A pharmacokinetic study of lipegfilgrastim in children with Ewing family of tumors or rhabdomyosarcoma

Abstract

Purpose

Neutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose of lipegfilgrastim and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy.

Methods

Enrolled patients received lipegfilgrastim (100 µg/kg) 24 h after the last chemotherapy treatment in week 1. Patients were stratified into three age groups: 2 to <6, 6 to <12, and 12 to <18 years. Blood samples for PK analyses were obtained at baseline and at 3, 8, 24, 30, 48, 72, 96, 144, and 240 h postdose for the two oldest groups and up to 144 h in the youngest group.

Results

Twenty-one patients were enrolled and received lipegfilgrastim, seven in each age group. Lipegfilgrastim exposure levels were comparable across age groups, with concentrations maintained over a prolonged period after a single injection. Differences in PD were mainly associated with chemotherapy type. Most investigator-reported adverse events were attributed to chemotherapy and not to lipegfilgrastim. Severe adverse events were noted in 57% of patients; febrile neutropenia, leukopenia, neutropenia, and thrombocytopenia were more frequent among the oldest patients.

Conclusions

Results support the use of a body weight-adjusted dose to achieve equivalent initial peak exposure levels of lipegfilgrastim in children of various ages.

http://ift.tt/2gShEXF

Life cycle environmental impacts of saffron production in Iran

Abstract

Saffron is regarded as an important crop in Iranian agricultural economics that needs to be investigated to produce the environmentally friendlier product. In the present study, saffron production as an important agricultural production system in Iran was evaluated thoroughly from an environmental point of view. Data were collected from saffron farmers in Southern Khorasan province of the country with face-to-face questionnaire method during cropping period of 2013–2014. The system boundary was considered from the production of raw input materials to the harvested saffron. In order to identify the main hotspot during cultivation, impact categories were considered using CML methodology and cumulative exergy demand (CExD) indicator. Based on the results, chemical fertilizers N and P were the main hotspots in abiotic depletion (AD), acidification (AC), global warming (GWP), and photochemical oxidation (PO) impact categories, while diesel fuel was the main hotspot in fresh water aquatic ecotoxicity (FE), marine aquatic ecotoxicity (ME), and terrestrial ecotoxicity (TE). Direct emission from diesel fuel combustion (saffron) was the main hotspot only in human toxicity (HT). The small farms had the highest amounts of AD, AC, EP, GWP, and PO indicators in comparison with the medium and large farms. Total CExD indicator for production of 1 kg saffron was 1894.23 MJ eq. Totally, large farms (bigger than 1 ha) had better environmental performance considering all the impact categories.

http://ift.tt/2gTenYe

Influence of the soil sealing on the geoaccumulation index of heavy metals and various pollution factors

Abstract

Soil sealing belongs to the most destructive and damaging processes to the soil environment. Soil sealing interrupts or greatly restricts the exchange of matter and energy between the biosphere, hydrosphere, and atmosphere and the soil environment. The aim of this study was to compare the content of heavy metals (Cd, Cr, Cu, Hg, Fe, Ni, Pb, Zn) of Ekranic Technosols by applying indicators such as geoaccumulation index (I _geo), enrichment factor (EF), and pollution load index (PLI), which allowed to determine quantitatively the impact of the soil sealing degree on the content of heavy metals and to distinguish natural from anthropogenic sources of origin of heavy metals. In general, 42 soils from different parts of the city of Toruń (NW Poland) were sampled and divided into three groups according to the degree of soil sealing: completely sealed with asphalt or concrete (A), semi-permeable (partially sealed with cobblestones and concrete paving slabs (B)), and reference (non-sealed) (C). The results indicate that the artificial sealing in urban areas slightly affects the content of heavy metals in soils. However, based on PLI, I _geo, and EF, it was found that the sealing has influence on soil properties and unsealed soil is the most exposed to the accumulation of pollutants.

http://ift.tt/2gTcL0M

The fate and transport of arsenic species in the aquatic ecosystem: a case study on Bestari Jaya, Peninsular Malaysia

