Cannabidiol (Epidyolex®) for severe behavioral manifestations in patients with tuberous sclerosis complex, mucopolysaccharidosis type III and fragile X syndrome: protocol for a series of randomized, placebo-controlled N-of-1 trials.

BACKGROUND: Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design. METHODS: We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants' natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials. DISCUSSION: These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. TRIAL REGISTRATION: EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .

Child characteristics associated with child quality of life and parenting stress in Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterised by severe intellectual disability, movement disorder, epilepsy, sleeping problems, and behavioural issues. Little is known on child health-related quality of life (HRQoL) in AS. AS family studies have reported elevated parenting stress and a high impact of the child's syndrome on the parent. It is unclear which factors influence child HRQoL and parenting stress/impact in AS. METHODS: We collected data prospectively through standardised clinical assessments of children with AS at the ENCORE Expertise centre for Angelman Syndrome at the Erasmus MC Sophia Children's Hospital. A linear regression analysis was conducted for the following outcome variables: (1) child HRQoL (Infant and Toddler Quality of Life Questionnaire); (2) the impact of the child's syndrome on the parent (Infant and Toddler Quality of Life Questionnaire); and (3) parenting stress (Parenting Stress Index). Predictor variables were child genotype, epilepsy, sleeping problems (Sleep Disturbance Scale for Children), cognitive developmental level (Bayley Cognition Scale), autistic features (Autism Diagnostic Observation Schedule) and emotional/behavioural problems (Child Behaviour Checklist). Covariates were sex, age and socio-economic status. RESULTS: The study sample consisted of 73 children with AS, mean age = 9.1 years, range = 2-18 years. Emotional/behavioural problems were the strongest significant predictor of lowered child HRQoL. Internalising problems were driving this effect. In addition, having the deletion genotype and higher age was related to lower child HRQoL. Sleeping problems were related to a higher impact of the child's syndrome on the parent. Finally, emotional/behavioural problems were associated with higher parenting stress. Cognitive developmental level, autistic features and epilepsy were not a significant predictor of child HRQoL and parenting stress/impact. CONCLUSIONS: These results suggest that interventions aimed at increasing child HRQoL and decreasing parenting stress/impact in AS should focus on child emotional/behavioural problems and sleeping problems, using a family-centred approach.

Background rates of x-ray transition-edge sensor micro-calorimeters under a frequency domain multiplexing readout for solar axion-like particles' detection.

We report on the x-ray background rate measured with transition-edge sensors (TES) micro-calorimeters under frequency-domain multiplexing (FDM) readout as a possible technology for future experiments aiming at a direct detection of axion-like particles. Future axion helioscopes will make use of large magnets to convert axions into photons in the keV range and x-ray detectors to observe them. To achieve this, a detector array with high spectral performance and extremely low background is necessary. TES are single-photon, non-dispersive, high-resolution micro-calorimeters and represent a possible candidate for this application. We have been developing x-ray TES micro-calorimeters and an FDM readout technology in the framework of the space-borne x-ray astronomical observatories. We show that the current generation of our detectors is already a promising technology for a possible axion search experiment, having measured an x-ray background rate of 2.2(2) × 10-4 cm-2 s-1 keV-1 with a cryogenic demonstrator not optimized for this specific application. We then make a prospect to further improve the background rate down to the required value (<10-7 cm-2 s-1 keV-1) for an axion-search experiment, identifying no fundamental limits to reach such a level.

[Functioning of the acute psychiatric emergency chain in Amsterdam-Amstelland during the COVID-19 pandemic]. / Functioneren van acute crisisketen psychiatrie in Amsterdam-Amstelland tijdens de coronapandemie.

