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Accurate predictions in forest operations can be used towards effective planning, costing, and maximizing the productivity of machines in mechanised cut-to-length (CTL) harvesting. There is a general and substantial gap in forwarder productivity data available for pine sawtimber in South Africa at present, and as the number of product assortments being harvested increase there is a need for more work to quantify the effects of extracting products of different dimensions. The aim of this study was to calculate the time consumption and productivity of two models of Ponsse forwarders (15 t and 20 t capacity) to consider and compare the effects of multiple variables including machine capabilities, product assortment, load size, extraction distance and fuel consumption. Productivity averaged at 34.08 m3 per productive machine hour excluding delays longer than one minute (PMH1) for the smaller machine, and 55.94 m3/PMH1 for the larger machine. Productivity and average log volume were strongly positively correlated. Regression models were created for each machine where load volume and extraction distance were both significant factors for predicting productivity. Average fuel consumption of the smaller machine was 15.55 l/PMH1 and 0.47 l/m3, and 20.57 l/PMH1 and 0.43 l/m3 for the larger machine. The product with the largest volume was found to require the least fuel per m3. The models developed could aid in predicting system productivity and potentially carbon emissions under similar conditions in a South African context of industrial plantation forestry.

Productivity of a mechanized P. patula cut-to-length harvesting operation was estimated and modelled using two methods of data collection: manual time study and follow-up study using StanForD stem files. The objective of the study was to compare the productivity models derived using these two methods to test for equivalence. Manual time studies were completed on four different machines and their operators. Two Ponsse Bear harvesters fitted with H8 heads, and two Ponsse Beaver harvesters, fitted with H6 heads, were included. All machines were equipped with Ponsse Opti2 information system. All four operators had approximately 1 year of experience working with their respective machines. The four machines worked in separate four-tree-wide harvesting corridors, and they each harvested 200 trees. Individual tree diameter at breast height (DBH), and height measurements were made manually. Subsequently, data on the trees in each study were extracted from the StanForD stem reports from each of the harvesters. Cycle times in the stem reports were determined based on the difference between consecutive harvest timestamps. The two methods were compared in terms of their abilities to estimate equivalent measures for tree DBH, volume, and productivity. In all four cases, significant differences were found between the DBH and volume measures derived using the two methods. Subsequently, the volume measures from the manual methods were used as the basis for productivity calculations. Results of the productivity comparisons found no significant differences between the models developed from the two methods. These results suggest that equivalent productivity models can be developed in terms of time using either method, however volume discrepancies indicate a need to reconcile bark and volume functions with the high variability experienced in the country.

Recent and increasing use of mechanized cut-to-length (CTL) operations in South Africa has been associated with greater diesel and lubricant requirements than was previously the case with motor-manual or semi-mechanized activities, placing a strain on the environmental and economic sustainability of operations. This case study explores diesel and lubricant consumption of a typical CTL pine saw timber operation, taking into account the stand and terrain factors, with the aim of setting baselines for these consumption rates as well as carbon emissions. Data analyzed was provided by Bosbok Ontginning, a contractor based in Mpumulanga, throughout their clear-fell operations over the 49 compartments from May 2014 to June 2015. The mean diesel consumption rate was found to be 0.64 l m-3 and 0.38 l m-3, while the lubricant consumption was 0.08 l m-3 and 0.03 l m-3 for the harvester and the forwarder, respectively. Carbon emissions from diesel were found to account for less than 1% of the carbon stored in the harvested timber. Statistical analysis showed that tree size, stand density and ground condition were not significant predictors of either diesel or lubricant consumption. Prior research suggests that other factors not included in this study (i.e. machine characteristics, operator habits and productivity) may have a more pronounced effect on diesel consumption. Future studies should therefore be conducted to analyze these factors within South African conditions as well as explore stand and terrain conditions more specifically and over more diverse stand and terrain conditions as well as machine types.

1. Hypertension is associated with a distension of the large arteries and consequently a marked reduction in arterial compliance, which does not result merely from the mechanical effects of elevated arterial pressure but also from early functional and/or structural changes in the arterial walls. This suggests that one of the aims of antihypertensive therapy should be to reverse these arterial abnormalities in the hope of protecting the patient from the atherosclerotic complications of hypertension. 2. Studies have been carried out to compare the effects of equieffective antihypertensive doses of pindolol and propranolol on the arterial circulation in patients suffering from essential hypertension. After 3 months therapy pindolol produced a dilatation of the brachial artery with an increase in arterial compliance and blood flow. In contrast, propranolol, despite comparable antihypertensive effects, did not influence brachial artery circulation. 3. These different effects on the arterial circulation presumably reflect the differing pharmacological properties of the two beta-adrenoceptor antagonists and suggest that the intrinsic sympathomimetic activity of pindolol may be responsible for the qualitative differences in the arterial responses to the two drugs. 4. The results reviewed here reveal that even when two drugs of the same class are used to treat patients with essential hypertension the effects of these agents on arterial haemodynamics can vary greatly and are unrelated to the degree of blood pressure lowering. Thus, pindolol, in contrast to propranolol, not only lowers blood pressure but also reverses some of the changes in arterial haemodynamics which are characteristic of hypertensive disease.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

The haemodynamic pattern of the common carotid artery was studied in men with sustained essential hypertension using pulsed Doppler methods before and after administration of vasodilating drugs. Captopril produced both a fall in vascular resistance and an increase in arterial diameter of the common carotid artery. Isosorbide dinitrate increased markedly the arterial diameter but did not change vascular resistance. Nitrendipine decreased vascular resistance with no change in the arterial diameter. In the common carotid circulation of patients with essential hypertension, vasodilating drugs may either dilate small arteries (nitrendipine), large arteries (isosorbide dinitrate), or both (captopril). [ABSTRACT FROM AUTHOR]

