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Maternal inhalation exposure to engineered nanomaterials (ENM) has been associated with microvascular dysfunction and adverse cardiovascular responses. Pregnancy requires coordinated vascular adaptation and growth that are imperative for survival. Key events in pregnancy hallmark distinct periods of gestation such as implantation, spiral artery remodeling, placentation, and trophoblast invasion. Angiotensin II (Ang II) is a critical vasoactive mediator responsible for adaptations and is implicated in the pathology of preeclampsia. If perturbations occur during gestation, such as those caused by ENM inhalation exposure, then maternal–fetal health consequences may occur. Our study aimed to identify the period of gestation in which maternal microvascular functional and fetal health are most vulnerable. Additionally, we wanted to determine if Ang II sensitivity and receptor density is altered due to exposure. Dams were exposed to ENM aerosols (nano-titanium dioxide) during three gestational windows: early (EE, gestational day (GD) 2–6), mid (ME, GD 8–12) or late (LE, GD 15–19). Within the EE group dry pup mass decreased by 16.3% and uterine radial artery wall to lumen ratio (WLR) increased by 25.9%. Uterine radial artery response to Ang II sensitivity increased by 40.5% in the EE group. Ang II receptor density was altered in the EE and LE group with decreased levels of AT(2)R. We conclude that early gestational maternal inhalation exposures resulted in altered vascular anatomy and physiology. Exposure during this time-period results in altered vascular reactivity and changes to uterine radial artery WLR, leading to decreased perfusion to the fetus and resulting in lower pup mass.

Low self-esteem is frequently identified as source of personality, anxiety and body image disorders among adolescent females. The Exercise Self-Esteem Model (EXSEM) is a framework that embodies the multidimensional and hierarchical structure of global self-esteem and its relationship to physical activity and has been effective in guiding the design of physical activity interventions. Although this model has been tested with a variety of populations, it remains to be validated in adolescent females. Additionally, we sought to expand the original model by investigating how additional parameters of body fat and cardiovascular fitness independently contributed to physical and global domains of self-esteem. Ninety-four adolescent females (Mage = 15.6 ± 1.7) completed validated measures of global self-esteem, physical self-esteem and physical self-efficacy. Participants completed the Physical Activity Questionnaire for Adolescents to quantify habitual physical activity levels. Objective physical measurements included height, weight, body fat and cardiovascular fitness. The newly proposed expanded-EXSEM model provided a good model-data fit tested using structural equation modeling (χ2 = 4.54 (p = .21), CFI = .99, RMSEA = 0.07, SRMR = 0.02) compared to the original EXSEM. Physical activity levels were significantly associated with both cardiovascular fitness and body fat and were a positive predictor of physical self-efficacy. Physical self-efficacy, cardiovascular fitness, and body fat were all predictors of physical self-esteem, which directly affected global self-esteem. Our data validates the expanded-EXSEM model in a sample of adolescent females and identifies targets for interventions to change global self-esteem as well as sub-domains of physical self-esteem. While changing fitness variables may be effective in targeting perceptions of body-esteem alone, physical activity participation still remains the primary determinant to bring about the cascade of positive changes in physical self-efficacy and self-esteem in this population.

INTRODUCTION: Ongoing developments in prenatal anomaly screening necessitate continuous updating of counsellors' knowledge. We explored the effect of a refresher counselling course on participants' knowledge of prenatal screening. METHODS: We investigated the association between knowledge and counsellors' working experience. Also, the association between knowledge and counsellors' attitude towards prenatal screening was determined. All counsellors in the North-West region of the Netherlands were invited to attend a refresher counselling course and fill in both a pre-course and a post-course questionnaire. The participants consisted of midwifes, sonographers and gynaecologists. A 55-item questionnaire assessed pre-course (T0) and post-course (T1) knowledge. At T0, counsellors' attitude towards the prenatal screening program was assessed and its association with knowledge analysed. RESULTS: Of 387 counsellors, 68 (18%) attended the course and completed both questionnaires. Knowledge increased significantly from 77.7% to 84.6% (p

Background: Increased nuchal translucency (NT) is associated with aneuploidy. When the karyotype is normal, fetuses are still at risk for structural anomalies and genetic syndromes. Our study researched the diagnostic yield of prenatal microarray in a cohort of fetuses with isolated increased NT (defined as NT ≥ 3.5 mm) and questioned whether prenatal microarray is a useful tool in determining the adverse outcomes of the pregnancy.Materials and Methods: A prospective study was performed, in which 166 women, pregnant with a fetus with isolated increased NT (ranging from 3.5 to 14.3 mm with a mean of 5.4 mm) were offered karyotyping and subsequent prenatal microarray when karyotype was normal. Additionally, all ongoing pregnancies of fetuses with normal karyotype were followed up with regard to postnatal outcome. The follow-up time after birth was maximally 4 years.Results: Totally, 149 of 166 women opted for prenatal testing. Seventy-seven fetuses showed normal karyotype (52%). Totally, 73 of 77 fetuses with normal karyotype did not show additional anomalies on an early first trimester ultrasound. Totally, 40 of 73 fetuses received prenatal microarray of whom 3 fetuses had an abnormal microarray result: two pathogenic findings (2/40) and one incidental carrier finding. In 73 fetuses with an isolated increased NT, 21 pregnancies showed abnormal postnatal outcome (21/73, 28.8%), 29 had a normal outcome (29/73, 40%), and 23 were lost to follow-up (23/73, 31.5%). Seven out of 73 live-born children showed an adverse outcome (9.6%).Conclusions: Prenatal microarray in fetuses with isolated increased NT had a 5% (2/40) increased diagnostic yield compared to conventional karyotyping. Even with a normal microarray, fetuses with an isolated increased NT had a 28.8% risk of either pregnancy loss or an affected child.

