The 16 EPA PAHs have played an exceptionally large role above all in environmental and analytical sciences in the last 40 years, but now there are good reasons to question their utility in many ...circumstances even though their use is so established and comfortable. Here we review the reasons why the list has been so successful and why sometimes it is seen as less relevant. Three groups of polycyclic aromatic compounds (PAC) are missing: larger and highly relevant PAHs, alkylated PACs, and compounds containing heteroatoms. Attempts to improve the situation for certain matrixes are known and here: (1) an updated list of PAHs (including the 16 EPA PAHs) for the evaluation of the toxicity in the environment (40 EnvPAHs); (2) a list of 23 NSO-heterocyclic compounds and 6 heterocyclic metabolites; and (3) lists of 10 oxy-PAHs and 10 nitro-PAHs are proposed for practical use in the future. A discussion in the scientific community about these lists is invited. Although the state of knowledge has improved dramatically since the introduction of the 16 EPA PAHs in the 1970s, this summary also shows that more research is needed about the toxicity, occurrence in the environment and chemical analysis, particularly of alkylated PAHs, higher molecular weight PAHs and substituted PACs such as amino-PAHs, cyano-PAHs, etc.. We also suggest that a long overdue discussion of an update of regulatory environmental PAH analysis is initiated.
The chemical group of polycyclic aromatic compounds (PAC), including the better-known subgroup of polycyclic aromatic hydrocarbons (PAH) and the heterocyclic aromatic compounds (NSO-PAC, ...heterocycles), comprise several thousand individual compounds. It is hard to find a comprehensive overview in the literature of these PACs that includes a substantial amount of relevant properties. Here an attempt is made to summarize the most studied but also some less well-known PACs. In addition to basic data such as recommended names, abbreviations, CAS numbers, molecular formulas, chemical structures, and exact mono-isotopic molecular weights, physico-chemical properties taken from the literature like boiling points, vapor pressures, water solubilities, Henry's Law constants, n-octanol-water partition coefficients (log K
OW
), and pK
a
are summarized. Selected toxicological data are listed indicating carcinogenic and mutagenic activity or effects on different organisms.
PAC nomenclature is a complex topic, so suggestions for practical use are made. Regarding available data, estimated (instead of measured) values should be used with caution because considerable deviations from experimentally determined values can occur. For an enhanced understanding of the behavior of single PACs in comparison with each other, some of the properties mentioned above are plotted vs. the number of rings or the degree of alkylation. Also, some physico-chemical data are correlated with different functional groups as substituents of the PAHs.
This article reveals that rather little is known about the less common PACs, e.g., higher molecular weight compounds, alkylated or otherwise substituted aromatics, for instance, keto-, oxo-, amino-, nitro-, cyano-PAHs, or some heterocyclic aromatic compounds, including their derivatives. It mirrors the limited state of knowledge about the variety of PACs that do not belong to the 16 EPA PAHs.
Background
The reported incidence of Philadelphia‐negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence ...and/or variations in the quality and coverage of the cancer registers.
Objective
We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers.
Methods
Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age‐standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated.
Results
A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000–2014. The age‐standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval CI 4.34–4.56)/100 000 person‐years. The age‐standardized incidence for polycythemia vera was 1.48 (1.42–1.54), for essential thrombocythemia 1.60 (1.53–1.66) and for primary myelofibrosis 0.52 (0.48–0.56)/100 000 person‐years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population.
Conclusion
The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population‐based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.
This article investigates potentials and environmental impacts related to household food waste minimization, based on a case study in Southern Sweden. In the study, the amount of avoidable and ...unavoidable food waste currently being disposed of by households was assessed through waste composition analyses and the different types of avoidable food waste were classified. Currently, both avoidable and unavoidable food waste is either incinerated or treated through anaerobic digestion. A hypothetical scenario with no generation of avoidable food waste and either anaerobic digestion or incineration of unavoidable food waste was compared to the current situation using the life-cycle assessment method, limited to analysis of global warming potential (GWP). The results from the waste composition analyses indicate that an average of 35% of household food waste is avoidable. Minimization of this waste could result in reduction of greenhouse gas emissions of 800–1400 kg/tonne of avoidable food waste. Thus, a minimization strategy would result in increased avoidance of GWP compared to the current situation. The study clearly shows that although modern alternatives for food waste treatment can result in avoidance of GWP through nutrient and energy recovery, food waste prevention yields far greater benefits for GWP compared to both incineration and anaerobic digestion.