By using simultaneous recording curves obtained with pulsed Doppler velocimetry and strain gauge mechanography, forearm arterial haemodynamics were studied in 26 patients with mild to moderate essential hypertension. Fifteen patients received a single oral dose of nicardipine 40 mg, and 11 patients were treated with nicardipine 30 mg three times daily for 3 months. In both groups of patients there was a similar and significant (P less than 0.001) reduction in mean, systolic, and diastolic pressures. There was a slight increase in heart rate (P less than 0.05) after the single dose, but no change after 3 months of treatment. The diameter, blood velocity, and blood flow of the brachial artery increased significantly in both treatment groups. The decrease in forearm vascular resistance was significant for both treatment groups. Brachial artery compliance increased (P less than 0.01) and characteristic impedance decreased (P less than 0.01) after both single-dose and long-term therapy with nicardipine. In patients who received nicardipine for 3 months, there were close correlations between the baseline serum calcium level and the percent change in vascular resistance (r = -0.73, P less than 0.01), blood flow (r = 0.89, P less than 0.001), and blood velocity (r = 0.91. P less than 0.001) of the forearm. No correlation was found between the baseline serum calcium and the change in arterial pressure. This study provided evidence that the blood-pressure-lowering effect of nicardipine was accompanied by a direct vasodilatory action in the small and large arteries of the forearm. An increase in peripheral blood flow with concomitant improvement of arterial compliance are the consequences of these arterial actions. [ABSTRACT FROM AUTHOR]

Brachial artery haemodynamics, including arterial diameter, blood flow velocity, blood flow and compliance of the brachial artery may be evaluated non-invasively in man, using pulsed Doppler methods. In patients with sustained untreated essential hypertension, brachial artery diameter is increased, blood flow is normal and arterial compliance is reduced independently of the level of blood pressure. Converting enzyme inhibition may reverse the large artery abnormalities, causing an increase in arterial diameter, blood flow and arterial compliance both in acute and long-term investigations. These changes in large arteries may contribute towards improved cardiovascular morbidity and less mortality in treated hypertensive patients. [ABSTRACT FROM AUTHOR]

1 Blood pressure, systemic arterial compliance, and diameter, blood flow velocity, volumic flow and impedance of the brachial artery were measured before and after intravenous administration of nitroglycerin (15 micrograms/min during 15 min) in 11 patients with sustained essential hypertension. 2 For the evaluation of the diameter of the brachial artery, a bidimensional pulsed Doppler was used, enabling the angle of the ultrasound beam relative to the flowing stream of blood to be measured with an error of less than 2%. 3 After nitroglycerin, systolic pressure significantly decreased (P less than 0.01) without significant change in diastolic and mean arterial pressures, cardiac index, stroke index and total peripheral resistance. 4 Systemic arterial compliance and brachial artery diameter significantly increased (P less than 0.001; P less than 0.01) while velocity and blood flow of the brachial artery were unchanged. 5 The pattern of the input impedance of the brachial artery was consistent with a predominant effect of nitroglycerin on the viscoelastic properties of peripheral large arteries. 6 The study provided evidence that, in hypertensive patients, nitroglycerin has a direct effect on peripheral large arteries, causing an increase in arterial diameter and compliance, thus leading to a predominant decrease in systolic pressure. [ABSTRACT FROM AUTHOR]

Die klassischen physischen Transaktionsplätze werden in den letzten Jahren immer mehr zugunsten von onlinebasierten Distributionskanälen verdrängt. Bei der Vermarktung landwirtschaftlicher Betriebsmittel ist diese Entwicklung besonders interessant, da sich durch den Anstieg der Einkaufspreise und den EU-weit steigenden Anteil der Vorleistungen (~60 % des Wertes der Enderzeugung) die Suche nach optimierenden Maßnahmen entlang der gesamten Wertschöpfungskette verschärft. Mittels einer standardisierten Online-Befragung wurden quantitative Antworten von 303 Landwirten ermittelt, die über statistische Auswertungen zu folgenden Ergebnissen geführt haben: Die Nutzung des onlinebasierten Einkaufens von Betriebsmitteln ist deutschlandweit flächig verbreitet. Die Nutzerstruktur der Online-Kunden erweist sich als alters-, betriebsgrößen-, ortsunabhängig und ist losgelöst von der Betriebsausrichtung. Als Hauptmotiv für die Beschaffung von Betriebsmitteln über E-Commerce-Kanäle wurden Zeitvorteile ermittelt, was im Widerspruch zu den in der Literatur genannten Kostenvorteilen steht. Entscheidender Hemmfaktor für die Nutzung von E-Commerce-Strukturen ist eine gute Versorgung flächig verteilter Standorte des Landhandels. Dies könnte ein Anknüpfungspunkt für den physischen Landhandel sein, indem z. B. digitalisierte Beratungssysteme für den Online-Handel etabliert werden oder weitere Vermarktungstools aufgebaut werden, die mit Farmmanagementsystemen verknüpft werden.

Reticulated porous ceramic (RPC) made of ceria are promising structures used in solar thermochemical redox cycles for splitting CO2 and H2O. They feature dual-scale porosity with mm-size pores for effective radiative heat transfer during reduction and µm-size pores within its struts for enhanced kinetics during oxidation. In this work, the detailed 3D digital representation of the complex dual-scale RPC is obtained using synchrotron submicrometer tomography and X-ray microtomography. Total and open porosity, pore size distribution, mean pore diameter, and specific surface area are extracted from the computer tomography (CT) scans. The 3D digital geometry is then applied in direct pore level simulations (DPLS) of Fourier’s law within the solid and the fluid phases for the accurate determination of the effective thermal conductivity at each porosity scale and combined, and for fluid-to-solid thermal conductivity from 10−5 to 1. Results are compared to predictions by analytical models for structures with a wide range of porosities 0.09–0.9 in both the strut’s µm-scale and bulk’s mm-scale. The morphological properties and effective thermal conductivity determined in this work serve as an input to volume-averaged models for the design and optimization of solar chemical reactors.