γ-ray irradiation effect on deuterium permeation through three kinds of ceramic coatings with different crystal structures has been investigated. Deuterium permeation flux through the coatings increased during γ-ray irradiation at 250–300 °C, but changes in the permeation flux were not detected at above 300 °C. The permeation flux through an erbium oxide coating increased due to crack formation during a permeation experiment at 500 °C. After deterioration of the coating, the γ-ray irradiation effect on permeation through the coating was similar to that of reduced activation ferritic/martensitic steel F82H substrate. On the other hand, an yttrium oxide coating had an amorphous structure and started crystallization at 500 °C. Although the irradiation effect before the crystallization was derived from the F82H substrate, the effect derived from the coating was detected after crystallization because the rate-determining process of permeation shifted to the coating. Compared to the results at 300 °C before and after crystallization, the irradiation effect decreased, proving that the ceramic coatings reduced the deuterium permeation as well as the γ-ray irradiation effect.

Ceramic coatings have been investigated as tritium permeation barrier for several decades; however, there is little knowledge about irradiation effects on the coatings. In this study, yttrium oxide coatings were fabricated on reduced activation ferritic/martensitic steel substrates by radio frequency reactive magnetron sputtering, and their microstructures were investigated after iron-ion irradiation under various parameters with damage concentration of up to 20 displacement per atom. The formation of voids and an amorphous layer was confirmed in all the irradiated samples. In addition, it was found that irradiation-induced grain growth proceeded with damage concentration, and the increase of grain size was proportional to damage concentration. Furthermore, a layer with few voids formed between the crystallized and amorphous layers for the irradiated samples with higher incident energy or higher dose. Defect recovery and heat-driven grain growth and/or crystallization occurred for the sample irradiated at 500 °C, resulting in a larger average grain size than those irradiated at room temperature. Further consideration of irradiation effects to the coatings under fusion-relevant irradiation conditions is necessary.

Durch erhebliche versorgungsstrukturelle Defizite wird die Notwendigkeit einer moglichst fruhen Diagnose und Therapieeinleitung bei Rheumatoider Arthritis (RA) von der Mehrheit der Patienten in Deutschland verpasst. Die Herausforderung ist, den individuellen Anspruch eines bestmoglichen Therapieergebnisses mit einem gesellschaftlich tragfahigen Mittelaufwand in Einklang zu bringen. Das transsektorale Versorgungsnetzwerk ADAPTHERA zielt darauf ab, die fruhe RA-Diagnose und Behandlung in Rheinland-Pfalz zu verbessern. Fur die retrospektive Triage Analyse wurden 1045 Anfragen nachverfolgt. Zur Auswertung des klinischen Verlaufs wurde eine 143 Patienten umfassende Subkohorte analysiert. Quartalsweise wurden klinische und laborchemische Routineparameter erfasst, eine Batterie an Fragebogen ausgefullt und das therapeutische Regime bei Bedarf angepasst. Insgesamt konnten 454 Patienten eingeschlossen werden. Die mittlere Wartezeit betrug 23,9 (SD = 18) Tage. Der mittlere Beobachtungszeitraum in der Subkohorte lag bei 29,2 (SD = 12,7) Monaten, wobei die Halfte der Patienten binnen 3 Monaten vorstellig wurde. Fast 75 % der Patienten befanden sich nach 2 Jahren in Remission. Eine nachhaltige Remission konnte fur 74,8 % (6 Monate) respektive 53,5 % (12 Monate) beschrieben werden. Besonders Patienten mit rascher Remissionsinduktion profitierten im Sinne langerer Remissionen (p = 0,03). Ein sehr fruhes Krankheitsstadium (VERA) war mit einer seltener notwendigen Biologikatherapie assoziiert (p = 0,022). Der Ansatz eines Versorgungsnetzwerkes ist kein Allheilmittel, es kann aber eine deutliche Verbesserung der Versorgung bewirken. Kernpunkt zur Minimierung der kapazitaren Auslastung ist dabei eine moglichst zielgenaue Zuweisung und eine akkurate Triage.

Background Pregnancy is associated with many rapid biological adaptations that support healthy development of the growing fetus. One of which is critical to fetal health and development is the coordination between maternal liver derived substrates and vascular delivery. This crucial adaptation can be potentially derailed by inhalation of toxicants. Engineered nanomaterials (ENM) are commonly used in household and industrial products as well as in medicinal applications. As such, the potential risk of exposure remains a concern, especially during pregnancy. We have previously reported that ENM inhalation leads to upregulation in the production of oxidative species. Therefore, we aimed to determine if maternal nano-TiO2 inhalation exposure resulted in altered H2O2 production capacity and changes in downstream redox pathways. Additionally, we investigated whether this persisted into adulthood within the F1 generation and how this impacted F1 gestational outcomes and F2 fetal health and development. We hypothesized that maternal nano-TiO2 inhalation exposure during gestation would result in upregulated H2O2 in the F0 dams as well as her F1 offspring, resulting in gestational vascular dysfunction in the F1 dams yielding smaller F2 generation pups. Results Our results indicate upregulation of hepatic H2O2 production capacity in F0 dams, F1 offspring at 8 weeks and F1 females at gestational day 20. H2O2 production capacity was accompanied by a 2-fold increase in phosphorylation of the redox sensitive transcription factor NF-κB. In cell culture, naïve hepatocytes exposed to F1-nano-TiO2 plasma increased H2O2 production. Overnight exposure of these hepatocytes to F1 plasma increased H2O2 production capacity in a partially NF- κB dependent manner. Pregnant F1- nano-TiO2 females exhibited estrogen disruption (29.81 ± 8.8 pg/ml vs. 12.12 ± 3.1 pg/ml sham-control) and vascular dysfunction similar to their directly exposed mothers. F1-nano-TiO2 uterine artery H2O2 production capacity was also elevated 2-fold. Dysfunctional gestational outcomes in the F1-nano-TiO2 dams resulted in smaller F2 pups (4.93 ± 0.47 g vs. 5.78 ± 0.09 g sham-control pups). Conclusion In conclusion, this manuscript provides critical evidence of redox dysregulation across generations following maternal ENM inhalation. Furthermore, the dysfunctional gestational outcomes observed in the F1-nano-TiO2 generation impact the development of F2 offspring. In total, this data provides strong initial evidence that maternal ENM exposure has robust biological impacts that persists in at least two generations.

