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RESEARCH QUESTION: How do cumulative live birth rates (CLBR), cumulative multiple live birth rates (CMLBR) and dropout rates over six IVF and intracytoplasmic sperm injection (ICSI) cycles change over time? DESIGN: Prospective longitudinal cohort (n = 16,073 patients; 48,946 cycles) starting a first fresh assisted reproductive technology cycle between 1 January 2014 and 31 December 2016, with follow-up until 31 December 2017. Outcomes between the periods 2014-2017 and 2009-2012 were compared. RESULTS: Conservative estimates of CLBR after six complete cycles were significantly higher in women younger than 35 years after every cycle: one to three, adjusted P-value [p adj] < 0.0001; four, p = 0.01; five, p adj = 0.03; six, p adj = 0.04) and after the first cycle in women aged 35-37 years (p adj = 0.04) in 2014-2017 versus 2009-2012. For an optimal estimate, the CLBR was significantly higher after the first three cycles in women younger than 35 years (all p adj < 0.0001) and after the first cycle in women aged 35-37 years (p adj = 0.04). The CMLBR rate decreased from 5.1% ± 0.19 (SE) to 4.1% ± 0.16 for the conservative estimate and from 8.6% ±0.37 (SE) to 6.7% ± 0.30 for the optimal estimate after six complete cycles for the whole cohort. Dropout rates of complete cycles were 26.5% 29.4%, 33.4%, 38.9% and 47.3% after the first to fifth cycle, respectively. Compared with 2009-2012, the dropout rate in the current period was significantly higher for the first (P < 0.0001) and second (P = 0.0124) cycle. CONCLUSION: Over six complete IVF/ICSI cycles, CLBR and dropout rates increased and multiple live birth rates decreased when 2014-2017 was compared with 2009-2012. ispartof: REPRODUCTIVE BIOMEDICINE ONLINE vol:42 issue:4 pages:717-724 ispartof: location:Netherlands status: published

Miniaturization of the sensor active areas to length scales of the order of the analyte has been sought as means to reduce device footprints, and to capitalize on the novel optical and electronic enhancements that arise at this scale. However, little is known on what to expect of the sensor behaviour if the sensor footprints are shrunk to the dimensions of the order of analyte themselves. Our results demonstrate the densities and kinetics of adsorption of analyte to significantly increase with decrease in the sensor footprints to dimensions of the order of few multiples of analyte dimensions. Such increase is found to be generic, irrespective of the nature of interactions that drive adsorption, exhibiting qualitative similarity for electrostatic adsorption of nanoparticles, chemisorption of primary oligonucleotides, or complementary base pairing with target nucleotides. The carryover of these benefits onto a macroscopic sensor however requires high density nanopatterns exhibiting significant fill factors withtout compromising inter-feature isolation. The impact of feature dimensions, pattern fill factors, analyte concentrations, presence of convective flow, or the density of receptors are investigated using quantitative and real-time measurements of the nanostructure-analyte interactions using nanopatterned QCM sensors. The results indicate significant opportunities for rational design of nanopatterned macroscopic sensors, as well as nanoscopic sensors with sensor active areas of the order of analyte dimensions, e.g., electromagnetic hot-spots, or nanowire sensors.

Antimicrobial peptide loaded poly(2-hydroxyethyl methacrylate) particles were synthesized in supercritical carbon dioxide via one-pot free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate and a cross-linker. Discrete particles with a well-defined spherical morphology and a diameter as low as 450 nm have been obtained in mild conditions. The encapsulation and release of the peptide were confirmed by antimicrobial tests that demonstrated for the first time a sustained release of the peptide from poly(2-hydroxyethyl methacrylate) microgels prepared by one-pot dispersion polymerization in supercritical carbon dioxide and then dispersed in water.

The immobilization of proteins to impart specific functions to surfaces is topical for chemical engineering, healthcare and diagnosis. Layer-by-Layer (LbL) self-assembly is one of the most used method to immobilize macromolecules on surfaces. It consists in the alternate adsorption of oppositely charged species, resulting in the formation of a multilayer. This method in principle allows any charged object to be immobilized on any surface, from aqueous solutions. However, when it comes to proteins, the promises of versatility, simplicity and universality that the LbL approach holds are unmet due to the heterogeneity of protein properties. In this review, the literature is analyzed to make a generic approach emerge, with a view to facilitate the LbL assembly of proteins with polyelectrolytes (PEs). In particular, this review aims at guiding the choice of the PE and the building conditions that lead to the successful growth of protein-based multilayered self-assemblies.