BACKGROUND: At the start of the COVID-19 pandemic, there were fears that a higher proportion of patients with a psychiatric disorder would find themselves in crisis due to the threat of COVID-19 and the impact of the restrictions. If the emergency mental health department would become blocked this could work through to emergency rooms (ER). Acute psychiatry is also assessed at the ER due to lack of space in the emergency mental health department, this is called ‘overflow’. There already was the fear that the virus would flood the hospitals with SARS-CoV-2 infected patients. The emergency mental health department and hospitals agreed that the psychiatric assessments and admissions would take place at the mental health departments as much as possible. AIM: To describe and evaluate the use of measures taken and set up facilities in Amsterdam-Amstelland to minimize psychiatric assessments in the emergency room during the COVID-19 pandemic. Secondly, to present how psychiatric assessments and admissions were conducted safely if there was suspicion or infection with SARS-CoV-2. METHOD: Use of acute psychiatric crisis monitor, the minutes of regional acute care counsel and literature. RESULTS: People with a psychiatric crisis were rarely suspected to be infected with SARS-CoV-2. There was always
sufficient capacity in COVID-19 wards in the mental health department. During the lockdown, we managed to
minimize overflow from the mental health emergency department to emergency rooms. Conclusion During the COVID-19 pandemic effective collaboration between healthcare partners was achieved in Amsterdam-Amstelland, so that psychiatric assessments and admissions with (suspected) COVID-19 could be conducted safely. Interventions to relieve the emergency room from overflow during lockdown were effective.

Improving person-centered occupational health care for workers with chronic health conditions: a feasibility study.

BACKGROUND: Person-centered care is needed to effectively support workers with chronic health conditions. Person-centered care aims to provide care tailored to an individual person's preferences, needs and values. To achieve this, a more active, supportive, and coaching role of occupational and insurance physicians is required. In previous research, two training programs and an e-learning training with accompanying tools that can be used in the context of person-centered occupational health care were developed to contribute to this changing role. The aim was to investigate the feasibility of the developed training programs and e-learning training to enhance the active, supportive, and coaching role of occupational and insurance physicians needed for person-centered occupational health care. Information about this is important to facilitate implementation of the tools and training into educational structures and occupational health practice. METHODS: A qualitative study was conducted, with N = 29 semi-structured interviews with occupational physicians, insurance physicians, and representatives from occupational educational institutes. The aim was to elicit feasibility factors concerning the implementation, practicality and integration with regard to embedding the training programs and e-learning training in educational structures and the use of the tools and acquired knowledge and skills in occupational health care practice after following the trainings and e-learning training. Deductive analysis was conducted based on pre-selected focus areas for a feasibility study. RESULTS: From an educational perspective, adapting the face-to-face training programs to online versions, good coordination with educational managers and train-the-trainer approaches were mentioned as facilitating factors for successful implementation. Participants underlined the importance of aligning the occupational physicians' and insurance physicians' competences with the educational content and attention for the costs concerning the facilitation of the trainings and e-learning training. From the professional perspective, factors concerning the content of the training and e-learning training, the use of actual cases from practice, as well as follow-up training sessions were reported. Professionals expressed good fit of the acquired skills into their consultation hour in practice. CONCLUSION: The developed training programs, e-learning training and accompanying tools were perceived feasible in terms of implementation, practicality, and integration by occupational physicians, insurance physicians and educational institutes.

The multitarget fecal immunochemical test versus the fecal immunochemical test for programmatic colorectal cancer screening: a cross-sectional intervention study with paired design.

BACKGROUND: Many screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program. METHOD: The mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants. DISCUSSION: The outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist =.

[Quality assurance for the treatment of muscle-invasive and metastasized bladder carcinoma in Germany : An initiative of the Working Groups Urological Oncology (AUO) and Internal Oncology (AIO) in the German Cancer Society (DKG)]. / Qualitätssicherung zur Therapie des muskelinvasiven und metastasierten Harnblasenkarzinoms in Deutschland : Eine Initiative der Arbeitsgemeinschaften Urologische Onkologie (AUO) und Internistische Onkologie (AIO) in der Deutschen Krebsgesellschaft (DKG).

