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Objectives: Patient and public involvement is regarded as vital in fostering high-quality care. While involvement has clear societal advantages, it is still widely viewed as tokenistic and surrounded by issues of representation. This study aims to understand how patients and informal caregivers can be trained to effectively contribute to improved quality of healthcare services., Design: Using an action research approach, a 15-week training programme for patients and informal caregivers called the Patient As a Person Academy was developed, tested and evaluated in three development cycles. Evaluation methods varied per development cycle and included open-ended questionnaires (N=27) and semistructured interviews (N=35) as well as agile evaluation sessions of all 15 training sessions., Setting and Participants: We purposively sampled patients and informal caregivers who had prior experience in patient and public involvement. Patients and informal caregivers who participated as patient and partner educators in health professions education in the Netherlands could participate., Intervention: Participants followed the Patient As a Person Academy, a 15-week training programme that aims to prepare patients and informal caregivers to become patient partners., Results: Participants reported that the Patient As a Person Academy's focus on self-management skills, understanding healthcare professionals' perspectives and communication skills helped them to engage in meaningful dialogue with healthcare professionals as patient partners and made them more confident in their roles. However, tailoring towards individual participants' levels of acceptance of illness and reflexivity was needed. Participants reported that, next to the training programme, peer-to-peer coaching and guidance towards roles in quality improvement initiatives would be necessary to optimise their contributions., Conclusions: Initiatives like the Patient As a Person Academy may alleviate the problems of tokenism in patient and public involvement. However, extensively preparing patients and informal caregivers raises issues around representation., Competing Interests: Competing interests: Both MHB and SR initiated and were board members of Patient as a Person Foundation when the study was conducted. They received no financial remuneration for their contributions. The other authors have no competing interests to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coastal areas are an important source of methane (CH 4 ). However, the exact origins of CH 4 in the surface waters of coastal regions, which in turn drive sea-air emissions, remain uncertain. To gain a comprehensive understanding of the current and future climate change feedbacks, it is crucial to identify these CH 4 sources and processes that regulate its formation and oxidation. This study investigated coastal CH 4 dynamics by comparing water column data from six stations located in the brackish Tvärminne Archipelago, Baltic Sea. The sediment biogeochemistry and microbiology were further investigated at two stations (i.e., nearshore and offshore). These stations differed in terms of stratification, bottom water redox conditions, and organic matter loading. At the nearshore station, CH 4 diffusion from the sediment into the water column was negligible, because nearly all CH 4 was oxidized within the upper sediment column before reaching the sediment surface. On the other hand, at the offshore station, there was significant benthic diffusion of CH 4 , albeit the majority underwent oxidation before reaching the sediment-water interface, due to shoaling of the sulfate methane transition zone (SMTZ). The potential contribution of CH 4 production in the water column was evaluated and was found to be negligible. After examining the isotopic signatures of δ 13 C-CH 4 across the sediment and water column, it became apparent that the surface water δ 13 C-CH 4 values observed in areas with thermal stratification could not be explained by diffusion, advective fluxes, nor production in the water column. In fact, these values bore a remarkable resemblance to those detected below the SMTZ. This supports the hypothesis that the source of CH 4 in surface waters is more likely to originate from ebullition than diffusion in stratified brackish coastal systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Coastal zones account for 75% of marine methane emissions, despite covering only 15% of the ocean surface area. In these ecosystems, the tight balance between methane production and oxidation in sediments prevents most methane from escaping into seawater. However, anthropogenic activities could disrupt this balance, leading to an increased methane escape from coastal sediments. To quantify and unravel potential mechanisms underlying this disruption, we used a suite of biogeochemical and microbiological analyses to investigate the impact of anthropogenically induced redox shifts on methane cycling in sediments from three sites with contrasting bottom water redox conditions (oxic-hypoxic-euxinic) in the eutrophic Stockholm Archipelago. Our results indicate that the methane production potential increased under hypoxia and euxinia, while anaerobic oxidation of methane was disrupted under euxinia. Experimental, genomic, and biogeochemical data suggest that the virtual disappearance of methane-oxidizing archaea at the euxinic site occurred due to sulfide toxicity. This could explain a near 7-fold increase in the extent of escape of benthic methane at the euxinic site relative to the hypoxic one. In conclusion, these insights reveal how the development of euxinia could disrupt the coastal methane biofilter, potentially leading to increased methane emissions from coastal zones.

Internal phosphorus (P) loading is widely recognized as a major cause of lake eutrophication. One conventional paradigm states that the magnitude of internal loading through P diffusion is constrained by the presence of iron (Fe) oxides in surface sediments under oxic conditions near the sediment-water interface (SWI). However, biogeochemical P dynamics in Fe-rich sedimentary systems are still not fully understood, especially in eutrophic lakes where intensively coupled organic matter (OM) remineralization and reductive dissolution of Fe-bound P (Fe-P) exist concurrently. Here, we assess the diagenetic processes that govern sedimentary P cycling in two eutrophic Fe-rich lakes in southern Finland, Lake Hiidenvesi and Lake Kytäjärvi, using a combination of porewater and solid-phase analyses. Coupled reductive dissolution of Fe-P and OM remineralization controlled P regeneration in both lakes, with Fe-P acting as the dominant source for porewater P. Vivianite formation likely immobilized sedimentary P in the deepest basin of Hiidenvesi. Elevated P diffusion rates were observed at shallow sites under oxic bottom water conditions in summer in both lakes, stimulated by enhanced remineralization of both freshly- (mostly phytoplankton-origin) and earlier-deposited OM under elevated temperatures. Areas overlain by oxic bottom water contributed more benthic P fluxes to the water column compared to anoxic/hypoxic areas in both lakes during all sampling seasons. Our study suggests that in shallow eutrophic settings with high OM deposition and elevated temperatures, remineralization in upper sediments regenerates P efficiently enough to support a significant amount of P release to the water column even under sedimentary molar Fe/P ratios >20. We also discuss the implication of our findings for lake restoration strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Catatonia in children and adolescents is not rare and, as in adults, has a favorable outcome, provided it is recognized and treated promptly. Nevertheless, in clinical practice we encounter several obstacles in terms of diagnosis and treatment in this population of patients. We describe a 14-year-old boy with an intellectually disability and autism spectrum disorder (ASD) in which clinicians did not diagnose catatonia until 1 year after the development of symptoms. Moreover, hesitations surrounding the correct treatment led to its delayed initiation. With this case report we aim to contribute to reduced reluctance and increased alertness in the treatment of catatonia in adolescents with developmental disorders.

