Fatigue in long-duration travel diaries

This paper introduces a new long-duration travel diary survey undertaken in a small town and rural environment, which complements the existing urban Mobidrive survey of 1999. Policy-making is dominated by the 1-day view of the world provided by the usual diaries. Long-duration surveys can balance this by highlighting the strong intrapersonal variance in choices, modes used and other aspects of travel behaviour. They also allow us to gain an understanding of the activity space of the travellers. The new 2003 Thurgau data followed the protocol of the earlier study, but developed the set of questions further. These new questions concerned the social context of respondents as well as trip-related items, such as planning horizon of the activity, previous frequency of visits or the groups involved in the trip or activity. The descriptive and model-based analysis of the data showed that respondent fatigue is not an issue in either survey. Where significant deviations from a steady number of reported trips were found, they showed positive tendencies, i.e. learning. The skill accrued in the intensive round of contacts between respondent and interviewer is significant. Papers on travel diaries tend not to report interviewer effects, although their impacts are clearly discernable. The analysis shows that the four interviewers employed in this survey had a substantial effect on the number of reported trip

Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles

Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano-delivery system for therapeutic nucleic acids. The great effort put in the development of ionizable lipids with increased in vivo potency brought LNPs from the laboratory benches to the FDA approval of patisiran in 2018 and the ongoing clinical trials for mRNA-based vaccines against SARS-CoV-2. Despite these success stories, several challenges remain in RNA delivery, including what is known as “endosomal escape.” Reaching the cytosol is mandatory for unleashing the therapeutic activity of RNA molecules, as their accumulation in other intracellular compartments would simply result in efficacy loss. In LNPs, the ability of ionizable lipids to form destabilizing non-bilayer structures at acidic pH is recognized as the key for endosomal escape and RNA cytosolic delivery. This is motivating a surge in studies aiming at designing novel ionizable lipids with improved biodegradation and safety profiles. In this work, we describe the journey of RNA-loaded LNPs across multiple intracellular barriers, from the extracellular space to the cytosol. In silico molecular dynamics modeling, in vitro high-resolution microscopy analyses, and in vivo imaging data are systematically reviewed to distill out the regulating mechanisms underlying the endosomal escape of RNA. Finally, a comparison with strategies employed by enveloped viruses to deliver their genetic material into cells is also presented. The combination of a multidisciplinary analytical toolkit for endosomal escape quantification and a nature-inspired design could foster the development of future LNPs with improved cytosolic delivery of nucleic acids

Nanosuspensions and microneedles roller as a combined approach to enhance diclofenac topical bioavailability

Topical application of the anti-inflammatory drug diclofenac (DCF) reduces the severity of systemic unwanted effects compared to its oral administration. A number of transdermal formulations are available on the market and routinely used in clinical and home-care settings. However, the amount of DCF delivered across the skin remains limited and often insufficient, thus making the oral route still necessary for achieving sufficient drug concentration at the inflamed site. In attempting to improve the transdermal penetration, we explored the combined use of DCF nanosuspensions with a microneedle roller. Firstly, DCF nanosuspensions were prepared by a top-down media milling method and characterized by spectroscopic, thermal and electron microscopy analyses. Secondly, the pore-forming action of microneedle rollers on skin specimens (ex vivo) was described by imaging at different scales. Finally, DCF nanosuspensions were applied on newborn pig skin (in vitro) in combination with microneedles roller treatment, assessing the DCF penetration and distribution in the different skin layers. The relative contribution of microneedle length, nanosuspension stabilizer and application sequence could be identified by systemically varying these parameters

特別支援教育専攻学生を対象とした障害理解のための教材開発(2)―糖尿病・血友病等の「自己注射」場面を中心にした教材―

　特別支援教育専攻学生の指導では、対象とする障害児・者が活用する機器・道具を提示し、その使用法の解説がなされてきた。これは感覚・情報系障害領域では指導上意義がある。また肢体不自由・運動障害系では、車イスや生活補助具、障害体験グッズなどが障害理解教材として活用されてきた。しかし病弱教育領域では、子どもの困難理解につながる「病気体験」は、健常学生にはできない。そこで教員は、病院見学、療養生活の映像資料等を活用し、病気の影響や困難をイメージさせる方法をとることが多い。本研究では糖尿病および血友病を例にとり、病気による「困難」を体験・体感させる教材について検討した。糖尿病・血友病の自己注射モデルを提示し、その作製・改善とそれを使用した授業経過を分析対象とした。学生による試作及び改良モデルは、自己注射実施時の困難・不安・躊躇を「体感」させることを目的としているが、作製過程そのものが、学生による困難・不安・躊躇といった自己注射実施を必要とする疾患のもつ障害特性の理解を促進することが推察された