BACKGROUND: The S3-guideline on bladder cancer recommends radical cystectomy and cisplatin-based perioperative chemotherapy (POC) for muscle-invasive bladder cancer (MIBC). Recommendation for metastatic urothelial cancer (mUC) is cisplatin-based or immuno-oncological (IO) treatment in platinum-ineligible patients (pts) or as 2nd-line therapy. OBJECTIVES: Aim of the study was to obtain representative data on clinical routine treatment of MIBC and mUC in Germany. MATERIALS AND METHODS: A nationwide survey was performed to obtain data on stage-related patient volume in hospitals and office-based physicians. Based on these results, a representative sample of treatment data was collected retrospectively from pts with MIBC and mUC. RESULTS: Data from 956 pts (MIBC 576; mUC: 380) were collected. Of the MIBC pts, 49.8% received a systemic therapy (80.4% of them received cisplatin/gemcitabine) and 50.2% were treated with a cystectomy without POC. Significant factors for cystectomy without POC were higher age > 75 years (odds ratio [OR] 4.91, 95% confidence interval [CI] 3.01-8.11, p < 0.001) and platinum-ineligible pts (OR 2.15, 95% CI 1.30-3.59; p = 0.003). Treatment decision without interdisciplinary tumor board was also correlated with no POC (OR 2.43, 95% CI 1.65-3.61, p < 0.001). In mUC platinum-pretreated pts generally receive IO therapy (OR 12.07, 95% CI 6.94-21.82, p < 0.001). Other significant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71, p < 0.001), higher age > 75 years (OR 2.83, 95% CI 1.43-5.73, p = 0.003) and platinum-ineligible pts (OR 2.57, 95% CI 1.30-5.71, p = 0.007). CONCLUSIONS: The "gold standard" cisplatin/gemcitabine is established in Germany if pts are treated with POC. Nonetheless half of the MIBC pts did not receive a POC, especially if the treatment decision is not discussed in a tumor board. In mUC IO therapy is established as 2nd-line therapy after a platinum-based treatment. Although the guideline recommendations are largely implemented, there is potential for optimization, especially in the establishment of interdisciplinary tumor boards.

An Assessment of the Potential Economic Impacts of the Invasive Polyphagous Shot Hole Borer (Coleoptera: Curculionidae) in South Africa.

Studies addressing the economic impacts of invasive alien species are biased towards ex-post assessments of the costs and benefits of control options, but ex-ante assessments are also required to deal with potentially damaging invaders. The polyphagous shot hole borer Euwallacea fornicatus (Coleoptera: Curculionidae) is a recent and potentially damaging introduction to South Africa. We assessed the potential impact of this beetle by working across economic and biological disciplines and developing a simulation model that included dynamic mutualistic relations between the beetle and its symbiotic fungus. We modeled the potential growth in beetle populations and their effect on the net present cost of damage to natural forests, urban trees, commercial forestry, and the avocado industry over 10 yr. We modeled high, baseline, and low scenarios using discount rates of 8, 6, and 4%, and a plausible range of costs and mortality rates. Models predicted steady growth in the beetle and fungus populations, leading to average declines in tree populations of between 3.5 and 15.5% over 10 yr. The predicted net present cost was 18.45 billion international dollars (Int. $), or about 0.66% of the country's GDP for our baseline scenario ($2.7 billion to $164 billion for low and high scenarios). Most of the costs are for the removal of urban trees that die as a result of the beetle and its fungal symbiont, as has been found in other regions. We conclude that an ex-ante economic assessment system dynamics model can be useful for informing national strategies on invasive alien species management.

How to identify clinically significant diabetes distress using the Problem Areas in Diabetes (PAID) scale in adults with diabetes treated in primary or secondary care? Evidence for new cut points based on latent class analyses.

