The Upper Cretaceous Bauru Group deposits furnished several species of Crocodylomorpha, especially notosuchians. However, little is known about the feeding habits of this diverse group of ...crocodylomorphs. The dental histology is a destructive approach that can provide important information on tooth growth and feeding habits of fossil vertebrates. So far, few studies dealt with crocodylomorph dental histology and the ones available mainly focused on fossil and living neosuchians. In this work, we analyse the dental histology of three notosuchians commonly found in the Upper Cretaceous rocks of the Bauru Group: juvenile and adult Baurusuchidae, a large Sphagesauridae, and Mariliasuchus amarali. Our analyses indicate that tooth formation varied in these three taxa. In Mariliasuchus, a tooth took less than 2 months to be completely grown. On the other hand, in Sphagesauridae and Baurusuchidae, the tooth formation could take about 6 months to be completed. Mariliasuchus and Sphagesauridae have proportionally thicker enamel in comparison to Baurusuchidae. Additionally, the enamel thickness and its substantial development in the chewing area in Sphagesauridae indicate that apical advanced notosuchians are more adapted to process food items than more basal forms like Mariliasuchus.
Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by ...controlling a robot arm through a closed-loop brain-machine interface (BMIc) that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles) from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations.
We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small ...lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio HR 95% CI, 0.206 0.159-0.265; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.
To investigate whether the wide variation in the frequency of bronchopulmonary dysplasia (BPD) between hospitals is due to differences in delivery room intubation rates.
Data on 1260 infants of birth ...weight <1500 g and 23-31 weeks gestational age, born in 1999-2002 and surviving to 36 weeks, were collected; 196 (15.6%) developed BPD defined as oxygen need at 36 weeks postmenstrual age. Generalised estimating equations and conditional logistic models adjusting for centre, gestational age, propensity score for intubation, and other potential confounders were used.
Rates of BPD, delivery room intubation and mechanical ventilation for >24 h differed significantly between hospitals. Centres with high delivery room intubation rates had higher ventilation and BPD rates. Hospitals ventilating more often also did so for a longer time. Although delivery room intubation was associated with BPD in unadjusted analyses, neither delivery room intubation nor brief (<24 h) mechanical ventilation were risk factors for BPD in multivariate analyses adjusting for gestational age, case mix and other pre- and perinatal factors, indicating no causal effect or unmeasured confounding. Significant risk factors for developing BPD were low gestational age, prolonged ventilation (>24 h: adjusted OR (aOR) 2.4; >7 days: aOR 14.9), male sex (aOR 1.7), being small for gestational age (SGA; aOR 4.3) and late-onset sepsis (aOR 2.2). After taking into account these variables/procedures, centre differences remained significant but explained only about 5% of variance.
Differences in BPD frequency between hospitals are explained by differences in procedures, chiefly mechanical ventilation, rather than by differences in initial management or case mix. Delivery room intubation and brief mechanical ventilation did not increase BPD risk.
The first in this series of five papers concerns the evaluation and management of renal injuries. The authors of this paper come from four continents and seven countries, and they reviewed all papers ...on renal injury published between 1966 and April 2002. The results of the authors’ deliberations are present here as a consensus document.
OBJECTIVE
To determine the optimal evaluation and management of renal injuries by review of the world's English‐language literature on the subject.
METHODS
A consensus conference convened by the World Health Organization and the Societé Internationale d’Urologie met to critically review reports of the diagnosis and treatment of renal trauma. The English‐language literature about renal trauma was identified using Medline, and additional cited works not detected in the initial search obtained. Evidence‐based recommendations for the diagnosis and management of renal trauma were made with reference to a five‐point scale.
RESULTS
There were many Level 3 and 4 citations, few Level 2, and one Level 1 which supported clinical practice patterns. Findings of nearly 200 reviewed citations are summarized.
CONCLUSIONS
Published reports on renal trauma still rely heavily on expert opinion and single‐institution retrospective case series. Prospective trials of the most significant issues, when possible, might improve the quality of evidence that dictates the behaviour of practitioners.
Lifelines play a crucial and essential role in human life and in economic development. The resilience of those systems under extreme events as earthquakes is a primary requirement, especially when ...large amount of toxic and flammable material are transported.
In this work, the seismic vulnerability of buried gas and liquid pipelines has been analyzed, starting from a large number of damage data to pipelines collected from post-earthquake reconnaissance reports.
Seismic fragility formulations and threshold values for the earthquake intensity with respect to the release of content from different types of pipelines have been derived. The main outcome of the work is therefore a novel seismic assessment tool which is able to cover the needs of industrial risk assessment procedures and land use planning requirements.