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios., Competing Interests: J.E. has received research funding from bioMérieux and has served as a consultant for bioMérieux. AL has received research funding from BioFire, Cepheid, and Luminex. J.M.B.L. has served as a consultant for bioMérieux and has also participated in other BioFire clinical studies. B.S. has received research funding from BioFire, Becton, Dickinson and Company, and DiaSorin.

To learn what mothers know about newborn bloodspot screening (NBS), the procedure, and the sources used, a pilot study was performed. An online questionnaire was developed, with the first part focused on characteristics and the NBS procedure, and the second on knowledge, information sources, and health care providers (HCPs). This questionnaire was accessible until 200 answers were received. The characteristics of respondents were representative for the population. Mothers gave verbal consent in 69.5% of cases, 12.5% did not, and 18% stated that no consent was requested. The 'knowledge' part contained 12 closed questions, five multiple-choice questions on sources, and assessments (5-point Likert scores) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory was poorly known, and post-analysis sample handling procedures were poorly understood. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was provided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 for clarity, timing appropriateness, sufficiency, and usefulness. The knowledge level and consent practices were reasonably good. Key HCP were midwives and nurses, the leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.

Previous studies have demonstrated that e-SO x can regulate the sedimentary release of phosphorus (P) in brackish and marine sediments. When e-SO x is active, an iron (Fe) and manganese (Mn) oxide rich layer is formed near the sediment surface, which prevents P release. When e-SO x becomes inactive, the metal oxide layer is reduced via sulfide-mediated dissolution, and P is subsequently released to the water column. Cable bacteria have been shown to also occur in freshwater sediments. In these sediments, sulfide production is limited, and the metal oxide layer would thus dissolve less efficiently, leaving the P trapped at the sediment surface. This lack of an efficient dissolution mechanism implies that e-SO x could play an important role in the regulation of P availability in eutrophied freshwater streams. To test this hypothesis, we incubated sediments from a eutrophic freshwater river to investigate the impact of cable bacteria on sedimentary cycling of Fe, Mn and P. High-resolution depth profiling of pH, O 2 and ΣH 2 S complemented with FISH analysis and high-throughput gene sequencing showed that the development of e-SO x activity was closely linked to the enrichment of cable bacteria in incubated sediments. Cable bacteria activity caused a strong acidification in the suboxic zone, leading to the dissolution of Fe and Mn minerals and consequently a strong release of dissolved Fe 2+ and Mn 2+ to the porewater. Oxidation of these mobilized ions at the sediment surface led to the formation of a metal oxide layer that trapped dissolved P, as shown by the enrichment of P-bearing metal oxides in the top layer of the sediment and low phosphate in the pore and overlying water. After e-SO x activity declined, the metal oxide layer did not dissolve and P remained trapped at the surface. Overall, our results suggested cable bacteria can play an important role to counteract eutrophication in freshwater systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The Perceptual Crossing Experiment (PCE) captures the capacity for social contingency detection using real-time social interaction dynamics but has not been externally validated. We tested ecological and convergent validity of the PCE in a sample of 208 adolescents from the general population, aged 11 to 19 years. We expected associations between PCE performance and (a) quantity and quality of social interaction in daily life, using Experience Sampling Methodology (ESM; ecological validity) and (b) self-reported social skills using a questionnaire (convergent validity). We also expected PCE performance to better explain variance in ESM social measures than self-reported social skills. Multilevel analyses showed that only self-reported social skills were positively associated with social experience of company in daily life. These initial results do not support ecological and convergent validity of the PCE. However, fueled by novel insights regarding the complexity of capturing social dynamics, we identified promising methodological advances for future validation efforts.

Background: To our knowledge, this is the first description of long-term nutritional management in a dog with paroxysmal dyskinesia., Case Summary: An obese 9-year-old, male entire, German Spitz was presented for dietary management after being diagnosed with calcium oxalate urolithiasis and suspected pancreatitis. Since he was seven years old, the dog has had a history of neurological signs, which were thought to be epileptic seizures. He was treated with phenobarbital and potassium bromide and was clinically controlled. For his nutritional advice, aiming to minimize one of the most important risk factors for the diseases, a weight loss program was started and successfully executed. However, 10 months later, the dog restarted presenting neurological episodes at a high frequency (3x/week). Based on videos and the characteristics of the neurological signs, the dog was diagnosed with paroxysmal dyskinesia. To investigate the role of gluten intake on this patient's neurological signs, a dietary trial with a commercial hypoallergenic diet (gluten-free; hydrolyzed protein) was followed. During the 3 months of the dietary trial, four neurologic episodes related to food indiscretion occurred. Upon the decrease in neurological episodes, the anti-seizure drugs were slowly discontinued. During this period, the dog presented only two neurologic episodes that were related to the days that the anti-seizure drugs were decreased. For 4 months the dog remained episode-free. However, a change in the dog's diet to another gluten-free diet (higher fat) led the dog to vomit and experience another neurologic episode. Once the dog was back to the previous gluten-free diet, it clinically improved, and no other clinical signs were reported by the client during the next 5 months., Conclusion: Although a relationship between gluten and paroxysmal dyskinesia cannot be confirmed, the dog's improvement after the nutritional management and the removal of the anti-seizure therapy is supportive of dietary association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baptista da Silva, Hermans, Ruiz-Suárez, Verdoodt, Bhatti and Hesta.)

Mast cells (MCs) are innate immune cells with a versatile set of functionalities, enabling them to orchestrate immune responses in various ways. Aside from their known role in allergy, they also partake in both allograft tolerance and rejection through interaction with regulatory T cells, effector T cells, B cells and degranulation of cytokines and other mediators. MC mediators have both pro- and anti-inflammatory actions, but overall lean towards pro-fibrotic pathways. Paradoxically, they are also seen as having potential protective effects in tissue remodeling post-injury. This manuscript elaborates on current knowledge of the functional diversity of mast cells in kidney transplants, combining theory and practice into a MC model stipulating both protective and harmful capabilities in the kidney transplant setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 van der Elst, Varol, Hermans, Baan, Duong-van Huyen, Hesselink, Kramann, Rabant, Reinders, von der Thüsen, van den Bosch and Clahsen-van Groningen.)