INTRODUCTION: The Problem Areas of Diabetes (PAID) questionnaire is a frequently used measure to assess diabetes-distress. The aim of this study was to identify clinically meaningful levels of diabetes-distress, using latent class analyses (LCA), and to determine which groups were at increased risk of elevated diabetes-distress in terms of sex, age, type of diabetes and glycaemic control. METHODS: Data were derived from four studies (total N=2966, 49% female, age range 18-95 years, 43% type 1 diabetes, diabetes duration range 0-79 years). LCAs were performed to examine possible latent groups in the distribution of answers on the individual PAID items. Demographic and diabetes-related characteristics were added to the model to estimate their effects on latent class membership and receiver operating curves curves to determine cut-offs. RESULTS: Three levels of diabetes distress were distinguished with defined cut-off scores and labelled as: low, moderate and high diabetes distress. Levels of distress did not associate with distinct clusters of items. Older people were more likely to be part of the low distress class; women and people with high HbA1c were more likely to be part of the high distress class. Sensitivity and specificity of the commonly used cut-off of 40 for high distress are 0.95 and 0.97, respectively. To distinguish the moderate distress group, cut-off scores of 17 and 39 are optimal with a sensitivity of 0.93 and a specificity of 0.94. CONCLUSION: Three levels of diabetes-distress can be distinguished: low, moderate and high diabetes distress. Younger people, women and people with poor glycaemic control are at an increased risk for high levels of distress. A cut-off of 40 is satisfactory to detect people with high levels of diabetes-distress; a score of 0-16 indicates low diabetes distress and a score of 17-39 moderate diabetes distress.

Severe psychological impact and impaired quality of life after a spontaneous haemoperitoneum in pregnancy in women with endometriosis and their partners.

BACKGROUND: Spontaneous Haemoperitoneum in Pregnancy (SHiP) is a rare, but life-threatening complication of pregnancy that occurs predominantly in the third trimester of pregnancy and is associated with adverse pregnancy outcomes. Recently the largest case series in literature was published describing 11 Dutch cases of SHiP in women with endometriosis. PURPOSE: To investigate experiences, psychological impact, and quality of life after SHiP. METHODS: A mixed-methods study was performed in women with a history of SHiP and their partners, including all known cases in the Netherlands between 2007 to 2015. Semi-structured in-depth interviews were organized between 2016 and 2017 and analysed thematically with a framework approach. Participants were asked to complete questionnaires investigating the impact of the event (Impact of Event Scale) and Quality of Life (RAND-36). RESULTS: Out of a total of 11 known cases, 7 women agreed for be individually interviewed. From these, all women described a freeze response at the moment of SHiP, combined with either an anxious reaction or a survival mode mind-set. All women received psychological help after SHiP. Still, the feeling of not being heard by the medical staff was present in all women. Other themes such as postpartum period, bonding with their child, effect on daily life, reviving the event, and future pregnancies were also identified in the interviews. In regard to their partners, 3 were interviewed, hence no saturation was achieved. Finally, the questionnaires showed lower Quality of Life and an impact score of ≥ 8/10. CONCLUSION: SHiP had a profound impact on women and their partners. Dedicated psychological help should be offered to all women after experiencing SHiP.

Voltage Fluctuations in ac Biased Superconducting Transition-Edge Sensors.

We present a detailed analysis of the fundamental noise sources in superconducting transition-edge sensors (TESs), ac voltage biased at MHz frequencies and treated as superconducting weak links. We have studied the noise in the resistive transition as a function of bath temperature of several detectors with different normal resistances and geometries. We show that the "excess" noise, typically observed in the TES electrical bandwidth, can be explained by the equilibrium Johnson noise of the quasiparticles generated within the weak link. The fluctuations at the Josephson frequency and higher harmonics contribute significantly to the measured voltage noise at the detector bandwidth through the nonlinear response of the weak link with a sinusoidal current-phase relation.

Re-evaluating randomized clinical trials of psychological interventions: Impact of response shift on the interpretation of trial results.