•Data from detailed waste composition analyses of household food waste are presented.•A division of avoidable and unavoidable household food waste is proposed.•On average, 35% of the Swedish household food waste is avoidable.•The carbon footprint from avoidable food waste reaches 800–1400 kg/ton.
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In this study, the use of cubosomes for topical delivery of the antimicrobial peptide (AMP) LL-37 was investigated. Topical delivery of AMPs is of great interest for treatment of skin ...infections caused by bacteria, such as Staphylococcus aureus. AMP containing cubosomes were produced by three different preparation protocols and compared: (i) pre-loading, where LL-37 was incorporated into a liquid crystalline gel, which thereafter was dispersed into nanoparticles, (ii) post-loading, where LL-37 was let to adsorb onto pre-formed cubosomes, and (iii) hydrotrope-loading, where LL-37 was incorporated during the spontaneously formed cubosomes in an ethanol/glycerol monooleate mixture. Particle size and size distribution were analyzed using dynamic light scattering (DLS), liquid crystalline structure by small angle x-ray scattering (SAXS) and release of LL-37 by a fluorescamine assay. Proteolytic protection of LL-37 as well as bactericidal effect after enzyme exposure was investigated. The skin irritation potential of cubosomes was examined by an in vitro epidermis model. Finally, the bacterial killing property of the cubosomes was examined by an ex vivo pig skin wound infection model with Staphylococcus aureus. Data showed that a high loading of LL-37 induced formation of vesicles in case of cubosomes prepared by sonication (pre-loading). No release of LL-37 was observed from the cubosomes, indicating strong association of the peptide to the particles. Proteolysis studies showed that LL-37 was fully protected against enzymatic attacks while associated with the cubosomes, also denoting strong association of the peptide to the particles. As a consequence, bactericidal effect after enzyme exposure remained, compared to pure LL-37 which was subjected to proteolysis. No skin irritation potential of the cubosomes was found, thus enabling for topical administration. The ex vivo wound infection model showed that LL-37 in pre-loaded cubosomes killed bacteria most efficient.
Monitoring survival of cancer patients using data collected by population‐based cancer registries is an important component of cancer control. In this setting, patient survival is often summarized ...using net survival, that is survival from cancer if there were no other possible causes of death. Although net survival is the gold standard for comparing survival between groups or over time, it is less relevant for understanding the anticipated real‐world prognosis of patients. In this review, we explain statistical concepts targeted towards patients, clinicians and healthcare professionals that summarize cancer patient survival under the assumption that other causes of death exist. Specifically, we explain the appropriate use, interpretation and assumptions behind statistical methods for competing risks, loss in life expectancy due to cancer and conditional survival. These concepts are relevant when producing statistics for risk communication between physicians and patients, planning for use of healthcare resources, or other applications when consideration of both cancer outcomes and the competing risks of death is required. To reinforce the concepts, we use Swedish population‐based data of patients diagnosed with cancer of the breast, prostate, colon and chronic myeloid leukaemia. We conclude that when choosing between summary measures of survival it is critical to characterize the purpose of the study and to determine the nature of the hypothesis under investigation. The choice of terminology and style of reporting should be carefully adapted to the target audience and may range from summaries for specialist readers of scientific publications to interactive online tools aimed towards lay persons.
High resolution MALDI MS in combination with solvent free sample preparation was employed to characterize a petroleum pitch and a coal tar pitch. The elemental formulas of thousands of mass ...spectrometric peaks were assigned according to the accurate masses. Large polycyclic aromatic hydrocarbons (LPAHs) were found to be the major components in the complex mixtures. Iso-abundance plots were introduced to sort and visualize the molecular constituents into different types based on the carbon and double bond equivalence (DBE) numbers. The differences between the petroleum pitch and the coal tar pitch could be easily observed by comparing their iso-abundance plots. LPAHs in the investigated petroleum pitch possess broad carbon number and DBE number distributions and there is no significant change in the signal intensity between even and odd carbon numbered LPAH species. On the contrary, a smaller variety of carbon number and DBE number distribution of LPAH species is found in the investigated coal tar pitch and LPAHs with even carbon numbers are present in a significantly higher amount in comparison to the odd numbered species. Ion mobility mass spectrometry was used to differentiate the petroleum pitch from coal tar pitch and provides additional molecular size information of complex pitch samples.