Vibrio parahaemolyticus , Vibrio vulnificus and non-O1/non-O139 Vibrio cholerae are the Vibrio spp. of highest relevance for public health in the EU through seafood consumption. Infection with V. parahaemolyticus is associated with the haemolysins thermostable direct haemolysin (TDH) and TDH-related haemolysin (TRH) and mainly leads to acute gastroenteritis. V. vulnificus infections can lead to sepsis and death in susceptible individuals. V. cholerae non-O1/non-O139 can cause mild gastroenteritis or lead to severe infections, including sepsis, in susceptible individuals. The pooled prevalence estimate in seafood is 19.6% (95% CI 13.7-27.4), 6.1% (95% CI 3.0-11.8) and 4.1% (95% CI 2.4-6.9) for V. parahaemolyticus , V. vulnificus and non-choleragenic V. cholerae , respectively. Approximately one out of five V. parahaemolyticus -positive samples contain pathogenic strains. A large spectrum of antimicrobial resistances, some of which are intrinsic, has been found in vibrios isolated from seafood or food-borne infections in Europe. Genes conferring resistance to medically important antimicrobials and associated with mobile genetic elements are increasingly detected in vibrios. Temperature and salinity are the most relevant drivers for Vibrio abundance in the aquatic environment. It is anticipated that the occurrence and levels of the relevant Vibrio spp. in seafood will increase in response to coastal warming and extreme weather events, especially in low-salinity/brackish waters. While some measures, like high-pressure processing, irradiation or depuration reduce the levels of Vibrio spp. in seafood, maintaining the cold chain is important to prevent their growth. Available risk assessments addressed V. parahaemolyticus in various types of seafood and V. vulnificus in raw oysters and octopus. A quantitative microbiological risk assessment relevant in an EU context would be V. parahaemolyticus in bivalve molluscs (oysters), evaluating the effect of mitigations, especially in a climate change scenario. Knowledge gaps related to Vibrio spp. in seafood and aquatic environments are identified and future research needs are prioritised., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Introduction: Organizational digitalization is a phenomenon that is becoming more widespread and holistic; that is responsible for more employees being affected by digital work and working from home. While introducing remote work offers numerous economic benefits for organizations, this transition must be aligned with employees' needs rather than in an authoritarian manner. Our research aimed to investigate how sub-factors of technostress, directly and indirectly, influence the satisfaction and desire to work from home., Methods: We conducted a cross-sectional survey with a sample of 361 office workers with at least two years of experience who have spent some time working from home. We checked our hypotheses with a path model., Results: Our research found that techno-insecurity and techno-complexity have a minimal direct influence on the desire to work from home. However, the desire to work from home significantly decreases through various mediation pathways via the status sub-factor (which can be seen as one of the latent benefits of remote work) and through satisfaction with working from home. Our model explains 33.7% of the variance in the desire to work from home., Discussion: This suggests that leaders have a task of great significance: to decrease the technostress employees are exposed to and to draw the attention of researchers to the fact that technostress has more complex indirect effects than previously assumed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Simon, Buzás, Rosta-Filep, Faragó, Pachner and Kiss.)

Listeria monocytogenes (in the meat, fish and seafood, dairy and fruit and vegetable sectors), Salmonella enterica (in the feed, meat, egg and low moisture food sectors) and Cronobacter sakazakii (in the low moisture food sector) were identified as the bacterial food safety hazards most relevant to public health that are associated with persistence in the food and feed processing environment (FFPE). There is a wide range of subtypes of these hazards involved in persistence in the FFPE. While some specific subtypes are more commonly reported as persistent, it is currently not possible to identify universal markers (i.e. genetic determinants) for this trait. Common risk factors for persistence in the FFPE are inadequate zoning and hygiene barriers; lack of hygienic design of equipment and machines; and inadequate cleaning and disinfection. A well-designed environmental sampling and testing programme is the most effective strategy to identify contamination sources and detect potentially persistent hazards. The establishment of hygienic barriers and measures within the food safety management system, during implementation of hazard analysis and critical control points, is key to prevent and/or control bacterial persistence in the FFPE. Once persistence is suspected in a plant, a 'seek-and-destroy' approach is frequently recommended, including intensified monitoring, the introduction of control measures and the continuation of the intensified monitoring. Successful actions triggered by persistence of L. monocytogenes are described, as well as interventions with direct bactericidal activity. These interventions could be efficient if properly validated, correctly applied and verified under industrial conditions. Perspectives are provided for performing a risk assessment for relevant combinations of hazard and food sector to assess the relative public health risk that can be associated with persistence, based on bottom-up and top-down approaches. Knowledge gaps related to bacterial food safety hazards associated with persistence in the FFPE and priorities for future research are provided., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment., Materials and Methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al., Results: Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μ Sv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μ Sv (testes) and 48 μ Sv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs., Conclusion: The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De Saint-Hubert, Boissonnat, Schneider, Bäumer, Verbeek, Esser, Wulff, Stuckmann, Suesselbeck, Nabha, Dabin, Vasi, Radonic, Rodriguez, Simon, Journy, Timmermann, Thierry-Chef and Brualla.)

Iron oxide-copper-gold (IOCG) deposits are a globally important source of copper, gold and critical commodities. Despite their relevance, IOCG deposits remain an ill-defined clan, with a range of characteristics that has complicated development of the general genetic model. Here we focus on the Candelaria IOCG deposit in Chile and reveal that by using micro-textural and compositional variations in actinolite, a common alteration mineral found in many IOCG deposits, we can constrain the evolution of these systems. We demonstrate that Candelaria formed by the superposition of at least two pulses of mineralization with a late Cu-rich event overprinting and superimposed over an early, and probably higher temperature, iron oxide-apatite (IOA) mineralization event. These distinct pulses were likely caused by episodic injections of magmatic-hydrothermal fluids from crystallizing magmas at depth. Our data provide empirical evidence of grain-to-deposit scale compositional and potentially temperature changes in an IOCG system. The results support the use of actinolite chemistry as a novel approach to understand the formation of IOCG deposits and a potential tool for vectoring in exploration., (© 2023. The Author(s).)