Proceedings of the Merck & Elsevier Young Chemists Symposium (MEYCS 2018)

Dear participants, welcome to the 18th edition of the Merck & Elsevier Young Chemists Symposium, formerly SAYCS and MYCS. This conference is an international scientific event organized by the Young Group of the Italian Chemical Society (SCI Giovani) with the financial support of Merck and Elsevier. This symposium is fully devoted to young researchers, such as MSc and PhD students, post-doc fellows and young researchers in companies. All the disciplines of Chemistry are covered: analytical, physical, industrial, organic, inorganic, theoretical, pharmaceutical, biological, environmental, macromolecular and electrochemistry. This year, a special emphasis will be given to chemistry from knowledge to innovation: how chemistry is increasingly present in all of the fields that are essential for human life, and how chemical fundamentals are pushing novel technologies? This year we have the exceptional number of 212 participants; we thank you for the great trust shown towards SCI Giovani, Merck and Elsevier. Enjoy the conference

Polyphosphoester-stabilized cubosomes encapsulating a Ru(II) complex for the photodynamic treatment of lung adenocarcinoma

The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential of a cubosome formulation stabilized in water against coalescence utilizing a polyphosphoester analog of Pluronic F127 as a stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn)2(bpy-morph)](PF6)2 (bpy-morph = 2,2'-bipyridine-4,4'-diylbis(morpholinomethanone)), PS-Ru. The photophysical characterization of PS-Ru revealed its robust capacity to induce the formation of singlet oxygen (1O2). Furthermore, the physicochemical analysis of the PS-Ru-loaded cubosomes dispersion demonstrated that the encapsulation of the photosensitizer within the nanoparticles did not disrupt the three-dimensional arrangement of the lipid bilayer. The biological tests showed that PS-Ru-loaded cubosomes exhibited significant phototoxic activity when exposed to the light source, in stark contrast to empty cubosomes and to the same formulation without irradiation. This promising outcome suggests the potential of the formulation in overcoming the drawbacks associated with the clinical use of RPCs in photodynamic therapy for anticancer treatments

Textural variations in Neogene pelagic carbonate ooze at DSDP Site 593, southern Tasman Sea, and their paleoceanographic implications

Changes in Neogene sediment texture in pelagic carbonate-rich oozes on the Challenger Plateau, southern Tasman Sea, are used to infer changes in depositional paleocurrent velocities. The most obvious record of textural change is in the mud:sand ratio. Increases in the sand content are inferred to indicate a general up-core trend towards increasing winnowing of sediments resulting from increasing flow velocity of Southern Component Intermediate Water (SCIW), the forerunner of Antarctic Intermediate Water. In particular, the intervals c. 19-14.5 Ma, c. 9.5-8 Ma, and after 5 Ma are suggested to be times of increased SCIW velocity and strong sediment winnowing. Within the mud fraction, the fine silt to coarse clay sizes from 15.6 to 2 µm make the greatest contribution to the sediments and are composed of nannofossil plates. During extreme winnowing events it is the fine silt to very coarse clay material (13-3 µm) within this range that is preferentially removed, suggesting the 10 µm cohesive silt boundary reported for siliciclastic sediments does not apply to calcitic skeletal grains. The winnowed sediment comprises coccolithophore placoliths and spheres, represented by a mode at 4-7 µm. Further support for seafloor winnowing is gained from the presence in Hole 593 of a condensed sedimentary section from c. 18 to 14 Ma where the sand content increases to c. 20% of the bulk sample. Associated with the condensed section is a 6 m thick orange unit representing sediments subjected to particularly oxygen-rich, late early to early middle Miocene SCIW. Together these are inferred to indicate increased SCIW velocity resulting in winnowed sediment associated with faster arrival of oxygen-rich surface water subducted to form SCIW. Glacial development of Antarctica has been recorded from many deep-sea sites, with extreme glacials providing the mechanism to increase watermass flow. Miocene glacial zones Mi1b-Mi6 are identified in an associated oxygen isotope record from Hole 593, and correspond with times of particularly invigorated paleocirculation, bottom winnowing, and sediment textural changes

