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Productivity in the Pleistocene glacial Southern Ocean was probably enhanced owing to iron fertilization by aeolian dust. Marine sediments indicate such an increase north of the modern Antarctic Polar Front but reduced biogenic activity south of it. However, quantitative estimates for the integrated net effect are difficult to obtain. Here we use the SO42−isotopic composition and other geochemical ice core records from the Atlantic sector of the Southern Ocean to reconstruct net changes in integrated biogenic sulfur productivity in the surface ocean over the penultimate glacial termination. We show that biogenic SO42−aerosol contributes 58% and 85% to the sulfate budget in Dronning Maud Land during glacial and interglacial times, respectively, and that biogenic sulfate is derived predominately from the seasonal sea ice zone. Using our quantitative reconstruction of biogenic aerosol production in the Southern Ocean source region, we show that the average biogenic sulfate production integrated over the Atlantic sector was 16% higher in the penultimate glacial 137,000–153,000 years ago compared with the later Last Interglacial 120,000–125,000 years ago. An intermittent decrease in productivity observed during early peak interglacial warming suggests that a reduction in the seasonal sea ice zone may disrupt Southern Ocean ecosystems.

Ecomorphological studies have been developed in the most diverse coastal environments worldwide, playing a key role in the comprehension of the relationship between ecological niche and morphology. Such approach has been useful to better understand the coexistence of fishes with similar body shape by the biological implications that ecomorphological indices have in the feeding habits differentiating species niche. Engraulidae is a fish family that play primary roles in pelagic trophic webs, and many of its representatives are typically by-catch components that have not received fair attention in trophic ecology studies. This study aimed to evaluate the ecomorphological relationships of five engraulids on a Brazilian tropical sandy beach. Eleven ecomorphological features related to diet and locomotion from juveniles of Anchoa januaria(Steindachner, 1879), Anchoa tricolor(Spix & Agassiz, 1829), Anchovia clupeoides(Swainson, 1839), Anchoviella lepidentostole(Fowler, 1911) and Lycengraulis grossidens(Spix & Agassiz, 1829) were calculated and employed in cluster and principal component analysis. The differences in the species ecomorphological indices evidence niche divergence among them, with morphologically close species presenting distinct feeding preferences, and those with common feeding preferences showing distinct morphology despite their phylogenetically proximity. Our results contribute to a better understanding of trophic web structures and coexistence strategies developed by morphologically close species to avoid competition in coastal environments.

Active smoking and the A blood group are associated with pancreatic adenocarcinoma (PC) risk. However, potential interactions between those risk factors and the role of passive smoking have been little investigated. We aimed to explore specific and joint associations of passive and active smoking, and effect modification by the ABO blood group in French women. The study included 96,594 women from the E3N prospective cohort, mean age: 49 years (SD 6.7). Information on active and passive smoking was reported at inclusion and throughout follow‐up. Cases were classified according to the International Classification of Diseases 10. Associations with passive and active smoking and effect modification by the ABO blood group were investigated with multivariable Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI). During a 24‐year median follow‐up, 346 incident PC cases were identified. Current smoking compared with never and former smoking (HR 1.51 [95% CI 1.08–2.10]), and passive smoking in childhood compared with no childhood exposure (HR 1.47 [95% CI 1.08–2.00]) were associated with increased PC risk, but not passive exposure in adulthood (HR 1.16 [95% CI 0.91–1.47]). Exposure to both passive smoking in childhood and current smoking was associated with a stronger risk (HR 2.80 [95% CI 1.42–5.52]) than exposure to both current smoking and passive smoking only in adulthood (HR 1.68 [95% CI 1.10–2.57]) compared with neither passive nor active smoking. Associations between active smoking and PC risk were strongest in the O or B groups, while associations with passive smoking were strongest in the A or AB blood groups, but the interaction terms were not statistically significant. Both current smoking and passive smoking in childhood were associated with PC risk, with a maximal risk of current smokers exposed to passive smoking during childhood. Possible interactions between blood groups and active or passive smoking must be investigated in a larger series.

Data on COVID-19 vaccine acceptability among parents of children with multisystem inflammatory syndrome (MIS-C) are limited. In this cohort of children with MIS-C, enrolled in the Swissped RECOVERY trial (NCT 04826588), comparing intravenous immunoglobulins or methylprednisolone, who, in accordance with Swiss guidelines, were recommended for SARS-CoV-2 vaccination, 65% (73/112) of parents reported being vaccinated against SARS-CoV-2 before the MIS-C, while 70% were vaccinated after the MIS-C episode of their child. None of the children were vaccinated before the occurrence of the MIS-C, and only 9% (5/56) received the COVID-19 vaccine after the MIS-C. The predominant barriers to COVID-19 vaccination were concerns over potential side effects and insufficient support from their doctors. This emphasizes the crucial role of health care providers in promoting COVID-19 vaccination among children.

