Derivation of environmental quality standards for free cyanide incorporating censored data into species sensitivity distributions.

Free cyanide is considered to be the most toxic form of cyanides to aquatic life. Due to its broad range of uses and subsequent potential widespread emissions to surface water, the environmental effects of free cyanide have been extensively researched. Regulatory bodies have proposed water quality standards for free cyanide, but these are regularly debated and implementation has been inconsistent due to monitoring challenges. The aim of the present study was therefore to derive new environmental quality standards (EQS) for free cyanide according to the Water Framework Directive (WFD). Ecotoxicity data from previous derivations and an additional literature search were gathered and individually (re) evaluated on reliability. The pooled acute ecotoxicity dataset consisted of reliable results for 35 species, distributed over 8 taxonomic groups. The pooled chronic ecotoxicity dataset consisted of results for 13 species, distributed over 7 taxonomic groups. WFD criteria for deriving a species sensitivity distribution (SSD) were met, if censored data points were included. Using the R-package ETX 3.0, an SSD including censored data was constructed and acute and chronic HC5 values of 17 and 0.66 µg/L, respectively, were derived. Comparisons were made with alternative SSDs constructed by transforming or discarding the censored data. Applying a default assessment factor (AF) of 10 to the HC5 from the acute SSD resulted in a MAC-EQS of 1.7 µg CN-/L for freshwater and marine water. Careful consideration was given to addressing the uncertainty around the chronic HC5 value for the selection of an AF of 3, resulting in an AA-EQS of 0.22 µg CN-/L for freshwater and 0.044 µg CN-/L for marine water by applying an additional AF of 5. It is concluded that the current environmental quality standards for free cyanide are the first to be derived according to the WFD guidance, using only reliable data and including censored values.

Secondary integrated analysis of multi-tissue transcriptomic responses to a combined lifestyle intervention in older adults from the GOTO nonrandomized trial.

Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 ( https://onderzoekmetmensen.nl/nl/trial/27183 ), NL-OMON27183 , primary outcomes have been previously reported in ref. 1), a moderate 13-week combined lifestyle intervention on the transcriptomes of postprandial blood, subcutaneous adipose tissue (SAT) and muscle tissue in healthy older adults, the overlap in effect between tissues and their relation to whole-body parameters of metabolic health. The GOTO intervention has virtually no effect on the postprandial blood transcriptome, while the SAT and muscle transcriptomes respond significantly. In SAT, pathways involved in HDL remodeling, O2/CO2 exchange and signaling are overrepresented, while in muscle, collagen and extracellular matrix pathways are significantly overexpressed. Additionally, we find that the effects of the SAT transcriptome closest associates with gains in metabolic health. Lastly, in males, we identify a shared variation between the transcriptomes of the three tissues. We conclude that the GOTO intervention has a significant effect on metabolic and muscle fibre pathways in the SAT and muscle transcriptome, respectively. Aligning the response in the three tissues revealed a blood transcriptome component which may act as an integrated health marker for metabolic intervention effects across tissues.

Using non-randomized trials to assess the clinical benefit of systemic anti-cancer treatments: Viable or not?

BACKGROUND: The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs). METHODS: Using the RCTs underpinning cieBOM recommendations issued between 2015 and 2017, we searched for matching NRTs and applied the NRT-related assessment criteria by cieBOM to them. We then compared the assessment outcomes to the respective RCT-based cieBOM recommendations. Further, we investigated how the assessments would change when applying different response-related thresholds and adding a progression-free survival (PFS) threshold. RESULTS: For 13 of the 37 eligible recommendations, a matching NRT was found. Two treatments were assessed positively and six negatively; five treatments were non-assessable. Two positive recommendations matched a positive NRT-based assessment; one matching negative assessment was found, and one treatment could not be assessed based on either trial results. Adding a > 6 months PFS threshold decreased the number of non-assessable NRTs (five to two). CONCLUSIONS: Limited publications and inconsistent data reporting hampered the viability of NRTs for clinical benefit assessments of SACTs beyond the scope of rare indications. Further, response-related assessment criteria alone might not fully grasp the clinical benefit of novel SACTs. NRT-based assessments should be considered with caution due to uncertainty of the trial results.