BACKGROUND: Effectiveness of psychological treatment is often assessed using patient-reported health evaluations. However, comparison of such scores over time can be hampered due to a change in the meaning of self-evaluations, called 'response shift'. Insight into the occurrence of response shift seems especially relevant in the context of psychological interventions, as they often purposefully intend to change patients' frames of reference. AIMS: The overall aim is to gain insight into the general relevance of response shift for psychological health intervention research. Specifically, the aim is to re-analyse data of published randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions targeting different health aspects, to assess (1) the occurrence of response shift, (2) the impact of response shift on interpretation of treatment effectiveness, and (3) the predictive role of clinical and background variables for detected response shift. METHOD: We re-analysed data from RCTs on guided internet delivered cognitive behavioural treatment (CBT) for insomnia in the general population with and without elevated depressive symptoms, an RCT on meaning-centred group psychotherapy targeting personal meaning for cancer survivors, and an RCT on internet-based CBT treatment for persons with diabetes with elevated depressive symptoms. Structural equation modelling was used to test the three objectives. RESULTS: We found indications of response shift in the intervention groups of all analysed datasets. However, results were mixed, as response shift was also indicated in some of the control groups, albeit to a lesser extent or in opposite direction. Overall, the detected response shifts only marginally impacted trial results. Relations with selected clinical and background variables helped the interpretation of detected effects and their possible mechanisms. CONCLUSION: This study showed that response shift effects can occur as a result of psychological health interventions. Response shift did not influence the overall interpretation of trial results, but provide insight into differential treatment effectiveness for specific symptoms and/or domains that can be clinically meaningful.

Differences in Comorbidities Between Women and Men Treated with Elective Repair for Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis.

OBJECTIVES: Elective abdominal aortic aneurysm (AAA) repair is performed to prevent rupture. For reasons as yet unknown, the 30-day mortality risk after elective AAA repair is higher in women than in men. We hypothesised that this higher risk might be related to differences in comorbidity. METHODS: Systematic review (PROSPERO CRD42019133314) according to PRISMA guidelines. A search in the EMBASE/MEDLINE/CENTRAL databases identified 1870 studies that included patients who underwent elective AAA repair (final search February 17th, 2021). Ultimately, 28 studies were included and all reported comorbidities were categorised into 17 comorbidity groups. Additionally, 15 groups of clearly defined comorbidities were used for sensitivity analysis. For both groups, meta-analyses of each comorbidity were performed to estimate the difference in pooled prevalence between women and men with a random effects model. RESULTS: When analysing data of all reported comorbidities (17 groups), smoking [risk difference (RD) 11%, 95% confidence interval (CI) 4-18], diabetes (RD 3%, 95% CI 2-4), ischaemic heart disease (RD 12%, 95% CI 8-16), arrhythmia (RD 3%, 95% CI 0.4-5), liver disease (RD 0.1%, 95% CI 0.01-0.2), and cancer (RD 3%, 95% CI 2-4)) were less prevalent in women, whereas, hypertension (RD 4%, 95% CI 3-6) and pulmonary disease (RD 4%, 95% CI 3-5) were more prevalent in women. At the time of surgery women were significantly older than men (74.9 years versus 72.4; mean difference 2.4 years (95% CI 2.1-2.7)). In the sensitivity analysis of 15 comorbidity groups, the same comorbidities remained significantly different between women and men, except smoking and arrhythmia. Women had a higher mortality risk than men (RD 1%, 95% CI 1-2). CONCLUSIONS: Although women undergoing elective AAA repair have fewer baseline comorbidities than men, their 30-day mortality risk is higher. In-depth studies on the cause of death in women after elective AAA repair are needed to explain this discrepancy in mortality.

Frequency shift algorithm: Application to a frequency-domain multiplexing readout of x-ray transition-edge sensor microcalorimeters.

In the frequency-domain multiplexing (FDM) scheme, transition-edge sensors (TESs) are individually coupled to superconducting LC filters and AC biased at MHz frequencies through a common readout line. To make efficient use of the available readout bandwidth and to minimize the effect of non-linearities, the LC resonators are usually designed to be on a regular grid. The lithographic processes, however, pose a limit on the accuracy of the effective filter resonance frequencies. Off-resonance bias carriers could be used to suppress the impact of intermodulation distortions, which, nonetheless, would significantly affect the effective bias circuit and the detector spectral performance. In this paper, we present a frequency shift algorithm (FSA) to allow off-resonance readout of TESs, while preserving the on-resonance bias circuit and spectral performance, demonstrating its application to the FDM readout of an x-ray TES microcalorimeter array. We discuss the benefits in terms of mitigation of the impact of intermodulation distortions at the cost of increased bias voltage and the scalability of the algorithm to multi-pixel FDM readout. We show that with FSA, in the multi-pixel and frequencies shifted on-grid, the line noises due to intermodulation distortion are placed away from the sensitive region in the TES response and the x-ray performance is consistent with the single-pixel, on-resonance level.