With climate projections questioning the future survival of stony corals and their dominance as tropical reef builders, it is critical to understand the adaptive capacity of corals to ongoing climate change. Biological mediation of the carbonate chemistry of the coral calcifying fluid is a fundamental component for assessing the response of corals to global threats. The Tara Pacific expedition (2016-2018) provided an opportunity to investigate calcification patterns in extant corals throughout the Pacific Ocean. Cores from colonies of the massive Porites and Diploastrea genera were collected from different environments to assess calcification parameters of long-lived reef-building corals. At the basin scale of the Pacific Ocean, we show that both genera systematically up-regulate their calcifying fluid pH and dissolved inorganic carbon to achieve efficient skeletal precipitation. However, while Porites corals increase the aragonite saturation state of the calcifying fluid (Ω cf ) at higher temperatures to enhance their calcification capacity, Diploastrea show a steady homeostatic Ω cf across the Pacific temperature gradient. Thus, the extent to which Diploastrea responds to ocean warming and/or acidification is unclear, and it deserves further attention whether this is beneficial or detrimental to future survival of this coral genus., (© 2023. The Author(s).)

An assessment was conducted on the level of inactivation of relevant pathogens that could be present in processed animal protein of porcine origin intended to feed poultry and aquaculture animals when methods 2 to 5 and method 7, as detailed in Regulation (EU) No 142/2011, are applied. Five approved scenarios were selected for method 7. Salmonella Senftenberg, Enterococcus faecalis , spores of Clostridium perfringens and parvoviruses were shortlisted as target indicators. Inactivation parameters for these indicators were extracted from extensive literature search and a recent EFSA scientific opinion. An adapted Bigelow model was fitted to retrieved data to estimate the probability that methods 2 to 5, in coincidental and consecutive modes, and the five scenarios of method 7 are able to achieve a 5 log 10 and a 3 log 10 reduction of bacterial indicators and parvoviruses, respectively. Spores of C. perfringens were the indicator with the lowest probability of achieving the target reduction by methods 2 to 5, in coincidental and consecutive mode, and by the five considered scenarios of method 7. An expert knowledge elicitation was conducted to estimate the certainty of achieving a 5 log 10 reduction of spores of C. perfringens considering the results of the model and additional evidence. A 5 log 10 reduction of C. perfringens spores was judged: 99-100% certain for methods 2 and 3 in coincidental mode; 98-100% certain for method 7 scenario 3; 80-99% certain for method 5 in coincidental mode; 66-100% certain for method 4 in coincidental mode and for method 7 scenarios 4 and 5; 25-75% certain for method 7 scenario 2; and 0-5% certain for method 7 scenario 1. Higher certainty is expected for methods 2 to 5 in consecutive mode compared to coincidental mode., (© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: EOSedge™ * (EOS Imaging, Paris, France) is an X-ray imaging system using automatic exposure control (AEC) with tube current modulation, in order to optimize dose deposition in patients., Purpose: This study aims at characterizing EOSedge organ dose deposition in comparison to a digital radiography (DR) system and the previous EOS system (EOS-1st generation), in relation to their respective image quality levels., Method: Organ doses were measured in an anthropomorphic female adult phantom and a 5-year-old pediatric phantom using optically stimulated luminescence (OSL) dosimeters, which were carefully calibrated within the studied energy range. Organ doses were recorded on the EOSedge and the Fuji Visionary DRF (Fujifilm Medical Systems U.S.A., Inc, Lexington, MA). The resulting effective doses were compared to the EOS-1st-generation values present in the literature. Image quality assessment was carried out on end-user images. Quantitative image quality metrics were computed for all tested modalities on a quality assurance phantom. Qualitative assessment of EOSedge image quality was based on anthropomorphic phantom acquisitions against the EOS-1st-generation system, and on clinical images against the tested DR system., Results: For a full-spine exam, and on the female adult phantom (respectively, the pediatric phantom), an effective dose of 92 μSv (respectively, 32 μSv) was obtained on EOSedge, and 572 μSv (respectively, 179 μSv) on the DR system; these values were compared to effective dose values of 290 μSv (respectively, 200 μSv) from the literature on EOS-1st generation, leading to an effective dose reduction factor of 6 with respect to the DR system, and of 3-6 with respect to EOS-1st generation. EOSedge provides the best compromise between contrast-to-noise ratio (CNR) and dose, with more consistent CNR values than the other tested modalities, in a range of attenuation from 10 to 40 cm of poly(methyl methacrylate) (PMMA). Within this range, EOSedge is also comparable to DR for 10 and 20 cm of PMMA, and better than DR for 30 and 40 cm of PMMA, both in terms of spatial resolution and low-contrast detection. The anatomical landmarks of interest in the follow-up of spinal deformities can be detected in all tested modalities., Conclusion: Results showed that EOSedge provides significant dose reduction factors for full spine imaging in both adults and children compared to the other tested modalities, without compromising image quality. We believe that this work could help raise awareness on the capabilities of modern X-ray systems, when equipped with appropriate AEC strategies, to perform ultra-low-dose, long-axis images., (© 2022 American Association of Physicists in Medicine.)