Sedimentation record in the Konkan-Kerala Basin: implications for the evolution of the Western Ghats and the Western Indian passive margin

The Konkan and Kerala Basins constitute a major depocentre for sediment from the onshore hinterland of Western India and as such provide a valuable record of the timing and magnitude of Cenozoic denudation along the continental margin. This paper presents an analysis of sedimentation in the Konkan-Kerala Basin, coupledwith a mass balance study, and numerical modelling of flexural responses to onshore denudational unloading and o¡shore sediment loading in order to test competing conceptual models for the development of high-elevation passive margins. The Konkan-Kerala Basin contains an estimated 109,000 km<sup>3</sup>; of Cenozoic clastic sediment, a volume difficult to reconcile with the denudation of a downwarped rift flank onshore, and more consistent with denudation of an elevated rift flank. We infer from modelling of the isostatic response of the lithosphere to sediment loading offshore and denudation onshore that flexure is an important component in the development of the Western Indian Margin.There is evidence for two major pulses in sedimentation: an early phase in the Palaeocene, and a second beginning in the Pliocene. The Palaeocene increase in sedimentation can be interpreted in terms of a denudational response to the rifting between India and the Seychelles, whereas the mechanism responsible for the Pliocene pulse is more enigmatic

Microbial population dynamics in model sewage treatment plants and the fate and effect of gold nanoparticles

Indexación ScopusAdequate functioning of a sewage treatment plant (STP) is essential to protect the down-stream aquatic environment (ECHA 2017), and information on the degradability of chemicals and their toxicity to activated sludge microorganisms is required. An environmental realistic higher tier test is a STP simulation test as described in OECD 303A (2001) which for nanoparticles can also be used to study their sorption behavior to activated sludge. However, information is limited on the influence of synthetic sewage on the microbial community of the activated sludge. A modified community can result in modifications of the sludge floccules affecting the sorption behavior. The main objective of our study was to show whether a representative microbial diversity remains under standardized test conditions as described in OECD 303A (2001) using synthetic sewage as influent. Furthermore, we investigated whether just considering the functional properties of a STP (elimina-tion of dissolved organic carbon; nitrification), is sufficient for an assessment of gold nanoparticles (AuNPs) or whether the influence on microbial diversity also needs to be considered. AuNPs were used as a case study due to their rising medical applications and therefore increasing probability to reach the sewer and STP. The results can provide significant input for the interpretation of results from the regulatory point of view. To deliver these objectives, the general changes of the microbial population in activated sludge and its influence on the degradation activity (dissolved organic carbon (DOC) and inorganic nitrogen) using freshly collected sludge from the municipal STP in an artificial test system as a model STP in accordance with OECD 303A (2001) were assessed. Additionally, we evaluated the potential impact of AuNPs and its dispersant on the microbial composition and the overall impact on the function of the STP in terms of DOC degradation and nitrogen removal to observe if an assessment based on functional properties is sufficient. The bacteria composition in our study, evaluated at a class level, revealed commonly described environmental bacteria. Proteobacteria (β, α, δ) accounted for more than 50% but also nitrifying bacteria as Nitrospira were present. Our results show that mainly within the first 7 days of an acclimatization phase by addition of synthetic sewage, the bacterial community changed. Even though AuNPs can have antibacterial properties, no adverse effects on the function and structure of the microorganisms in the STP could be detected at concentrations of increased modeled PEC values by a factor of about 10,000. Complementary to other metallic nanomaterials, gold nanomaterials also sorb to a large extent to the activated sludge. If activated sludge is used as fertilizer on agricultural land, gold nanoparticles can be introduced into soils. In this case, the effect on soil (micro)organisms must be investigated more closely, also taking into account the structural diversity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.https://www.mdpi.com/2305-6304/9/3/5