Performance and uniformity of a kilo-pixel array of Ti/Au transition-edge sensor microcalorimeters.

Uniform large transition-edge sensor (TES) arrays are fundamental for the next generation of x-ray space observatories. These arrays are required to achieve an energy resolution ΔE < 3 eV full width at half maximum (FWHM) in the soft x-ray energy range. We are currently developing x-ray microcalorimeter arrays for use in the future laboratory and space-based x-ray astrophysics experiments and ground-based spectrometers. In this contribution, we report on the development and the characterization of a uniform 32 × 32 pixel array with 140 × 30 µm2 Ti/Au TESs with the Au x-ray absorber. We report on extensive measurements on 60 pixels in order to show the uniformity of our large TES array. The averaged critical temperature is Tc = 89.5 ± 0.5 mK, and the variation across the array (∼1 cm) is less than 1.5 mK. We found a large region of detector's bias points between 20% and 40% of the normal-state resistance where the energy resolution is constantly lower than 3 eV. In particular, results show a summed x-ray spectral resolution ΔEFWHM = 2.50 ± 0.04 eV at a photon energy of 5.9 keV, measured in a single-pixel mode using a frequency domain multiplexing readout system developed at SRON/VTT at bias frequencies ranging from 1 MHz to 5 MHz. Moreover, we compare the logarithmic resistance sensitivity with respect to temperature and current (α and ß, respectively) and their correlation with the detector's noise parameter M, showing a homogeneous behavior for all the measured pixels in the array.

Patients' and rheumatologists' perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis-an international survey within the GLORIA study.

OBJECTIVE: To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA. METHODS: Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys. RESULTS: A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map. CONCLUSIONS: RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.

Infectious Bronchitis Virus Types Affecting European Countries-A Review.

Since its first detection in Europe in the 1940s, infectious bronchitis virus has continued to be one of the major respiratory pathogens affecting the European poultry industry. The development of effective and widely used vaccines for both broilers (live attenuated) and breeders and layers (live attenuated and inactivated) helped improve the health and welfare of poultry but never eliminated the problem. The main reason is the continual emergence of new infectious bronchitis variants (serotypes or genotypes). This review discusses the most prevalent genotypes of the last few decades in Europe. Some of these genotypes seem to be local European types; others have an origin outside Europe.

Estudio recapitulativo- Tipos del virus de la bronquitis infecciosa que afectan a los países europeos: Una revisión. Desde su primera detección en Europa en la década de los 1940s, el virus de la bronquitis infecciosa ha seguido siendo uno de los principales patógenos respiratorios que afectan a la industria avícola europea. El desarrollo de vacunas eficaces y ampliamente utilizadas tanto para pollos de engorde (vivos atenuados) como para reproductoras y ponedoras (vivos atenuados e inactivados) ayudó a mejorar la salud y el bienestar de las aves comerciales, pero nunca eliminó el problema. El problema principal es la aparición continua de nuevas variantes de bronquitis infecciosa (serotipos o genotipos). Esta revisión analiza los genotipos más prevalentes en las últimas décadas en Europa. Algunos de estos genotipos parecen ser tipos europeos locales; otros tienen un origen fuera de Europa.

State of the art: understanding and integration of the social context in diabetes care.

