RESULTS The authors observed high usefulness and accuracy ratings for anatomy-based approaches (Ia and Ib). Postprocessing of rTMS-based tractograms (IIb) led to more balanced perceived information content but did not improve the usefulness for surgical planning and risk assessment. Landmark-based tractography (Ia and Ib) was most successful in delineating major language tracts (98% success), whereas rTMS-based tractography (IIa and IIb) frequently failed to reveal streamlines and provided less complete tractograms than the landmark-based approach (p < 0.001). The lesion-focused landmark-based (Ib) and the rTMS-enhanced (III) approaches were the most preferred methods. CONCLUSIONS The lesion-focused landmark-based approach (Ib) achieved the best ratings and enabled visualization of the principal language tracts in almost all cases. The rTMS-enhanced approach (III) was positively evaluated by the experts because it can reveal cortico-subcortical connections, but the functional relevance of these connections is still unclear. The use of regions of interest derived solely from cortical rTMS mapping (IIa and IIb) leads to cluttered images that are of limited use in clinical practice.

In order to implement the concepts of smart grid and residential automation, this article presents a SmartPlug prototype for power consumption monitoring in smart homes. It is a device that, when coupled to the sockets, measures electrical voltage and current, and thereafter provides the power consumption to the consumer using the power line communication (PLC) technology. With the knowledge of the consumption, provided by the smart metering, of each outlet, the consumer is able to establish the concept of segmented energy consumption, which is an important allied of energy saving and power demanding. With commercial current and voltage sensors, the SmartPlug was built using the Arduino platform and the end user interface was created using the open source software ScadaBR. After performance evaluation in a laboratory, tests in real electrical plants were performed to validate the prototype, considering bit rates and signal spectrum in the PLC systems.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage- such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in the inhibition of secondary brain injury can result as a potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in the clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies based on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

BACKGROUND: Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia. METHODS: In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0–10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set. RESULTS: Of 564 eligible participants randomized to receive tenapanor (n=423) or sevelamer carbonate (n=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (n=128) or placebo (n=127) during the randomized withdrawal period. In the efficacy analysis set (n=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was −1.4 mg/dl (P

Early detection of cardiovascular dysfunctions directly caused by acute ischemic stroke (AIS) has become paramount. Researchers now generally agree on the existence of a bidirectional interaction between the brain and the heart. In support of this theory, AIS patients are extremely vulnerable to severe cardiac complications. Sympathetic hyperactivity, hypothalamic–pituitary–adrenal axis, the immune and inflammatory responses, and gut dysbiosis have been identified as the main pathological mechanisms involved in brain–heart axis dysregulation after AIS. Moreover, evidence has confirmed that the main causes of mortality after AIS include heart attack, congestive heart failure, hemodynamic instability, left ventricular systolic dysfunction, diastolic dysfunction, arrhythmias, electrocardiographic anomalies, and cardiac arrest, all of which are more or less associated with poor outcomes and death. Therefore, intensive care unit admission with continuous hemodynamic monitoring has been proposed as the standard of care for AIS patients at high risk for developing cardiovascular complications. Recent trials have also investigated possible therapies to prevent secondary cardiovascular accidents after AIS. Labetalol, nicardipine, and nitroprusside have been recommended for the control of hypertension during AIS, while beta blockers have been suggested both for preventing chronic remodeling and for treating arrhythmias. Additionally, electrolytic imbalances should be considered, and abnormal rhythms must be treated. Nevertheless, therapeutic targets remain challenging, and further investigations might be essential to complete this complex multi-disciplinary puzzle. This review aims to highlight the pathophysiological mechanisms implicated in the interaction between the brain and the heart and their clinical consequences in AIS patients, as well as to provide specific recommendations for cardiovascular management after AIS.

To date, no meta-analytical study evaluating the benefits of resistance exercise intervention on muscular strength and power and functional capacity in acute hospitalized older adults was conducted. Then, to synthesize the emerging evidence on the effects of resistance exercise intervention on muscular strength and power and functional capacity in acute hospitalized older adults, two independent authors performed a systematic search (PubMed, Scopus, Web of Science, and SciELO) until January 2021. Randomized clinical trials were included regarding the effects of resistance exercise and hospital usual care. The Cochrane Collaboration assessment tool was used to analyze the risk of bias. The comparisons included muscular strength (isometric handgrip strength and one-repetition maximum test of leg press), muscular power (output during leg press exercise), and functional capacity (timed-up-and-go, and short physical performance battery). Resistance exercise intervention increased muscular strength (isometric handgrip strength: mean difference = 2.50 kg, 95% confidence interval (CI) = 1.33, 3.67; and one-repetition maximum test of leg press: mean difference = 19.28 kg, 95% confidence interval = 14.70, 23.86) and muscular power (mean difference = 29.52 W, 95% confidence interval = 28.84, 30.21), and functional capacity (timed-up-and-go: mean difference = 3.40 s, 95% confidence interval = 0.47, 6.36; and short physical performance battery: mean difference = 1.29 points, 95% confidence interval = 0.10, 2.48) at discharge compared with hospital usual care. This meta-analysis endorses the increase of muscular strength and power gains and improving the functional capacity in favor of resistance exercise intervention in acute hospitalized older adults. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020203658 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00446-7.