It is increasingly argued that public management should build on a service logic instead of the prevailing manufacturing logic of New Public Management (NPM). Drawing from three cases in Swedish ...public healthcare, key features of a service logic such as value creation, co-production, and collaboration are prominent in formal documents and everyday talk. However, the 67 interviews in this study reveal that the service logic ideal is practically unreachable in a context impregnated by NPM. Instead, we suggest that street-level bureaucrats often need to address service logic expectations (public values, relationship-building, etc.) using an NPM logic (measurements, control, etc.).
Essentials
Limited data on hemostatic benefits of platelet transfusion (PT) exist.
44 healthy subjects had a single dose of ticagrelor or clopidogrel ± autologous PT post‐dosing.
PT did not reverse ...ticagrelor's antiplatelet effects and had minimal impact post clopidogrel.
Post‐ticagrelor, PT is unlikely to be beneficial, and the benefits post‐clopidogrel are unknown.
Summary
Background
Antiplatelet agents increase bleeding risk. Few data on hemostatic benefits of platelet transfusion exist.
Objective
To assess the effect of autologous platelet transfusion on ticagrelor‐mediated and clopidogrel‐mediated platelet inhibition in a single‐center, open‐label, randomized, cross‐over study (NCT01744288).
Methods
Forty‐four healthy subjects received ticagrelor (180 mg) or clopidogrel (600 mg; two functional CYP2C19 alleles *1 or *17 required) with or without platelet transfusion (14‐day washout). Subjects received one autologous platelet apheresis unit (approximately six pooled donor platelet units) 24 h (n = 15) or 48 h (n = 13) after ticagrelor or 48 h after clopidogrel (n = 16). Platelet apheresis was conducted 72 h before transfusion. Aspirin (81 mg per day) was taken from after apheresis until 24 h before transfusion. P2Y12 reaction units (PRUs) and inhibition of platelet aggregation (IPA) induced by ADP were measured.
Results
Mean age and body mass index were 30 years (standard deviation SD 6 years) and 26.9 kg m−2 (SD 4.0 kg m−2), respectively; 98% of subjects were men, and 39 of 44 completed treatment. Platelet transfusion 24 h after ticagrelor had minimal effects on IPA or PRU values within 48 h after transfusion. Platelet transfusion 48 h after ticagrelor also had minimal effects on IPA or PRU values at most post‐transfusion times. Platelet transfusion 48 h after clopidogrel, versus no transfusion, had a small reversing effect on IPA (24 h, 36 h, and 48 h) and PRU values (12 h, 24 h, and 36 h) after transfusion.
Conclusions
Autologous platelet transfusion is unlikely to be of clinical benefit in reversing the antiplatelet effects of ticagrelor. The clinical relevance of the small effects seen with clopidogrel is unknown.
Ximelagatran was the first orally available direct thrombin inhibitor under clinical development that also reached the market. Ximelagatran was tested in an extensive clinical programme. Short-term ...use (<12 days) in humans including the phase III clinical trials did not indicate any hepatotoxic potential. Increased hepatic enzyme levels were first observed at a higher frequency when evaluating the long-term (>35 days) use of ximelagatran (incidence of >3× upper limit of normal (ULN) plasma ALT was 7.9%). The frequency of elevated total bilirubin levels was similar in the ximelagatran and the comparator groups. However, the combination of ALT > 3×ULN and total bilirubin >2×ULN was 0.5% among patients treated with ximelagatran and 0.1% among patients in the comparator group. Symptoms such as fever and rash potentially indicating hypersensitivity (immunologic type of reaction) were low and did not differ between ximelagatran and the comparators. The withdrawal of ximelagatran from the market and termination of the ximelagatran development program was triggered by safety data from a 35-day study, indicating that severe hepatic injury in a patient could develop after exposure to the drug has been completed and that regular liver function monitoring may not mitigate the possible risk of severe hepatic injury. As for many drugs causing liver injury, the standard preclinical toxicological studies provided no indication that ximelagatran affected hepatic functions. In addition, extensive investigations using human-based in vitro models have not been able to define mechanisms explaining the pattern of hepatic injury observed in long-term clinical trials. A pharmacogenomic study provided evidence that the ALT increases were associated with major histocompatibility complex (MHC) alleles DRB1’07 and DQA1*02 suggesting a possible immunogenic pathogenesis. This example provides important clues to the mechanism of idiosyncratic drug-induced liver toxicity.
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