We review the past 25 years of research addressing challenges people living with diabetes experience in their daily lives related to social contexts, i.e. in their family, at work and in society at large, and identify research gaps. We found that young people with diabetes, as they develop through to adulthood, are exposed to considerable risks to their physical and mental health. Family-system interventions have had mixed outcomes. Research in this area would benefit from attention to ethnic/cultural diversity, and involving fathers and other family members. In adults with diabetes, social support relates to better diabetes outcomes. While family member involvement in care is likely to affect health and psychosocial outcomes of the person with diabetes, key elements and mediators of effective family interventions need to be identified. The challenges of diabetes management at work are under-researched; distress and intentional hyperglycaemia are common. When depression is comorbid with diabetes, there are increased work-related risks, e.g. unemployment, sickness absence and reduced income. Research to support people with diabetes at work should involve colleagues and employers to raise awareness and create supportive environments. Stigma and discrimination have been found to be more common than previously acknowledged, affecting self-care, well-being and access to health services. Guidance on stigma-reducing choice of language has been published recently. Resilience, defined as successful adaptation to adversity such as stigma and discrimination, requires studies relevant to the specific challenges of diabetes, whether at diagnosis or subsequently. The importance of the social context for living well with diabetes is now fully recognized, but understanding of many of the challenges, whether at home or work, is still limited, with much work needed to develop successful interventions.

The cognitive and psychological effects of living with type 1 diabetes: a narrative review.

Across the lifespan, type 1 diabetes mellitus has a profound (neuro)psychological impact. In young people, type 1 diabetes can interfere with psychosocial development and hamper school performance. In adulthood, it can interfere with work life, relationships and parenting. A substantial minority of adults with type 1 diabetes experience coping difficulties and high diabetes-related distress. In youth and adulthood, type 1 diabetes is related to mild cognitive decrements as well as affective disorders, such as depression and anxiety. There is limited literature available that explores the interaction between cognitive and psychological comorbidity and underlying mechanisms. The aims of the present narrative review were to summarize the current state of the literature regarding both cognitive and psychological comorbidities in type 1 diabetes across the lifespan, and to explore potential links between the two domains of interest to make suggestions for future research and clinical practice.

Serum Iron Analytes in Healthy and Diseased Florida Manatees (Trichechus manatus latirostris).

Serum iron concentration is usually decreased in true iron deficiency and with inflammatory disease in man and domestic animals. Serum total iron binding capacity (TIBC) may be increased in true iron deficiency and decreased with inflammatory disease. This prospective study was designed to measure serum iron analytes in healthy free-ranging and housed Florida manatees (Trichechus manatus latirostris) of both sexes and various ages and to evaluate the effects of diseases common to manatees on these analytes. Blood samples were collected without anticoagulant from 137 healthy free-ranging manatees, 90 healthy housed manatees and 74 free-ranging diseased manatees, and serum was prepared by centrifugation. Serum iron concentration and unsaturated iron binding capacity were measured colourimetrically, and TIBC and percent transferrin saturation with iron were calculated. Serum amyloid A (SAA) was measured to assist in the health assessment of manatees and provide evidence of inflammation in diseased manatees. Based on the serum iron analytes, iron availability was lower in immature manatees compared with adults, and it was lower in housed manatees compared with free-ranging manatees. In contrast to other mammals studied, serum iron concentration was elevated rather than depressed in late pregnancy. Serum iron concentrations and transferrin saturation with iron percentages were significantly lower, and SAA concentrations were significantly higher, in diseased (ill and injured) manatees compared with healthy manatees. Serum iron concentration and transferrin saturation with iron values were negatively correlated with SAA concentrations, and manatees with the highest SAA concentrations had lower serum TIBC values. These findings indicate that inflammation is the major factor responsible for alterations in iron analytes in diseased manatees. Consequently, hypoferraemia may be used as supportive evidence of inflammatory disease in manatees (unless haemorrhage is also present). A decision threshold of ≤13.8 µmol/l was determined for hypoferraemia using receiver operating curve analysis. Based on studies in man and domestic animals, iron therapy is unnecessary for manatees with hypoferraemia associated with inflammation and has the potential for causing tissue damage and increased susceptibility to bacterial infections.