A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of radiosensitizers, i.e.gold nanoparticles (AuNPs) into triple negative breast cancer (TNBC) cells. This “Trojan horse” approach promotes a specific and massive accumulation of radiosensitizers in TNBC cells, thus avoiding the fast turnover of small-sized AuNPs and the need for high doses of AuNPs for treatment. Application of X-rays resulted in a significant increase of the therapeutic effect while delivering the same dose, showing the possibility to use roughly half dose of X-rays to obtain the same radiotoxicity effect. These data suggest that this hybrid nanoplatform acts as a promising tool for applications in enhancing cancer radiotherapy effects with lower doses of X-rays.

Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89–2.32) to 3.01 (2.68–3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01–4.14) and 3.03 (2.69–3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

The emergence of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) led to the widespread use of anti-inflammatory treatments in the absence of evidence from randomised controlled trials (RCTs). We aimed to assess the effectiveness of intravenous methylprednisolone compared with intravenous immunoglobulins.

Here, we present a holistic encapsulation method for perovskite solar cells to address both optical performance losses at the air-cell interface as well as intrinsic and extrinsic stability challenges. Our one-step method provides shielding to PSCs from oxygen and moisture-induced degradation as well as in situpatterning for light management. As a result of embedding the antireflective coating onto the front side of the cell, the power conversion efficiency (PCE) of the PSCs was increased from 14.1 ± 0.8 % to 15.6 ± 0.8 %, indicating an 8 % relative improvement. Moreover, the encapsulated devices kept their initial performance after 90 % relative humidity and water immersion tests. The outdoor exposure test showed no degradation for the encapsulated cells after 24 h of resting at −17 °C and maximum wind speeds of 7 m/s on average. Additionally, the encapsulation strategy was instrumental in mitigating oxygen and humidity-induced degradation during ISOS-LC tests, retaining up to 80 % of the initial performance for the encapsulated devices after 360 h. This research establishes in situencapsulation and patterning as a promising solution for reducing optical losses and extrinsic instabilities in PSCs. The choice of flexible encapsulant enables it to be used for both rigid and flexible PSCs in a wide range of applications.

Cellulose nanocrystal and gold nanoparticles are assembled, in a unique way, to yield a novel modular glyconanomaterial whose surface is then easily engineered with one or two different headgroups, by exploiting a robust click chemistry route. We demonstrate the potential of this approach by conjugating monosaccharide headgroups to the glyconanomaterial and show that the sugars retain their binding capability to C-type lectin receptors, as also directly visualized by cryo-TEM.

Purpose: Extracorporeal ultrafiltration is an attractive alternative to diuretics for removing excess plasma water in critically ill patients suffering from fluid overload. In continuous renal replacement therapy (CRRT), ultrafiltration occurs in isolated form (SCUF) or supplemented by replacement fluid infusion (CVVH) and the net fluid removal rate is controlled by peristaltic pumps. In this work, a pump-free solution for regulating the ultrafiltration rate in CRRT applications is presented. Methods: The system consists of a motorized clamp on the ultrafiltration line, whose intermittent opening is modulated with a closed-loop control system based on monitoring of ultrafiltrate collected and any replacement fluid infused. The system was tested on two platforms for SCUF and CVVH, with “low-flux” and “high-flux” hemofilter, with various ultrafiltration setpoints and patient net weight loss targets. Results: In all configurations the set ultrafiltration rate was achieved with a maximum error of 5% and the values recorded were kept within ± 100 ml/h with respect to the setpoint, as recommended by international standard IEC 60601-2-16. The net fluid removal trend was highly correlated with that expected (95%&lt;R2&lt;99%) and the weight loss target was reached in the expected time. For low ultrafiltration rates (60-150 ml/h) the system accuracy was better with the “low-flux” hemofilter. Conclusion: The developed clamp system represents a valid alternative to state-of-the-art solutions with peristaltic pumps in terms of performance, with potential usability advantages. The compliance with safety requirements given by international standard IEC 60601-2-16 is a prerequisite for clinical use.

This article publishes for the first time a previously unidentified letter written and signed by Vincenzo Monti, housed at the Provincia Minoritica di Cristo Re dei Frati Minori dell’Emilia Romagna Archive in Bologna. The letter is dated 27 January 1807 and is addressed to Antonio Raineri Biscia, a young multilingual orientalist scholar from Forlì, in reply to a letter which he had sent to Monti on 8 January from Florence. The letter reveals that even before coming into contact with Amedeo Peyron, Monti showed a certain degree of interest in Eastern studies. The article contextualises the letter, providing an analysis of the document together with key biographical and bibliographical details concerning the recipient. The article also publishes three letters that Raineri Biscia wrote to Monti, all of which are housed in the Campori autograph collection at the Biblioteca Universitaria Estense in Modena; these letters are cited (but not published) in Luca Frassineti’s Supplemento all’epistolario di Monti.

ABSTRACTLifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We calculated polygenic scores (PGS) to quantify genetic predisposition to these phenotypes using training (N= 7,431) and validation (N= 4,307) samples. Using paired genetic-methylation data (N= 4,307), gene–environment interactions (i.e., PGS × lifestyle) were assessed using linear mixed-effects models with outcomes: 1) methylation at sites found to be strongly associated with smoking (1,061 CpGs), alcohol consumption (459 CpGs), and BMI (85 CpGs) and 2) two epigenetic ageing measures, PhenoAgeand GrimAge. In the validation sample, PGS explained ~1.4% (P= 1 × 10−14), ~0.6% (P= 2 × 10−7), and ~8.7% (P= 7 × 10−87) of variance in smoking initiation, alcohol consumption, and BMI, respectively. Nominally significant interaction effects (P< 0.05) were found at 61, 14, and 7 CpGs for smoking, alcohol consumption, and BMI, respectively. There was strong evidence that all lifestyle-related phenotypes were positively associated with PhenoAgeand GrimAge, except for alcohol consumption with PhenoAge. There was weak evidence that the association of smoking with GrimAgewas attenuated in participants genetically predisposed to smoking (interaction term: −0.022, standard error [SE] = 0.012, P= 0.058) and that the association of alcohol consumption with PhenoAgewas attenuated in those genetically predisposed to drink alcohol (interaction term: −0.030, SE = 0.015, P= 0.041). In conclusion, genetic susceptibility to unhealthy lifestyles did not strongly modify the association between observed lifestyle behaviour and blood DNA methylation. Potential associations were observed for epigenetic ageing measures, which should be replicated in additional studies.

This work reports the first CMOS molecular electronics chip. It is configured as a biosensor, where the primary sensing element is a single molecule “molecular wire” consisting of a ∼100 GΩ, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule. The current through the molecular wire under a dc applied voltage is monitored with millisecond temporal resolution. The detected signals are millisecond-scale, picoampere current pulses generated by each transient probe-target molecular interaction. Implemented in a 0.18 μm CMOS technology, 16k sensors are arrayed with a 20 μm pitch and read out at a 1 kHz frame rate. The resulting biosensor chip provides direct, real-time observation of the single-molecule interaction kinetics, unlike classical biosensors that measure ensemble averages of such events. This molecular electronics chip provides a platform for putting molecular biosensing “on-chip” to bring the power of semiconductor chips to diverse applications in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.

Atmospheric aerosols are important drivers of Arctic climate change through aerosol–cloud–climate interactions. However, large uncertainties remain on the sources and processes controlling particle numbers in both fine and coarse modes. Here, we applied a receptor model and an explainable machine learning technique to understand the sources and drivers of particle numbers from 10 nm to 20 μm in Svalbard. Nucleation, biogenic, secondary, anthropogenic, mineral dust, sea salt and blowing snow aerosols and their major environmental drivers were identified. Our results show that the monthly variations in particles are highly size/source dependent and regulated by meteorology. Secondary and nucleation aerosols are the largest contributors to potential cloud condensation nuclei (CCN, particle number with a diameter larger than 40 nm as a proxy) in the Arctic. Nonlinear responses to temperature were found for biogenic, local dust particles and potential CCN, highlighting the importance of melting sea ice and snow. These results indicate that the aerosol factors will respond to rapid Arctic warming differently and in a nonlinear fashion.

We assessed mortality risks associated with source-specific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 μg/m3increase) across five identified sources. On a 1 μg/m3basis, the residual oil-related PM2.5had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5mass, suggesting that past estimates using the generic PM2.5exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.

Purpose: Despite the absorption of oral thyroxine (T4) occurs in the small bowel, several patients with gastric disorders show an increased need for T4. In vitro evidence suggested that medium pH variations interfere with T4 dissolution. This study was aimed at finding the proof of concept of a direct relationship between the minimal effective dose of T4 and the actual gastric juice pH. Patients and methods: Among 311 consecutively thyroxine-treated patients, 61 bearing Hashimoto’s thyroiditis (52 F/9 M; median age = 51 years) who complained persistent dyspepsia and/or upper abdominal symptoms following a noninvasive workup for gastrointestinal disorders, underwent EGDS with multiple biopsies and gastric juice pH measurement. All patients accepted to take thyroxine in fasting conditions, abstaining from eating or drinking for one hour. Results: Thyroxine requirement increased along with the rising gastric pH (ρ= 0.4229; p= 0.0007). A multivariate analysis revealed that gastric pH was, beside body mass index, the far more important independent variable in determining the effective dose of T4 (p= 0.001). The ROC curve revealed that the pH threshold for an increased thyroxine requirement was at 2.28, being the AUC by 78%. Subdividing patients by the histologic findings, it appeared a significant increase (p= 0.0025) along with the progressive damage of gastric mucosa. Conclusion: The in vivo measurement of gastric pH highlighted its key role in determining the minimal effective dose of oral T4 and may explain the interference of food, of some drugs and gut disorders on levothyroxine treatment