Lab-on-a-chip (LOC) applications have emerged as invaluable physical and life sciences tools. The advantages stem from advanced system miniaturization, thus, requiring far less sample volume while allowing for complex functionality, increased reproducibility, and high throughput. However, LOC applications necessitate extensive sensor miniaturization to leverage these inherent advantages fully. Atom-sized quantum sensors are highly promising to bridge this gap and have enabled measurements of temperature, electric and magnetic fields on the nano- to microscale. Nevertheless, the technical complexity of both disciplines has so far impeded an uncompromising combination of LOC systems and quantum sensors. Here, we present a fully integrated microfluidic platform for solid-state spin quantum sensors, like the nitrogen-vacancy (NV) center in diamond. Our platform fulfills all technical requirements, such as fast spin manipulation, enabling full quantum sensing capabilities, biocompatibility, and easy adaptability to arbitrary channel and chip geometries. To illustrate the vast potential of quantum sensors in LOC systems, we demonstrate various NV center-based sensing modalities for chemical analysis in our microfluidic platform, ranging from paramagnetic ion detection to high-resolution microscale NV-NMR. Consequently, our work opens the door for novel chemical analysis capabilities within LOC devices with applications in electrochemistry, high-throughput reaction screening, bioanalytics, organ-on-a-chip, or single-cell studies.

Objectives: Phenobarbital (PB) is the most common antiseizure drug (ASD) used for the management of feline epilepsy. In dogs, PB is known to cause serum liver enzyme induction and hepatotoxicity, especially after administration long term or in high concentrations. In cats, insufficient evidence is available to draw similar conclusions. The aim of this study was to evaluate the effect of PB administration on the serum biochemistry profile of epileptic cats. As an additional objective, other adverse effects arising, related to PB treatment, were recorded., Methods: Medical records of four veterinary centres were retrospectively reviewed for epileptic cats receiving PB treatment. Cats were included if they had a diagnosis of idiopathic epilepsy or structural epilepsy; a normal baseline serum biochemistry profile; at least one follow-up serum biochemistry profile; no concurrent disease or had not received medication that could possibly influence liver function or lead to serum liver enzyme induction. Alkaline phosphatase, alanine aminotransferase (ALT), aspartate transaminase and gamma-glutamyl transferase activities, and total bilirubin, bile acids, glucose, albumin, total protein, urea and creatinine concentrations before and during PB administration were recorded. PB serum concentration was also recorded, when available., Results: Thirty-three cats (24 males, nine females) with a median age of 3 years (range 2 months to 12 years) met the inclusion criteria. Idiopathic or structural epilepsy was diagnosed in 25 (76%) and eight (24%) cats, respectively. The follow-up period ranged from 9 to 62 months. This study found an increase in ALT in three cats, possibly related to a PB serum concentration >30 µg/ml. No statistically significant increase in serum liver enzymes or other evaluated biochemistry parameters was found by comparing pre- and post-treatment parameters., Conclusions and Relevance: PB administration did not result in hepatic enzyme induction or other biochemical abnormalities in cats. This strengthens the safety profile of PB as an ASD in cats.

Hypoxia has occurred intermittently in the Baltic Sea since the establishment of brackish-water conditions at ∼8,000 years B.P., principally as recurrent hypoxic events during the Holocene Thermal Maximum (HTM) and the Medieval Climate Anomaly (MCA). Sedimentary phosphorus release has been implicated as a key driver of these events, but previous paleoenvironmental reconstructions have lacked the sampling resolution to investigate feedbacks in past iron-phosphorus cycling on short timescales. Here we employ Laser Ablation (LA)-ICP-MS scanning of sediment cores to generate ultra-high resolution geochemical records of past hypoxic events. We show that in-phase multidecadal oscillations in hypoxia intensity and iron-phosphorus cycling occurred throughout these events. Using a box model, we demonstrate that such oscillations were likely driven by instabilities in the dynamics of iron-phosphorus cycling under preindustrial phosphorus loads, and modulated by external climate forcing. Oscillatory behavior could complicate the recovery from hypoxia during future trajectories of external loading reductions., (© 2021 The Authors.)

Coastal waters worldwide suffer from increased eutrophication and seasonal bottom water hypoxia. Here, we assess the dynamics of iron (Fe), manganese (Mn), and phosphorus (P) in sediments of the eutrophic, brackish Gulf of Finland populated by cable bacteria. At sites where bottom waters are oxic in spring, surface enrichments of Fe and Mn oxides and high abundances of cable bacteria were observed in sediments upon sampling in early summer. At one site, Fe and P were enriched in a thin layer (~ 3 mm) just below the sediment-water interface. X-ray absorption near edge structure and micro X-ray fluorescence analyses indicate that two-thirds of the P in this layer was associated with poorly crystalline Fe oxides, with an additional contribution of Mn(II) phosphates. The Fe enriched layer was directly overlain by a Mn oxide-rich surface layer (~ 2 mm). The Fe oxide layer was likely of diagenetic origin, formed through dissolution of Fe monosulfides and carbonates, potentially induced by cable bacteria in the preceding months when bottom waters were oxic. Most of the Mn oxides were likely deposited from the water column as part of a cycle of repeated deposition and remobilization. Further research is required to confirm whether cable bacteria activity in spring indeed promotes the formation of distinct layers enriched in Fe, Mn, and P minerals in Gulf of Finland sediments. The temporal variations in biogeochemical cycling in this seasonally hypoxic coastal system, potentially controlled by cable bacteria activity, have little impact on permanent sedimentary Fe, Mn, and P burial., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 The Authors. Limnology and Oceanography published by Wiley Periodicals LLC on behalf of Association for the Sciences of Limnology and Oceanography.)