Abstract

The field of arsenic pollution research has grown rapidly in recent years. Arsenic constitutes a broad range of elements from the Earth's crust and is released into the environment from both anthropogenic and natural sources due to its relative mobility under different redox conditions. The toxicity of arsenic is described in its inorganic form, as inorganic arsenic compounds can leach into different environments. Sampling was carried out in the Bestari Jaya catchment while using a land use map to locate the site, and experiments were conducted via sequential extraction and inductively coupled plasma optical emission spectroscopy to quantify proportions of arsenic in the sediment samples. The results show that metals in sediments of nonresidual fractions, which are more likely to be likely released into aquatic environments, are more plentiful than the residual sediment fractions. These findings support the mobility of heavy metals and especially arsenic through sediment layers, which can facilitate remediation in environments heavily polluted with heavy metals.

http://ift.tt/2h9ArK5

Photo-Fenton and Fenton-like processes for the treatment of the antineoplastic drug 5-fluorouracil under simulated solar radiation

Abstract

In the present study, photo-Fenton and Fenton-like processes were investigated for the degradation and mineralization of the antineoplastic drug 5-fluorouracil (5-FU). For the optimization of photo-Fenton treatment under simulated solar light (SSL) radiation, the effects of several operating parameters (i.e., 5-FU concentration, Fe³⁺, and oxidant concentration) on the treatment efficiency were studied. According to the results, SSL/[Fe(C₂Ο₄)₃]³⁻/Η₂Ο₂ process was the most efficient, since faster degradation of 5-FU and higher mineralization percentages were achieved. All the applied processes followed quite similar transformation routes which include defluorination-hydroxylation as well as pyrimidine ring opening, as demonstrated by the transformation products identified by high resolution mass spectrometry analysis. The toxicity of the treated solutions was evaluated using the Microtox assay. In general, low toxicity was recorded for the initial solution and the solution at the end of the photocatalytic treatment, while an increase in the overall toxicity was observed only at the first stages of SSL/Fe³⁺/Η₂Ο₂ and SSL/Fe³⁺/S₂O₈²⁻ processes.

http://ift.tt/2h9Bz0o

Variations in root morphology among 18 herbaceous species and their relationship with cadmium accumulation

Abstract

This study aims to investigate whether root system morphology is involved in the interspecific variations in Cd accumulation in herbaceous plants. Biomasses, root morphology, and Cd accumulation of 18 herbaceous species were determined under 0, 2, and 10 mg kg⁻¹ Cd conditions. Significant variations were found in biomass production, root system morphology, and Cd accumulation among the 18 species. Cd concentrations in the shoot had negative correlations with the biomass of roots and shoots in the 2 mg kg⁻¹ Cd treatment. Total amounts of Cd in plants showed positive correlations with the biomass of roots and shoots, total root lengths, root surface areas, root volumes, and proportions of the fine roots (diameter <0.2 mm). Percentages of Cd in shoots were positively related to specific root lengths, root surface areas, and plant biomasses but negatively correlated with proportions of roots in the 0.6–0.8-mm diameter class. High-biomass species (rapeseed, Indian mustard, and four-o'clock) have high Cd uptake capacity due to their large root system. Longer and thinner roots might contribute to higher capacity for transferring Cd from roots to shoots, while coarse roots (i.e., diameter of 0.6–0.8 mm) could retain more Cd in the tissues and, consequently, reduce Cd transfer from roots to shoots.

http://ift.tt/2gTiO5h

Disability-adjusted life years and economic cost assessment of the health effects related to PM 2.5 and PM 10 pollution in Mumbai and Delhi, in India from 1991 to 2015

Abstract

Particulate air pollution is becoming a serious public health concern in urban cities in India due to air pollution-related health effects associated with disability-adjusted life years (DALYs) and economic loss. To obtain the quantitative result of health impact of particulate matter (PM) in most populated Mumbai City and most polluted Delhi City in India, an epidemiology-based exposure–response function has been used to calculate the attributable number of mortality and morbidity cases from 1991 to 2015 in a 5-year interval and the subsequent DALYs, and economic cost is estimated of the health damage based on unit values of the health outcomes. Here, we report the attributable number of mortality due to PM₁₀ in Mumbai and Delhi increased to 32,014 and 48,651 in 2015 compared with 19,291 and 19,716 in year 1995. And annual average mortality due to PM_2.5 in Mumbai and Delhi was 10,880 and 10,900. Premature cerebrovascular disease (CEV), ischemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD) causes are about 35.3, 33.3, and 22.9% of PM_2.5-attributable mortalities. Total DALYs due to PM10 increased from 0.34 million to 0.51 million in Mumbai and 0.34 million to 0.75 million in Delhi from average year 1995 to 2015. Among all health outcomes, mortality and chronic bronchitis shared about 95% of the total DALYs. Due to PM₁₀, the estimated total economic cost at constant price year 2005 US$ increased from 2680.87 million to 4269.60 million for Mumbai City and 2714.10 million to 6394.74 million for Delhi City, from 1995 to 2015, and the total amount accounting about 1.01% of India's gross domestic product (GDP). A crucial presumption is that in 2030, PM₁₀ levels would have to decline by 44% (Mumbai) and 67% (Delhi) absolutely to maintain the same health outcomes in year 2015 levels. The results will help policy makers from pollution control board for further cost–benefit analyses of air pollution management programs in Mumbai and Delhi.