Background Pregnancy is associated with many rapid biological adaptations that support healthy development of the growing fetus. One of which is critical to fetal health and development is the coordination between maternal liver derived substrates and vascular delivery. This crucial adaptation can be potentially derailed by inhalation of toxicants. Engineered nanomaterials (ENM) are commonly used in household and industrial products as well as in medicinal applications. As such, the potential risk of exposure remains a concern, especially during pregnancy. We have previously reported that ENM inhalation leads to upregulation in the production of oxidative species. Therefore, we aimed to determine if F0 dam maternal nano-TiO2 inhalation exposure (exclusively) resulted in altered H2O2 production capacity and changes in downstream redox pathways in the F0 dams and subsequent F1 pups. Additionally, we investigated whether this persisted into adulthood within the F1 generation and how this impacted F1 gestational outcomes and F2 fetal health and development. We hypothesized that maternal nano-TiO2 inhalation exposure during gestation in the F0 dams would result in upregulated H2O2 production in the F0 dams as well as her F1 offspring. Additionally, this toxicological insult would result in gestational vascular dysfunction in the F1 dams yielding smaller F2 generation pups. Results Our results indicate upregulation of hepatic H2O2 production capacity in F0 dams, F1 offspring at 8 weeks and F1 females at gestational day 20. H2O2 production capacity was accompanied by a twofold increase in phosphorylation of the redox sensitive transcription factor NF-κB. In cell culture, naïve hepatocytes exposed to F1-nano-TiO2 plasma increased H2O2 production. Overnight exposure of these hepatocytes to F1 plasma increased H2O2 production capacity in a partially NF-κB dependent manner. Pregnant F1- nano-TiO2 females exhibited estrogen disruption (12.12 ± 3.1 pg/ml vs. 29.81 ± 8.8 pg/ml sham-control) and vascular dysfunction similar to their directly exposed mothers. F1-nano-TiO2 uterine artery H2O2 production capacity was also elevated twofold. Dysfunctional gestational outcomes in the F1-nano-TiO2 dams resulted in smaller F1 (10.22 ± 0.6 pups vs. sham-controls 12.71 ± 0.96 pups) and F2 pups (4.93 ± 0.47 g vs. 5.78 ± 0.09 g sham-control pups), and fewer F1 male pups (4.38 ± 0.3 pups vs. 6.83 ± 0.84 sham-control pups). Conclusion In conclusion, this manuscript provides critical evidence of redox dysregulation across generations following maternal ENM inhalation. Furthermore, dysfunctional gestational outcomes are observed in the F1-nano-TiO2 generation and impact the development of F2 offspring. In total, this data provides strong initial evidence that maternal ENM exposure has robust biological impacts that persists in at least two generations.

In fusion power plants a tritium permeation barrier is required in order to prevent the loss of the fuel. Moreover, the tritium permeation barrier is necessary to avoid that the radioactive tritium accumulates in the first wall, the cooling system, and other parts of the power plant. Oxide thin films, e.g. Al2O3, Er2O3 and Y2O3, are promising candidates as tritium permeation barrier layers. With regard to the application, this is especially true for yttrium due to its favorably short decay time after neutron activation compared to the other candidates. The Y2O3 layers with thicknesses from 100 nm to 500 nm are deposited on both sides of Eurofer substrates by RF magnetron sputter deposition. Some of the samples are additionally deposited with palladium thin films to analyse the limited regime. During the annealing in the experiments the palladium layers do not show any crack formation or delamination, verified by scanning electron microscopy. After annealing the cubic crystal structure of the Y2O3 layers is verified by X-ray diffraction. The cubic phase contains a small amount of a monoclinic phase, which is eliminated after the permeation measurements. The permeation reduction factors of the samples are determined in gas-driven deuterium permeation experiments. A permeation reduction of 5000 of the yttria thin film is verified. The diffusion limited regime is identified by the pressure dependence of the permeation measurement and by permeation experiments with the palladium top layers on the Y2O3 thin films. Furthermore, the activation energy of the permeation through the yttria thin films is determined. Pre-annealing times for more than 70 h of the Y2O3 thin films and permeation measurements with temperature cycles for 20 days are performed to show the stability of the permeation flux and hence the microstructure of the barrier layers. Measurement times at each constant temperature level of more than 25 h are required for the stabilization of each permeation flux to a constant value. The permeation measurement setup is enhanced to enable a continuously running equipment for these measurement times.

BackgroundAlthough work ability is considered a key element of quality of life for working people, work is underexposed in current treatment in people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). Most people with RA or axSpA attend a physiotherapist (PT). Physiotherapy can effectively improve physical fitness, which is associated with work ability. Therefore, PTs might play an important role in optimizing work ability of people with RA or axSpA.ObjectivesDeveloping a personalized, multimodal, PT-led, work-oriented intervention for working people with RA or axSpA who have a reduced work ability, through a co-creation process.MethodsA systematic co-creation process with all relevant stakeholders was conducted following the Medical Research Council (MRC)-framework for complex interventions (see Figure 1). In step 1, all relevant clinical guidelines and treatment protocols were assessed. Based on the results of this assessment, a draft version of the intervention was developed, consisting of mandatory (i.e., work-oriented intake, patient education, exercise therapy, referral-roadmap of work-related professionals) and optional treatment modalities (i.e., workplace-intervention, self-management course). In step 2, focus groups with people with RA/axSpA, PTs and occupational/rheumatology experts were organized and qualitatively analysed. In the focus groups, barriers and facilitators of work-oriented treatments and necessary adaptations to the draft intervention were discussed. In step 3, a pre-test was performed to test the feasibility of the intervention in a primary physiotherapy setting, which was evaluated in the group of PTs participating in the pre-test in step 4. Finally, in step 5, a final focus group with researchers in this field was held to discuss the findings from previous steps in this co-creation process and to agree on necessary adaptations in the final intervention.Figure 1.Process of systematic development of co-created, work-oriented physiotherapist-led intervention following the MRC-framework.ResultsAfter developing the draft intervention, we conducted two focus groups with people with RA/axSpA (n=16; 4 with RA, 12 with axSpA), one focus group with PTs (n=12) and one focus group with occupational/rheumatology experts (n=9; 2 rheumatologists, 2 nurse specialists, 1 physiatrists, 1 physician assistant, 1 nurse practitioner, 1 labour expert and 1 occupational therapist). People with RA or axSpA emphasized 3 aspects: i) PTs should have adequate expertise in RA/axSpA, ii) high potential for a role of ‘buddy’ by PTs to support them in work-related problems, and iii) most PTs currently lack adequate expertise on work-related problems. PTs and experts underlined the importance of extensive training of PTs on work-related laws and regulations and adequate (work-related) interprofessional collaboration. After revision of the draft intervention, the intervention was tested for feasibility by three PTs and three working people (2 with RA, 1 with axSpA), who indicated that the intervention was feasible and that the developed intervention facilitated PTs to support people in optimizing their work ability. However, adequate training on providing this intervention was recognized to be essential. In a final focus group with researchers (n=6), consensus was reached on minor adjustments to the intervention that were based on findings from previous steps.ConclusionThrough a systematic co-creation process based on the MRC-framework, we have been able to develop a personalized, multimodal, PT-led, work-oriented intervention for working people with RA or axSpA and a reduced work ability. The (cost-)effectiveness of this intervention is currently being tested in a large trial (Physiotherapy WORKs study).AcknowledgementsThis study is funded by the Dutch Arthritis Society (ReumaNederland) and the Scientific College of Physical Therapy (WCF) of the Royal Dutch Society for Physical Therapy (KNGF). This study is registered in the Netherlands Trial Register under number NL9343.Disclosure of InterestsNone declared