AIMS Physiologically based pharmacokinetic (PBPK) models have been previously developed for betamethasone and buprenorphine for pregnant women. The goal of this work was to replicate and reassess these models using data from recently completed studies. METHODS Betamethasone and buprenorphine PBPK models were developed in Simcyp V19 based on prior publications using V17 and V15. Ability to replicate models was verified by comparing predictions in V19 to those previously published. Once replication was verified, models were reassessed by comparing predictions to observed data from additional studies in pregnant women. Model performance was based upon visual inspection of concentration vs. time profiles, and comparison of pharmacokinetic parameters. Models were deemed reproducible if parameter estimates were within 10% of previously reported values. External validations were considered acceptable if the predicted area under the concentration-time curve (AUC) and peak plasma concentration fell within 2-fold of the observed. RESULTS The betamethasone model was successfully replicated using Simcyp V19, with ratios of reported (V17) to reproduced (V19) peak plasma concentration of 0.98-1.04 and AUC of 0.95-1.07. The model-predicted AUC ratios ranged from 0.98-1.79 compared to external data. The previously published buprenorphine PBPK model was not reproducible, as we predicted intravenous clearance of 70% that reported previously (both in Simcyp V15). CONCLUSION While high interstudy variability was observed in the newly available clinical data, the PBPK model sufficiently predicted changes in betamethasone exposure across gestation. Model reproducibility and reassessment with external data are important for the advancement of the discipline. PBPK modelling publications should contain sufficient detail and clarity to enable reproducibility.

Background We evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS). Methods Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer’s lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease from 9 to 3 cmH2O. Animals were then further ventilated for 10 min at PEEP = 3 cmH2O, euthanized, and their lungs and kidneys removed for molecular biology analysis. Results At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate. Conclusion In the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.

Breast cancer is one of the most common diseases among women worldwide with about 25% of new cases each year. In Brazil, 59,700 new cases of breast cancer were expected in 2019, according to the Brazilian National Cancer Institute (INCA). Survival analysis has been an useful tool for the identifying the risk and prognostic factors for cancer patients. This work aims to characterize the prognostic value of demographic, clinical and pathological variables in relation to the survival time of 2,092 patients diagnosed with breast cancer in Parana State, Brazil, from 2004 to 2016. In this sense, we propose a Bayesian analysis of survival data with long-term survivors by using Weibull regression models through integrated nested Laplace approximations (INLA). The results point to a proportion of long-term survivors around 57:6% in the population under study. In regard to potential risk factors, we namely concluded that 40-50 year age group has superior survival than younger and older age groups, white women have higher breast cancer risk than other races, and marital status decreases that risk. Caution on the general use of these results is nevertheless advised, since we have analyzed population-based breast cancer data without proper monitoring by a healthprofessional.

PURPOSE This study aimed to assess the pain scores at the insertion of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) among nulligravidas, parous women with previous vaginal delivery and parous women with elective caesarean-delivery without any previous labour or cervix dilation. MATERIALS AND METHODS The present research is a prospective, single-cohort study that included 413 women aged 15-49 years who opted for LNG-IUS placement for contraception or treatment of heavy menstrual bleeding. Women who participated in the present study were not submitted to any pharmacological pain-relieving intervention to perform the procedure. Pain at insertion was evaluated by using a Visual Analogue Scale (VAS). Pain was classified as absent (0), mild (1-3), moderate (4-6), or severe (7-10). The women were divided as: (1) nulligravidas, (2) parous women with a previous vaginal delivery, or (3) parous women with elective caesarean-delivery without any previous labour or cervix dilation. RESULTS Nulligravidas women presented a higher mean pain score, when compared to women with elective caesarean-delivery and women with previous vaginal delivery (6.6 ± 2.0 vs 5.5 ± 2.1 and 3.9 ± 2.4, respectively; p

BackgroundBetamethasone (BMZ) is used to accelerate fetal lung maturation in women with threatened preterm birth, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone.MethodsThis study prospectively enrolled women, gestational ages 23–34 weeks, who received betamethasone for threatened preterm birth. Maternal demographics, prenatal history, and neonatal outcomes were abstracted from hospital records. RDS was the primary outcome. Associations between RDS diagnosis and maternal demographics, prenatal history, and betamethasone dosing were evaluated in a case-control analysis and multivariable regression adjusted for gestational age at delivery. Secondary analyses limited the cohort to women who delivered within 1 or 2 weeks of betamethasone dosing.ResultsOf 209 deliveries, 90 (43 %) resulted in neonatal RDS. Within the overall cohort and controlling for gestational age at birth, RDS was only associated with cesarean births compared to vaginal births (adjusted OR 1.17 [1.06–1.29]). Route of delivery was also the only significant factor related to RDS in the 83 neonates delivered within 7 days of BMZ dosing. However, among 101 deliveries within 14 days of betamethasone dosing and controlling for gestational age at birth, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS rates than those without PPROM (57.9 % vs. 80.2 %, adjusted OR 0.81 [0.67–0.99]). Maternal age, BMI, race, and ethnicity were not associated with RDS in the regression models.ConclusionsOf maternal characteristics analyzed, only delivery by cesarean was associated with neonatal RDS after antenatal betamethasone use.