Effect of COVID-19 lockdown on maternity care and maternal outcome in the Netherlands: a national quasi-experimental study.

OBJECTIVES: The COVID-19 pandemic and associated lockdowns disrupted health care worldwide. High-income countries observed a decrease in preterm births during lockdowns, but maternal pregnancy-related outcomes were also likely affected. This study investigates the effect of the first COVID-19 lockdown (March-June 2020) on provision of maternity care and maternal pregnancy-related outcomes in the Netherlands. STUDY DESIGN: National quasi-experimental study. METHODS: Multiple linked national registries were used, and all births from a gestational age of 24+0 weeks in 2010-2020 were included. In births starting in midwife-led primary care, we assessed the effect of lockdown on provision of care. In the general pregnant population, the impact on characteristics of labour and maternal morbidity was assessed. A difference-in-regression-discontinuity design was used to derive causal estimates for the year 2020. RESULTS: A total of 1,039,728 births were included. During the lockdown, births to women who started labour in midwife-led primary care (49%) more often ended at home (27% pre-lockdown, +10% [95% confidence interval: +7%, +13%]). A small decrease was seen in referrals towards obstetrician-led care during labour (46%, -3% [-5%,-0%]). In the overall group, no significant change was seen in induction of labour (27%, +1% [-1%, +3%]). We found no significant changes in the incidence of emergency caesarean section (9%, -1% [-2%, +0%]), obstetric anal sphincter injury (2%, +0% [-0%, +1%]), episiotomy (21%, -0% [-2%, +1%]), or post-partum haemorrhage: >1000 ml (6%, -0% [-1%, +1%]). CONCLUSIONS: During the first COVID-19 lockdown in the Netherlands, a substantial increase in homebirths was seen. There was no evidence for changed available maternal outcomes, suggesting that a maternity care system with a strong midwife-led primary care system may flexibly and safely adapt to external disruptions.

An ultra high-endurance memristor using back-end-of-line amorphous SiC.

Integrating resistive memory or neuromorphic memristors into mainstream silicon technology can be substantially facilitated if the memories are built in the back-end-of-line (BEOL) and stacked directly above the logic circuitries. Here we report a promising memristor employing a plasma-enhanced chemical vapour deposition (PECVD) bilayer of amorphous SiC/Si as device layer and Cu as an active electrode. Its endurance exceeds one billion cycles with an ON/OFF ratio of ca. two orders of magnitude. Resistance drift is observed in the first 200 million cycles, after which the devices settle with a coefficient of variation of ca. 10% for both the low and high resistance states. Ohmic conduction in the low resistance state is attributed to the formation of Cu conductive filaments inside the bilayer structure, where the nanoscale grain boundaries in the Si layer provide the pre-defined pathway for Cu ion migration. Rupture of the conductive filament leads to current conduction dominated by reverse bias Schottky emission. Multistate switching is achieved by precisely controlling the pulse conditions for potential neuromorphic computing applications. The PECVD deposition method employed here has been frequently used to deposit typical BEOL SiOC low-k interlayer dielectrics. This makes it a unique memristor system with great potential for integration.

Applying a cost-based pricing model for innovative cancer treatments subject to indication expansion: A case study for pembrolizumab and daratumumab.

BACKGROUND: Expanding the indication of already approved immuno-oncology drugs presents treatment opportunities for patients but also strains healthcare systems. Cost-based pricing models are discussed as a possibility for cost containment. This study focuses on two drugs, pembrolizumab (Keytruda) and daratumumab (Darzalex), to explore the potential effect of indication broadening on the estimated price when using the cost-based pricing (CBP) model proposed by Uyl-de Groot and Löwenberg (2018). METHODS: The model was used to calculate cumulative yearly prices, cumulative prices per indication, and non-cumulative indication-based prices using inputs such as research and development (R&D) costs, manufacturing costs, eligible patient population, and a profit margin. A deterministic stepwise analysis and scenario analysis were conducted to examine how sensitive the estimated price is to the different input assumptions. RESULTS: The yearly cumulative cost-based prices (CBPs) ranged from €52 to €885 for pembrolizumab per vial and €823 to €31,941 for daratumumab per vial. Prices were higher in initial years or indications due to smaller patient populations, decreased over time or after additional indications. Sensitivity analysis showed that the number of eligible patients had the most significant impact on the estimated price. In the scenario analysis the profit margin contributed most to a higher CBPs for both drugs. Lower estimates resulted from assumed lower R&D costs. DISCUSSION: The estimated CBPs are consistently lower than Dutch list prices for pembrolizumab (€2,861), mainly resulting from larger patient populations in registered indications. However, daratumumab's list prices fall within the range of modeled CBPs depending on the year or indication (€4,766). Both CBPs decrease over time or with additional indications. The number of eligible patients and initial R&D costs have the most significant influence on the CBPs. These findings contribute to the ongoing discussions on pharmaceutical pricing, especially concerning cancer drugs with expanding indications.