Steel components are required in the infrastructure and the facilities of the hydrogen economy. The high hydrogen pressures in the hydrogen economy lead to embrittlement and surface corrosion of the steels. For the functionality of the facilities it is necessary to suppress the embrittlement and the surface corrosion of the steels by protective layers, e.g. ceramic thin films. With regard to fusion power plants ceramic thin films on the structural steel materials are also required. These thin films work as a tritium permeation barrier that is necessary to prevent the loss of the radioactive fuel inventory. Oxide thin films, e.g. Al2O3, Er2O3, and Y2O3, are promising candidates as tritium permeation barrier layers. In terms of the application in the first wall, this is especially true for yttrium due to its favorably short decay time after neutron activation compared to the other candidates. The Y2O3 layers with thicknesses of 0.5 μm–1 μm are deposited on both substrate sides by RF magnetron sputter deposition. Since the microstructure of the barrier layer plays an important role for the permeation reduction, layers with three different magnetron process modes and thus three different microstructures are prepared. After annealing the cubic crystal structure of all thin films is verified by X-ray diffraction and the different microstructures are investigated by scanning electron microscopy and transmission electron microscopy. The Y2O3 stoichiometry of all thin films and a chromium oxide material segregation at the interface are verified by analysis methods such as X-ray photoelectron spectroscopy. The permeation reduction factors of all thin films are determined in gas-driven deuterium permeation experiments. Corresponding to the three different microstructures, reduction factors of 25, 45, and 1100 are identified. Thus, the permeation reduction is strongly dependent on the Y2O3 microstructure. The measurement results suggest that a high density of grain boundaries leads to a high hydrogen permeation.

In fusion power plants a tritium permeation barrier is required in order to prevent the loss of the fuel inventory. Moreover, the tritium permeation barrier is necessary to avoid that the situation the radioactive tritium accumulates in the first wall, the cooling system, and other parts of the power plant. Oxide thin films, e.g. Er2O3 and Y2O3, are promising candidates as tritium permeation barrier layers. With regard to the application, this is especially true for Y2O3 due to its favorably low activation behavior compared to the other candidates. Y2O3 thin films are deposited on the reduced activation steel Eurofer97 by means of magnetron sputtering. To quantify the permeation reduction factor of the Y2O3 thin films a new gas-driven deuterium permeation measurement setup was constructed. Comparing the permeation flux through a bare substrate and a coated Eurofer97 substrate, the permeation reduction factor can be determined. The measurement results suggest that the permeation reduction factor is in the same range as for Er2O3. Moreover, the morphological analysis and the permeation measurements indicate that the long term stability of the permeation barrier performance depends on the deuterium saturation in the Y2O3 thin film.

We examined the changes in salivary immunoglobulin A (SIgA) and the incidence of upper respiratory syndrome (URS) throughout a college cross-country season as well as the acute effect of a VO2max test on SIgA. Subjects were 22 cross country athletes (XC) (20.7±0.3 years) and 23 matched controls (C) (20.4±0.2 years). Saliva samples were collected pre and post VO2max and at four training time points (August – November). Weekly logs indicating S&S of URS from which a total symptom score (TSS) was calculated were collected. There was a significant decrease in SIgA F(1,43)=10.742, p

The use of systems in many introductory courses is limited and often implicit. Modeling two or more objects as a system and tracking the center of mass of that system is usually not included. Thinking in terms of the center of mass facilitates problem solving while exposing the importance of using conservation laws. We present below three laboratory activities that build this systems thinking for introductory physics students.

Micro solid oxide fuel cells (μ-SOFC) were manufactured with perovskite type proton conductors on silicon substrates and with structured Pt-grid electrodes. In order to miniaturize the μ-SOFCs and to shorten the ion path through the electrolyte, the thin film proton conductors were only ~ 510 nm thick. The thin films consist of 10 mol% yttrium-doped BaZrO3 (BZY10) and they were deposited by means of chemical solution deposition (CSD). CSD was applied, because it represents a highly attractive fabrication method, considering the relatively low investment costs and flexibility with regard to stoichiometry. The backsides of the μ-SOFCs on the substrates were opened by wet chemical and plasma etching to form the freestanding membranes. The completed μ-SOFCs resist up to a temperature of 450 °C. Their electrical properties, such as permittivity, and resistivity were investigated. By means of electrochemical impedance spectroscopy (EIS) in the temperature range of 100 °C to 450 °C, the resistivity properties and the activation energies of the model μ-SOFC were studied with humid hydrogen in nitrogen at the anode and different oxygen partial pressures at the cathode. The results provide a clear hint for a dominating protonic defect transport mechanism in the electrolyte. In the 450 °C measurement, the model μ-SOFCs reached an open circuit voltage of 600 mV with 100% oxygen at the cathode and humid hydrogen in nitrogen at the anode.