•The seismic vulnerability of buried gas and liquid pipelines is analyzed.•Damage states and risk states are defined.•Fragility functions for the vulnerability of pipelines are given.•Probit functions for the analysis of damage with respect to the seismic intensity are given.•Seismic threshold values for risk assessment and gas distribution are shown.
To investigate the behavior of circulating endothelin (ET)-1 concentrations in patients affected by systemic sclerosis, and to elucidate the possible relationships existing in this disease among ...plasma peptide levels, pulmonary hypertension, and lung fibrosis.
Circulating ET-1 levels were determined by reverse-phase, high-pressure liquid chromatography followed by sensitive radioimmunoassay in 20 patients affected by systemic sclerosis (18 women and 2 men, mean age 48.1 +/- 13.7 years) with or without pulmonary hypertension as evaluated by Doppler echocardiography, or lung fibrosis as measured by a score method based on lung examination by high-resolution computed tomography (HRCT). A group of 18 normal volunteers served as controls (15 women and 3 men, mean age 45.0 +/- 10.1 years).
Plasma ET-1 levels were significantly higher (P < 0.001) in patients with systemic sclerosis (1.72 +/- 0.28 pg/mL) than in control subjects (0.63 +/- 0.06 pg/mL). Pulmonary artery systolic hypertension was detected in 10 patients (50%) with systemic sclerosis (56.2 +/- 18.0 mm Hg, range 37 to 97) versus none of the control subjects (30.2 +/- 2.2 mm Hg, P < 0.0001). Lung fibrosis was present in 12 patients (60%), with an HRCT overall score of 9.0 +/- 4.6. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension (1.58 +/- 0.20 pg/mL) or without it (1.76 +/- 0.39 pg/mL, P = 0.188, not significant NS); or between patients with lung fibrosis (1.65 +/- 0.14 pg/mL) or without fibrosis (1.78 +/- 0.37 pg/mL, P = 0.290, NS). In particular, 6 patients had neither pulmonary hypertension nor lung fibrosis. In these patients, plasma ET-1 levels were similar compared with the others (1.85 +/- 0.49 versus 1.66 +/- 0.13, respectively; P = 0.180, NS). No correlations were observed between ET-1 levels and either pulmonary pressure levels or HRCT overall scores.
The use of a sensitive assay, highly selective for ET-1, showed higher levels of circulating peptide in patients affected by systemic sclerosis than in control subjects. Neither pulmonary hypertension nor lung fibrosis was accompanied by a further rise in plasma ET-1 concentrations.
Neutrophil extracellular traps (NET) expose modified antigens for autoantibodies in vasculitis. Little is known about levels and removal pathways of NET in systemic lupus erythematosus (SLE), ...especially in lupus nephritis (LN). We determined circulating levels and defined NET removal in large subsets of patients with incident SLE (iSLE), some of whom had new-onset nephritis.
Serum levels of NET (ELISA), DNase1/DNase1L3 (ELISA), and DNase activity (functional assay) were determined in 216 patients with iSLE 103 had incident LN (iLN), in 50 patients with other primary glomerulonephritis, and in healthy controls.
NET production by neutrophils purified from a random selection of patients was quantified as elastase/DNA release and by immunofluorescence techniques.
Serum NET levels were very high in iSLE/iLN compared to all groups of controls and correlated with anti-dsDNA, C3-C4, and proteinuria; iLN had the highest levels. DNase activity was decreased in iLN compared to SLE (20% had one-half DNase activity) despite similar serum levels of DNase1/DNase1L3. In these cases, pretreatment of serum with protein A restored DNase efficiency; 1 patient was homozygous for a c.289_290delAC variant of
.
NET production by neutrophils purified from LN, SLE, and normal controls was similar in all cases.
Patients with iLN have increased circulating NET and reduced DNase activity, the latter being explained by the presence of inhibitory substances in circulation and/or by rare
mutations. Accumulation of NET derives from a multifactorial mechanism, and is associated and may contribute to disease severity in SLE, in particular to renal lesions. (Clinical trial registration: The Zeus study was registered at ClinicalTrials.gov, study number NCT02403115).
Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain.
To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared ...with medical therapy (MT) alone.
Randomized clinical trial. (ClinicalTrials.gov: NCT01784848).
Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil.
Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m
were randomly assigned (1:1 ratio).
RYGB plus MT or MT alone.
The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg).
Among 100 patients (76% female; mean BMI, 36.9 kg/m
SD, 2.7), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 95% CI, 2.50 to 17.03;
0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (
0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B
and 2 patients required reoperation.
Single-center, nonblinded trial.
RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity.
Ethicon, represented in Brazil by Johnson & Johnson do Brasil.
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