Aluminum hydroxide (AH) salts are widely used as vaccine adjuvants and controlling antigen-AH interactions is a key challenge in vaccine formulation. In a previous work, we have developed a quartz crystal microbalance (QCM) platform, based on stable AH-coated sensors, to explore the mechanisms of model antigen adsorption. The QCM study of bovine serum albumin (BSA) adsorption at different pH and ionic strength (I) values showed that protein adsorption on AH adjuvant at physiological pH cannot be explained mainly by electrostatic interactions, in contrast with previous reports. Here, we exploit further the developed QCM platform to investigate the role of phosphate-hydroxyl ligand exchanges in the adsorption mechanism of BSA, human serum albumin (HSA) and ovalbumin (OVA) on two commercial AH adjuvants. BSA adsorption decreased on immobilized AH particles previously treated with KH2PO4, highlighting the role of exchangeable sites on AH particles in the adsorption process. BSA and OVA were dephosphorylated by treatment with an acid phosphatase to decrease their phosphate content by about 80% and 25%, respectively. Compared to native BSA, adsorption of dephosphorylated BSA decreased significantly on one AH adjuvant at pH 7. Adsorption of dephosphorylated OVA was comparable to the one of native OVA. Further QCM assays showed that phospho-amino acids (PO4-serine and PO4-threonine) displaced previously adsorbed BSA and OVA from AH particles in conditions that were depending on the protein and the AH. Taken together, these observations suggest that phosphate-hydroxyl ligand exchange is an important adsorption mechanism of proteins on AH. These results moreover confirm that the developed AH-coated QCM sensors offer a new platform for the study of antigen adsorption, to the benefit of vaccine formulation.

The high specific strength and stiffness and excellent damping behavior promote the use of flax fibre composites in the construction sector. However, the limited compatibility between raw flax fibres and bio-epoxy resin often leads to composites with mechanical properties well below their theoretical capacities. Moreover, the incomplete understanding of the intrinsic non-linear mechanical behavior of flax fibre composites forces the application of larger safety factors. In this study, three chemical treatments are applied to improve the interphase properties and gain further insight in the longitudinal tensile behavior of flax fibre bio-epoxy composites. Both alkali and APS treatment result in a threefold improvement in the transverse flexural strength to ∼30MPa. Both treatments additionally shift the weakest link to the elementary fibre interphase strength. Analysis of the longitudinal tensile stress-strain curves of UD flax fibre composites results in a tri-linear shape that is preserved after treatment.

Objective Burnout is a multidimensional stress syndrome that is particularly prevalent in physician populations. While the literature expands on preventive and curative interventions, relatively little is known about factors that may hamper their success. The aim of this study was (1) to identify the specific challenges to treat physician burnout and (2) to explore the origins of these challenges. Methods We conducted semi-structured interviews with twelve psychologists who had treated physicians with burnout and performed thematic analysis of data. Results Psychologists identified two specific challenges in treating physician burnout. First, physicians were reluctant to seek help from health professionals and tended to so at more severe stages of exhaustion. Second, physicians were feeling uncomfortable in the role of patient, and many of them had difficulties to accept treatment. Psychologists suggested the following causes of these challenges: (1) most physicians did not have a general practitioner, (2) they felt guilty about reducing their workload, and (3) tended to confuse professional and personal engagement. According to participants, medical education, the professional culture and the image of the profession in the wider community were likely factors contributing to physicians’ reluctance to seek and accept care. Discussion This research showed that the specific challenges to treat physician burnout are mostly related to their reluctance to ask for help and to put their trust in other caregivers. Among the reasons for this behavior, most are linked with physician's representation of professional identity as enduring and selfless. Conclusion Further studies are needed to explore how medical education and professional culture can be changed to reduce the risk of physician burnout and facilitate care when it nonetheless arises.