Applications of colloidal particles in the fields of i.e. biosensors, molecular targeting, or drug-delivery require their functionalization with biologically active and specific molecular ligands. Functionalization protocols often result in a heterogeneous population of particles with a varying density, spatial distribution and orientation of the functional groups on the particle surface. A lack of methods to directly resolve these molecular properties of the particle's surface hampers optimization of functionalization protocols and applications. Here quantitative single-molecule interaction kinetics is used to count the number of ligands on the surface of hundreds of individual nanoparticles simultaneously. By analyzing the waiting-time between single-molecule binding events we quantify the particle functionalization both accurately and precisely for a large range of ligand densities. We observe significant particle-to-particle differences in functionalization which are dominated by the particle-size distribution for high molecular densities, but are substantially broadened for sparsely functionalized particles. From time-dependent studies we find that ligand reorganization on long timescales drastically reduces this heterogeneity, a process that has remained hidden up to now in ensemble-averaged studies. The quantitative single-molecule counting therefore provides a direct route to quantification and optimization of coupling protocols towards molecularly controlled colloidal interfaces.

The majority of patients in Germany miss out on the necessity of early diagnosis and initiation of therapy for rheumatoid arthritis (RA) caused by considerable structural deficits in the health care system. The challenge is to reconcile the individual demand for the best possible therapy result with a sustainable expenditure of resources.The cross-sectoral regional care network ADAPTHERA aims to improve early RA diagnosis and treatment in Rhineland-Palatinate. The retrospective triage analyses of suspected early onset RA patients was performed by tracing the selection process of all available enquiries (n = 1045). For analysis of the clinical course of the disease, a subset comprising 143 patients with a minimum observation time of 12 months (5 consecutive visits) was available. Clinical and laboratory parameters were collected quarter yearly, self-administered questionnaires were filled out and the treatment was adapted if necessary.A total of 454 patients were included. The mean waiting time was 23.9 (SD = 18) days. The mean observation period in the subcohort was 29.2 (SD = 12.7) months, with about 50% of the patients presenting within 3 months. Almost 75% of the patients were in remission after 2 years. A sustained remission could be described for 74.8% (6 months) and 53.5% (12 months), respectively. Especially patients with rapid remission induction benefited in terms of longer remissions (p = 0.03). A very early stage of the disease (VERA) was associated with a rarely necessary biologic therapy (p = 0.022).The approach of a supply network is not a panacea, but it might improve healthcare for patients with early onset RA. In order to minimize resource utilization, a pinpoint referral and accurate triage of potential cases are crucial.

There are different equations to describe relations between different classes of Love–Shida numbers. In this study with the use of the time-varying gravitational potential an integral relation was obtained which connects tidal Love–Shida numbers (h, l, k), load numbers (h' , l' , k'), potential free Love–Shida numbers generated by normal (h" , l" , k") and horizontal (h''' , l''' , k''') stresses. The equations obtained in frame of present study is the only one which holds for every type of Love–Shida numbers, describes a relationship not between different, but the same type of Love–Shida numbers, does not follow from the sixth-order differential equation system of motion usually applied to calculate the Love–Shida numbers.

Ziel des Rheuma-Netzwerks ADAPTHERA („risikoadaptierte Rheumatherapie“) ist es, eine flachendeckende Verbesserung der rheumatologischen Versorgung durch Koordination der Behandlung in einem landesweiten, transsektoralen Netzwerk zu erreichen. Begleitende biomedizinische Forschungsprojekte, Schulungskonzepte sowie der Aufbau eines Rheumaregisters (Daten- und Biomaterialsammlung) sollen daruber hinaus fur eine stetige und nachhaltige Optimierung der Versorgung sorgen. In der Pilotphase 2012–2015 lag der Fokus des als „Landesleitprojekt“ im Rahmen der Initiative Gesundheitswirtschaft Rheinland-Pfalz (RL-P) geforderten ADAPTHERA Netzwerkes auf der Optimierung der Fruhdiagnose der rheumatoiden Arthritis, bei der bekanntermasen ein erhebliches Versorgungsdefizit besteht. Durch die intensive, dauerhafte und koordinierte Kooperation aller Versorgungspartner auf dem Gebiet der Rheumatologie (niedergelassene Hausarzte und Orthopaden, niedergelassene Schwerpunktrheumatologen, das ACURA-Rheumazentrum RL-P, die Universitatsmedizin Mainz, die Rheumaorthopaden sowie die Arbeitsgemeinschaft Rheumatologie RL-P) ist ein bundesweit einzigartiges flachendeckendes Angebot mit nachweisbarer Versorgungsoptimierung in Rheinland-Pfalz entstanden. Unterstutzt wurde das Netzwerk dabei durch die hervorragende Zusammenarbeit mit der Kassenarztlichen Vereinigung RL-P und der Selbsthilfeorganisation Rheumaliga. Die bei Projektstart gesetzten Ziele werden am Ende der Pilotphase erreicht: - deutliche Verbesserung der Fruhdiagnostik der rheumatoiden Arthritis (durchschnittlich 23,7 Tage Dauer bis zur Diagnosestellung durch Rheumatologen) - krankenkassenubergreifender Zugang (unabhangig von einer bestimmten Kasse) - flachendeckend (nachweislich Teilnahme von Hausarzten aus ganz RL-P) - Aufbau von Daten- und Biomaterialiensammlung etabliert als Grundlage fur Biomarkerforschung und Aufbau eines Rheuma-Registers Rheinland-Pfalz.

