Efficacy and safety of deferasirox at low and high iron burdens: results from the EPIC magnetic resonance imaging substudy

The effect of deferasirox dosing tailored for iron burden and iron loading based on liver iron concentration (LIC) was assessed over 1 year in less versus more heavily iron-overloaded patients in a substudy of the Evaluation of Patients' Iron Chelation with ExjadeA (R). Deferasirox starting dose was 10-30 mg/kg/day, depending on blood transfusion frequency, with recommended dose adjustments every 3 months. Therapeutic goals were LIC maintenance or reduction in patients with baseline LIC < 7 or a parts per thousand yen7 mg Fe/g dry weight (dw), respectively. Changes in LIC (R2-magnetic resonance imaging) and serum ferritin after 1 year were assessed. Adverse events (AEs) and laboratory parameters were monitored throughout. Of 374 patients, 71 and 303 had baseline LIC < 7 and a parts per thousand yen7 mg Fe/g dw, respectively; mean deferasirox doses were 20.7 and 27.1 mg/kg/day (overall average time to dose increase, 24 weeks). At 1 year, mean LIC and median serum ferritin levels were maintained in the low-iron cohort (-0.02 A +/- 2.4 mg Fe/g dw, -57 ng/mL; P = not significant) and significantly decreased in the high-iron cohort (-6.1 A +/- 9.1 mg Fe/g dw, -830 ng/mL; P < 0.0001). Drug-related gastrointestinal AEs, mostly mild to moderate, were more frequently reported in the < 7 versus a parts per thousand yen7 mg Fe/g dw cohort (39.4 versus 20.8 %; P = 0.001) and were not confounded by diagnosis, dosing, ethnicity, or hepatitis B and/or C history. Reported serum creatinine increases did not increase in low- versus high-iron cohort patients. Deferasirox doses of 20 mg/kg/day maintained LIC < 7 mg Fe/g dw and doses of 30 mg/kg/day were required for net iron reduction in the high-iron cohort, with clinically manageable safety profiles. The higher incidence of gastrointestinal AEs at lower iron burdens requires further investigation

STUDY ON THE DISPOSAL OF WASTE FROM THE HYDROGEN GENERATION BY ALUMINUM OXIDATION IN ALKALINE SOLUTION

In face of the current high energy consumption and demand worldwide, a change to a sustainable energy matrix became one of the pillars for global sustainability. The use of renewable energy has been one of the most attractive subjects in recent years. Several public policies in this matter have been suggested and there are ongoing efforts toward their implementation. The United Nations (UN) proposed what is called the 2030 Agenda, which considers 17 Sustainable Development Goals (SDG) to be achieved by the year 2030. In support of the 2030 Agenda, research on the production of fuels from clean and sustainable sources is being conducted by the scientific community around the world. Fossil fuels are finite and also a major source of environmental pollutants, therefore the choice of using renewable sources of energy tends to be an increasingly growing and attractive alternative. Hydrogen is a fuel with a high heating value and is known as the most abundant gaseous element and simplest in chemical structure. The scientific community researching fuel cells has given much attention to the generation and storage of hydrogen. Besides the electrolytic hydrogen production and the reforming of fossil fuels (e.g., natural gas), hydrogen can be generated by metallic means, for example, by oxidation of aluminum in an alkaline solution. The use of recyclable metals, such as aluminum in this study, is an option for sustainable hydrogen generation processes. Nevertheless, like any chemical reaction, part of the products generated are waste, and some are even harmful to the environment, which makes the production of sustainable fuels unfeasible in case of not finding an appropriate technological industrial destination for such waste. The herein study comprises the investigation of the industrial and technological applications of the products of the hydrogen generation reaction from aluminum. Mastering the chemical reaction parameters of that reaction is paramount for the optimal design of a hydrogen generation system. The disposal of the waste is relevant since it makes the energy supply chain complete and sustainable