Layer-by-layer (LbL) assembly is a surface modification method which may bring complexity to biointerfaces designed to control cell-material interactions. This work aims at investigating the LbL assembly of two extracellular matrix proteins, collagen (Col) and fibronectin (Fn), on polystyrene substrates. LbL assembly, which is widely applied to polyelectrolytes, is not easily transferred to proteins. Different buffers and conditions are tested, and LbL assembly is compared to the simultaneous adsorption of Fn and Col. Build-up and properties of the films are monitored using quartz crystal microbalance, ellipsometry, water contact angle measurements, and atomic force microscopy. Results show that denatured Col leads to smoother films, and that the addition of a polyethyleneimine anchoring layer increases film thickness. A more regular construction and thicker films are obtained with Hepes (pH 7.4) compared to other buffers. However, the LbL assembly is not sustainable and stops after the deposition of a few layers. Films obtained by simultaneous adsorption have lower water contact angles, different morphologies, lower water content and are as thick or thicker compared to the ones prepared by the LbL method. The present work shows that collagen and fibronectin are not involved in a true LbL assembly process. The obtained biointerfaces however exhibit different properties compared to those obtained by the one-step adsorption of these proteins. These differences could be exploited to control cell fate.

Graphite rods were modified by substituted aryldiazonium salts allowing subsequent laccase immobilisation and direct electron transfer at the cathode. Two covalent enzyme immobilisation methods were performed with carboxy and amino substituted grafted groups, either via the formation of an amide bond or a Schiff base between the glycosidic groups of the enzyme and the amino groups on the electrode surface, respectively. Laccase adsorption efficiency was consistently compared to the covalent attachment method on the same carbon surface, showing that the latter method led to a higher immobilisation yield when the electrode surface was functionalised with carboxylic groups, as shown from both laccase activity measurement towards an organic reducing substrate, ABTS, and quantitative XPS analysis. Both analytical methods led to similar laccase surface coverage estimations. From activity measurements, when laccase was covalently immobilised on the electrode functionalised with carboxylic groups, the surface coverage was found to be 43 ± 2% whereas it was only 10 ± 3% when laccase was adsorbed. Biocatalysed dioxygen reduction current was also higher in the case of covalent immobilisation. For the first time, oxidised laccase performances were compared to unmodified laccase, showing significant improved efficiency when using oxidised laccase: the current obtained with oxidised laccase was 141 ± 37 μA cm− 2 compared to 28 ± 6 μA cm− 2 for unmodified laccase after covalent immobilisation of the enzyme on a graphite electrode functionalised with carboxylic groups.

Administration of antibiotics by inhalation can greatly improve drug targeting to the site of respiratory infections. In addition, dry powder inhalers are particularly convenient for the patients. The purposes of this study were to demonstrate the interest of pulmonary temocillin delivery to reach high temocillin concentrations locally in the lungs as well as to prepare a spray-dried temocillin powder for inhalation using a minimal amount of generally recognized as safe excipients. Intratracheal instillation of a temocillin solution allowed to reach higher and more sustained drug concentrations in the lungs than intravenous injection in mice, although a 10-fold lower temocillin dose was delivered intratracheally than systemically. A spray-dried powder of pure temocillin presented a fine particle fraction of 9% of the dose loaded in the inhaler. However, the incorporation of 0.5% to 20% of dipalmitoylphosphatidylcholine (DPPC) in the powder increased the fine particle fraction 4- to 5-fold. X-ray photoelectron spectroscopy and X-ray diffraction revealed that DPPC concentrated at the particle surface with its aliphatic chains laterally packed. The minimal amount of DPPC needed to improve the aerosol performance of temocillin supports the use of this excipient in the formulation of cohesive antibiotic powders for inhalation.