espanolEl registro de lupus de la Sociedad Espanola de Reumatologia (RELESSER) es un registro multicentrico de pacientes con lupus eritematoso sistemico seguidos en servicios de reumatologia espanoles, que contiene cuantiosa informacion sobre 4.024 pacientes. Hasta la fecha han sido publicados 14 analisis sobre la fase transversal del registro. Se describen los resultados mas relevantes, a criterio de los autores, concernientes a las caracteristicas clinicas acumuladas, nivel de actividad, tratamientos, refractariedad, dano y mortalidad. Se revisan asimismo los resultados de analisis especificos sobre el lupus incompleto, la nefritis lupica, las manifestaciones respiratorias, los eventos cardiovasculares, las infecciones graves, las neoplasias, la fibromialgia, el lupus en varones, el lupus en latinoamericanos y el lupus de inicio juvenil, comparando los diferentes subgrupos con el total de la cohorte. RELESSER se ha constituido como uno de los registros clinicos de lupus eritematoso sistemico mas importantes del mundo, resultando altamente productivo en terminos de generacion de conocimiento de la enfermedad en pacientes espanoles, util tambien para toda la comunidad cientifica. EnglishThe lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors’ perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

Objective Anatomical risk factors predisposing to ACL (anterior cruciate ligament) and/or avulsion fractures of tibial spines (AFET) have been reported in paediatric patients with controversial results. Our aim is to compare morphometric parameters in magnetic resonance imaging (MRI) of patients with immature skeleton presenting AFET or ACL rupture versus healthy controls. Methods Observational study of a transverse cohort where all those patients with immature skeleton presenting ACL rupture or AFET were collected consecutively. A control group of patients with open physis and MRI reported without lesions was added. A trained observer measured in each MRI with previously standardized technique: (A) the width of the intercondylar femoral notch, (B) the opening angle of the intercondylar femoral notch. Results The sample was composed of 11 patients with ACL rupture, 11 patients with TEA and 11 normal controls. The opening angle of the intercondylar femoral notch, measured in axial and coronal sections, was significantly lower in those patients with ACL rupture versus healthy controls (p = .0256 and p = .0097). The rest of the variables studied did not present significant differences between groups. Conclusion In patients with an immature skeleton, a narrower femoral intercondylar notch is associated with ACL rupture, while those with an ETF do not present a distinctive bone anatomy versus healthy controls. These findings suggest that bone morphometric parameters are associated with a lesional or other pattern in open-knee.

The lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors' perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

OBJECTIVES To ascertain whether systemic administration of mitochondria-rich fraction isolated from mesenchymal stromal cells would reduce lung, kidney, and liver injury in experimental sepsis. DESIGN Animal study. SETTING Laboratory investigation. SUBJECTS Sixty C57BL/6 male mice. INTERVENTIONS Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. At 24 hours after surgery, cecal ligation and puncture and Sham animals were further randomized to receive saline or mitochondria-rich fraction isolated from mesenchymal stromal cells (3 × 106) IV. At 48 hours, survival, peritoneal bacterial load, lung, kidney, and liver injury were analyzed. Furthermore, the effects of mitochondria on oxygen consumption rate and reactive oxygen species production of lung epithelial and endothelial cells were evaluated in vitro. MEASUREMENTS AND MAIN RESULTS In vitro exposure of lung epithelial and endothelial cells from cecal ligation and puncture animals to mitochondria-rich fraction isolated from mesenchymal stromal cells restored oxygen consumption rate and reduced total reactive oxygen species production. Infusion of exogenous mitochondria-rich fraction from mesenchymal stromal cells (mitotherapy) reduced peritoneal bacterial load, improved lung mechanics and histology, and decreased the expression of interleukin-1β, keratinocyte chemoattractant, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in lung tissue, while increasing keratinocyte growth factor expression and survival rate in cecal ligation and puncture-induced sepsis. Mitotherapy also reduced kidney and liver injury, plasma creatinine levels, and messenger RNA expressions of interleukin-18 in kidney, interleukin-6, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in liver, while increasing nuclear factor erythroid 2-related factor-2 and superoxide dismutase-2 in kidney and interleukin-10 in liver. CONCLUSIONS Mitotherapy decreased lung, liver, and kidney injury and increased survival rate in cecal ligation and puncture-induced sepsis.

Background: In WDM networks, there is a crucial need to monitor signal degradation factors in order to maintain the quality of transmission. This is more critical in dynamic optical networks as non-linear impairments are network state dependent. Moreover, PLIs are accumulative in nature, so the overall impact is increased tremendously as the length of signal path is increased. The interactions between different impairments along the path also influence their overall impact. Objective: Among the different impairments, the present work focuses on phase modulations owing to the intensities of signals themselves as well as the neighboring signals. It includes the influence of SPM, SPM and XPM, system parameters like signal power, wavelength and fiber parameters like attenuation coefficient, dispersion coefficient and their influence on Q-value and BER. Methods: The analysis is done through a single and two-channel transmitter system with varied power, wavelengths and system parameters. The corresponding optical spectrums are analysed. Results & Conclusion: It has been found that SPM and XPM pose broadening effect on spectrum without any effect on temporal distributions. The magnitude of signal power is among the parameters significantly influencing the broadening of spectrum. The higher the power, the more the magnitude of broadening. It has been found that in order to neglect the impact of input power; its magnitude must be kept below 20 mW. Also, the dispersion and attenuation value need to be carefully as they pose counteracting effect to SPM and XPM for certain values and hence can be used as compensation measures without any additional cost.

Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction.We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction.Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period.SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs.None.For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Background Some traditional single-leg squat tests focused on number of repetitions may not demand precise control of lower limb dynamic alignment, especially in the frontal and transverse planes. The primary objective of this study was to evaluate test–retest reliability and construct validity of a novel single-leg squat test – the ‘precision-squat test’ (PST) – designed to assess performance under varying task demands that can impact the execution of lower limb movements. A secondary objective was to investigate whether musculoskeletal factors predict performance in the PST in healthy individuals. Methods Thirty healthy participants were assessed to verify test–retest reliability. To verify the test’s construct validity, we compared the performance of 21 anterior cruciate ligament reconstructed (ACLR) individuals and 21 matched controls. Finally, 36 healthy individuals were assessed to verify the musculoskeletal factors related to PST performance. All participants performed the PST: they executed single-leg squats while moving a laser pointer (attached to the thigh) between two targets. We varied target size and distance between targets to manipulate the task difficulty. Results Reliability of the PST was excellent at all demand levels (intraclass correlation coefficient (ICC)(3,2) > 0.93). Squat time increased under test conditions involving higher task difficulty (P Conclusions PST is a valid and reliable tool to assess performance of healthy and ACLR individuals. In addition, hip and knee strength are associated with performance during the test.

Individuals with neuromotor disabilities demonstrate motor control patterns characterized by a decreased capacity to adapt to contextual change. Task-oriented training is one promising intervention...

La teoría de solución de problemas de inventiva (TRIZ), es el resultado del análisis minucioso de patentes a nivel mundial, forma parte de un sistema de principios y algoritmos donde se amplifica la posibilidad de encontrar soluciones innovadoras a problemas científicos, superando la inercia psicológica basada en paradigmas. El presente trabajo propone un análisis biológico utilizando la herramienta analítica TRIZ con el uso del Análisis Campo-Sustancia (Su-Field) originalmente destinado a resolver problemas de ingeniería para determinar el efecto antagónico de Trichoderma asperelloides frente a Fusarium, patógeno presentado en plantas de cítricos encontrando como el resultado final ideal el uso de T. asperelloides como agente de control patógeno en plantas de cítricos (Citrus sinensis) en el norte de Veracruz, México.

Physical activity is an important part of clinical assessment. However, objective measurement can be expensive and burdensome. The current study validated a single activity question for use in clinical assessment. Ninety-seven older women (mean age = 73.7 years, SE = 0.7) completed an activity questionnaire and measurement of anthropometrics, body composition, and strength. Activity level was reported as not active , somewhat active , active , and very active . Activity level was significantly related to hours of light, moderate, and vigorous activity; body mass index (BMI); waist circumference; percent fat and lean mass; and strength ( p < 0.05). When activity levels were collapsed into two groups (not active + somewhat active, and active + very active), women in the high activity group ( n = 48) were significantly ( p < 0.05) more active, had healthier BMI and waist circumference values, less fat and more lean mass, and were stronger than women in the low activity group ( n = 49). A single activity question is valid for use in clinical assessment. [ Journal of Gerontological Nursing, 46 (12), 15–22.]

On the Ground • We surveyed residents across Oklahoma about their awareness of prescribed fire. • Most respondents expressed support for prescribed fire for managing rangelands. • Although there was support for prescribed fire, few individuals implemented it. • Of the several reasons given for not burning, the most common were lack of training, lack of equipment, and choosing not to burn.

Methylmercury (MeHg) intoxication is associated with hypertension, hypercholesterolemia, and atherosclerosis by mechanisms that are not yet fully understood. We investigated the effects of MeHg intoxication in atherosclerosis-prone (ApoE-KO) and resistant C57BL/6 mice. Mice were submitted to carotid stenosis surgery (to induce atherosclerosis faster) and received water or MeHg solution (20 mg/L) for 15 days. Tail plethysmography was performed before and after MeHg exposure. Food and MeHg solution intakes were monitored weekly. On the 15th day, mice were submitted to intravital fluorescence microscopy of mesenteric vasculature to observe in vivo leukocyte rolling and adhesion. Results showed that despite the high hair and liver Hg concentrations in the MeHg group, food and water (or MeHg solution) consumption and liver function marker levels were similar to those in controls. MeHg exposure increased total cholesterol, the atherogenic (non-HDL) fraction and systolic and diastolic blood pressure. MeHg exposure also induced inflammation, as seen by the increased rolling and adhered leukocytes in the mesenteric vasculature. Atherosclerosis lesions were more extensive in the aorta and carotid sites of MeHg-ApoE knockout mice. Surprisingly, MeHg exposure also induced atherosclerosis lesions in C57BL/6 mice, which are resistant to atherosclerosis formation. We concluded that MeHg intoxication might represent a risk for cardiovascular diseases since it accelerates atherogenesis by exacerbating several independent risk factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s43188-020-00066-x) contains supplementary material, which is available to authorized users.