MICROALGAE BIOPOLYMERS: A REVIEW

Algae are ubiquitous organisms whose capabilities have drawn much attention as of late in the bioengineering field due to their potential to enable a wide range of bioproducts. Microalgae are ideal organisms for the application of the biorefinery concept since they can be grown in wastewater and, at the same time, produce many products of commercial interest. These microorganisms are also known for their resilience to extreme environmental conditions and suitable cell growth rates. Beyond the known potential for biofuel production, these microorganisms can still produce other compounds, being lipids, pigments, vitamins, proteins, and polysaccharides, whose applications go from pharmaceutical to agricultural industries. Recently, the research focus has been directed to the biopolymer-producing ability of both micro- and macroalgae, as they can be rather varied and useful to many applications. However, this is still an ongoing research field, and new data are frequently added in the literature, notably on biomass processing, which can be done with the intent of use into dyes, bioplastics, paints, and even as biochar in solid fuel cells. Microalgae-based biopolymers can be used in a wide range of products, nevertheless, the resulting process efficiency and yields depend on the extraction process utilized, as well as on the microalgae species used and the culture conditions. Furthermore, the polymer extraction can be done directly with common solvents at atmospheric pressure or with other fluids, such as supercritical CO2 or subcritical solvents, and assisted by specific treatments, e.g., ultrasound and microwave. The residual biomass can still be used to produce other less valuable products, such as feedstock, and energy via combustion. In this sense, the present work aims to provide a state-of-the-art review on microalgae biopolymers. Issues related to the efficiency of current treatment methods, industrial applications, and environmental performance are presented and discussed. Besides, the perspectives in this area of knowledge are also a contribution of the present work, the extent to which scientific research is still under development

Evaluation of the Universal Screening Strategy in Qatar for the Management of Pregnant Women Carrying Group B Streptococci

Group B Streptococcus infection (GBS) has emerged as a serious disease, infecting 18,000 people in the United States annually including life-threatening illness in about 8,000 newly-born infants. To evaluate the efficiency of the current universal screening strategy for the management of GBS carriers a retrospective analysis was made of the records of 1,620 pregnant women in Qatar, 550 of whom were found to be carriers. These latter were then used as a group to be compared with 450 uninfected pregnant women in terms of nationality, parity, age, treatment, and outcome. Young and nullipara pregnant women had a high incidence of GBS but there was no significant effect on birth mortality and morbidity regardless of whether or not they received treatment with antibiotics. It is suggested that the cost of screening for GBS at the 35 th week of gestation cannot be justified.qscienc

Language in India www.languageinindia.com 12 : 2 February 2012 Taher Bahrani and Rahmatollah Soltani An Overview on How to Utilize Authentic Language Input for Language Teaching 800 LANGUAGE IN INDIA Strength for Today and Bright Hope for Tomorrow An Over

Abstract Today, the application of various audiovisual mass media programs such as films and cartoons has gone beyond the boundaries of entertainment. As a matter of fact, various types of audiovisual programs can be used as a rich source of authentic language input for language teaching. The pedagogical values of authentic materials have been emphasized by many researchers. In fact, many researchers agree on the fact that authentic language input from various audiovisual programs has the potential to provide the necessary language input for language learning. In the same line, the present paper aims at highlighting the pedagogical values of films and cartoons as two types of programs which have the optimal potential to enhance language learning if they are utilized properly in language classrooms

Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: Protocol for a multicentre, international, prospective cohort study

Introduction Congenital anomalies are the fifth leading cause of death in children <5 years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally. Methods and analysis The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung''s disease). Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of postoperative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. Ethics and dissemination At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal

Systemic Delivery of an Adjuvant CXCR4-CXCL12 Signaling Inhibitor Encapsulated in Synthetic Protein Nanoparticles for Glioma Immunotherapy