Introduction: Working from home has become increasingly prevalent due to the COVID-19 pandemic, creating new challenges for organizations and employees. According to the latent deprivation model proposed by Jahoda, work provides latent benefits alongside its material rewards, and losing such benefits leads to a decline in well-being. Organizational affective commitment, or affective commitment within the organization, is a prominent concept in organizational psychology that is linked to lower workforce fluctuation and increased work performance. The present research examined the impact of time spent working from home on affective commitment by examining Jahoda's "latent functions," including social contact and collective purpose, representing an innovative application of the latent deprivation model in the context of home office., Methods: Using an online questionnaire, we collected data from 456 participants (239 female and 217 male) who had been employed for at least 2 years and who had spent a proportion of their time working from home in March and April 2021. The data were analyzed using a path model, in which the potential adverse effect of time spent in home office on affective commitment to the workplace was mitigated by latent functions., Results: Specifically, we found that more time spent in home office was associated with a decrease in social contact, the impact of which on affective commitment was mediated through the perception of collective purpose., Discussion: Our findings emphasize the role of the latent benefits of work experienced by employees even when working from home, and the role of those benefits in supporting employees' commitment to the workplace. We argue that a deeper understanding of such factors is vital, as working from home is expected to remain widespread even after the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Simon, Aranyi, Faragó, Pachner and Kiss.)

The MAGIX code (a French acronym standing for Automatic Gamma and X-ray Measurement) is a software developed to analyze γ/X spectra on the topic of severe accident diagnosis. Indeed, the gamma spectra obtained after a severe reactor core accident are complex because they are composed of hundreds of lines of short-lived fission products and Fukushima accident demonstrated a lack in robustness of data interpretation during a crisis. MAGIX allows a complete and entirely automatic analysis of the spectra, with identification of radionuclides and calculation of activities. It can analyze spectra measured by detectors with excellent resolution such as HPGe detectors as well as detectors with medium resolution (e.g. CZT and LaBr 3 ). For most detectors, the analysis of the spectra can be done without a detection efficiency curve because its process can include the calculation of a relative detection efficiency. MAGIX accepts spectra corresponding to any experimental setup (energy slope, energy range, resolution, absorber, etc.). However, these experimental conditions can have an impact on the quality of the results. Results on spectra simulated in different configurations showed that the analysis of the HPGe spectrum with the user defined efficiency and with the MAGIX detection efficiency were close. Furthermore, they also showed that the accuracy of activities was similar with increasing energy slopes but decreased with resolution degradation, with fewer correctly identified radionuclides in this case., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of this work was to assess the level of microbial contamination and resistance of bacteria isolated from a highthroughput heavy pig slaughterhouse (approx. 4600 pigs/day) towards antimicrobials considered as critical for human, veterinary or both chemotherapies. Samples, pre-operative and operative, were obtained in 4 different surveys. These comprised environmental sampling, i.e. air (n total = 192) and surfaces (n total = 32), in four different locations. Moreover, a total of 40 carcasses were sampled in two different moments of slaughtering following Reg. (CE) 2073/2005. Overall, 60 different colonies were randomly selected from VRBGA plates belonging to 20 species, 15 genera and 10 families being Enterobacteriaceae , Moraxellaceae and Pseudomonadaceae the most represented ones. Thirty-seven isolates presented resistance to at least one molecule and seventeen were classified as multi-drug resistant. Enterobacteriaceae , particularly E. coli , displayed high MIC values towards trimethoprim, ampicillin, tetracycline and sulphametoxazole with MIC max of 16, 32, 32 and 512 mg/L, respectively. Moreover, isolated Pseudomonas spp. showed high MIC values in critical antibiotics such as ampicillin and azithromycin with MIC max of 32 and 64 mg/L, respectively. Additionally, in vitro biofilm formation assays demonstrated that fifteen of these isolates can be classified as strong biofilm formers. Results demonstrated that a high diversity of bacteria containing antibiotic resistant and multiresistant species is present in the sampled abattoir. Considering these findings, it could be hypothesised that the processing environment could be a potential diffusion determinant of antibiotic resistant bacteria through the food chain and operators., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest. Funding: This work was funded by The Italian, (©Copyright: the Author(s).)

Purpose: Encapsulation of cytotoxic drugs for a localized release is an effective way to increase the therapeutic window of such agents. In this article we present the localized release of doxorubicin (DOX) from phosphatidyldiglycerol (DPPG 2 ) based thermosensitive liposomes using MR-HIFU mediated hyperthermia in a swine model., Materials and Methods: German landrace pigs of weights between 37.5 and 53.5 kg received a 30-min infusion of DOX containing thermosensitive liposomes (50 mg DOX/m 2 ). The pigs' biceps femoris was treated locally in two separate target areas with mild hyperthermia using magnetic resonance guided high intensity focused ultrasound, starting 10 min and 60 min after initiation of the infusion, respectively. The pharmacokinetics and biodistribution of DOX were determined and an analysis of the treatment parameters' influence was performed., Results: Compared to untreated tissue, we found a 15-fold and a 7-fold increase in DOX concentration in the muscle volumes that had undergone hyperthermia starting 10 min and 60 min after the beginning of the infusion, respectively. The pharmacokinetic analysis showed a prolonged circulation time of DOX and a correlation between the AUC of extra-liposomal DOX in the bloodstream and the amount of DOX accumulated in the target tissue., Conclusions: We have demonstrated a workflow for MR-HIFU hyperthermia drug delivery that can be adapted to a clinical setting, showing that HIFU-hyperthermia is a suitable method for local drug release of DOX using DPPG 2 based thermosensitive liposomes in stationary targets. Using the developed pharmacokinetic model, an optimization of the drug quantity deposited in the target via the timing of infusion and hyperthermia should be possible., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Magnetite is the main constituent of iron oxide-apatite (IOA) deposits, which are a globally important source of Fe and other elements such as P and REE, critical for modern technologies. Geochemical studies of magnetite from IOA deposits have provided key insights into the ore-forming processes and source of mineralizing fluids. However, to date, only qualitative estimations have been obtained for one of the key controlling physico-chemical parameters, i.e., the temperature of magnetite formation. Here we reconstruct the thermal evolution of Andean IOA deposits by using magnetite thermometry. Our study comprised a > 3000 point geochemical dataset of magnetite from several IOA deposits within the Early Cretaceous Chilean Iron Belt, as well as from the Pliocene El Laco IOA deposit in the Chilean Altiplano. Thermometry data reveal that the deposits formed under a wide range of temperatures, from purely magmatic (~ 1000 to 800 °C), to late magmatic or magmatic-hydrothermal (~ 800 to 600 °C), to purely hydrothermal (< 600 °C) conditions. Magnetite cooling trends are consistent with genetic models invoking a combined igneous and magmatic-hydrothermal origin that involve Fe-rich fluids sourced from intermediate silicate magmas. The data demonstrate the potential of magnetite thermometry to better constrain the thermal evolution of IOA systems worldwide, and help refine the geological models used to find new resources., (© 2021. The Author(s).)