The University causes changes in the lifestyles of academics, during graduation and after graduation. Many do not work in the area that was graduated and some even do not finish college, today it is a reality observed in all higher education courses and some cases intensified due to the size of the hours and other peculiarities. In view of this premise, we sought to identify the influence of the dynamics of the Agronomic Engineering Course at the State University of Mato Grosso, New Xavantina campus on why students drop out of college, and feedback from those who have already graduated. Evaluate the professional perspective of the labor market by trained students. To observe the motivational factors in the avoidance of graduates in the course of agronomy. Analyze the trajectories of professional development throughout the university experience that lead to different expectations and ways of preparing for the job market. A questionnaire was applied through innovative teaching approaches using Web 2.0 tools, in particular Google Docs, "forms". The questionnaire link was provided by email, SMS, Facebook, Instagran and WhatsApp to the target audience. It is concluded that the evasion in the University of Mato Grosso State Nova Xavantina campus occurred for three reasons: the agronomy course was the second choice of the academic, and the lack of knowledge of the course and support of family members. Based on the perspectives of post-graduates, one can conclude that: (1) the greatest difficulty was to obtain employment, (2) about 81% are working in their training area, (3) the agronomy course was the first option of the trained students, that is, they began the course aware of the difficulties, and yet they persevered and concluded the course.

Objectives We hypothesized that a time-controlled adaptive ventilation strategy would open and stabilize alveoli by controlling inspiratory and expiratory duration. Time-controlled adaptive ventilation was compared with volume-controlled ventilation at the same levels of mean airway pressure and positive end-release pressure (time-controlled adaptive ventilation)/positive end-expiratory pressure (volume-controlled ventilation) in a Pseudomonas aeruginosa-induced pneumonia model. Design Animal study. Setting Laboratory investigation. Subjects Twenty-one Wistar rats. Interventions Twenty-four hours after pneumonia induction, Wistar rats (n = 7) were ventilated with time-controlled adaptive ventilation (tidal volume = 8 mL/kg, airway pressure release ventilation for a Thigh = 0.75-0.85 s, release pressure (Plow) set at 0 cm H2O, and generating a positive end-release pressure = 1.6 cm H2O applied for Tlow = 0.11-0.14 s). The expiratory flow was terminated at 75% of the expiratory flow peak. An additional 14 animals were ventilated using volume-controlled ventilation, maintaining similar time-controlled adaptive ventilation levels of positive end-release pressure (positive end-expiratory pressure=1.6 cm H2O) and mean airway pressure = 10 cm H2O. Additional nonventilated animals (n = 7) were used for analysis of molecular biology markers. Measurements and main results After 1 hour of mechanical ventilation, the heterogeneity score, the expression of pro-inflammatory biomarkers interleukin-6 and cytokine-induced neutrophil chemoattractant-1 in lung tissue were significantly lower in the time-controlled adaptive ventilation than volume-controlled ventilation with similar mean airway pressure groups (p = 0.008, p = 0.011, and p = 0.011, respectively). Epithelial cell integrity, measured by E-cadherin tissue expression, was higher in time-controlled adaptive ventilation than volume-controlled ventilation with similar mean airway pressure (p = 0.004). Time-controlled adaptive ventilation animals had bacteremia counts lower than volume-controlled ventilation with similar mean airway pressure animals, while time-controlled adaptive ventilation and volume-controlled ventilation with similar positive end-release pressure animals had similar colony-forming unit counts. In addition, lung edema and cytokine-induced neutrophil chemoattractant-1 gene expression were more reduced in time-controlled adaptive ventilation than volume-controlled ventilation with similar positive end-release pressure groups. Conclusions In the model of pneumonia used herein, at the same tidal volume and mean airway pressure, time-controlled adaptive ventilation, compared with volume-controlled ventilation, was associated with less lung damage and bacteremia and reduced gene expression of mediators associated with inflammation.

TAGLINE: Eliminate Waste, Build Quality, Empower Team. Every construction project is characterized by being complex. Over the years, the efficiency and performance of the construction industry in the Philippines have been declining. Plus, the reality is that construction has been one of the largest polluters ever-since it started. This study proposes a plan of action that addresses these situations by introducing the concept of lean construction principles and value management. The purpose of this study is to integrate the sustainability of the construction industry in the Philippines. Sustainability was measured through triple-bottom-line. The paper explores the idea by reviewing different literatures to support theories and statements. It expands to measure the performances of the construction related to firms/companies in the Philippines, through four major categories, namely philosophy, process, people/partner and plant. The results were collected, analyzed and validated through different statistical treatments. For the last part, the researchers came up with a program that consisted of 20-suggested strategies which would help on eliminating waste, building quality and empowering team.

On 11 March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19) a pandemic. In recent months, with the spread of COVID-19, there has been growing interest in preventive...

Background Umbilical cord (UC) abnormalities are related to neurological outcome and death; specific molecular factors that might be involved are, as yet, unknown; however, protein-coding genes insulin-like growth factor 2 (IGF2) and cyclin-dependent kinase inhibitor 1C (CDKN1C) have been identified as potential candidates. Methods An analytical observational study was carried out. Newborn UCs were collected, along with their clinical and morphological features. Immunohistochemical analysis was made on paraffin-embedded sections and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in fresh UC tissue for the assessment of gene expression. Results A total of 100 newborns were included. A significant association was found between long UC and prematurity [odds ratio (OR) 9] and long UC and respiratory distress (OR 4.04). Gestational diabetes (OR 8.55) and hypertensive disorders of pregnancy (HDP) (OR 4.71) were found to be related to short UCs. The frequency for abnormal UC length was higher than expected. UC length was positively correlated with maternal, newborn and placental weight. No statistical association was found between IGF2 and CDKN1C (p57) expression and UC length; however, there was a tendency for higher CDKN1C expression in short UCs, while, on the contrary, higher IGF2 expression for long UCs. Conclusion UC length was observed to be associated with maternal and newborn complications. Protein expression, messenger RNA (mRNA) activity and the activity of said genes seem to be related to UC length.