Considering multifetal pregnancy reduction in triplet pregnancies: do we forget the emotional impact on fathers? A qualitative study from The Netherlands.

STUDY QUESTION: What factors influence the decision-making process of fathers regarding multifetal pregnancy reduction or maintaining a triplet pregnancy, and how do these decisions impact their psychological well-being? SUMMARY ANSWER: For fathers, the emotional impact of multifetal pregnancy reduction or caring for triplets is extensive and requires careful consideration. WHAT IS KNOWN ALREADY: Multifetal pregnancy reduction is a medical procedure with the purpose to reduce the number of fetuses to improve chances of a healthy outcome for both the remaining fetus(es) and the mother, either for medical reasons or social considerations. Aspects of the decision whether to perform multifetal pregnancy reduction have been rarely investigated, and the impact on fathers is unknown. STUDY DESIGN, SIZE, DURATION: Qualitative study with semi-structured interviews between October 2021 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fathers either after multifetal pregnancy reduction from triplet to twin or singleton pregnancy or ongoing triplet pregnancies 1-6 years after the decision were included. The interview schedule was designed to explore key aspects related to (i) the decision-making process whether to perform multifetal pregnancy reduction and (ii) the emotional aspects and psychological impact of the decision. Thematic analysis was used to identify patterns and trends in the father's data. The process involved familiarization with the data, defining and naming themes, and producing a final report. This study was a collaboration between a regional secondary hospital (OLVG) and a tertiary care hospital (Amsterdam University Medical Center, Amsterdam UMC), both situated in Amsterdam, The Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: Data saturation was achieved after 12 interviews. Five main themes were identified: (i) initial responses and emotional complexity, (ii) experiencing disparities in counselling quality and post-decision care, (iii) personal influences on the decision journey, (iv) navigating parenthood: choices, challenges, and emotional adaptation, and (v) shared wisdom and lessons. For fathers, the decision whether to maintain or reduce a triplet pregnancy is complex, in which medical, psychological but mainly social factors play an important role. In terms of psychological consequences after the decision, this study found that fathers after multifetal pregnancy reduction often struggled with difficult emotions towards the decision; some expressed feelings of doubt or regret and were still processing these emotions. Several fathers after an ongoing triplet had experienced a period of severe stress in the first years after the pregnancy, with major consequences for their mental health. Help in emotional processing was not offered to any of the fathers after the decision or birth. LIMITATION, REASONS FOR CAUTION: While our study focuses on the multifetal pregnancy reduction process in the Amsterdam region, we recognize the importance of further investigation into how this process may vary across different regions in The Netherlands and internationally. We acknowledge the potential of selection bias, as fathers with more positive experiences might have been more willing to participate. Caution is needed in interpreting the role of the mother in the recruitment process. Additionally, the time span of 1-6 years between the decision and the interviews may have influenced emotional processing and introduced potential reporting bias. WIDER IMPLICATIONS OF THE FINDINGS: The emotional impact of multifetal pregnancy reduction or caring for triplets is significant, emphasizing the need for awareness among caregivers regarding the emotional challenges faced by fathers. A guided trajectory might optimize the decision-making and primarily facilitate the provision of appropriate care thereafter to optimize outcomes around decisions with potential traumatic implications. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The barriers and needs of transgender men in pregnancy and childbirth: A qualitative interview study.