In the context of reducing the patient dose coming from CT scanner examinations without penalizing the diagnosis, the assessment of both patient dose and image quality (IQ) with relevant metrics is crucial. The present study represents the first stage in a larger work, aiming to compare and optimize CT protocols using dose and IQ new metrics. We proposed here to evaluate the capacity of the Non-PreWhitening matched filter with an eye (NPWE) model observer to be a robust and accurate estimation of IQ. We focused our work on two types of clinical tasks: a low contrast detection task and a discrimination task. We designed a torso-shaped phantom, including Plastic Water ® slabs with cylindrical inserts of different diameters, sections and compositions. We led a human observer study with 13 human observers on images acquired in multiple irradiation and reconstruction scanning conditions (voltage, pitch, slice thickness, noise level of the reconstruction algorithm, energy level in dual-energy mode and dose), to evaluate the behavior of the model observer compared to the human responses faced to changing conditions. The model observer presented the same trends as the human observers with generally better results. We rescaled the NPWE model on the human responses by scanning conditions (kVp, pitch, slice thickness) to obtain the best agreement between both observer types, estimated using the Bland-Altman method. The impact of some scanning parameters was estimated using the correct answer rate given by the rescaled NPWE model, for both tasks and each insert size. In particular, the comparison between the dual-energy mode at 74 keV and the single-energy mode at 120 kVp showed that, if the 120 kVp voltage provided better results for the smallest insert at the lower doses for both tasks, their responses were equivalent in many cases., (© 2021 Institute of Physics and Engineering in Medicine.)

Most known porphyry Cu deposits formed in the Phanerozoic and are exclusively associated with moderately oxidized, sulfur-rich, hydrous arc-related magmas derived from partial melting of the asthenospheric mantle metasomatized by slab-derived fluids. Yet, whether similar metallogenic processes also operated in the Precambrian remains obscure. Here we address the issue by investigating the origin, fO 2 , and S contents of calc-alkaline plutonic rocks associated with the Haib porphyry Cu deposit in the Paleoproterozoic Richtersveld Magmatic Arc (southern Namibia), an interpreted mature island-arc setting. We show that the ca. 1886-1881 Ma ore-forming magmas, originated from a mantle-dominated source with minor crustal contributions, were relatively oxidized (1‒2 log units above the fayalite-magnetite-quartz redox buffer) and sulfur-rich. These results indicate that moderately oxidized, sulfur-rich arc magma associated with porphyry Cu mineralization already existed in the late Paleoproterozoic, probably as a result of recycling of sulfate-rich seawater or sediments from the subducted oceanic lithosphere at that time.

This study aimed to evaluate the molecular characteristics of methicillin resistant Staphylococcus aureus (MRSA) isolated in the swine chain in Northern Italy. A sample of 50 fattening units located in Lombardy was selected. Five cutaneous samples at slaughtering and three environmental samples at farm were collected from each unit giving a total of 250 and 150 samples, respectively. A total of 25 MRSA isolates were isolated from 400 samples, in 17 different fattening units. At farm, 12 out of 250 samples were positive for MRSA (4,8 %), and 13 out of 150 samples at slaughter were identified as MRSA (8,7 %), giving an overall incidence among samples of 6,25 % (n = 25). Molecular characterization was carried out using multi-locus sequence typing (MLST) and spa -typing. Outcomes showed that most of the isolates belonged to ST398, carrying spa -types t899, t011, t18498, t1939, t1200, and t304. Nonetheless, three isolates were identified as ST97 (t1730 and t4795), and one as ST30, showing spa -type t318. Furthermore, a novel ST was identified, namely 5422, showing spa -type t1730. Heterogeneity in genotypes within the same farm was also found in different fattening units, with concern for the possibility of the exchange of genetic determinants among different lineages. Genetic diversity among MRSA isolates in pig fattening units has been observed, highlighting the possibility that some isolates could be able to infect different hosts, including human., Competing Interests: Conflict of interests: The authors declare no conflict of interests., (©Copyright: the Author(s).)

The main aim of the present study was to evaluate the level of antibiotic resistance, prevalence and virulence features of methicillin-resistant Staphylococcus aureus (MRSA) isolated from heavy swine at abattoir level and farming environments in Lombardy (Northern Italy). With this scope, 88 different heavy swine farms were surveyed, obtaining a total of n = 440 animal swabs and n = 150 environmental swabs. A total of n = 87 MRSA isolates were obtained, with an overall MRSA incidence of 17.50% ( n = 77) among animal samples and a 6.67% ( n = 10) among environmental. Molecular characterisation using multilocus sequence typing (MLST) plus spa -typing showed that sequence type ST398/t899 and ST398/t011 were the most commonly isolated genotypes, although other relevant sequence types such as ST1 or ST97 were also found. A lack of susceptibility to penicillins, tetracycline and ceftiofur was detected in >91.95, 85.05 and 48.28% of the isolates, respectively. Resistance to doxycycline (32.18%), enrofloxacin (27.59%) and gentamicin (25.29%) was also observed. Additionally, a remarkable level of antibiotic multiresistance (AMR) was observed representing a 77.01% ( n = 67) of the obtained isolates. Genetic analysis revealed that 97.70% and 77.01% of the isolates harboured at least one antibiotic resistance or enterotoxin gene, respectively, pointing out a high isolate virulence potential. Lastly, 55.17% ( n = 48) were able to produce measurable amounts of biofilm after 24 h. In spite of the current programmes for antibiotic reduction in intensively farming, a still on-going high level of AMR and virulence potential in MRSA was demonstrated, making this pathogen a serious risk in swine production chain, highlighting once more the need to develop efficient, pathogen-specific control strategies.

