Substrate conformal imprint fabrication process of synthetic antiferromagnetic nanoplatelets

Methods to fabricate and characterize monodisperse magnetic nanoplatelets for fluid/bio-based applications based on spintronic thin-film principles are a challenge. This is due to the required top-down approach where the transfer of optimized blanket films to free particles in a fluid while preserving the magnetic properties is an uncharted field. Here, we explore the use of substrate conformal imprint lithography (SCIL) as a fast and cost-effective fabrication route. We analyze the size distribution of nominal 1.8 um and 120 nm diameter platelets and show the effect of the fabrication steps on the magnetic properties which we explain through changes in the dominant magnetization reversal mechanism as the size decreases. We show that SCIL allows for efficient large-scale platelet fabrication and discuss how application-specific requirements can be solved via process and material engineering

Understanding the effect of an educational intervention to optimize HIV testing strategies in primary care in Amsterdam - results of a mixed-methods study.

BACKGROUND: In the Netherlands, general practitioners (GPs) play a key role in provider-initiated HIV testing, but opportunities for timely diagnosis are regularly missed. We implemented an educational intervention to improve HIV testing by GPs from 2015 to 2020, and observed a 7% increase in testing in an evaluation using laboratory data. The objective for the current study was to gain a deeper understanding of whether and how practices and perceptions of GPs' HIV/sexually transmitted infection (STI) testing behaviour changed following the intervention. METHODS: We performed a mixed-methods study using questionnaires and semi-structured interviews to assess self-reported changes in HIV/STI testing by participating GPs. Questionnaires were completed by participants at the end of the final educational sessions from 2017 through 2020, and participating GPs were interviewed from January through March 2020. Questionnaire data were analysed descriptively, and open question responses were categorised thematically. Interview data were analysed following thematic analysis methods. RESULTS: In total, 101/103 participants completed questionnaires. Of 65 participants that were included in analyses on the self-reported effect of the programme, forty-seven (72%) reported it had changed their HIV/STI testing, including improved STI consultations, adherence to the STI consultation guideline, more proactive HIV testing, and more extragenital STI testing. Patients' risk factors, patients' requests and costs were most important in selecting STI tests ordered. Eight participants were interviewed and 15 themes on improved testing were identified, including improved HIV risk-assessment, more proactive testing for HIV/STI, more focus on HIV indicator conditions and extragenital STI testing, and tools to address HIV during consultations. However, several persistent barriers for optimal HIV/STI testing by GPs were identified, including HIV-related stigma and low perceived risk. CONCLUSIONS: Most GPs reported improved HIV/STI knowledge, attitude and testing, but there was a discrepancy between reported changes in HIV testing and observed increases using laboratory data. Our findings highlight challenges in implementation of effective interventions, and in their evaluation. Lessons learned from this intervention may inform follow-up initiatives to keep GPs actively engaged in HIV testing and care, on our way to zero new HIV infections

Role of age in presentation, response to therapy and outcome of autoimmune hepatitis

Background: Few studies with diverging results and a small sample size have compared autoimmune hepatitis (AIH) in the elderly to younger patients.Aim: To unbiasedly investigate the role of age in behaviour and treatment outcome of AIH.Methods: All patients with probable or definite AIH type 1 in four tertiary academic centres were included in this retrospective- and since 2006 prospective-cohort study. Influence of age on presentation, remission and outcome of AIH were investigated.Results: 359 patients were included. Presence of cirrhosis at AIH diagnosis around 30% was independent of age. ALAT was higher at age 30-60 years on AIH diagnosis, and above age 60 there were less acute onset, less jaundice and more concurrent autoimmune disease. Remission was reached in 80.2%, incomplete remission in 18.7%, only 1.1% (all aged 50-65) was treatment-refractory. Age was not an independent predictor of remission, while cirrhosis was. Above age 45 there was more diabetes, above age 60 more loss of remission. Rate of progression to cirrhosis was 10% in the 10 years after diagnosis and unrelated to age at AIH diagnosis. With onset below age 30, there was more development of decompensated cirrhosis over time. With higher age at AIH diagnosis there was a lower survival free of liver-related death or liver transplantation.Conclusions: AIH presents at all ages. Age influences features at diagnosis, but not response to treatment, while survival without liver-related death or liver transplantation decreases with higher age at diagnosis.</p

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Background No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60-202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790-0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25-142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%-24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%-9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%-11.4%); C-statistic 0.744 [95% CI 0.644-0.844]). Conclusions A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated

Role of age in presentation, response to therapy and outcome of autoimmune hepatitis