Glioblastoma (GBM) is an aggressive primary brain cancer, with a 5 year survival of ∼5%. Challenges that hamper GBM therapeutic efficacy include (i) tumor heterogeneity, (ii) treatment resistance, (iii) immunosuppressive tumor microenvironment (TME), and (iv) the blood-brain barrier (BBB). The C-X-C motif chemokine ligand-12/C-X-C motif chemokine receptor-4 (CXCL12/CXCR4) signaling pathway is activated in GBM and is associated with tumor progression. Although the CXCR4 antagonist (AMD3100) has been proposed as an attractive anti-GBM therapeutic target, it has poor pharmacokinetic properties, and unfavorable bioavailability has hampered its clinical implementation. Thus, we developed synthetic protein nanoparticles (SPNPs) coated with the transcytotic peptide iRGD (AMD3100-SPNPs) to target the CXCL2/CXCR4 pathway in GBM via systemic delivery. We showed that AMD3100-SPNPs block CXCL12/CXCR4 signaling in three mouse and human GBM cell cultures in vitro and in a GBM mouse model in vivo. This results in (i) inhibition of GBM proliferation, (ii) reduced infiltration of CXCR4+ monocytic myeloid-derived suppressor cells (M-MDSCs) into the TME, (iii) restoration of BBB integrity, and (iv) induction of immunogenic cell death (ICD), sensitizing the tumor to radiotherapy and leading to anti-GBM immunity. Additionally, we showed that combining AMD3100-SPNPs with radiation led to long-term survival, with ∼60% of GBM tumor-bearing mice remaining tumor free after rechallenging with a second GBM in the contralateral hemisphere. This was due to a sustained anti-GBM immunological memory response that prevented tumor recurrence without additional treatment. In view of the potent ICD induction and reprogrammed tumor microenvironment, this SPNP-mediated strategy has a significant clinical translation applicability.Fil: Alghamri, Mahmoud S.. University Of Michigan Medical School; Estados UnidosFil: Banerjee, Kaushik. University Of Michigan Medical School; Estados UnidosFil: Mujeeb, Anzar A.. University Of Michigan Medical School; Estados UnidosFil: Mauser, Ava. University of Michigan; Estados UnidosFil: Taher, Ayman. University Of Michigan Medical School; Estados UnidosFil: Thalla, Rohit. University Of Michigan Medical School; Estados UnidosFil: McClellan, Brandon L.. University Of Michigan Medical School; Estados UnidosFil: Varela, Maria L.. University Of Michigan Medical School; Estados UnidosFil: Stamatovic, Svetlana M.. University Of Michigan Medical School; Estados UnidosFil: Martinez Revollar, Gabriela. University Of Michigan Medical School; Estados UnidosFil: Andjelkovic, Anuska V.. University Of Michigan Medical School; Estados UnidosFil: Gregory, Jason V.. University of Michigan; Estados UnidosFil: Kadiyala, Padma. University Of Michigan Medical School; Estados UnidosFil: Calinescu, Alexandra. University Of Michigan Medical School; Estados UnidosFil: Jiménez, Jennifer A.. University of Michigan; Estados UnidosFil: Apfelbaum, April A.. University of Michigan; Estados UnidosFil: Lawlor, Elizabeth R.. University of Washington; Estados UnidosFil: Carney, Stephen. University of Michigan; Estados UnidosFil: Comba, Andrea. University Of Michigan Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Faisal, Syed Mohd. University Of Michigan Medical School; Estados UnidosFil: Barissi, Marcus. University Of Michigan Medical School; Estados UnidosFil: Edwards, Marta B.. University Of Michigan Medical School; Estados UnidosFil: Appelman, Henry. University Of Michigan Medical School; Estados UnidosFil: Sun, Yilun. Case Western Reserve University; Estados UnidosFil: Gan, Jingyao. University of Michigan; Estados UnidosFil: Ackermann, Rose. University of Michigan; Estados UnidosFil: Schwendeman, Anna. University of Michigan; Estados UnidosFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Olin, Michael R.. University of Minnesota; Estados UnidosFil: Lahann, Joerg. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria G.. University of Michigan; Estados Unido

FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T_regs). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T_regsas a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated <it>in vitro </it>and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease.</p> <p>Methods</p> <p>Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease.</p> <p>Results</p> <p>A co-existence of B7-H1⁺T lymphocytes and FOXP3⁺T_regswas evidenced by the highly significant correlation of these molecules (<it>P </it>< .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3⁺T_regs, B7-H1⁺and PD-1⁺TIL synergistically correlated with high histological grade (III) (<it>P </it>< .001), estrogen receptor negative status (<it>P </it>= .017), and the presence of severe lymphocytic infiltration (<it>P </it>= .022).</p> <p>Conclusion</p> <p>Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T_regsand B7-H1/PD-1 molecules.</p

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&lt;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&lt;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