In a fusion reactor, strict control of tritium is required from the viewpoints of sufficient fuel balance and radiological hazard. Fabrication of tritium-impermeable ceramic coatings is a promising solution, and ceramic coatings have been investigated for several decades. In recent years, several irradiation tests have been conducted for the ceramic coatings to understand irradiation effects on their characteristics and functions. However, there are few experimental reports on multi-irradiation tests of neutrons and alpha particles produced by nuclear reactions and radioactive decay of tritium. In this study, yttrium oxide coatings were fabricated by reactive and non-reactive radio frequency magnetron sputtering, and their microstructures and deuterium permeation behaviors were investigated after heavy ion irradiation and helium implantation tests simulating irradiation damage by neutrons and generated alpha particles. All irradiated samples showed the formation of an amorphous layer and a nanocrystalline layer or region. In particular, an iron-helium-simultaneous-irradiated sample contained voids including nanometer-size spheres, indicating the formation of helium bubbles. The irradiated samples showed grain growth and/or crystallization at a higher temperature than the unirradiated samples during deuterium permeation tests. That suggests that the voids and the helium bubbles prevented structural change at low temperatures. Moreover, the helium bubbles tended to be more stable than the voids. On the other hand, nickel-single and nickel-helium-sequential-irradiated coatings deposited by non-reactive sputtering showed few voids and helium bubbles, resulting in a different behavior of deuterium permeation.

Tailings storage facilities (TSFs) are an essential infrastructure of mineral processing, but they represent a significant physical, chemical and biological hazard and must, therefore, be strictly and responsibly sited, managed and closed. Tailings can, for example, be dispersed by many processes (such as sinkholes, earthquakes, intense rainfall and flood events, and wind), substandard design and construction, and seepage. The stability and behaviour of TSFs needs to be continuously monitored and one highly effective way of doing this is through satellite Earth observation (EO). The EO industry is witnessing a technological revolution. Large and long-lifespan satellite sensors that have been the staple of national space agencies and commercial satellite manufacturers are now being complemented by constellations of low-cost, short-lifespan ‘cube sats’ by companies with the ambition to image the whole earth daily. Satellites with synthetic aperture radar (SAR) sensors are also collecting high volumes of data, with the added benefit of being able to do so day or night and in different weather conditions. The range of data options and capabilities these provide open opportunities for novel data analysis techniques for TSFs. One of these is satellite InSAR (interferometric SAR; a technique used to map millimetric-precision changes in ground height over time), which is already used by mining companies to reduce risk in and of their operations. From monitoring the stability of TSFs, through to assessments of impacts of natural hazards, InSAR allows rapid and accurate targeting of high-risk areas and structures to identify those that require subsequent investigation through ground-based methods. To demonstrate the application of EO data and InSAR in identifying pre- and post-failure mine activities and TSF deformation, the authors will present a case study across Cadia mine, New South Wales, Australia, which had a localised TSF failure on 9 March 2018. The InSAR results presented show that low-magnitude subsidence signals were observed across the TSF dam during the year preceding the collapse. In January 2018 a notable change in behaviour was observed, with a concentrated area of subsidence focused on the region which initially failed on 9 March 2018. Furthermore, post-collapse InSAR measurements show an increased rate of subsidence for regions either side of the failure zone. Review of medium- and high-resolution satellite images show that the failure was phased, with an initial failure and then a subsequent failure at least two days after 9 March 2018. It also highlights what might be construction activity associated with a dam raise prior to failure.

Normalized Cut is a well-established divisive image segmentation method, which we adapt in this paper for the segmentation of laser point clouds in urban areas. Our focus is on polyhedral objects with planar surfaces. Due to its target function, Normalized Cut favours cuts with “short cut lines” or “small cut surfaces”, which is a drawback for our application. We therefore modify the target function, weighting the similarity measures with distance-dependent weights. We call the induced minimization problem “Distance-weighted Cut” ( DWCut ). The new target function leads to a generalized eigenvalue problem, which is slightly more complicated than the corresponding problem for the Normalized Cut; on the other hand, the new target function is easier to interpret and avoids some drawbacks of the Normalized Cut. We point out an efficient method for the numerical solution of the eigenvalue problem which is based on a Krylov subspace method. DWCut can be beneficially combined with an aggregation in order to reduce the computational effort and to avoid shortcomings due to insufficient plane parameters. We present examples for the successful application of the Distance-weighted Cut principle and evaluate its results by comparison with the results of corresponding manual segmentations.

The primary purpose of this study was to examine the effect of acute maximal exercise (VO2max test) on salivary immunoglobulin A (SIgA) responses in adolescent females. A secondary aim was to examine the relationship between resting SIgA levels and VO2max, physical activity, body composition, and diet.Fifty healthy female adolescents completed a laboratory-based VO2max test, assessment of body composition via hydrodensitometry, a validated physical activity questionnaire (PAQ-A), and a three-day food diary. Unstimulated saliva was collected before, and 5 and 120 minutes after VO2max testing. Absolute SIgA (µg/mL) concentration was determined using an enzyme-linked immunosorbent assay. Secretion rate of SIgA (µg/min) was calculated by multiplying absolute SIgA concentration by saliva flow rate (SFR, µL/min).A significant increase in absolute SIgA concentration (146.8±59.2 µg/mL) was noted immediately after VO2max testing (P0.05) and returned to pre-exercise levels (120.1±54.1 µg/mL) by 120-min post-exercise (P0.05). No significant VO2max test effects were observed for SIgA secretion rate and SFR (P0.05). VO2max values (41.92±6.36 mL/kg/min) were correlated with body fat percentage (r=-0.59; P0.01), PAQ-A total score (r=0.48; P0.01), and acute changes in absolute SIgA levels (r=0.28; P0.05). No significant associations were observed between dietary measures and resting SIgA levels or SFR (P0.05) except for dietary fiber which correlated with resting absolute SIgA concentration (r=0.29; P0.05).Findings indicate that acute graded maximal exercise results in a transient increase in absolute SIgA concentration and that these changes are associated with individual VO2max values.

Objective: To study the pregnancy outcomes of women with a dichorionic triamniotic triplet pregnancy that was reduced to a singleton pregnancy and to review the literature. Methods: We performed a nationwide retrospective cohort study. We compared time to delivery and perinatal mortality in dichorionic triplet pregnancies reduced to singletons with ongoing dichorionic triplet pregnancies and primary singleton pregnancies. Additionally, we reviewed the literature on the subject. Results: We studied 46 women with a reduced dichorionic triplet pregnancy and 42 women with an ongoing dichorionic triplet pregnancy. Median gestational age at delivery was 38.7 vs. 32.8 weeks, respectively (p < 0.001). Delivery Conclusion: Multifetal pregnancy reduction in women with a dichorionic triplet pregnancy to a singleton pregnancy prolongs median gestational age at birth. No statistically significant association was found with miscarriage and perinatal survival rates.