Oxide dispersion-strengthened (ODS) Eurofer steel was laser welded using a short pulse duration and a designed pattern to minimise local heat accumulation. With a laser power of 2500 W and a duration of more than 3 ms, a full penetration can be obtained in a 1 mm thick plate. Material loss was observed in the fusion zone due to metal vaporisation, which can be fully compensated by the use of filler material. The solidified fusion zone consists of an elongated dual phase microstructure with a bimodal grain size distribution. Nano-oxide particles were found to be dispersed in the steel. Electron backscattered diffraction (EBSD) analysis shows that the microstructure of the heat-treated joint is recovered with substantially unaltered grain size and lower misorientations in different regions. The experimental results indicate that joints with fine grains and dispersed nano-oxide particles can be achieved via pulsed laser beam welding using filler material and post heat treatment.

Objective: To minimize children's injuries due to car accidents, children must be transported in approved child restraint systems (CRS). The European Union optimized child protection by implementing R129 legislation for CRS in 2013. However, compliance with CRS recommendations after introduction of this newer standard has been scarcely evaluated. The main objectives of this study were to determine the prevalence of various types of CRS misuse and to investigate the use of ISOFIX and i-Size seats and parental knowledge regarding safe transportation of children in cars 5 years after the introduction of the newer R129 standard., Methods: During a cross-sectional observational study in the summer of 2018, parking lots of sites in the Netherlands were visited by researchers. Arriving or departing Dutch drivers who transported children under 9 years old were interviewed by means of a questionnaire and the misuse of CRS was directly observed using a checklist. Misuse was defined as CRS inappropriate for the child (based on height and weight) and/or CRS wrongly installed in the car and/or child improperly restrained in CRS., Results: In total, 392 drivers and 470 children were included in the study. Results showed that 83% of the children were transported with at least 1 misuse of their CRS: 7% of the CRS were inappropriate for the child, 49% of the CRS were wrongly installed in the car, and 59% of the children were improperly restrained in a CRS. Most CRS were installed using the seat belt (88%) compared to ISOFIX (12%). ISOFIX usage did not result in less CRS installation misuse ( P =  .338). The number of observed i-Size CRS was low ( n  = 13, 3%). Most drivers were familiar with ISOFIX (76%), but only 13% of the drivers had heard of i-Size., Conclusions: For 9 out of 10 children, CRS misuse was observed. Many children were transported in an appropriate CRS, but various mistakes were made when installing the CRS in the car and restraining children in the CRS. Moreover, ISOFIX usage did not result in statistically significant less CRS installation misuse compared to traditional seat belt usage, and i-Size CRS are still rather unknown 5 years after their introduction.

Alternative care environments for regular nursing homes are highly warranted to promote health and well-being of residents with dementia that are part of an age-friendly and dementia-friendly city and society. Insight is lacking on how to translate evidence-based knowledge from theory into a congruent conceptual model for innovation in current practice. This study reports on the co-creation of an alternative nursing home model in the Netherlands. A participatory research approach was used to co-create a conceptual framework with researchers, practitioners and older people following an iterative process. Results indicate that achieving positive outcomes for people with dementia, (in)formal caregivers, and the community is dependent on how well the physical, social and organizational environment are congruently designed. The theoretical underpinnings of the conceptual model have been translated into "the homestead," which is conceptualized around three main pillars: activation, freedom and relationships. The Homestead Care Model is an illustrative example of how residential care facilities can support the development of age-friendly communities that take into consideration the needs and requirements of older citizens. However, challenges remain to implement radical changes within residential care. More research is needed into the actual implementation of the Homestead Care Model.

Introduction: Debridement is often a necessary step in wound care. In burn care, typically, surgery or enzymes are used for this purpose., Objective: In a real-life retrospective study, the autolytic debridement properties of a concentrated surfactant gel (CSG) were assessed., Materials and Methods: Thirty patients who had burns that ranged from superficial partial thickness to full thickness and did not exceed 10% total body surface area were evaluated retrospectively with regard to outcomes of their treatment with CSG alone or in combination with bacitracin ointment (CSG-BA). Both materials were applied daily. The hypothesis of the study was that CSG, by providing moisture to the wound in combination with debridement via micelle action, would provide debridement without the need for surgery or enzymes and would lead to healing times similar to those for wounds treated with other modalities. Burn depth was determined visually., Results: Of the CSG-treated burns, 88.2% were mixed partial thickness, deep partial, or full thickness, and 64.7% of these lesions reepithelialized completely or showed satisfactory healing progression within a time frame that is similar to published results with other treatment modalities. Secondary autografting was necessary in 1 lesion., Conclusions: On average, the CSG-BA-treated burns were less deep and smaller than the CSG alone. All wounds reached complete healing or showed continued healing progress.

Graphene quantum dots (QDs) are intensively studied as platforms for the next generation of quantum electronic devices. Fine tuning of the transport properties in monolayer graphene QDs, in particular with respect to the independent modulation of the tunnel barrier transparencies, remains challenging and is typically addressed using electrostatic gating. We investigate charge transport in back-gated graphene mechanical break junctions and reveal Coulomb blockade physics characteristic of a single, high-quality QD when a nanogap is opened in a graphene constriction. By mechanically controlling the distance across the newly formed graphene nanogap, we achieve reversible tunability of the tunnel coupling to the drain electrode by 5 orders of magnitude, while keeping the source-QD tunnel coupling constant. The break junction device can therefore become a powerful platform to study the physical parameters that are crucial to the development of future graphene-based devices, including energy converters and quantum calorimeters.