OBJECTIVE: Transgender and gender diverse individuals are individuals whose gender identity differs from their sex assigned at birth. The discordance between gender identity and sex assignment may cause significant psychological distress: gender dysphoria. Transgender individuals may choose to undergo gender-affirming hormone treatment or surgery, but some decide to (temporarily) refrain from surgery and gender affirming hormone treatment and hence retain the possibility to become pregnant. Pregnancy may enhance feelings of gender dysphoria and isolation. To improve perinatal care for transgender individuals and their health care providers, we conducted interviews to explore the needs and barriers of transgender men in family planning, pregnancy, childbirth, puerperium and perinatal care. DESIGN: In this qualitative study five in-depth semi-structured interviews were conducted with Dutch transgender men who had given birth while identifying on the transmasculine spectrum. The interviews were conducted online through a video remote-conferencing software program (n=4) or live (n=1). Interviews were transcribed verbatim. An inductive approach was used to find patterns and collect data from the participants' narratives and constant comparative method was adapted in analysing the interviews. MEASUREMENTS AND FINDINGS: The experiences of transgender men regarding the preconception period, pregnancy and puerperium and with perinatal care varied widely. Though all participants expressed overall positive experiences, their narratives emphasized they had to overcome substantial hurdles pursuing pregnancy. For instance the necessity to prioritise becoming pregnant over gender transitioning, lack of support by healthcare providers and increased gender dysphoria and isolation during pregnancy KEY CONCLUSIONS: Since pregnancy in transgender men enhances feelings of gender dysphoria, transgender men comprise a vulnerable group in perinatal care. Health care providers are perceived as feeling unaccustomed for the care of transgender patients, as they are perceived to often lack the right tools and knowledge to provide adequate care. Our findings help strengthen the foundation of insight in the needs and hurdles of transgender men pursuing pregnancy and therefore may guide health care providers to provide equitable perinatal care, and emphasize the necessity of patient-centred gender-inclusive perinatal care. A guideline including the option for consultation of an expertise center is advised to facilitate patient-centered gender-inclusive perinatal care.

Flexible Memristor Devices Using Hybrid Polymer/Electrodeposited GeSbTe Nanoscale Thin Films.

We report on the development of hybrid organic-inorganic material-based flexible memristor devices made by a fast and simple electrochemical fabrication method. The devices consist of a bilayer of poly(methyl methacrylate) (PMMA) and Te-rich GeSbTe chalcogenide nanoscale thin films sandwiched between Ag top and TiN bottom electrodes on both Si and flexible polyimide substrates. These hybrid memristors require no electroforming process and exhibit reliable and reproducible bipolar resistive switching at low switching voltages under both flat and bending conditions. Multistate switching behavior can also be achieved by controlling the compliance current (CC). We attribute the switching between the high resistance state (HRS) and low resistance state (LRS) in the devices to the formation and rupture of conductive Ag filaments within the hybrid PMMA/GeSbTe matrix. This work provides a promising route to fabricate flexible memory devices through an electrodeposition process for application in flexible electronics.

Confining the growth of mesoporous silica films into nanospaces: towards surface nanopatterning.

The combination of lithographic methods and sol gel bottom-up techniques is a promising approach for nanopatterning substrates. The integration and scalable fabrication of such substrates are of great interest for the development of nanowire-based materials opening potentialities in new technologies. We demonstrate the deposition of ordered mesoporous silica into nanopatterned silica substrates by dip coating. Using scanning electron microscopy and grazing incidence small angle X-ray scattering, the effect of the sol composition on the pore ordering was probed. Optimising the sol composition using anodic alumina membranes as confined spaces, we showed how the pH controlled the transformation from circular to columnar mesophase. Vertical mesopores were obtained with very good repeatability. The effect of the sol chemistry on the surfactant curvature was then shown to be similar in nanopatterned substrates made by e-beam lithography.

Screening for adolescent idiopathic scoliosis is more accurate when performed by healthcare professionals compared to untrained parents: a diagnostic accuracy study.