When used with deproteinized bovine bone mineral (DBBM) delivered as a particulate, the sub‐periosteal peri‐implant augmented layer (SPAL) technique was effective in completely correcting up to 92% of peri‐implant buccal bone dehiscences. The use of a DBBM block (bDBBM), however, may result in an improvement of the peri‐implant bone dehiscence as well as a relevant lateral bone augmentation since its mechanical properties may ensure a better dimensional stability at flap manipulation than particulate DBBM. The aim of the present a proof‐of‐principlecase report is to investigate if SPAL may be successfully used to obtain bone augmentation at peri‐implant dehi scence sites when used with bDBBM. Lateral bone augmentation was performed using the SPAL technique at two implants showing a buccal peri‐implant bone dehiscence immediately after their placement. A partial‐thickness flap was elevated, leaving the periosteal layer on the buccal cortical bone plate. The periosteal layer was, in turn, elevated to create a pouch, which was used to stabilize a bDBBM graft at the peri‐implant buccal bone dehiscences. At re‐entry, exposed implant surfaces were completely covered by new thick hard tissue up to their most coronal portion. A free epithelial‐connective tissue graft was used to augment the peri‐implant soft tissue phenotype. When used to accommodate bDBBM over the most coronal portion of an exposed implant, SPAL may successfully lead to an increase in peri‐implant buccal tissue thickness.

Aerosols play an important yet uncertain role in modulating the radiation balance of the sensitive Arctic atmosphere. Organic aerosol is one of the most abundant, yet least understood, fractions of the Arctic aerosol mass. Here we use data from eight observatories that represent the entire Arctic to reveal the annual cycles in anthropogenic and biogenic sources of organic aerosol. We show that during winter, the organic aerosol in the Arctic is dominated by anthropogenic emissions, mainly from Eurasia, which consist of both direct combustion emissions and long-range transported, aged pollution. In summer, the decreasing anthropogenic pollution is replaced by natural emissions. These include marine secondary, biogenic secondary and primary biological emissions, which have the potential to be important to Arctic climate by modifying the cloud condensation nuclei properties and acting as ice-nucleating particles. Their source strength or atmospheric processing is sensitive to nutrient availability, solar radiation, temperature and snow cover. Our results provide a comprehensive understanding of the current pan-Arctic organic aerosol, which can be used to support modelling efforts that aim to quantify the climate impacts of emissions in this sensitive region.

Bronze artifacts constitute a fundamental portion of Cultural Heritage, but effective methodologies for the removal of corrosion layers, such as those produced by the “bronze disease”, are currently missing. We propose the formulation and application of novel poly(2-hydroxyethyl methacrylate) (pHEMA) networks semi-interpenetrated (SIPN) with poly(acrylic acid) (PAA) to achieve enhanced capture of copper ions and removal of corrosion products. The pHEMA/PAA SIPNs were designed to improve previous pHEMA/poly(vinylpyrrolidone) (PVP) networks, taking advantage of the chelating ability of pH-responsive carboxylic groups in PAA. Increasing the pH ionizes carboxyls, increases the porosity in pHEMA/PAA, and leads to the co-presence of enol and enolate forms of vinylpyrrolidone (VP), changing the macroporosity and decreasing the mesh size in pHEMA/PVP. The ion–matrix interaction is stronger in pHEMA/PAA, where the process occurs through an initial diffusion-limited step followed by diffusion in smaller pores or adsorption by less available sites. In pHEMA/PVP, the uptake is probably controlled by adsorption as expected, considering the porogen role of PVP in the network. Upon application of the SIPNs loaded with tetraethylenpentamine (TEPA) onto corroded bronze, copper oxychlorides dissolve and migrate inside the gels, where Cu(II) ions form ternary complexes with TEPA and carboxylates in PAA or carbonyls in PVP. The removal of oxychlorides is more effective and faster for pHEMA/PAA than its /PVP counterpart. The selective action of the gels preserved the cuprite layers that are needed to passivate bronze against corrosion, and the pH-responsive behavior of pHEMA/PAA allows full control of the uptake and release of the Cu(II)–TEPA complex, making these systems appealing in several fields even beyond Cultural Heritage conservation (e.g., drug delivery, wastewater treatment, agricultural industry, and food chemistry).