Background: Adverse events are common in high-risk surgical patients, but early detection is difficult. Recent innovations have resulted in wireless and 'wearable' sensors, which may capture patient deterioration at an early stage, but little is known regarding their ability to timely detect events. The objective of this study is to describe the ability of currently available wireless sensors to detect adverse events in high-risk patients., Methods: A descriptive analysis was performed of all vital signs trend data obtained during an observational comparison study of wearable sensors for vital signs monitoring in high-risk surgical patients during the initial days of recovery at a surgical step-down unit (SDU) and subsequent traumatology or surgical oncology ward. Heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO 2 ) were continuously recorded. Vital sign trend patterns of patients that developed adverse events were described and compared to vital sign recordings of patients without occurrence of adverse events. Two wearable patch sensors were used (SensiumVitals and HealthPatch), a bed-based mattress sensor (EarlySense) and a patient-worn monitor (Masimo Radius-7)., Results: Twenty adverse events occurred in 11 of the 31 patients included. Atrial fibrillation (AF) was most common (20%). The onset of AF was recognizable as a sudden increase in HR in all recordings, and all patients with new-onset AF after esophagectomy developed other postoperative complications. Patients who developed respiratory insufficiency showed an increase in RR and a decrease in SpO 2 , but an increase in HR was not always visible. In patients without adverse events, temporary periods of high HR and RR are observed as well, but these were transient and less frequent., Conclusions: Current systems for remote wireless patient monitoring on the ward are capable of detecting abnormalities in vital sign patterns in patients who develop adverse events. Remote patient monitoring may have potential to improve patient safety by generating early warnings for deterioration to nursing staff., Competing Interests: Declaration of Competing interest MJMB is part-time employee of Luscii Healthtech BV (Health ICT company, Amsterdam, The Netherlands)., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Only truly long-term follow-up can determine the ultimate outcome in prostate cancer. Most studies have a median follow-up of less than 10 years and then project outcomes out to 15 and 20 years. We sought to follow patients for at least 20 years. Materials and Methods . We followed 754 prostate cancer patients treated with radical prostatectomy from 1988 to 1995 for a median follow-up (in survivors) of 23.9 years. We excluded lymph node and seminal vesicle positive patients and an additional 47 patients that did not have baseline prostate-specific antigen (PSA). This left 581 patients for analysis., Results: With the factors of PSA, Gleason score, and extraprostatic extension/margin positivity, we could partition patients into three risk groups for biochemical failure (low, intermediate, and high). In further analysis, we found that the risk of metastatic disease in the first two groups was almost identical (4% and 5%, respectively), while it was 19% in the high-risk group. High-risk patients were those with PSA >20 ng/ml and/or Gleason >7, or Gleason 7 + PSA 10-20 + epe (and or margin) positive. They had a 22% prostate cancer mortality., Conclusion: In patients with truly long-term follow-up after prostatectomy for prostate cancer, the risk of metastatic disease and cancer death is very low. Patients with the lower risk findings do not appear to benefit from routine follow-up after 10 years free of biochemical recurrence. With a higher risk of later failure, we recommend that the higher risk patients be followed at least intermittently for another 5 years (out to 15 years)., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Gregory P. Swanson et al.)

Mast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which is a hematological disease that is characterized by the accumulation of mast cells due to clonal proliferation. This association suggests an important role for mast cells in cardiovascular disease. Indeed, the evidence establishing the contribution of mast cells to the development and progression of atherosclerosis is continually increasing. Mast cells may contribute to plaque formation by stimulating the formation of foam cells and causing a pro-inflammatory micro-environment. In addition, these cells are able to promote plaque instability by neo-vessel formation and also by inducing intraplaque hemorrhage. Furthermore, mast cells appear to stimulate the formation of fibrosis after a cardiac infarction. In this review, the available data on the role of mast cells in cardiovascular disease are summarized, containing both in vitro research and animal studies, followed by a discussion of human data on the association between cardiovascular morbidity and diseases in which mast cells are important: Kounis syndrome, mastocytosis and allergy., Competing Interests: The authors declare no conflict of interest.

Oxygen depletion in coastal waters may lead to release of toxic sulfide from sediments. Cable bacteria can limit sulfide release by promoting iron oxide formation in sediments. Currently, it is unknown how widespread this phenomenon is. Here, we assess the abundance, activity, and biogeochemical impact of cable bacteria at 12 Baltic Sea sites. Cable bacteria were mostly absent in sediments overlain by anoxic and sulfidic bottom waters, emphasizing their dependence on oxygen or nitrate as electron acceptors. At sites that were temporarily reoxygenated, cable bacterial densities were low. At seasonally hypoxic sites, cable bacterial densities correlated linearly with the supply of sulfide. The highest densities were observed at Gulf of Finland sites with high rates of sulfate reduction. Microelectrode profiles of sulfide, oxygen, and pH indicated low or no in situ cable bacteria activity at all sites. Reactivation occurred within 5 days upon incubation of an intact sediment core from the Gulf of Finland with aerated overlying water. We found no relationship between cable bacterial densities and macrofaunal abundances, salinity, or sediment organic carbon. Our geochemical data suggest that cable bacteria promote conversion of iron monosulfides to iron oxides in the Gulf of Finland in spring, possibly explaining why bottom waters in this highly eutrophic region rarely contain sulfide in summer.

An important field in robotics is the optimization of controllers. Currently, robots are often treated as a black box in this optimization process, which is the reason why derivative-free optimization methods such as evolutionary algorithms or reinforcement learning are omnipresent. When gradient-based methods are used, models are kept small or rely on finite difference approximations for the Jacobian. This method quickly grows expensive with increasing numbers of parameters, such as found in deep learning. We propose the implementation of a modern physics engine, which can differentiate control parameters. This engine is implemented for both CPU and GPU. Firstly, this paper shows how such an engine speeds up the optimization process, even for small problems. Furthermore, it explains why this is an alternative approach to deep Q-learning, for using deep learning in robotics. Finally, we argue that this is a big step for deep learning in robotics, as it opens up new possibilities to optimize robots, both in hardware and software.

A new design for transparent high-pressure nozzles is presented in this work. This new design enables using the innovative Selective Laser Etching (SLE) method to manufacture transparent nozzles with outstanding accuracy. Therefore, not only the simultaneous visualization of the flow mechanics inside and outside the nozzle is enabled, but the manufacturing method applied also allows for the realization of individual nozzle geometries. Thus, nozzle internal flow phenomena (e.g., cavitation, swirl, and air inlet) and their influence on primary breakup can be analyzed with realistic nozzle geometries, e.g., for automotive applications. In addition, targeted three dimensional nozzle geometric parameters can be designed and manufactured in order to get specific tailor-made spray characteristics (e.g., droplet size distribution, spray angle, and penetration length). The basis for the transparent nozzle design is a two-parted nozzle, consisting of a re-machined original serial nozzle body and a transparent nozzle tip. The innovative SLE is used to produce the geometry of the transparent nozzle tip in fused silica, and laser polishing is utilized to achieve a maximum optical quality of nozzle surfaces for visualization. Bonding of both nozzle parts is achieved by a specially designed adhesive method. For a first feasibility study, a transparent nozzle with a simplified nozzle geometry is manufactured and used for a first study. In this study, simultaneous investigation of nozzle internal flow phenomena and their impact on spray breakup are visualized. First microscopic images of the nozzle internal flow show the formation of cavitation, its effect on nozzle internal temperature (apparent by differences in the fluid refractive index), and also the corresponding impact on spray breakup during injection. The penetration of ambient gas into the nozzle is verified at the end of injection as well as the influence of this air on the spray formation during the start of injection.