BACKGROUND: Many countries ended their professional scoliosis screening due to ongoing controversies. Discontinuation resulted in a shift of screening responsibility from trained healthcare professionals to untrained parents. PURPOSE: To compare the diagnostic accuracy of picture-based scoliosis screening between parents and healthcare professionals. METHODS: In this cross-sectional diagnostic accuracy study, parents and healthcare professionals assessed pictures of 28 children (20 AIS & 8 non-scoliosis). Each child had two photographs (standing position & full-flexion during forward-bending test) that were presented simultaneously. Lumbar and thoracic curves were represented with a range in severity (10 to > 40°). The assessors had to answer whether they detected an abnormality that ought to be referred to a specialist. Measures of accuracy were calculated for both groups and various curve severities. RESULTS: All pictures were assessed by 101 parents and 122 healthcare professionals. The sensitivity for detecting scoliosis was significantly lower in untrained parents (63.8%, [95% CI: 61.7-65.9%]) compared to healthcare professionals (73.4%, [95% CI: 71.6-75.2%]; p < 0.001), while the specificity was not significantly different (63.6%, [95% CI: 60.2-66.9%] vs. 65.3%, [95% CI: 62.2-68.3%]; p = 0.49). Healthcare professionals consistently recognized the gibbus as a warning sign when referring patients, while untrained parents highlighted various regions, including the spine, gibbus and scapula regions. CONCLUSION: The sensitivity of screening for scoliosis was significantly lower when it was performed by parents, while the false-positive rate was similar to healthcare professionals. The window of opportunity for conservative treatment may be missed when parents rather than professionals are responsible for screening.

Trends in survival and costs in metastatic melanoma in the era of novel targeted and immunotherapeutic drugs.

BACKGROUND: The objective of this study was to evaluate trends in survival and health care costs in metastatic melanoma in the era of targeted and immunotherapeutic drugs. MATERIALS AND METHODS: Data on survival and health care resource use were retrieved from the Dutch Melanoma Treatment Registry. The Kaplan-Meier method was used to estimate overall survival. Health care costs and budget impact were computed by applying unit costs to individual patient resource use. All outcomes were stratified by year of diagnosis. RESULTS: Baseline characteristics were balanced across cohort years. The percentage of patients receiving systemic treatment increased from 73% in 2013 to 90% in 2018. Patients received on average 1.85 [standard deviation (SD): 1.14] lines of treatment and 41% of patients received at least two lines of treatment. Median survival increased from 11.8 months in 2013 [95% confidence interval (CI): 10.7-13.7 months] to 21.1 months in 2018 (95% CI: 18.2 months-not reached). Total mean costs were €100 330 (SD: €103 699); systemic treatments accounted for 84% of the total costs. Costs for patients who received systemic treatment [€118 905 (SD: €104 166)] remained reasonably stable over the years even after the introduction of additional (combination of) novel drugs. From mid-2013 to 2018, the total budget impact for all patients was €452.79 million. CONCLUSION: Our study shows a gain in survival in the era of novel targeted and immunotherapeutic drugs. These novel drugs came, however, along with substantial health care costs. Further insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in the treatment of patients with metastatic melanoma.

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

Cost-effectiveness of adjuvant systemic therapies for patients with high-risk melanoma in Europe: a model-based economic evaluation.

BACKGROUND: The introduction of adjuvant systemic treatment has significantly improved recurrence-free survival in patients with resectable high-risk melanoma. Adjuvant treatment with immune checkpoint inhibitors and targeted therapy, however, substantially impacts health care budgets, while the number of patients with melanoma who are treated in the adjuvant setting is still increasing. To evaluate the socioeconomic impact of the three adjuvant treatments, a cost-effectiveness analysis (CEA) was carried out. MATERIALS AND METHODS: Data were obtained from the three pivotal registration phase III clinical trials on the adjuvant treatment of patients with resected high-risk stage III in melanoma (KEYNOTE-054, CheckMate 238, and COMBI-AD). For this CEA, a Markov model with three health states (no evidence of disease, recurrent/progressive disease, and death) was applied. From a societal perspective, different adjuvant strategies were compared according to total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. To evaluate model uncertainty, sensitivity analyses (deterministic and probabilistic) were carried out. RESULTS: In the adjuvant setting, total costs (per patient) were €168 826 for nivolumab, €194 529 for pembrolizumab, and €211 110 for dabrafenib-trametinib. These costs were mainly determined by drug acquisition costs, whereas routine surveillance costs varied from €126 096 to €134 945. Compared with routine surveillance, LYs improved by approximately 1.41 for all therapies and QALYs improved by 2.02 for immune checkpoint inhibitors and 2.03 for targeted therapy. This resulted in incremental cost-effectiveness ratios of €21 153 (nivolumab), €33 878 (pembrolizumab), and €37 520 (dabrafenib-trametinib) per QALY gained. CONCLUSIONS: This CEA compared the three EMA-approved adjuvant systemic therapies for resected stage III melanoma. Adjuvant treatment with nivolumab was the most cost-effective, followed by pembrolizumab. Combination therapy with dabrafenib-trametinib was the least cost-effective. With the increasing number of patients with high-risk melanoma who will be treated with adjuvant treatment, there is an urgent need to reduce drug costs while developing better prognostic and predictive tools to identify patients who will benefit from adjuvant treatment.