A metrological framework for statistical analysis of number of layers and stacking order in mass-produced graphene using Raman spectroscopy is presented. The method is based on two complementary protocols, denominated by 2D and G. The 2D–protocol is based on the parameterized principal component analysis of the two-phonon 2D band, and it measures interlayer coupling. A neural-network algorithm for spectral denoising was also developed to improve the outcome. The G–protocol explores the intensity of the bond-stretching G band, and provides information about the number of layers. The method is suitable for automated statistical analysis of heterogeneous graphene-based systems with relatively low computational cost, as shown here for graphene flakes prepared by the liquid-phase exfoliation of graphite.

Summary Among the many disparities for which Brazil is known is the difference in performance across students who attend the three administrative levels of Brazilian public schools: federal, state and municipal. Our main goal is to investigate whether student performance in the Brazilian Mathematical Olympics for Public Schools is associated with school administrative level and student gender. For this, we propose a hurdle hierarchical beta model for the scores of students who took the examination in the second phase of these Olympics, in 2013. The mean of the beta model incorporates fixed and random effects at the student and school levels. We explore different distributions for the random school effect. As the posterior distributions of some fixed effects change in the presence, and distribution, of the random school effects, we also explore models that constrain random school effects to the orthogonal complement of the fixed effects. We conclude that male students perform slightly better than female students and that, on average, federal schools perform substantially better than state or municipal schools. However, some of the best municipal and state schools perform as well as some federal schools. We hypothesize that this is due to individual teachers who successfully motivate and prepare their students to perform well in the mathematical Olympics.

This paper introduces a data-driven method to compute voltage magnitude, and power loss sensitivity coefficients in unbalanced low voltage network with high photovoltaic (PV) distributed generation penetration. Implementation of the proposed method is based on the Least-Squares estimator and does not require knowledge of network model parameters, but only requires measurement of voltage magnitude, active, and reactive power. To overcome the data collinearity problem, the sensitivity coefficients are estimated using ridge regression. To track changes in the network operating conditions, the coefficients are updated using the Recursive Least-Squares and to avoid instability in the estimation process during low excitation periods, the method uses the concept of directional forgetting in which old data are discarded only when new information are available. Effectiveness of the proposed method is demonstrated by a case study where the impact of active and reactive power injection is estimated. Besides that, it is also shown how sensitivity coefficients can be useful to establish how each photovoltaic inverter can contribute to set a cooperative control, by achieving losses minimization and ensuring voltage level within limits set by the standards.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury. Methods Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with VT, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar VT; secondary outcomes were lung and diaphragm damage. Results At VT = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 ± 2.2 vs. 8.0 ± 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 ± 0.6 vs. 7.0 ± 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-α) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased VT, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation. Conclusions In the mild lung injury model use herein, at the same VT, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.

The scope of the present research aims at demonstrating the 3D printing use in the manufacturing of microchannels for chemical process applications. A comparison among digital model processing applications for 3D print (slicers) and a print layer thickness analysis were performed. The 3D print fidelity was verified in several devices, including the microchannels' printing with and without micromixer zones. In order to highlight the 3D print potential in Chemical Engineering, the biodiesel synthesis was also carried out in a millireactor manufactured by 3D printing. The millireactor operated under laminar flow regime with a total flow rate of 75.25 ml ∙ min−1 (increment of about 130 times over traditional microdevices used for biodiesel production). The printed millireactor provided a maximum yield of Ethyl Esters of 73.51% at 40 °C, ethanol:oil molar ratio of 7 and catalyst concentration of 1.25 wt% and residence time about 10 s. As a result of flow rate increment attained in the millireactor, the number of required units for scaling-up the chemical processes is reduced. Using the approach described in the present research, anyone could produce their own millireactor for chemical process in a simple way with the aid of a 3D printer.

Background: Muscle provides a reservoir for water to maintain fluid volume and blood pressure, so older adults may be at risk for orthostatic hypotension due to muscle loss with age. Objectives: To evaluate the association between muscle loss with age and postural blood pressure. Design: Longitudinal comparison of overnight changes in hydration, postural blood pressure, and strength. Setting: Community field study. Participants: Sixty-nine men and women (76.0 ± 0.8 years) with low (Low) or normal (Normal) muscle based on the Lean Mass Index. Measurements: Body composition was measured with bioelectrical impedance analysis. Postural blood pressure was measured sequentially (lying, sitting, standing). Strength was measured with a handgrip dynamometer, Arm Curl test, and Chair Stand test. Results: On Day 1, Low had less hydration and a significant drop in postural systolic blood pressure compared to Normal (lying to standing: -11.06 ± 2.36 vs. +1.14 ± 2.20 mmHg, p < 0.001). Overnight, both groups lost significant total body water, while fluid volume was unchanged. On Day 2, both groups experienced significant drops in postural systolic blood pressure, although the drop in Low was more profound and significantly greater than Normal (lying to standing: -16.85 ± 2.50 vs. -3.89 ± 2.52 mmHg, p = 0.001). On both days, Normal compensated for postural changes with increases in postural diastolic blood pressure not observed in Low. Only Low experienced significant overnight decreases in all strength measures. Conclusions: In older men and women, muscle loss with age is accompanied by loss of hydration and less stable early morning postural systolic blood pressure that increase risk for orthostatic hypotension and can also increase risk for falls.

