Update on Bone Grafting Materials Used in Dentistry in the Bone Healing Process: Our Experience from Translational Studies to Their Clinical Use

The use of bone grafts is important to preserve the alveolar bone ridge height and volume indispensable for dental implant placement. Despite the highly successful outcomes for the implant-supported overdentures, it seems that a majority of edentulous individuals have not pursued implant-based rehabilitation. Among the reasons cited for this, discrepancy between highly successful therapy and its acceptance is the cost of the treatment. Therefore, the development of biomaterials for bone grafting with comparable characteristics and biological effects than those renowned internationally is necessary. In addition, domestic manufacture would reduce the high costs in public health arising from the application of these biomaterials in the dental field. The aim of the following chapter is to offer an update on one bone grafting material frequently used in dentistry through an assessment of anorganic bovine bone graft in small and medium experimental models as well as its clinical use

Preparation and characterization of micro-nano engineered targets for high-power laser experiments

[EN] The continuous development of ultra-fast high-power lasers (HPL) technology with the ability of working at unprecedented repetition rates, between 1 and 10 Hz, is raising the target needs for experiments in the different areas of interest to the HPL community. Many target designs can be conceived according to specific scientific issues, however to guarantee manufacturing abilities that enable large number production and still allow for versatility in the design is the main barrier in the exploitation of these high repetition rate facilities. Here, we have applied MEMS based manufacturing processes for this purpose. In particular, we have focused on the fabrication and characterization of submicrometric conductive membranes embedded in a silicon frame. These kinds of solid targets are used for laser-driven particle acceleration through the so-called Target Normal Sheath Acceleration mechanism (TNSA). They were obtained by top-down fabrication alternating pattern transfer, atomic layer deposition, and selective material etching. The adaptability of the approach is then analyzed and discussed by evaluating different properties of targets for use in laser-driven particle acceleration experiments. These characteristics include the surface properties of membranes after fabrication and the high density of the target array. Finally, we were able to show their efficiency for laser-driven proton acceleration in a series of experiments with a 3 TW table-top laser facility, achieving stable proton acceleration up to 2 MeV.The authors highly appreciate the collaboration of Radosys (Budapest) which provided CR-39 detector material, etching bath, and readout equipment. This project has been financed by the Spanish Ministry for Economy and Competitiveness within the Retos-Colaboracion 2015 initiative, ref. RTC-2015-3278-1. P. Mur has received a grant of the Garantia Juvenil 2015 program. This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MEINCOM.Zaffino, R.; Seimetz, M.; Quirión, D.; Ruiz-De La Cruz, A.; Sánchez, I.; Mur, P.; Benlliure, J.... (2018). Preparation and characterization of micro-nano engineered targets for high-power laser experiments. Microelectronic Engineering. 194:67-70. https://doi.org/10.1016/j.mee.2018.03.011S677019

Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries

IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS:The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES:Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS

Correction: Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

[This corrects the article DOI: 10.1371/journal.pbio.3001480.]

Kinematics of Ten Early-Type Galaxies from HST and Ground-Based Spectroscopy

We present stellar kinematics for a sample of 10 early-type galaxies observed using the STIS aboard the Hubble Space Telescope, and the Modular Spectrograph on the MDM Observatory 2.4-m telescope. The spectra are used to derive line-of-sight velocity distributions (LOSVDs) of the stars using a Maximum Penalized Likelihood method. We use Gauss-Hermite polynomials to parameterize the LOSVDs and find predominantly negative h4 values (boxy distributions) in the central regions of our galaxies. One galaxy, NGC 4697, has significantly positive central h4 (high tail weight). The majority of galaxies have a central velocity dispersion excess in the STIS kinematics over ground-based velocity dispersions. The galaxies with the strongest rotational support, as quantified with v_MAX/sigma_STIS, have the smallest dispersion excess at STIS resolution. The best-fitting, general, axisymmetric dynamical models (described in a companion paper) require black holes in all cases, with masses ranging from 10^6.5 to 10^9.3 Msun. We replot these updated masses on the BH/sigma relation, and show that the fit to only these 10 galaxies has a slope consistent with the fits to larger samples. The greatest outlier is NGC 2778, a dwarf elliptical with relatively poorly constrained black hole mass. The two best candidates for pseudobulges, NGC 3384 and 7457, do not deviate significantly from the established relation between black hole and sigma. Neither do the three galaxies which show the most evidence of a recent merger, NGC 3608, 4473, and 4697.Comment: 43 pages, accepted for publication in the Astrophysical Journal, high resolution version found at http://hoku.as.utexas.edu/~gebhardt/pinkney.p

Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense

Infectious diseases have been paramount among the threats to health and survival throughout human evolutionary history. Natural selection is therefore expected to act strongly on host defense genes, particularly on innate immunity genes whose products mediate the direct interaction between the host and the microbial environment. In insects and mammals, the Toll-like receptors (TLRs) appear to play a major role in initiating innate immune responses against microbes. In humans, however, it has been speculated that the set of TLRs could be redundant for protective immunity. We investigated how natural selection has acted upon human TLRs, as an approach to assess their level of biological redundancy. We sequenced the ten human TLRs in a panel of 158 individuals from various populations worldwide and found that the intracellular TLRs—activated by nucleic acids and particularly specialized in viral recognition—have evolved under strong purifying selection, indicating their essential non-redundant role in host survival. Conversely, the selective constraints on the TLRs expressed on the cell surface—activated by compounds other than nucleic acids—have been much more relaxed, with higher rates of damaging nonsynonymous and stop mutations tolerated, suggesting their higher redundancy. Finally, we tested whether TLRs have experienced spatially-varying selection in human populations and found that the region encompassing TLR10-TLR1-TLR6 has been the target of recent positive selection among non-Africans. Our findings indicate that the different TLRs differ in their immunological redundancy, reflecting their distinct contributions to host defense. The insights gained in this study foster new hypotheses to be tested in clinical and epidemiological genetics of infectious disease

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding