Patient and physician satisfaction in an observational study with methyl aminolevulinate daylight-photodynamic therapy in the treatment of multiple actinic keratoses of the face and scalp in 6 European countries

BACKGROUND Guidelines recommend treating actinic keratoses (AKs) as they are recognized as precursors of invasive squamous cell carcinoma. OBJECTIVE The objective of this study was to collect real-world clinical data on the use of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for the treatment of face and scalp AK in Europe. METHODS A prospective, multicenter, non-interventional study was conducted in six European countries in patients receiving a single treatment of MAL DL-PDT for face and/or scalp AK. Patient-reported outcomes were assessed by patient questionnaires at baseline and at 3 months after treatment, efficacy was assessed at 3 months using a 6-point global improvement scale, and adverse events (AE) were recorded at each visit. RESULTS Overall, 325 patients were enrolled from 52 investigational centres, 314 of whom attended the 3-month visit. Most patients had multiple lesions (58.4% had >10 lesions) with lesions mainly located on the scalp (60.0%) and/or forehead (54.2%). AKs were predominantly grade I (39.4%) or grade II (33.2%), and 10.5% of patients had grade III lesions. The proportions of patients and physicians that were overall satisfied to very satisfied with the MAL DL-PDT treatment were 80.4% and 90.3%, respectively. The vast majority of patients (90.0%) would consider using MAL DL-PDT again if needed. Physician-assessed efficacy at 3 months was at least much improved in 83.5% of patients, with 45.9% of patients requiring no retreatment. Related AEs were reported in 15% of patients. CONCLUSION Use of MAL DL-PDT for multiple face and/or scalp AKs resulted in high levels of patient and physician satisfaction in clinical practice in Europe, reflecting the good efficacy and high tolerability of this convenient procedure

Влияние механической активации гидрида титана на его взаимодействие с азотом и кислородом

Показано, что размол гидрида титана в планетарной мельнице приводит к повышению удельной поверхности порошка, росту микроискажений кристаллической решетки, уменьшению содержания в нем водорода и повышению химической активности, что позволяет получать нитрид титана из него в среде азота уже при температуре 500 °С. За счет кислорода, адсорбирован ного механически активированным порошком при нагревании в атмосфере азота, происходят реакции окисления атомов титана, в результате чего образуется низший оксид Tі2О.Показано, що подрібнення гідриду титану в планетарному млині приводить до підвищення питомої поверхні порошку, зростанню дефектів кристалічної ґратки, зменшенню вмісту в ній водню і підвищенню хімічної активності. Це дає змогу досягти повного перетворення механічно активованого гідриду в нітрид титану вже за температури 500 °С і витримці упродовж однієї години в середовищі азоту. За рахунок кисню, адсорбованого механічно активованим порошком при нагрівання в атмосфері азоту, проходять реакції окиснення, в результаті чого утворюється нижчий оксид Ti2O.Milling of titanium hydride in planetary mill is shoun to increase the speci surface area of powder, to decrease the hydrogen content in it and to intensity chemical activity. This makesit possible to obtain titanium nitride from the titanium hydride in a nitrogen atmosphere at as low temperature as 500 °C . Thanks to the presence of oxygen adsorbed by mechanically activated powder under heating in a nitrogen atmosphere? Reaction of intramolecular oxidation -reduction, of titanium takes place, which results in forming the lower oxide Ti2O

A synthetic metabolic network for physicochemical homeostasis

One of the grand challenges in chemistry is the construction of functional out-of-equilibrium networks, which are typical of living cells. Building such a system from molecular components requires control over the formation and degradation of the interacting chemicals and homeostasis of the internal physical-chemical conditions. The provision and consumption of ATP lies at the heart of this challenge. Here we report the in vitro construction of a pathway in vesicles for sustained ATP production that is maintained away from equilibrium by control of energy dissipation. We maintain a constant level of ATP with varying load on the system. The pathway enables us to control the transmembrane fluxes of osmolytes and to demonstrate basic physicochemical homeostasis. Our work demonstrates metabolic energy conservation and cell volume regulatory mechanisms in a cell-like system at a level of complexity minimally needed for life