The American College of Clinical Pharmacy (ACCP) and the American Society of Health-System Pharmacists (ASHP) share a common vision that all pharmacists involved with direct patient care will be required to complete a postgraduate residency prior to entering practice by 2020. This requirement will impact most pharmacy school graduates. The number of residency programs available will have to grow significantly; however, the current rate of growth is not nearly sufficient to create enough residency training programs by 2020. Barriers to increasing the number of residency positions include the cost of creating residency positions, the pharmacy residency teaching model, and the need for qualified preceptors. Solutions to overcome these barriers include the following: utilizing residents to provide needed services, coverage, and scholarship activity; converting to a residency model similar to the medical model, which allows for a 1:6 preceptor to resident ratio; developing preceptor training programs and standardizing teaching certificates, which could be accomplished by establishing relationships with colleges of pharmacy; and encouraging smaller community hospitals to develop residency programs, which could be accomplished by partnering with nearby academic medical centers or other community hospitals. Now is the time to embrace this opportunity for change and improvement in the pharmacy education system. Pharmacy professionals need to come together to overcome this challenge.

Background High-alert medications pose a greater risk of causing significant harm to patients if used in error. The Joint Commission requires that hospitals define institution-specific high-alert medications and implement processes to ensure safe medication use. Method Nursing, pharmacy, and prescribers were asked to voluntarily complete a 34-question survey to assess their knowledge, experience, and perceptions regarding high-alert medications in an academic hospital. Results The majority of respondents identified the organization's high-alert medications, the consequences of an error involving a high-alert medication, and the reversal agent. Most of the risk-reduction strategies within the institution were viewed as being effective by respondents. Forty-five percent of the respondents utilized a high-alert medication in the previous 24 hours. Only 14.2% had experienced an error with a high-alert medication in the previous 12 months, with 46% being near misses. The survey found the 5 rights for medication administration were not being utilized consistently. Respondents indicated that work experience or hospital orientation is the preferred learning experience for high-alert medications. Conclusions This study assessed all disciplines involved in the medication use process. Perceptions about high-alert medications differ between disciplines. Ongoing discipline-specific education is required to ensure that individuals accept accountability in the medication use process and to close knowledge gaps on high-alert medications and risk-reduction strategies.

Pansharpening has proven to be a valuable method for resolution enhancement of multi-band images when spatially high-resolving panchromatic images are available in addition. In principle, pansharpening can beneficially be applied to hyperspectral images as well. But whereas the grey values of multi-spectral images comprise at most relative information about the registered intensities, calibrated hyperspectral images are supposed to provide absolute reflectivity values of the respective material surfaces. This physical significance of the hyperspectral data should be preserved within the pansharpening process as much as possible. In this paper we compare several common pansharpening methods such as Principal Component Fusion, Wavelet Fusion, Gram-Schmidt transform and investigate their applicability for hyperspectral data. Our focus is on the impact of the pansharpening on material classifications. Apart from applying common quality measures, we compare the results of material classifications from hyperspectral data, which were pansharpened by different methods. In addition we propose an alternative pansharpening method which is based on an initial segmentation of the panchromatic image with an additional use of map vector data.

Tritium permeation through structural materials is a critical issue in fusion reactors from the viewpoints of sufficient fuel balance and radiological hazard. Ceramic coatings have been investigated as tritium permeation barrier for several decades; however, irradiation effects of the coatings on permeation are not elucidated. In this work, yttrium oxide coatings were fabricated on reduced activation ferritic/martensitic steels by radio frequency magnetron sputtering, and their microstructures and deuterium permeation behaviors were investigated before and after iron-ion irradiation at different temperatures. An as-deposited coating had a columnar structure and transformed into a granular one after annealing. An amorphous layer formed near the coating-substrate interface of irradiated coatings, and its thickness became thinner with increasing irradiation temperature. Voids of approximately 20 nm in diameter also formed in the irradiated coatings. Deuterium permeation flux of the sample irradiated to 1 dpa at room temperature was the lowest among the unirradiated and irradiated samples, and a permeation reduction factor indicated up to 390. The amorphous layer disappeared after deuterium permeation measurements due to damage recovery, while the voids remained and aggregated. The irradiation damage would accelerate nucleation of the crystal, resulting in a decrease of the permeation flux.

Onder redactie van AnneLoes van Staa, Ada ter Maten-Speksnijder en Lausanne Mies. Dit boek helpt verpleegkundigen, studenten verpleegkunde en verpleegkundig specialisten het zelfmanagement van mensen met chronische aandoeningen te ondersteunen. Dat behoort tot de kerntaak van elke verpleegkundige. Het boek geeft daarvoor de kennis, traint de vaardigheden en bespreekt de gewenste attitude, zoals een open houding, goede gespreksvoering en samenwerking met de patient en andere (mantel)zorgverleners.

Objective To determine the degree in variation of oral liquid pediatric compounding practices in Michigan pharmacies. Design Cross-sectional survey study. Setting All types of inpatient and outpatient pharmacies across the state of Michigan, excluding nuclear pharmacies and long-term care facilities. Participants 244 Michigan pharmacies. Intervention An online survey tool was used to assess the current compounding practices of 147 oral liquid pediatric medications. The survey was e-mailed or faxed to hospitals, chain pharmacies, and independent pharmacies. Pharmacists were also mailed a follow-up postcard, and the Michigan Pharmacists Association publicized the project through its journal and annual meeting. Main outcome measures Pharmacy demographics; number of compounding pharmacies; number of medications compounded; awareness of compounding errors; results of compounding errors; and number of concentrations compounded per medication. Results The majority of respondents were from outpatient pharmacies, but inpatient and other types of pharmacies were also represented. The majority of participating pharmacies compound fewer than five oral liquid medications per week. Awareness of errors was low overall, with no errors believed to result in permanent harm or death. The number of concentrations compounded per medication ranged from 1 to 9, with the majority of pharmacies compounding more than 3 concentrations per medication. Conclusion There is a considerable degree of variation in current oral pediatric liquid compounding practices in Michigan pharmacies. This variability poses a significant risk to patient safety.