Objectives: To review our two institutional experiences regarding the historical referral patterns of bladder cancer patients to receive radiation therapy, characteristics of these referred patients, and their treatment outcomes., Methods: A retrospective review was performed analyzing patients who underwent radiation therapy for bladder cancer from 2005 to 2015 ( n = 69) at two regional referral institutions. The age-adjusted Charlson comorbidity index (AACCI) was calculated for each patient. Patients were divided into three groups: definitive concurrent chemoradiation (CCR), aggressive radiation (AR) alone ≥ 50 Gy, or palliative radiation alone (PR) < 50 Gy. Gastrointestinal (GI) and genitourinary (GU) acute toxicities were recorded., Results: The median overall AACCI score was 7, which correlates to a two-year expected survival of 55% ± 11%. Thirty-five (50.7%) patients received CCR, 19 (27.5%) received AR, and 15 (21.7%) received PR. Patients presented with hematuria ( n = 43, 62%), pain ( n = 18, 26%), or obstruction ( n = 12, 17%). Of symptomatic patients, treatment improved hematuria in 86%, pain in 75%, and obstruction in 42%. Twenty-two recurrences (32%) were identified at follow-up. Local, regional, and distant recurrences developed in 20%, 14%, and 17% of patients who received CCR. There were two grade 3 GU toxicities and one grade 3 GI toxicity; all grade 3 toxicities were in patients receiving CCR., Conclusions: Bladder preservation is possible with chemoradiation therapy; however, urologists rarely refer patients for consideration of chemoradiation. The limited patients who are referred for radiation generally have limited life expectancy, significant comorbidities, or have advanced disease amenable only to palliation. Palliative radiation improves symptoms with minimal toxicity., Competing Interests: Competing interests: The authors have declared that no competing interests exist., (© 2013-2018, Bladder, All rights reserved.)

In this paper we present four λ/2-wave plates made out of fused silica glass for operation in the terahertz frequency range. The design of the wave plates is based on form birefringence. They were fabricated by selective laser-induced etching resulting in a series of glass bars separated by air grooves. Wave plates operating at single, two and several frequencies were designed, fabricated and characterized.

Trichomonas vaginalis is the most common sexually transmitted parasitical infection worldwide. T. vaginalis can carry a virus: Trichomonas vaginalis virus (TVV). To date, four TVV species have been described. Few studies have investigated TVV prevalence and its clinical importance. We have developed a nested reverse-transcriptase PCR, with novel, type specific primers to directly detect TVV RNA in T. vaginalis positive clinical samples. A total of 119T. vaginalis positive clinical samples were collected in Amsterdam and "s-Hertogenbosch, the Netherlands, from 2012 to 2016. For all samples T. vaginalis was genotyped using multi-locus sequence typing. The T. vaginalis positive samples segregated into a two-genotype population: type I (n=64) and type II (n=55). All were tested for TVV with the new TVV PCR. We detected 3 of the 4 TVV species. Sequencing of the amplified products showed high homology with published TVV genomes (82-100%). Half of the T. vaginalis clinical samples (n=60, 50.4%) were infected with one or more TVV species, with a preponderance for TVV infections in T. vaginalis type I (n=44, 73.3%). Clinical data was available for a subset of samples (n=34) and we observed an association between testing positive for (any) TVV and reporting urogenital symptoms (p=0.023). The nested RT-PCR allowed for direct detection of TVV in T. vaginalis positive clinical samples. This may be helpful in studies and clinical settings, since T. vaginalis disease and/or treatment outcome may be influenced by the protozoa"s virus., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

Acute and chronic wound infections create clinical, economic, and patient-centered challenges best met by multidisciplinary wound care teams providing consistent, valid, clinically relevant, safe, evidence-based management across settings. To develop an evidence-based wound infection guideline, PubMed, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature databases were searched from inception through August 1, 2017 using the terms (or synonyms) wound infection and risk factor, significant, diagnosis, prevention, treatment, or surveillance. Studies on parasitic infections, in vitro studies, and non-English publications were excluded. The 19-member International Consolidated Wound Infection Guideline Task Force (ICWIG TF), hosted by the Association for the Advancement of Wound Care (AAWC), reviewed publications/assessed levels of evidence, developed recommendations, and verified representation of all major recommendations from 27 multidisciplinary wound infection documents. Using a web-based survey, practitioners were invited to assess the clinical relevance and strength of each recommendation using standardized scores. Survey responses from 42 practitioners, including registered nurses (RNs), Wound Care Certified and advanced practice RNs, physical therapists, physicians, podiatrists, and scientists from 6 countries were returned to AAWC staff, tabulated in a spreadsheet, and analyzed for content validity. Respondents had a median of >15 years of military or civilian practice and managed an average of 15.9 ± 23 patients with infected wounds per week. Recommendations supported by strong evidence and/or content validated as relevant by at least 75% of respondents qualified for guideline inclusion. Most (159, 88.8%) of the 179 ICWIG recommendations met these criteria and were summarized as a checklist to harmonize team wound infection management across specialties and settings. Most of the 20 recommendations found not to be valid were related to the use of antibiotics and antiseptics. After final ICWIG TF review of best evidence supporting each recommendation, the guideline will be published on the AAWC website.

Reservoir computing is a bioinspired computing paradigm for processing time-dependent signals. The performance of its analog implementation is comparable to other state-of-the-art algorithms for tasks such as speech recognition or chaotic time series prediction, but these are often constrained by the offline training methods commonly employed. Here, we investigated the online learning approach by training an optoelectronic reservoir computer using a simple gradient descent algorithm, programmed on a field-programmable gate array chip. Our system was applied to wireless communications, a quickly growing domain with an increasing demand for fast analog devices to equalize the nonlinear distorted channels. We report error rates up to two orders of magnitude lower than previous implementations on this task. We show that our system is particularly well suited for realistic channel equalization by testing it on a drifting and a switching channel and obtaining good performances.