Objectives: The objectives of this study were to describe the clinical and etiologic profile and outcomes of children with hemophagocytic lymphohistiocytosis (HLH) in a tertiary care hospital in South India., Methods: This is a combined 2-year prospective (2017 to 2018) and 5-year retrospective (2012 to 2016) descriptive study in which children from birth to 18 years who satisfied the HLH-2004 diagnostic criteria were included. Case details from patient records were analyzed., Results: Fifty-three cases were enrolled of which 20 were prospective and 33 were retrospective. Fever, hepatomegaly, anemia, and hyperferritinemia were the common presentations. Infectious triggers were found in 33 (62%) cases. Five cases were secondary to rheumatic diseases, and 8 were primary HLH. Bacterial (14 cases) followed by viral infections (10 cases) were the leading triggers. Scrub typhus (6 cases) and dengue (4 cases) were the most common infectious agents. Major complications include febrile neutropenia (38%) and multiorgan dysfunction (26%). One child developed secondary malignancy. The most frequently used immunosuppressive drug for the treatment of HLH was steroid (70%), while 28% of cases recovered with only supportive therapy. The overall mortality was 41%., Conclusions: Infections were the most common triggers for HLH of which tropical infectious agents constituted the majority. Treatment with steroids alone or regimens without cytotoxic drugs may result in resolution of secondary HLH with mild to moderate disease activity. Without stem cell transplant, primary HLH has a high mortality rate.

Background & Aims: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH., Methods: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined., Results: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively)., Conclusion: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes., Lay Summary: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation., Competing Interests: Conflict of interest LS reports grants and personal fees from Actelion, grants and personal fees from MSD, grants and personal fees from GSK, outside the submitted work. MH reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants from GSK, grants and personal fees from MSD, personal fees from Ferrer, personal fees from Acceleron, outside the submitted work. GS reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants from GSK, grants and personal fees from MSD, outside the submitted work. OS reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants from GSK, grants and personal fees from MSD, personal fees from Ferrer, personal fees from Gossamer Bio, personal fees from Acceleron, outside the submitted work. DM reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from MSD, outside the submitted work. PDG reports personal fees from Actelion, MSD, Bayer, outside the submitted work. XJ reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from Merck, outside the submitted work. DS reports personal fees from Intercept, personal fees from Biotest, personal fees from Abbvie , personal fees from Gilead sciences, outside the submitted work. PDG reports personal fees and non-financial support from ACTELION, personal fees and non-financial support from BAYER - MSD, personal fees and non-financial support from NOVARTIS, personal fees and non-financial support from VIFOR, personal fees from ABBOTT, personal fees and non-financial support from SERVIER, personal fees from ASTRA-ZENECA, non-financial support from AMGEN, outside the submitted work. NL reports personal fees and other from MSD, personal fees from AMICUS THERAPEUTICS, other from BMS, personal fees from NOVARTIS, personal fees from ASTRA-ZENECA, personal fees from BAYER, personal fees from AKCEA, outside the submitted work. MG, NE, MF, MJ, SR, DHL, CT, CC, GP, AC, PM, EAM, BD, RT, CB, HB, ACS, MR, NF, SP, DB, PM, VC, EB, AC, FD, CF, PH, JCDV have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Magnetite (Fe 3 O 4 ) is an iron ore mineral that is globally mined especially for steel production. It is denser (5.15 g/cm 3 ) than Earth's crust (~2.7 g/cm 3 ) and is expected to accumulate at the bottom of melt-rich magma reservoirs. However, recent studies revealed heterogeneous fluid bubble nucleation on oxide minerals such as magnetite during fluid degassing in volcanic systems. To test if the attachment on fluid bubbles is strong enough to efficiently float magnetite in silicate magma, decompression experiments were conducted at geologically relevant magmatic conditions with subsequent annealing to simulate re-equilibration after decompression. The results demonstrate that magnetite-bubble pairs do ascend in silicate melt, accumulating in an upper layer that grows during re-equilibration. This outcome contradicts the paradigm that magnetite must settle gravitationally in silicate melt.

The genetic link between magmas and ore deposit formation is well documented by studies of fossil hydrothermal systems associated with magmatic intrusions at depth. However, the role of explosive volcanic processes as active agents of mineralization remains unexplored owing to the fact that metals and volatiles are released into the atmosphere during the eruption of arc volcanoes. Here, we draw on observations of the uniquely preserved El Laco iron deposit in the Central Andes to shed new light on the metallogenic role of explosive volcanism that operates on a global scale. The massive magnetite (Fe 3 O 4 ) ore bodies at El Laco have surface structures remarkably similar to basaltic lava flows, stimulating controversy about their origin. A long-standing debate has endured because all proposed models were constructed based exclusively on samples collected from surface outcrops representing the uppermost and most altered portion of the deposit. We overcome this sampling bias by studying samples retrieved from several drill cores and surface outcrops. Our results reveal complex lithological, textural and geochemical variations characterized by magmatic-like features and, most notably, a systematic increase in titanium concentration of magnetite with depth that account for an evolving system transitioning from purely magmatic to magmatic-hydrothermal conditions. We conclude that El Laco, and similar deposits worldwide, formed by a synergistic combination of common magmatic processes enhanced during the evolution of caldera-related explosive volcanic systems.

Background: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France., Methods: Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network., Results: Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect's duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients., Conclusion: Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.