http://ift.tt/2h9xUQl

Perturbations and 3R in carbon management

Abstract

Perturbations in various carbon pools like biological, geological, oceanic, and missing carbon sink affect its global data, which are generally neglected or ignored in routine calculations. These natural and anthropogenic events need to be considered before projecting a sustainable carbon management plan. These plans have both general and experimental aspects. General plans should focus on (a) minimizing emission; (b) maximizing environmentally sound reuse, reduce, and recycling; (c) effective treatment; and (d) converting carbon into valuable products with atom economy. Experimental carbon management plans involving various biological and chemical techniques with limitation in terms of research level and economic feasibility. Chemical options have benefits of higher productivity and wider product range, but it suffers from its higher-energy requirements and environmental unfriendliness. In contrast to this, biological options are more selective and less energy intensive, but their productivity is very low. Hence, there is a requirement of hybrid process where the benefits of both the options, i.e., biological and chemical, can be reaped. In view of above, the proposed review targets to highlight the various perturbations in the global carbon cycle and their effects; study the currently practiced options of carbon management, specifically in light of 3R principle; and propose various new hybrid methods by compatible combinations of chemical and biological processes to develop better and safer carbon management. These methods are hypothetical so they may require further research and validations but may provide a comprehensive base for developing such management methods.

http://ift.tt/2gTcBGF

Intraoral scanners – The FAQs

British Dental Journal 221, 803 (2016). doi:10.1038/sj.bdj.2016.961

David Claridge, CAD/CAM Product Specialist at Carestream Dental, addresses the key FAQs he is most often faced with when it comes to intraoral scanners.

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What's in a name? Nominative determinism in the UK dental workforce

British Dental Journal 221, 773 (2016). doi:10.1038/sj.bdj.2016.950

Author: J. Sleigh

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Oral health: Case report: Unusual sugar binge

British Dental Journal 221, 744 (2016). doi:10.1038/sj.bdj.2016.929

Author: K. Quinlan

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Diamante filling material

British Dental Journal 221, 806 (2016). doi:10.1038/sj.bdj.2016.966

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On your marks, get set... ROT!

British Dental Journal 221, 744 (2016). doi:10.1038/sj.bdj.2016.930

Author: B. T. H. E. Grincher

http://ift.tt/2gJJVLc

Gastrointestinal diseases and their oro-dental manifestations: Part 1: Crohn's disease

British Dental Journal 221, 794 (2016). doi:10.1038/sj.bdj.2016.954

Authors: C. X. W. Tan, H. S. Brand, N. K. H. de Boer & T. Forouzanfar

http://ift.tt/2gJNjG0

Working conditions: Elfless hard labour

British Dental Journal 221, 745 (2016). doi:10.1038/sj.bdj.2016.931

Author: B. Elf

http://ift.tt/2gJN51o

An oral health routine yule love

British Dental Journal 221, 805 (2016). doi:10.1038/sj.bdj.2016.962

http://ift.tt/2gJOpSh

Dental trauma: Ho, ho, hospitalised

British Dental Journal 221, 745 (2016). doi:10.1038/sj.bdj.2016.932

Author: D. Kay

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Christmas White Paper

British Dental Journal 221, 743 (2016). doi:10.1038/sj.bdj.2016.928

Author: Stephen Hancocks

http://ift.tt/2gJJror

Infection control: Mistletoe threat

British Dental Journal 221, 745 (2016). doi:10.1038/sj.bdj.2016.933

Author: A. Bore

http://ift.tt/2gJSSEf

Motivational interviewing in general dental practice: A review of the evidence

British Dental Journal 221, 785 (2016). doi:10.1038/sj.bdj.2016.952

Authors: E. J. Kay, D. Vascott, A. Hocking & H. Nield

http://ift.tt/2gJFUX6