Background and Objectives: Needle-induced nerve trauma and intraneural injection can lead to neurologic injury during peripheral nerve blocks. In this study, we assessed the utility of opening injection pressure (OIP), time to OIP, and rate of rise to OIP in detecting needle-nerve contact and intraneural injection., Methods: Five common ultrasound-guided blocks of the femoral, saphenous, subgluteal sciatic, tibial, and common peroneal nerves were simulated in 10 fresh cadavers. Opening injection pressure was defined as peak psi in the 60-second interval during which the injection is initiated. Pressure-time curves were constructed separately for intraneural and perineural injections for each of the 5 nerves studied., Results: Opening injection pressure was higher for intraneural than for perineural injections (P < 0.001), ranging from 21.5 psi (1111.9 mm Hg) to 25.8 psi (1334.2 mm Hg) for intraneural injections and from 3.8 psi (196.5 mm Hg) to 6.1 psi (315.5 mm Hg) for perineural injections. Time to OIP tended to be shorter for intraneural than for perineural injections, particularly for the subgluteal sciatic, tibial, and common peroneal nerves. Curves of intraneural injections had steep slopes with high peaks; curves of perineural injections had low slopes followed by plateaus. Rise to OIP was greater for intraneural than for perineural injections., Conclusions: In our fresh human cadaver model, OIP detected intraneural needle placement. Monitoring of OIP could be useful in detecting and/or preventing intraneural injection during nerve blocks in the clinical setting.

Background: Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment., Aims: This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke., Methods: In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549)., Results: In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45-1.35, p  = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower ( p  = 0.055), whereas total number of days treated with antibiotics were higher ( p  = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections ( p  < 0.0001)., Conclusion: PCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.

Aims: To evaluate the real-world effectiveness of vildagliptin and vildagliptin/metformin, combined with patient engagement, on glycemic outcomes. Patient engagement included both clinicians' engaging patients through education and counseling; and patients' self-engagement through disease awareness, lifestyle changes, and medication adherence., Methods: Prospective, observational, open-label, multi-center, pharmacoepidemiologic study of type 2 diabetes mellitus (T2DM) patients treated de novo with vildagliptin or vildagliptin/metformin. Data were collected at baseline (treatment initiation), 105±15d, and ≥145d., Results: The evaluable sample included 896 mainly male (58%), overweight (mean±SD BMI=30.3±5.4kg/m 2 ), in later middle age (mean±SD age=64±11years) patients. Over the three visits, mean(±SD) HbA1c levels declined from 8.1%(±1.0) to 7.3%(±1.0) to 7.2%(±0.9); HbA1c control rates rose from 7% to 36% to 43%. Mean±SD FPG levels decreased from 170(±49) to 141(±41) to 139(±42)mg/dL; control rates increased from 12% to 39% to 43% (all p<0.0001). Weight decreased nominally by 2kg (p=0.0290) and BMI by 0.8kg/m 2 (p<0.0001). Modeling showed patient engagement activities by clinicians and by patients to be major determinants of glycemic outcomes. No unknown safety signals were detected., Conclusions: Vildagliptin and vildagliptin/metformin are effective and safe oral agents in the management of T2DM, especially if part of a treatment program with active patient engagement by clinicians and empowered patients., (Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

We present the study on the sample transfer characteristics of two different microfluidic interfaces for 2D-CE . These interfaces were manufactured using two different microfabrication technologies: one was obtained via the classical photolithography-wet etching-anodic-bonding process; and the other was obtained via the selective laser-induced etching process. The comparison of the two interfaces, and an intact capillary as a reference, was made via the CE separation of amino acids (arginine and lysine) under different bulk flow conditions, with and without applying bias potential to the secondary channels. The influence on peak shapes, migration times, and repeatabiliy were evaluated., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Delay-coupled electro-optical systems have received much attention for their dynamical properties and their potential use in signal processing. In particular, it has recently been demonstrated, using the artificial intelligence algorithm known as reservoir computing, that photonic implementations of such systems solve complex tasks such as speech recognition. Here, we show how the backpropagation algorithm can be physically implemented on the same electro-optical delay-coupled architecture used for computation with only minor changes to the original design. We find that, compared to when the backpropagation algorithm is not used, the error rate of the resulting computing device, evaluated on three benchmark tasks, decreases considerably. This demonstrates that electro-optical analog computers can embody a large part of their own training process, allowing them to be applied to new, more difficult tasks.

Objective: Narrow-diameter implants are indicated for narrow sites, small interdental/interimplant spaces, or sites with congenitally missing teeth. They also offer a substitute for invasive augmentation procedures. The authors retrospectively evaluated the performance of a new 3.0-mm diameter implant for rehabilitating small anterior spaces., Method and Materials: This observational multicenter retrospective case series included consecutive patients needing single-unit restoration for mandibular and lateral maxillary incisors. The outcome variables were: implant survival, Plaque Index, pocket probing depth (PPD), Jemt's papilla index, bleeding on probing (BOP), and marginal bone remodeling., Results: In total, 45 patients received 58 3.0-mm implants placed in healed sites (n = 22), extraction sockets (n = 16), or sites with congenitally missing teeth (n = 20). Average follow-up time was 15.1 ± 5.2 months. Prosthetic loading was immediate (n = 23), early (n = 16), or delayed (n = 19). Two implants were lost, and two prosthetic complications occurred. One-year bone remodeling averaged -0.36 ± 0.85 mm (n = 44). PPD averaged 1.75 ± 0.58 mm. Neither BOP nor plaque was detected around implants., Conclusions: At 1-year follow-up, narrow 3.0-mm diameter implants placed in mandibular and lateral maxillary incisor sites demonstrate a high survival rate and support stable marginal bone levels and healthy soft tissue.