Introduction Given their major health consequences in the elderly, identifying people at risk of fall is a major challenge faced by clinicians. A lot of studies have confirmed the relationships between gait parameters and falls incidence. However, accurate tools to predict individual risk among independent older adults without a history of falls are lacking. Objective This study aimed to apply a supervised learning algorithm to a data set recorded in a two-year longitudinal study, in order to build a classification tree that could discern subsequent fallers based on their gait patterns. Methods A total of 105 adults aged >65 years, living independently at home and without a recent fall history were included in a two-year longitudinal study. All underwent physical and functional assessment. Gait speed, stride length, frequency, symmetry and regularity, and minimum toe clearance were recorded in comfortable, fast and dual task walking conditions in a standardized laboratory environment. Fall events were recorded using personal falls diaries. A supervised machine learning algorithm (J48) has been applied to the data recorded at inclusion in order to obtain a classification tree able to identify future fallers. Results Based on fall information from 96 volunteers, a classification tree correctly identifying 80% of future fallers based on gait patterns, gender, and stiffness, was obtained, with accuracy of 84%, sensitivity of 80%, specificity of 87%, a positive predictive value of 78%, and a negative predictive value of 88%. Discussion While the performances of the classification tree warrant further confirmation, it is the first predictive tool based on gait parameters that are identified (not clustered) allowing its use by other research teams. Conclusion This original longitudinal pilot study using a supervised machine learning algorithm, shows that gait parameters and clinical data can be used to identify future fallers among independent older adults.

To evaluate compatibility between a substrate and a thermoplastic polymer, the established methodology is to estimate their surface composition in terms of surface energy components, utilizing the results of contact angle measurements of probe liquids onto substrate and polymer surfaces at room temperature. Using this methodology, polymer surfaces are studied in solid state, however, during spreading of polymers on a substrate, polymers are in molten state and at high temperature, having different surface energies and more complex polymer/substrate interactions due to polymer chain mobility. This paper presents a model study with practical relevance to predict polymer/substrate compatibility including contact angle measurements at high temperature directly performed between molten thermoplastics; polypropylene (PP), polyvinylidene fluoride (PVDF) and maleic anhydride-grafted polypropylene (MAPP), on smooth glass fibres and plates. The values of total surface energy of thermoplastics at high temperature (260 °C) are down to 57% of that measured at room temperature, which has a strong influence on the wetting prediction. Surface energies of both the polymer and the substrate were found not to be the only factor controlling the wetting behaviour of molten polymers and the level of adhesion with the substrate, but also some intrinsic characteristics of the polymer melt play a role. We also observed that the wetting behaviour of molten MAPP is affected by the maleic anhydride (MA) content, demonstrating dramatically different results to room temperature measurements, which is suspected to be due to the formation of covalent bonds of MA groups with the glass surface enhancing the interface strength beyond the shear strength of MAPP.

Glass and stainless steel (StSteel, AISI304-2R), previously cleaned with ethanol (-Eth) or with ethanol and UV–Ozone treatment (-UVO), were soiled with quartz suspensions in water and in a β-lactoglobulin (β-LGB) solution, and dried. The cleanability (ease of quartz particle detachment) in water was evaluated using a radial-flow cell. The soiling suspension containing β-LGB was used as such or after heating for 4 h at 75 °C, which provoked coagulation of about 75% of β-LGB. The substrate–solution interfaces were characterized by X-ray photoelectron spectroscopy (XPS) analysis of conditioned substrates and by contact angle measurements. The substrate surfaces are covered by a layer of organic contaminants which are not removed by pre-cleaning or are adsorbed from the surroundings. The presence of β-LGB in the soiling suspension leads to protein adsorption, but a significant amount of contaminants remains at the surface. For three of the substrates tested (Glass-Eth, Glass-UVO, StSteel-UVO) the increase of cleanability when the soiling suspension contained β-LGB may be explained by lower capillary forces acting upon drying. Capillary forces are proportional to the liquid surface tension and depend in a less important way on substrate contact angle. However the order of cleanability observed for the substrates soiled with a suspension of quartz particles in water (Glass-Eth≅Glass-UVO

Introduction The SarcoPhAge project is an ongoing longitudinal study following community-dwelling elderly subjects with the objective to assess some health and functional consequences of sarcopenia. The sarcopenia diagnosis algorithm developed by the European Working Group on Sarcopenia in Older People (EWGSOP) and used in the present study needs further validation through cross-sectional and longitudinal studies. The aim of the present study is to assess, using this algorithm, the prevalence of sarcopenia and the clinical components linked to this geriatric syndrome. Methods Participants were community dwelling subjects aged 65 years or older. To diagnose sarcopenia, we applied the definition of the EWGSOP. Muscle mass was measured by dual-energy X-ray absorptiometry, muscle strength by a hydraulic dynamometer and physical performance by the SPPB test. Large amounts of socio-demographic, anamnestic and clinical data were collected in all subjects. Results over one year 534 subjects were recruited for this study (60.5% of women, mean age of 73.5 ± 6.16 years), among whom 73 subjects were diagnosed sarcopenic, which represents a global prevalence of 13.7%. Prevalence was 11.8% in men and 14.9% in women. Sarcopenic subjects were older; had a lower Body Mass Index, lower calf, waist, wrist and arm circumferences; presented more cognitive impairments (Mini-Mental State Examination), more comorbidities; were more often malnourished; and consumed more drugs. After adjustment for age, BMI, cognitive status, nutritional status, number of comorbidities and number of drugs, sarcopenic subjects had a worse physical health-related quality of life (SF-36) for the domain of physical functioning, were at higher risk of falls (Timed Up and Go test), were more frail (Fried), presented more often tiredness for the achievement of activities of daily living (Mobility-test), presented less fat mass and obviously less lean mass. Sarcopenic women were also more dependent for housekeeping and handling finances (Lawton scale) than non-sarcopenic ones. Conclusion Sarcopenia seems to be associated with many harmful clinical components making this geriatric syndrome a real public health burden. Follow-up data of the SarcoPhAge study will be helpful to assess the outcomes of sarcopenia based on the EWGSOP diagnosis algorithm and its different proposed cut-offs.

Hybridization of polyoxometalates (POMs) via an organic-inorganic association constitutes a new route to develop heterogeneous POM catalysts with tunable supramolecular architecture. As the structural stability of POMs is strongly influenced by the pH conditions, a quantitative understanding of the POMs-polymer association is important in practical applications. Herein, we use Quartz Crystal Microbalance (QCM) to systematically investigate the interactions of Keggin phosphotungstic acid POM with a polyampholyte polymer-coated QCM sensor as a function of pH. The mass of adsorbed POMs increases when pH decreases from 5.6 to 2, indicating that electrostatic forces play a major role in the formation of POM-polymer hybrids. This finding is complemented by AFM images that show an increase in the size of the hybrid entities from 5 to 12 nm as the pH decreases from 5.6 to 2. The POM adsorbed amount at a particular pH value reaches an equilibrium level with time. The hybrids further gain in adsorbed mass only when lowering the pH value of the POM solution. The hybrid structure formed above pH 2 shows resistance to leaching as indicated by the steady level of the adsorbed mass during a rinsing step with water. However, at pH 2, the rinsing step causes desorption of some weakly adsorbed POMs. It is shown that leached POMs can be re-adsorbed back into the polymer matrix during a second contact with a POM solution at pH 2. This adsorption-desorption cycles of POMs were successfully repeated. Our experiments shed light into the coexistence of tightly as well as loosely bound POMs in hybrid catalyst formed at pH 2. The loosely bound POMs can potentially act as homogeneous catalysts when desorbed. However, these leached POMs can be re-adsorbed back into the matrix, preserving the heterogeneous state of the catalyst. Our results show that QCM is a powerful technique to study in situ the dynamics of the adsorption of POMs on a polymer matrix under different pH conditions.

Physical adhesion was experimentally determined by measuring contact angles with different liquids on bamboo and glass fibers, using the Wilhelmy technique, and by applying the acid-base theory for calculating the surface energy components and the theoretical work of adhesion. The mechanical strength of the interfaces was assessed by single fibre pull-out tests. In order to consider the real mechanisms of interfacial failure of natural fiber composites, the fibre matrix interfacial bond strength was characterized by the critical local value of interfacial shear stress, τ_d, and the radial normal stress at the interface, σult, at the moment of crack initiation. Both interfacial parameters are used for correlating thermodynamic work of adhesion and practical adhesion. Pull-out tests (taking into account friction), XPS, and profilometry techniques were used to study the influence of rough natural fibre surfaces on the interface between the fibre and a thermoplastic matrix, by comparing the mechanical behaviour at the interface of a smooth optical glass fibre with that of rough natural fibres. The results suggest that the physical and chemical compatibility between the bamboo fibre and the matrix does not improve substantially the composite performance if compared with glass composites. The relatively low off-axis strength of the bamboo fibres is suggested as the main reason for the low stress transfer capability at the fibre-matrix interphase. Furthermore, the pull-out process may be friction-dominated in bamboo fibre systems. ispartof: Composites Science and Technology vol:109 issue:10 pages:40-47 status: published