Breast cancer image fusion consists of registering and visualizing different sets of a patient synchronized torso and radiological images into a 3D model. Breast spatial interpretation and visualization by the treating physician can be augmented with a patient-specific digital breast model that integrates radiological images. But the absence of a ground truth for a good correlation between surface and radiological information has impaired the development of potential clinical applications. A new image acquisition protocol was designed to acquire breast Magnetic Resonance Imaging (MRI) and 3D surface scan data with surface markers on the patient’s breasts and torso. A patient-specific digital breast model integrating the real breast torso and the tumor location was created and validated with a MRI/3D surface scan fusion algorithm in 16 breast cancer patients. This protocol was used to quantify breast shape differences between different modalities, and to measure the target registration error of several variants of the MRI/3D scan fusion algorithm. The fusion of single breasts without the biomechanical model of pose transformation had acceptable registration errors and accurate tumor locations. The performance of the fusion algorithm was not affected by breast volume. Further research and virtual clinical interfaces could lead to fast integration of this fusion technology into clinical practice., Highlights • MRI/3D surface scan fusion algorithm to create 3D breast cancer models. • A replicable clinical validation protocol for MRI/3D surface scan fusion algorithms. • Anthropometric study that quantifies breast deformations by area in MRI and 3D scans.

Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome.We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.73 mPatients randomized to bardoxolone methyl experienced preservation in eGFR relative to placebo at 48 and 100 weeks (between-group differences: 9.2 [97.5% confidence interval, 5.1 to 13.4;In adolescent and adult patients with Alport syndrome receiving standard of care, treatment with bardoxolone methyl resulted in preservation in eGFR relative to placebo after a 2-year study period; off-treatment results using all available data were not significantly different.A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome - CARDINAL (CARDINAL), NCT03019185.

Introduction: Pharmacotherapy for the acute respiratory distress syndrome (ARDS) has been tested in preclinical and clinical studies. However, to date, no pharmacological interventions have proven effective. This may be attributed to lack of proper identification of different ARDS phenotypes.Areas covered: We designed inclusive search strings and searched four bibliographic databases (Cochrane Database of Systematic Reviews, PubMed, Web of Science, and clinicaltrials.gov) to identify relevant research. Search results were mainly restricted to papers published from 2009 through 2019. ARDS is a heterogeneous syndrome, and its different phenotypes - defined according to clinical, radiological, and biological parameters - may affect response to therapy. The most promising pharmacological approaches to date have been based on ARDS pathophysiology. They focus on reducing inflammation and pulmonary edema, promoting selective vasodilation, and repairing alveolar epithelial and endothelial cells.Expert opinion: Pharmacotherapeutic approaches targeting ARDS pathophysiology have failed to exert beneficial effects. Personalized medicine targeting the different ARDS phenotypes has emerged as an option to improve survival. Identification of specific ARDS patient phenotypes that respond to specific therapies seems to be the most important challenge for the next decade. Additional research is warranted before personalized medicine approaches can be applied at bedside for ARDS patients.

Background: Early recurrence of Plasmodium vivax is a challenge for malaria control in the field, particularly because this species is associated with lower parasitemia, which hinders diagnosis and monitoring through blood smear testing. Early recurrences, defined as the persistence of parasites in the peripheral blood despite adequate drug dosages, may arise from resistance to chloroquine. The objective of the study was to estimate early recurrence of P. vivax in the Brazilian Amazon by using a highly-sensitive detection method, in this case, PCR. Methods: An ultra-sensitive qPCR that targeted mitochondrial DNA was used to compare a standard qPCR that targeted 18S rDNA to detect early recurrence of P. vivax in very low densities in samples from patients treated with chloroquine. Results: Out of a total of 312 cases, 29 samples (9.3%) were characterized as recurrences, from which 3.2% (10/312) were only detected through ultra-sensitive qPCR testing. Conclusions: Studies that report the detection of P. vivax early recurrences using light microscopy may severely underestimate their true incidence.

Assessing construction project performance through adapting an innovative approach can multiply the production of high-quality project outputs which is a catalyst to the socio-economic progress of a country. Preliminary data collection was employed through a meta-cognitive analysis of reviewing related literature which directs to the backbone of qualitative information that is relevant to the periodically experienced construction performance-influencing factors and to develop an assessment questionnaire about the influencing factors affecting the project performance. The IBM SPSS program was used to verify the reliability and consistency of the fundamental statistics of the questionnaire responses of cost, time and quality performance ratings. A predictive mathematical model was developed for forecasting cost, time, and quality performance rating employing Levenberg-Marquardt training algorithm with Hyperbolic Tangent Sigmoid function. The prediction model result shows a highly satisfying performance on its variance from the substantive values and suggests a high correlation between these values. The relative importance of the factors affecting the cost, time, and quality performance rating was calculated via sensitivity analysis through connection weights using Garson’s Algorithm to view the order of influence of the parameters that have great significance to the success of a project.