In a miniaturised flow switch fluid flows are controlled by reducing the local viscosity via absorption of laser radiation. Through this, the local flow rates are increased to switch the outlet port of a fluid flow carrying the analyte. The microfluidic chip is fabricated using Selective Laser-Induced Etching (SLE). SLE allows novel 3D-hydrodynamic focusing, realising circular shaped channel cross-sections and adapting interaction volume geometries to the profile of the laser radiation for optimised absorption. The performance of the switch is validated experimentally with a dyed analyte and video image processing. The ability to sort particles like cells is demonstrated at 8 Hz using polystyrene beads having a diameter of 8 μm.

Psychiatry is the largest medical specialty in Europe. Despite efforts to bring harmonisation, training in psychiatry in Europe continues to be very diverse. The Union Européenne des Médecins Spécialistes (UEMS) has issued as from 2000 a charter of requirements for the training in psychiatry with an additional European Framework for Competencies in Psychiatry in 2009. Yet these have not been implemented throughout Europe. In this paper, the diversity in training throughout Europe is approached from different angles: the cultural differences between countries with regards to how mental health care is considered and founded on, the cultural differences between people throughout Europe in all states. The position of psychotherapy is emphasised. What once was the cornerstone of psychiatry as medical specialty seems to have become a neglected area. Seeing the patient with mental health problems within his cultural context is important, but considering him within his family context. The purpose of any training is enabling the trainee to gain the knowledge and acquire the competencies necessary to become a well-equipped professional is the subject of the last paragraph in which trainees consider their position and early career psychiatrists look back to see whether what they were trained in matches with what they need in the working situation. Common standard for training and certification are a necessity within Europe, for the benefit of the profession of psychiatrist but also for patient safety. UEMS is advised to join forces with the Council of National Psychiatric Associations (NPAs) within the EPA and trainings and early career psychiatrist, to discuss with the users what standards should be implemented in all European countries and how a European board examination could ensure professional quality of psychiatrists throughout the continent.

Apoptosis of macrophages and vascular smooth muscle cells (VSMCs) in advanced atherosclerotic plaques contributes to plaque progression and instability. Caspase-3, a key executioner protease in the apoptotic pathway, has been identified in human and mouse atherosclerotic plaques but its role in atherogenesis is not fully explored. We therefore investigated the impact of caspase-3 deletion on atherosclerosis by crossbreeding caspase-3 knockout (Casp3 -/- ) mice with apolipoprotein E knockout (ApoE -/- ) mice. Bone marrow-derived macrophages and VSMCs isolated from Casp3 -/- ApoE -/- mice were resistant to apoptosis but showed increased susceptibility to necrosis. However, caspase-3 deficiency did not sensitize cells to undergo RIP1-dependent necroptosis. To study the effect on atherosclerotic plaque development, Casp3 +/+ ApoE -/- and Casp3 -/- ApoE -/- mice were fed a western-type diet for 16 weeks. Though total plasma cholesterol, triglycerides, and LDL cholesterol levels were not altered, both the plaque size and percentage necrosis were significantly increased in the aortic root of Casp3 -/- ApoE -/- mice as compared to Casp3 +/+ ApoE -/- mice. Macrophage content was significantly decreased in plaques of Casp3 -/- ApoE -/- mice as compared to controls, while collagen content and VSMC content were not changed. To conclude, deletion of caspase-3 promotes plaque growth and plaque necrosis in ApoE -/- mice, indicating that this antiapoptotic strategy is unfavorable to improve atherosclerotic plaque stability.

Background: Accumulating evidence suggests interactions between bone and energy metabolism in patients with type 2 diabetes (T2DM). Recently, the role of osteocalcin (OC), an osteoblast-specific protein, was suggested as a regulator of glucose metabolism and fat mass., Methods: We determined the circulating levels of OC with two different assays in T2DM patients. The relationship of OC with established biomarkers of bone and mineral metabolism as well as biomarkers related to cardiovascular risk was also investigated., Results: OC levels measured with both methods were significantly lower in T2DM patients in comparison to healthy individuals but assays were not commutable. In multiple regression analysis OC levels were negatively correlated to HbA1c and positively correlated to PTH 1-84 and Beta-crosslaps. OC levels were significantly correlated to NT-proBNP but not to hsTnT., Conclusions: Measurement of OC in T2DM might assist physicians for risk stratification of T2DM patients.

Objectives: Sepsis is associated with high mortality. Because early therapy has proven to decrease mortality, a risk stratification tool that quickly and easily quantifies mortality risk of patients will be helpful to guide appropriate treatment. We investigated five scores in terms of (a) predicting 28-day mortality and (b) their feasibility for use in the emergency department (ED)., Materials and Methods: We carried out a historical cohort study in the ED of Maastricht University Medical Centre (MUMC). Patients who fulfilled the criteria for sepsis were included if they had been admitted to the hospital by an internist between August 2009 and August 2010. The Mortality in Emergency Department Sepsis (MEDS), Confusion, Urea, Respiratory rate, Blood pressure, age>65 (CURB-65), Acute Physiology And Chronic Health Evaluation II (APACHE II), Rapid Acute Physiology Score (RAPS), and Rapid Emergency Medicine Score (REMS) scores were calculated using ED charts. The primary outcome was total 28-day mortality. Receiver operating characteristic curves and calibration plots were constructed to evaluate predictive accuracy. Feasibility was defined as the proportion of patients for whom all data were available., Results: We included 600 patients, of whom 90 (15%) died within 28 days. Discriminating ability for total 28-day mortality of the MEDS [area under the curve (AUC): 0.82, 95% confidence interval (CI) 0.78-0.87], CURB-65 (AUC: 0.78, 95% CI 0.73-0.83), and APACHE II (AUC: 0.71, 95% CI 0.64-0.79) was the highest, but only the difference between the MEDS and REMS (P=0.007) and the RAPS score (P<0.001) was significant. Both the MEDS and the CURB-65 had higher AUCs for predicting 28-day in-hospital mortality than the other three scores, but this was only significant for the MEDS score compared with the RAPS (P=0.003). Both the MEDS and the CURB-65 underestimated mortality, especially for the higher scores. The MEDS, CURB-65, REMS, and RAPS were most feasible as they could be calculated in more than 96% of patients., Conclusion: The MEDS and CURB-65 scores are the most adequate and feasible tools for the prediction of total 28-day mortality in septic patients presenting at the ED, but they need local recalibration before use in the ED.