The Effects of Hydrogen Annealing on Carbon Nanotube Field-Effect Transistors.

We have systematically investigated the effects of hydrogen annealing on Ni- and Al-contacted carbon nanotube field-effect transistors (CNTFETs), whose work functions have not been affected by hydrogen annealing. Measured results show that the electronic properties of single-walled carbon nanotubes are modified by hydrogen adsorption. The Ni-contacted CNTFETs, which initially showed metallic behavior, changed their p-FET behavior with a high on-current over 10 µA after hydrogen annealing. The on-current of the as-made p-FETs is much improved after hydrogen annealing. The Al-contacted CNTFETs, which initially showed metallic behavior, showed unipolar p-FET behavior after hydrogen annealing. We analyzed the energy band diagrams of the CNTFETs to explain experimental results, finding that the electron affinity and the bandgap of single-walled carbon nanotubes changed after hydrogen annealing. These results are consistent with previously reported ab initio calculations.

Low-Pressure CVD of GeE (E = Te, Se, S) Thin Films from Alkylgermanium Chalcogenolate Precursors and Effect of Deposition Temperature on the Thermoelectric Performance of GeTe.

The homologous series [GenBu3(EnBu)] (E = Te, Se, S; (1), (3) and (4)) and [GenBu2(TenBu)2] (2) have been synthesized as mobile oils in excellent yield (72-93%) and evaluated as single-source precursors for the low-pressure chemical vapor deposition (LPCVD) of GeE thin films on silica. Compositional and structural characterizations of the deposits have been performed by grazing-incidence X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray analysis, and Raman spectroscopy, confirming the phase purity and stoichiometry. Electrical characterization via variable-temperature Hall effect measurements is also reported. Given the strong interest in GeTe and its alloys for thermoelectric applications, variable-temperature Seebeck data were also investigated for a series of p-type GeTe films. The data show that it is possible to tune the thermoelectric response through intrinsic Ge vacancy regulation by varying the deposition temperature, with the highest power factor (40 µW/K2cm@629 K) and effective ZT values observed for the films deposited at higher temperatures.

Tungsten disulfide thin films via electrodeposition from a single source precursor.

We report a simple process for the electrodeposition of tungsten disulfide thin films from a CH2Cl2-based electrolyte using a tailored single source precursor, [NEt4]2[WS2Cl4]. This new precursor incorporates the 1 : 2 W : S ratio required for formation of WS2, and eliminates the need for an additional proton source in the electrolyte to remove excess sulfide. The electrochemical behaviour of [NEt4]2[WS2Cl4] is studied by cyclic voltammetry and electrochemical quartz crystal microbalance techniques, and the WS2 thin films are grown by potentiostatic electrodeposition.

An implantable device to treat multiple sclerosis: A discrete choice experiment on patient preferences in three European countries.