Background: Few studies with diverging results and a small sample size have compared autoimmune hepatitis (AIH) in the elderly to younger patients. Aim: To unbiasedly investigate the role of age in behaviour and treatment outcome of AIH. Methods: All patients with probable or definite AIH type 1 in four tertiary academic centres were included in this retrospective - and since 2006 prospective - cohort study. Influence of age on presentation, remission and outcome of AIH were investigated. Results: 359 patients were included. Presence of cirrhosis at AIH diagnosis around 30% was independent of age. ALAT was higher at age 30-60 years on AIH diagnosis, and above age 60 there were less acute onset, less jaundice and more concurrent autoimmune disease. Remission was reached in 80.2%, incomplete remission in 18.7%, only 1.1% (all aged 50-65) was treatment-refractory. Age was not an independent predictor of remission, while cirrhosis was. Above age 45 there was more diabetes, above age 60 more loss of remission. Rate of progression to cirrhosis was 10% in the 10 years after diagnosis and unrelated to age at AIH diagnosis. With onset below age 30, there was more development of decompensated cirrhosis over time. With higher age at AIH diagnosis there was a lower survival free of liver-related death or liver transplantation. Conclusions: AIH presents at all ages. Age influences features at diagnosis, but not response to treatment, while survival without liver-related death or liver transplantation decreases with higher age at diagnosis

Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety

Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. Of 162 patients participating in a long-term (> 4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38a dagger"56%) at baseline and 42 of 100 patients (42%; 95%CI32a dagger"52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9a dagger"67%) and 27% (95%CI4a dagger"50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. Patients with coiled intracranial aneurysms participating in long-term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months

Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement

Background and Aims: Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (noncirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. Methods: Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. Results: After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). Conclusions: The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone

Transhiatal vs extended transthoracic resection in oesophageal carcinoma: patients' utilities and treatment preferences

To assess patients' utilities for health state outcomes after transhiatal or transthoracic oesophagectomy for oesophageal cancer and to investigate the patients' treatment preferences for either procedure. The study group consisted of 48 patients who had undergone either transhiatal or transthoracic oesophagectomy. In an interview they were presented with eight possible health states following oesophagectomy. Visual Analogue Scale and standard gamble techniques were used to measure utilities. Treatment preference for either transhiatal or transthoracic oesophagectomy was assessed. Highest scores were found for the patients' own current health state (Visual Analogue Scale: 0.77; standard gamble: 0.97). Lowest scores were elicited for the health state ‘irresectable tumour’ (Visual Analogue Scale: 0.13; standard gamble: 0.34). The Visual Analogue Scale method produced lower estimates (P<0.001) than the standard gamble method for all health states. Most patient characteristics and clinical factors did not correlate with the utilities. Ninety-five per cent of patients who underwent a transthoracic procedure and 52% of patients who underwent a transhiatal resection would prefer the transthoracic treatment. No significant associations between any patient characteristics or clinical characteristics and treatment preference were found. Utilities after transhiatal or transthoracic oesophagectomy were robust because they generally did not vary by patient or clinical characteristics. Overall, most patients preferred the transthoracic procedure

A comparative study of legitimation strategies in hybrid regimes

The Institutions of Politics; Design, Workings, and implications ( do not use, ended 1-1-2020

The METEX study: Methotrexate versus expectant management in women with ectopic pregnancy: A randomised controlled trial

Background: Patients with ectopic pregnancy (EP) and low serum hCG concentrations and women with a pregnancy of unknown location (PUL) and plateauing serum hCG levels are commonly treated with systemic methotrexate (MTX). However, there is no evidence that treatment in these particular subgroups of women is necessary as many of these early EPs may resolve spontaneously. The aim of this study is whether expectant management in women with EP or PUL and with low but plateauing serum hCG concentrations is an alternative to MTX treatment in terms of treatment success, future pregnancy, health related quality of life and costs. Methods/Design: A multicentre randomised controlled trial in TheNetherlands. Hemodynamically stable patients with an EP visible on transvaginal ultrasound and a plateauing serum hCG concentration < 1,500 IU/L or with a persisting PUL with plateauing serum hCG concentrations < 2,000 IU/L are eligible for the trial. Patients with a viable EP, signs of tubal rupture/abdominal bleeding, or a contra-indication for MTX will not be included. Expectant management is compared with systemic MTX in a single dose intramuscular regimen (1 mg/ kg) in an outpatient setting. Serum hCG levels are monitored weekly; in case of inadequately declining, systemic MTX is installed or continued. In case of hemodynamic instability and/or signs of tubal rupture, surgery is performed. The primary outcome measure is an uneventful decline of serum hCG to an undetectable level by the initial intervention. Secondary outcomes are (re)interventions (additional systemic MTX injections and/or surgery), treatment complications, health related quality of life, financial costs, and future fertility. Analysis is performed according to the intention to treat principle. Quality of life is assessed by questionnaires before and at three time points after randomisation. Costs are expressed as direct costs with data on costs and used resources in the participating centres. Fertility is assessed by questionnaires after 6, 12, 18 and 24 months. Patients' preferences will be assessed using a discrete choice experiment. Discussion: This trial will provide guidance on the present management dilemmas in women with EPs and PULs with low and plateauing serum hCG concentrations