OBJECTIVE: The aim of this study was to compare screening performance for Down syndrome of the absolute risk (AR) method to the first trimester combined test (FCT) at different maternal ages. METHODS: There was a retrospective analysis of 32,448 FCT. AR was defined as final risk divided by maternal age risk. RESULTS: The likelihood of receiving a true prediction was comparable between both methods in all age groups. With the AR method, two extra Down syndrome cases were detected in women /=36 years, and the likelihood of receiving a false prediction decreased overall (OR 0.82, CI 0.77-0.87; P < 0.0001), in women aged 36-40 years (0.45, CI 0.41-0.51; P < 0.0001), in women aged 41-45 years (0.18, CI 0.13-0.26; P < 0.0001) and increased in women aged

Objective: To validate previously computed correction factors for free β-human chorionic gonadotrophin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies with hormone treatment and to determine the effect on false-positive rate (FPR). Methods: Retrospective study on 249 IVF and 250 ICSI cases and 20,190 controls. Correction factors 1.42 (PAPP-A), 1.17 (fβ-hCG) in IVF; 1.56 (PAPP-A) in ICSI were applied on the absolute serum concentrations. Analysis was done on log10-transformed multiples of medians (MoMs). Results: In the controls, mean PAPP-A and fβ-hCG MoM were 1.004 and 1.062. Before correction, mean PAPP-A MoM was significantly lower in IVF (0.757; p < 0.001) and in ICSI (0.671; p < 0.001) and after correction comparable (1.071; p = 0.053 in IVF; 1.048; p = 0.178 in ICSI). Before correction, mean fβ-hCG MoM was comparable (1.054; p = 0.59 in IVF and 1.051; p = 0.56 in ICSI) and after correction significantly higher in IVF (1.241; p < 0.001). After correction the likelihood for receiving a false-positive result was 1.03 in IVF pregnancies (95% CI 0.98-1.09; p = 0.248) and 1.02 in ICSI pregnancies (95% CI 0.97-1.07; p = 0.448). Conclusions: After correction the FPR in IVF and ICSI pregnancies with hormone treatment reduces to the observed FPR in the controls.

The aim of the rheumatology network ADAPTHERA ("risk-adapted rheumatology therapy") is to achieve a comprehensive improvement in rheumatology care by coordinating treatment in a regional, trans-sectoral network. Accompanying biomedical research projects, training concepts, and the construction of a rheumatology register (gathering data and biomaterials) should furthermore ensure the stable and sustainable optimisation of care. In the pilot phase (2012-2015) the focus of the ADAPTHERA network, required as a "regional key project" within the framework of the Initiative on Health Economy of Rheinland-Palatinate (RL-P), Germany, was placed on the optimisation of the early diagnosis of rheumatoid arthritis, where it is well-known that there is a significant care deficit.Through the intensive, stable, and coordinated cooperation of all health care partners in the field of rheumatology (registered general practitioners and orthopaedic specialists, registered core rheumatologists as well as the Association of Rheumatology of RL-P) a unique regional, comprehensive offer with verifiable care optimisation has been established in RL-P. The network is supported by outstanding collaboration with the Association of Statutory Health Insurance Physicians and the self-help organisation Rheumatology League.The aims that were established at the start of the project will be achieved by the end of the pilot phase:- significant improvement in the early diagnosis of rheumatoid arthritis (an average of 23.7 days until diagnosis by rheumatologists)- access covering all health insurance (regardless of the particular scheme the patients belong to)- comprehensive (verifiable participation of general practitioners from all over RL-P)- data and biomaterials collection, established as a basis for biomarker research, and a rheumatology register for RL-P.

Purpose The development, dissemination, and adoption of standard concentrations for compounded oral liquids for pediatric patients in Michigan are described. Summary A baseline assessment of current practices in Michigan revealed significant variations in the concentrations of commonly used oral liquid medicines for pediatric patients. A statewide collaborative initiative in Michigan was created to standardize the concentrations of compounded oral liquids for pediatric patients. Standard concentrations were proposed and adopted by key stakeholders. These standards were then disseminated across the state to prescribers and pharmacists, with encouragement to voluntarily adopt the standards as a patient safety measure. A follow-up survey was conducted to evaluate adoption of the standards. A total of 263 pharmacists responded to the survey. Standardization of the concentrations of compounded oral liquids in Michigan was welcomed by most pharmacies and is perceived to have reduced the risk for errors at transitions of care for children receiving compounded oral liquids. Awareness of the standardization initiative was acknowledged by 77% of survey respondents, and adoption of the standards was observed to some degree by 57% of survey respondents. In addition, 70% of survey respondents agreed or strongly agreed that adoption of the standards has improved patient safety in Michigan. Conclusion Standard drug concentrations for compounded oral liquids were developed for pediatric patients in Michigan. A survey after dissemination of the recommended standards confirmed general awareness of the initiative and adoption of the standards by a substantial proportion of respondents. Most respondents indicated a belief that creation of the standards improved patient safety.

As a part of a research project on the development of a low-cost sensor system for use on gyrocopters several investigations on the recording of aerial image blocks have been carried out during the last two years. The vibration of the gyrocopter platform is one of the critical factors that should be mitigated during the data collection. Apart from the wind-induced oscillation, the vibration induced by the motor, the propeller and the main rotor are prominent. To prevent negative impact to the imaging process, vibration absorbers are to be implemented on the sensor platform. One focus of this research is a comparison between the vibrations within the passenger area and the vibrations at the undercarriage of the gyrocopter. The comparison is based on the use of three synchronized micro-electro mechanical motion trackers (MEMS IMUs), one fixed on the gyrocopter floor and the others fixed on the struts of the gyrocopter. The results indicate that the propeller and rotorinduced vibrations are somewhat bigger within the passenger area. Fourier analysis shows that the rotor-induced vibration at a frequency of 12 Hz is predominant in all signals; its amplitude may vary strongly in time. Whereas the translational vibrations have negligible impact on the image quality, rotational vibrations around all three axes may effect significant blurring of aerial images according to common quality standards.