BACKGROUND: Persons with multiple sclerosis (MS) take their treatment via pills, injections or infusions. A novel mode of disease-modifying treatment administration, an implantable device, is under development. This study determined MS patient preferences for three modes of first-line treatment administration (implant, pills, injectables), and trade-offs regarding treatment characteristics. METHODS: A survey including a discrete choice experiment was conducted among MS patients in the Netherlands, France, and the United Kingdom. Respondents had to repeatedly choose between various treatment scenarios with four treatment characteristics: risk of relapse, reduction of disease progression, risk of side effects and mode of administration. Data was analysed using a panel latent class logit model. RESULTS: Based on the preferences of 753 MS patients (response rate 7%: 753/11202), two latent classes were identified (class probability of 74% vs 26%). Persons with relapsing-remitting MS and who administered medication via injections generally preferred any treatment over no treatment. Patients who could walk without an aid were more likely to prefer no treatment. Reducing disease progression was the most important treatment characteristic class 1. Mode of administration was the most important characteristic in class 2. Patients were willing to accept an increase in risk of relapse and disease progression to get their treatment via an implant rather than injections. Predicted uptake was the highest for the implant, followed by pills, injections, and no treatment. CONCLUSION: We found that a drug-delivery implant could be a potential addition to the MS treatment landscape: MS patients are willing to trade-off risk of relapse and disease progression for an implant, and predicted uptake for an implant is relatively high.

Direct observation of surface charge redistribution in active nanoscale conducting channels by Kelvin Probe Force Microscopy.

Surface-exposed uniformly doped silicon-on-insulator channels are fabricated to evaluate the accuracy of Kelvin Probe Force Microscopy (KPFM) measured surface potential and reveals the role of surface charge on the exposed channel operated in the ambient environment. First, the quality of the potential profile probed in the vacuum environment is assessed by the consistency of converted resistivity from KPFM result to the resistivity extracted by the other three methods. Second, in contrast to the simulated and vacuum surface potential profile and image, the ambient surface potential is bent excessively at the terminals of the channel. The excessive bending can be explained by the movement of surface charge under the drive of geometry induced strong local electric field from the channel and results in non-uniform distribution. The dynamic movement of surface charges is proved by the observation of time-dependent potential drift in the ambient measurement. The result suggests the surface charge effect should be taken into account of the measurement of the surface potential in the ambient environment and the design of charge sensitive devices whose surfaces are exposed to air or in ambient conditions in their operation.

Stress, anxiety and depression in 1466 pregnant women during and before the COVID-19 pandemic: a Dutch cohort study.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic has negatively affected many people's mental health with increased symptoms of stress, anxiety and depression in the general population. Anxiety and depression can have negative effects on pregnant women and result in poor neonatal outcomes. Therefore, we analyzed stress, anxiety and depression in pregnant women during the COVID-19 pandemic. MATERIALS AND METHODS: Cohort study of pregnant women during COVID-19 compared to pregnant women before COVID-19. Pregnant women were recruited through social media platforms from 21 May 2020 to 22 June 2020. Pregnant women ≥ 18 years of age, who master the Dutch language were included. The Hospital Anxiety and Depression Scale (HADS) and the Perceived Stress Scale (PSS-10) were analyzed. Demographic features were summarized using descriptive statistics. Possible differences in demographic variables between groups were compared using Mann Whitney U test and Chi-squared test. Significant demographic differences between groups were controlled for using logistical regression analysis or an independent one-way analysis of covariance. RESULTS: Thousand hundred and two pregnant women completed the questionnaires during COVID-19, and 364 pregnant women before COVID-19. We found no differences in clinically high levels of anxiety (HADS-A ≥ 8) and depression (HADS-D ≥ 8) in women during COVID-19 (19.5% and 13.2%, respectively) and women before COVID-19 (23.1% and 15.7%, respectively). A question was implemented whether participants related their stress level to COVID-19. Women who related their stress to the COVID-19 pandemic reported significantly higher overall stress levels on the PSS-10 compared to women with stress unrelated to COVID-19 (mean, 15.62; standard deviation [SD], 6.44 vs. mean, 10.28; SD, 5.48; p < 0.001). CONCLUSION: In contrast to previous studies, COVID-19 did not increase anxiety and depression levels in Dutch pregnant women. Women who related their perceived stress to the COVID-19 pandemic experienced higher stress levels than women who did not relate their stress to the COVID-19 pandemic, suggesting that interventions that specifically aim to reduce COVID-19 stress, may help to reduce overall stress levels in pregnant women during the pandemic.