Real-Time PCR-Based Mismatch Amplification Mutation Assay for Specific Detection of CS6-Expressing Allelic Variants of Enterotoxigenic Escherichia coli and Its Application in Assessing Diarrheal Cases and Asymptomatic Controls

Enterotoxigenic Escherichia coli (ETEC) expressing the colonization factor CS6 is widespread in many developing countries, including India. The different allelic variants of CS6, caused by point mutations in its structural genes, cssA and cssB, are designated AIBI, AIIBII, AIIIBI, AIBII, and AIIIBII. A simple, reliable, and specific mismatch amplification mutation assay based on real-time quantitative PCR (MAMA-qPCR) was developed for the first time for the detection of CS6-expressing ETEC, along with the identification of allelic variations. The assay was based on mismatched nucleotide incorporation at the penultimate base at the 3' ends of the reverse primers specific for cssA and cssB and was validated using 38 CS6-expressing ETEC isolates. This strategy was effective in detecting all the alleles containing single-nucleotide polymorphisms. Using MAMA-qPCR, we also tested CS6 allelic variants in 145 ETEC isolates from children with acute diarrhea and asymptomatic infections, with the latter serving as controls. We observed that the AIBI and AIIIBI allelic variants were mostly associated with cases rather than controls, whereas the AIIBII variants were detected mostly in controls. In addition, the AIBI and AIIIBI alleles were frequently associated with ETEC harboring the heat-stable toxin gene (est) alone or with the heat-labile toxin gene (elt), whereas the AIIBII allele was predominant in ETEC isolates harboring the elt gene. This study may help in understanding the association of allelic variants in CS6-expressing ETEC with the clinical features of diarrhea, as well as in ETEC vaccine studies

Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network

Private trade and monopoly structures : the East India Companies and the commodity trade to Europe in the eighteenth century

Our research is about the trade in material goods from Asia to Europe over this period, and its impact on Europe’s consumer and industrial cultures. It entails a comparative study of Europe’s East India Companies and the private trade from Asia over the period. The commodities trade was heavily dependent on private trade. The historiography to date has left a blind spot in this area, concentrating instead on corruption and malfeasance. Taking a global history approach we investigate the trade in specific consumer goods in many qualities and varieties that linked merchant communities and stimulated information flows. We set out how private trade functioned alongside and in connection with the various European East India companies; we investigate how this changed over time, how it drew on the Company infrastructure, and how it took the risks and developed new and niche markets for specific Asian commodities that the Companies could not sustain

Expedition 391 Preliminary Report : Walvis Ridge Hotspot: drilling Walvis Ridge, Southeast Atlantic Ocean, to test models of ridge hotspot interaction, isotopic zonation, and the hotspot reference frame