A dynamic multi-protein assembly known as the replisome is responsible for DNA synthesis in eukaryotic cells. In yeast, the hub protein Ctf4 bridges DNA helicase and DNA polymerase and recruits factors with roles in metabolic processes coupled to DNA replication. An important question in DNA replication is the extent to which the molecular architecture of the replisome is conserved between yeast and higher eukaryotes. Here, we describe the biochemical basis for the interaction of the human CTF4-orthologue AND-1 with DNA polymerase α (Pol α)/primase, the replicative polymerase that initiates DNA synthesis. AND-1 has maintained the trimeric structure of yeast Ctf4, driven by its conserved SepB domain. However, the primary interaction of AND-1 with Pol α/primase is mediated by its C-terminal HMG box, unique to mammalian AND-1, which binds the B subunit, at the same site targeted by the SV40 T-antigen for viral replication. In addition, we report a novel DNA-binding activity in AND-1, which might promote the correct positioning of Pol α/primase on the lagging-strand template at the replication fork. Our findings provide a biochemical basis for the specific interaction between two critical components of the human replisome, and indicate that important principles of replisome architecture have changed significantly in evolution., (© 2017 The Authors.)

The exploitation of synthetic lethality by small-molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the synthetic lethality approach. Herein, we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase α from the replisome in yeast extracts. Our study provides proof-of-principle evidence for the development of small-molecule inhibitors of the human CTF4 orthologue AND-1., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT)., Methods and Results: We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH., Conclusion: This study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.

Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-Å crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication.

We report on our recent efforts towards identifying bacteria in environmental samples by means of Raman spectroscopy. We established a database of Raman spectra from bacteria submitted to various environmental conditions. This dataset was used to verify that Raman typing is possible from measurements performed in non-ideal conditions. Starting from the same dataset, we then varied the phenotype and matrix diversity content included in the reference library used to train the statistical model. The results show that it is possible to obtain models with an extended coverage of spectral variabilities, compared to environment-specific models trained on spectra from a restricted set of conditions. Broad coverage models are desirable for environmental samples since the exact conditions of the bacteria cannot be controlled.

Aim: To test how certain patient factors would influence the decision of Dutch care providers regarding insulin dose adjustments. We hypothesize that some of these decisions would diverge from recent evidence and consensus statements., Methods: We developed narrative vignettes describing clinical scenarios of patients receiving basal insulin therapy. For each vignette, the respondents were asked to indicate whether they would advise a change in insulin dose. A total of 520 paper questionnaires were distributed among physicians and nurses in primary and secondary care in the Netherlands. Multivariate linear and logistic regression analyses were performed to identify factors associated with dosing decisions., Results: A total of 190 (37%) questionnaires were returned. In cases of a severe rather than mild hypoglycaemic event, care providers were nearly five times more likely to decrease the dose (odds ratio 4.77, 95% CI 1.65-13.75). Care providers were six times more likely to increase the dose when the patient's current dose was low (30 units) rather than high (90 units) (odds ratio 6.38, 95% CI 3.04-13.37). The plasma glucose concentration during a hypoglycaemic event and a known history of cardiovascular disease did not influence the care providers' dosing decisions., Conclusion: Evidence regarding the optimum insulin titration is not always translated into clinical practice. When formulating guidelines, misconceptions should be identified and addressed., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Background and Aims: The possibility to predict final insulin dose based on patient's characteristics would allow for efficient titration for patients with higher dose needs. The primary aim of this post-hoc analysis of the L2T3 study was to determine predictors for final dose. Specifically, we focused on the relationship between BMI and dose. The secondary aims were to investigate (i) the predictive value of BMI and age on final dose and (ii) the possibility to tailor the starting dose of insulin based on BMI and age., Methods and Results: We performed two stepwise regression analyses, one using all baseline characteristics, and one using physical characteristics and FPG which can be assessed "at the bedside" only. Furthermore, median [min, max] final doses of groups stratified according to BMI and age were calculated. BMI clearly correlated with final dose in IU (Pearson correlation 0.42 [0.37; 0.48], p < 0.001). Characteristics which can be assessed "at the bedside" that predict high final dose were allocation to detemir, absence or discontinuation of insulin secretagogues, high BMI, low age, male gender and high FPG. Final dose varied among strata (BMI ≥30 kg/m(2): 64 IU; BMI <30 kg/m(2): 38 IU, p < 0.001 and age <59 years: 52 IU; age ≥59 years: 44 IU, p < 0.001). All groups stratified for both BMI and age showed similarly low minimal final dose (5-17 IU)., Conclusion: Our data showed a high predictive value of BMI on final dose. However, it does not seem possible to tailor starting dose based on BMI and age., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The BAG6 complex resides in the cytosol and acts as a sorting point to target diverse hydrophobic protein substrates along their appropriate paths, including proteasomal degradation and ER membrane insertion. Composed of a trimeric complex of BAG6, TRC35 and UBL4A, the BAG6 complex is closely associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates., Methodology and Principal Findings: SGTA consists of an N-terminal dimerisation domain (SGTA&#95;NT), a central tetratricopeptide repeat (TPR) domain, and a glutamine rich region towards the C-terminus. Here we solve a solution structure of the SGTA dimerisation domain and use biophysical techniques to investigate its interaction with two different UBL domains from the BAG6 complex. The SGTA&#95;NT structure is a dimer with a tight hydrophobic interface connecting two sets of four alpha helices. Using a combination of NMR chemical shift perturbation, isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) experiments we have biochemically characterised the interactions of SGTA with components of the BAG6 complex, the ubiquitin-like domain (UBL) containing proteins UBL4A and BAG6. We demonstrate that the UBL domains from UBL4A and BAG6 directly compete for binding to SGTA at the same site. Using a combination of structural and interaction data we have implemented the HADDOCK protein-protein interaction docking tool to generate models of the SGTA-UBL complexes., Significance: This atomic level information contributes to our understanding of the way in which hydrophobic proteins have their fate decided by the collaboration between SGTA and the BAG6 complex.