Collagen is a large anisotropic and self-assembling extracellular matrix protein. Understanding and controlling its adsorption and assembly at interfaces is expected to increase our general knowledge of protein adsorption as well as to open the way to the development of biointerfaces of interest for biomaterials science and tissue engineering. The work related to type I collagen adsorption performed in our laboratory over the past twenty years is reviewed. Substrate chemical nature and adsorption conditions (collagen concentration, adsorption duration) were shown to affect collagen adsorbed amount and supramolecular organization. Collagen assemblies were formed starting from the interface, and assembly was favored by hydrophobic substrates and high adsorbed amount. Substrates were designed to better control collagen adsorption and assembly. The spatial control of adsorption was ensured by chemically heterogeneous substrates, which also affected collagen assembly when domains with a dimension smaller than the length of the collagen molecule (i.e. 300nm) were prepared. Mixed polymer brushes were used to achieve a temporal control of adsorption: adsorption and desorption were reversibly triggered by changes of pH and ionic strength. Layer-by-layer assembly of collagen in a nanoporous template was used to elaborate collagen-based nanotubes, which were further deposited on ITO glass substrates by electrophoretic deposition. Finally, the evaluation of cell behavior on the created biointerfaces showed that the control of collagen organization can be successfully used to alter cell behavior.

The goal of the present work was to evaluate in vitro and in vivo the influence of various types and compositions of natural hydrogels on the viability and metabolic activity of SCAPs.Two alginate, three hyaluronic-based (Corgel™) hydrogel formulations and Matrigel were characterized for their mechanical, surface and microstructure properties using rheology, X-ray photoelectron spectroscopy and scanning electron microscopy, respectively. A characterized SCAP cell line (RP89 cells) was encapsulated in the different experimental hydrogel formulations. Cells were cultured in vitro, or implanted in cyclosporine treated mice. In vitro cell viability was evaluated using a Live/Dead assay and in vitro cellular metabolic activity was evaluated with a MTS assay. In vivo cell apoptosis was evaluated by a TUNEL test and RP89 cells were identified by human mitochondria immunostaining.Hydrogel composition influenced their mechanical and surface properties, and their microstructure. In vitro cell viability was above 80% after 2 days but decreased significantly after 7 days (60-40%). Viability at day 7 was the highest in Matrigel (70%) and then in Corgel 1.5 (60%). Metabolic activity increased over time in all the hydrogels, excepted in alginate SLM. SCAPs survived after 1 week in vivo with low apoptosis (1%). The highest number of RP89 cells was found in Corgel 5.5 (140cells/mm(2)).Collectively, these data demonstrate that SCAP viability was directly modulated by hydrogel composition and suggest that a commercially available hyaluronic acid-based formulation might be a suitable delivery vehicle for SCAP-based dental pulp regeneration strategies.

tSorption of fluids during typical wetting experiments on natural fibers produces a zero receding contactangle situation, leading to an incomplete analysis of their wetting behavior. An acoustic vibration methodwas used to measure “equilibrium” contact angles on natural bamboo fibers. The correctness of the tech-nique is verified by performing the experiment with polyethylene terephthalate (PET) fibers and films,and comparing these results with the average of the cosine functions of the advancing and receding anglesfor a given system. Surface energies and components of the surface energies of bamboo and PET fiberswere estimated using the “equilibrium” contact angle data of various test liquids by using the acid–baseapproach. The results are in general agreement with X-ray photoelectron spectroscopy (XPS) analysis ofthe fiber’s surface. The findings contribute to a better understanding of the complex phenomena occur-ring during wetting of natural fibers and suggest that the contact angle obtained by forcing relaxationthrough acoustic vibration is a reliable method for study the wetting behavior of natural fibers.

Inadequate vitamin D status is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to assess the prevalence of inadequate vitamin D status in European women aged over 80 years. Assessments of serum 25-hydroxyvitamin D levels (25(OH)D) were performed on 8532 European women with osteoporosis or osteopenia of which 1984 were aged over 80 years. European countries included in the study were: France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-offs of 25(OH)D inadequacy were fixed