The construction process and construction management are highly reliant on the interaction between the triple constraints of project management of quality: scope, time, and cost. The industry has incorporated certain principles and technology, such as lean-based construction principles and Building Information Modeling (BIM), to maximize the time, quality, and cost-efficiency of various construction projects. Analysis and assessment of the factors and functionalities are needed to show their synergic relationships and determine their significant impact on the construction project using Structural Equation Modeling (SEM). To gather information, a survey was conducted on the different construction companies in the Philippines. The results generated a model interrelating the triple constraints of project management and how they are affected by incorporating BIM and lean construction principles. The models created established a significant relationship towards all the tripe constraints considering both individual and combined functionalities and factors. An interdisciplinary framework incorporating both BIM and lean principles is conformed to optimize construction stages based on the triple constraints of project management.

Management competencies are skills that incorporate the understanding, proficiencies and qualities essential for successful performance. Individuals in the top of the organizational hierarchy presents himself being an effective leader by immersing to a readily difficult activity in the project. Molding the important management competencies was found to be hard since the efficacy of a competent construction manager is dependent on countless administrative aspects. The current study intended to offer a construction management competency for human resource development in construction companies. Utilizing this competency model, the company could increase its performance capacity and productivity. This study developed a competency theory and a hybrid predictive model with specific foci on construction managers. The Management Competency Framework Assessment Instrument was developed, following an approach through factor-item analytic mode. Furthermore, this research constructs a predictive performance model using Artificial Neural Network through the factors associated to successful management performance. A sensitivity analysis was also implemented to assess the relative importance of individual factors to the effective construction performance.

The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin (STZ)-injected rats, but much less data exist for models of type 2 diabetes (T2DM). Diabetic polyuria has been proposed to explain bladder enlargement. We have collected data on bladder weight and blood glucose from 16 studies representing 9 distinct rodent diabetes (7 T2DM) and obesity models; some included arms with diets and/or pharmacological treatments. Data were analyzed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargements in STZ rats, minor if any enlargement in fructose-fed rats, db/db mice and mice on a high-fat diet. For the first time we report bladder weight data on 5 other models with presence and degree of bladder enlargement being heterogeneous across models. Bladder weight was correlated with plasma glucose in some but not other models, but correlations were moderate to weak except for RIP-LMCV mice. We conclude that the presence and extent of bladder enlargement varies markedly across diabetes models, particularly TD2M models; our data do not support the idea that bladder enlargement is primarily driven by glucose levels/glucosuria.

Aims NELA has been instrumental at improving perioperative care and 30–day mortality following emergency laparotomy (EmLap); long-term outcomes and follow-up are less well reported. This study aims to establish the unscheduled and scheduled service use of EmLap patients after discharge. Methods This is a single-centre service evaluation. Patients were included if they had an EmLap recorded from 2016-2019 at our local institute and were alive on discharge. Outcomes were 30-day readmission rate and outpatient follow-up. Results 944 patients were included. 11.9% re-presented to the surgical department within 30-days; 58.0% of these needed readmissions. The most common causes for re-presentation (n = 112) were management of a wound issue (15.2%), ongoing pain without evidence of complication (10.7%) and ongoing intra-abdominal sepsis (9.8%). 1-year survival was 81.4%. Of these (n = 856); 74.3% were invited to outpatients; DNA rate was 8.8%, with only 67.8% of patients having a follow-up review. Median time to follow up was 9 weeks. Patients were more likely to be invited for outpatient review if they had a new stoma (OR 2.56, 95% CI 1.81 – 3.56), and less likely if adhesiolysis was the primary procedure (OR 0.55, 95% 0.39-0.76). Patients who failed to attend an appointment were significantly younger (median age 53 vs. 60 years, p = 0.0033) and from more deprived areas (average WIMD 673.6 vs 977.3, p = 0.002). Conclusion This study demonstrates higher levels of unscheduled care and lower levels of scheduled care than expected. Care standards should be extended beyond the 30-day milestone to fully appreciate the morbidity associated from EmLap.

Aims The COVID-19 pandemic necessitated introduction of revised diagnostic pathways for assessing Urgent Suspected Cancer (USC) referrals. Combinations of FIT and MPCT were used to manage referrals and prioritise access to clinical services or invasive tests. The effectiveness of these pathways are evaluated in this study. Methods All consecutive patients referred from primary care on the USC pathway between 15th March – 15th June 2020 were included to reflect the effect of full lockdown measures. Data collected included demographics, presenting symptom(s), investigations and timelines and patient outcomes up to 90 days following initial referral. Results 816 patients across 8 sites in Wales were included in this initial analysis. 52.7% of patients were female with median age 69 (21 – 97) years. Of the 50.7% who had first-line clinical review, 70.5% were virtual consultations. 49.3% had primary investigations, with FIT in 31% of patients and MPCT in 18.3%. This was compliant with locally agreed pathways for 77.3% of referrals. COVID-response pathways achieved a 28.5% reduction in use of colonoscopy as first-line investigation and 84.3% of patients avoided face-to-face consultations altogether during this first wave of the pandemic. Overall, 5.6% of USC referrals were diagnosed with CRC. Median timescale from diagnosis to treatment for CRC was 82 (4 – 175) days. The NPV for FIT in this cohort was 99.5%. MPCT as the first modality had a NPV of 99%. Conclusion A modified investigation pathway maintained cancer diagnosis during the pandemic with improved resource utilisation to that used previously.

Importance Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures The primary end point was 90-day survival. Results Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11;P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration ClinicalTrials.gov Identifier:NCT02875873