Hotspot tracks (quasilinear chains of seamounts, ridges, and other volcanic structures) provide important records of plate motions, as well as mantle geodynamics, magma flux, and mantle source compositions. The Tristan-Gough-Walvis Ridge (TGW) hotspot track, extending from the active volcanic islands of Tristan da Cunha and Gough through a province of guyots and then along Walvis Ridge to the Etendeka flood basalt province, forms one of the most prominent and complex global hotspot tracks. The TGW hotspot track displays a tight linear age progression in which ages increase from the islands to the flood basalts (covering ~135 My). Unlike Pacific tracks, which are simple chains of seamounts that are often compared to chains of pearls, the TGW track is alternately a steep-sided narrow ridge, an oceanic plateau, subparallel linear ridges and chains of seamounts, and areas of what appear to be randomly dispersed seamounts. The track displays isotopic zonation over the last ~70 My. The zonation appears near the middle of the track just before it splits into two to three chains of ridge- and guyot-type seamounts. The older ridge is also overprinted with age-progressive late-stage volcanism, which was emplaced ~30–40 My after the initial eruptions and has a distinct isotopic composition. The plan for Expedition 391 was to drill at six sites, three along Walvis Ridge and three in the seamount (guyot) province, to gather igneous rocks to better understand the formation of track edifices, the temporal and geochemical evolution of the hotspot, and the variation in paleolatitudes at which the volcanic edifices formed. After a delay of 18 days to address a shipboard outbreak of the coronavirus disease 2019 (COVID-19) virus, Expedition 391 proceeded to drill at four of the proposed sites: three sites on the eastern Walvis Ridge around Valdivia Bank, an ocean plateau within the ridge, and one site on the lower flank of a guyot in the Center track, a ridge located between the Tristan subtrack (which extends from the end of Walvis Ridge to the island of Tristan da Cunha) and the Gough subtrack (which extends from Walvis Ridge to the island of Gough). One hole was drilled at Site U1575, located on a low portion of the northeastern Walvis Ridge north of Valdivia Bank. At this location, 209.9 m of sediments and 122.4 m of igneous basement were cored. The latter comprised 10 submarine lava units consisting of pillow, lobate, sheet, and massive lava flows, the thickest of which was ~21 m. Most lavas are tholeiitic, but some alkalic basalts were recovered. A portion of the igneous succession consists of low-Ti basalts, which are unusual because they appear in the Etendeka flood basalts but have not been previously found on Walvis Ridge. Two holes were drilled at Site U1576 on the west flank of Valdivia Bank. The first hole was terminated because a bit jammed shortly after penetrating igneous basement. Hole U1576A recovered a remarkable ~380 m thick sedimentary section consisting mostly of chalk covering a nearly complete sequence from Paleocene to Late Cretaceous (Campanian). These sediments display short and long cyclic color changes that imply astronomically forced and longer term paleoenvironmental changes. The igneous basement yielded 11 submarine lava units ranging from pillows to massive flows, which have compositions varying from tholeiitic basalt to basaltic andesite, the first occurrence of this composition recovered from the TGW track. These units are separated by seven sedimentary chalk units that range in thickness from 0.1 to 11.6 m, implying a long-term interplay of sedimentation and lava eruptions. Coring at Site U1577, on the extreme eastern flank of Valdivia Bank, penetrated a 154 m thick sedimentary section, the bottom ~108 m of which is Maastrichtian–Campanian (possibly Santonian) chalk with vitric tephra layers. Igneous basement coring progressed only 39.1 m below the sediment-basalt contact, recovering three massive submarine tholeiite basalt lava flows that are 4.1, 15.5, and >19.1 m thick, respectively. Paleomagnetic data from Sites U1577 and U1576 indicate that their volcanic basements formed just before the end of the Cretaceous Normal Superchron and during Chron 33r, shortly afterward, respectively. Biostratigraphic and paleomagnetic data suggest an east–west age progression across Valdivia Bank, becoming younger westward. Site U1578, located on a Center track guyot, provided a long and varied igneous section. After coring through 184.3 m of pelagic carbonate sediments mainly consisting of Eocene and Paleocene chalk, Hole U1578A cored 302.1 m of igneous basement. Basement lavas are largely pillows but are interspersed with sheet and massive flows. Lava compositions are mostly alkalic basalts with some hawaiite. Several intervals contain abundant olivine, and some of the pillow stacks consist of basalt with remarkably high Ti content. The igneous sequence is interrupted by 10 sedimentary interbeds consisting of chalk and volcaniclastics and ranging in thickness from 0.46 to 10.19 m. Paleomagnetic data display a change in basement magnetic polarity ~100 m above the base of the hole. Combining magnetic stratigraphy with biostratigraphic data, the igneous section is inferred to span >1 My. Abundant glass from pillow lava margins was recovered at Sites U1575, U1576, and U1578. Although the igneous penetration was only two-thirds of the planned amount, drilling during Expedition 391 obtained samples that clearly will lead to a deeper understanding of the evolution of the Tristan-Gough hotspot and its track. Relatively fresh basalts with good recovery will provide ample samples for geochemical, geochronologic, and paleomagnetic studies. Good recovery of Late Cretaceous and early Cenozoic chalk successions provides samples for paleoenvironmental study