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Summary: Stemness and pluripotency are mediated by transcriptional master regulators that promote self-renewal and repress cell differentiation, among which is the high-mobility group (HMG) box transcription factor SOX2. Dysregulated SOX2 expression, by contrast, leads to transcriptional aberrations relevant to oncogenic transformation, cancer progression, metastasis, therapy resistance, and relapse. Here, we report a post-transcriptional mechanism by which the cytosolic pool of SOX2 contributes to these events in an unsuspected manner. Specifically, a low-complexity region within SOX2’s C-terminal segment connects to the ribosome to modulate the expression of cognate downstream factors. Independent of nuclear structures or DNA, this C-terminal functionality alone changes metabolic properties and induces non-adhesive growth when expressed in the cytosol of SOX2 knockout cells. We thus propose a revised model of SOX2 action where nuclear and cytosolic fractions cooperate to impose cell fate decisions via both transcriptional and translational mechanisms.

Abstract Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates (“hibernation”). However, a newly isolated Pseudomonas aeruginosa phage, named Paride, can directly replicate and induce the lysis of deep-dormant hosts. While non-growing bacteria are notoriously tolerant to antibiotic drugs, the combination with Paride enables the carbapenem meropenem to eradicate deep-dormant cultures in vitro and to reduce a resilient bacterial infection of a tissue cage implant in mice. Our work might inspire new treatments for persistent bacterial infections and, more broadly, highlights two viral strategies to infect dormant bacteria (hibernation and direct replication) that will guide future studies on phage-host interactions.

Within the context of an aging global population, the demographic structure of emerging economies is undergoing a dramatic transformation. Emerging economies have a large population base and rapid economic development, but they are ill-prepared to deal with population aging. Limited resources force many older adults to face health issues such as chronic diseases and loss of physical independence, exacerbating the burden of traditional family and societal elderly care. Uncontrollable events such as the COVID-19 pandemic and regional conflicts have exacerbated the plight of older adults. Improving the quality of life and health of older adults has become a development priority in emerging economies in the face of a rapidly aging population. The development of smart cities has brought with it many available digital technologies, and the consequent development of smart aging offers endless possibilities for improving the quality of life and health of older people, making cities more inclusive of older people. Researchers from developed economies have attempted to address the health issues of older adults through a technology that combines physical exercise and digital technology called Exergame. However, existing projects are not suitable for older adults in emerging economies due to differences in national conditions. The aim of this project is therefore to propose a universal approach to designing a health-promoting Exergame system in the format of a virtual urban community to help emerging economies cope with aging populations, making cities more inclusive. To verify the feasibility of this approach, the authors designed an expandable Exergame called “Fit Islands”, using China as a case study. Based on the initial demonstration, the authors conducted functional tests. The result is that Fit Islands can meet the development objective of motivating Chinese older people to increase their physical activity, providing initial evidence of the feasibility of an Exergame system to promote healthy aging in emerging economies. The application of Fit Islands demonstrates the feasibility of the universal Exergame development method, which can, in principle, provide comprehensive and practical guidance for other countries.

Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here, we addressed how murine adult hippocampal NSC fate is regulated and described how scaffold attachment factor B (SAFB) blocks oligodendrocyte production to enable neuron generation. We found that SAFB prevents NSC expression of the transcription factor nuclear factor I/B (NFIB) by binding to sequences in the Nfib mRNA and enhancing Drosha-dependent cleavage of the transcripts. We show that increasing SAFB expression prevents oligodendrocyte production by multipotent adult NSCs, and conditional deletion of Safb increases NFIB expression and oligodendrocyte formation in the adult hippocampus. Our results provide novel insights into a mechanism that controls Drosha functions for selective regulation of NSC fate by modulating the post-transcriptional destabilization of Nfib mRNA in a lineage-specific manner.

Abstract Background Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both – HT and PS – to provide further evidence for a recovery-oriented treatment of psychiatric patients. Methods In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. Discussion This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients’ recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. Trial registration The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.

Prefabricated modules are being used to renovate the building envelope. However, compared to manual methods, the design and prefabricated module’s definition is time consuming. Therefore, it is necessary to improve the efficiency of the prefabricated layout definition processes by incorporating automation and computational design. The purpose of this paper is to present a semi-automated definition of the layout of the prefabricated modules with the only input of the existing building facade being the Point Cloud. In this research, a novel step-by-step workflow was developed. More precisely, an algorithm was developed that processes the coordinates of each point of the cloud and generates the layout of the prefabricated modules. To validate the workflow and the algorithm, four facades were tested, considering two parameters: (a) working time and (b) output accuracy. According to the results, it was concluded that spending more time achieving an accurate laser data acquisition can be a good strategy to obtain the primary layout with sufficient precision.

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in patient samples from multiple etiologies and stages.

Low-threshold e-health approaches in prevention to reduce suicide stigma are scarce. We developed an online program containing video reports on lived experience of suicide and evidence-based information on suicidality. We evaluated the program by a mixed methods design. We examined pre-post-changes of program completers (n = 268) in suicide literacy, suicide stigma (self and perceived), and self-efficacy expectation of being able to seek support in psychologically difficult situations using linear mixed models. To examine reported changes and helpful program elements 12-26 weeks after program completion, we content analyzed transcripts of telephone interviews (n = 16). Program completers showed more suicide literacy (Cohen's d = .74; p < .001), higher self-efficacy expectations to seek support (d = .09; p < .01), lower self-stigma (subscales glorification/normalization: d = -.13, p = .04; isolation/depression: d = -.14; p = .04; stigma: d = -.10; p = .07; n = 168) compared to baseline. We found no significant differences in perceived suicide stigma. We identified lived experience reports, the possibility of sharing own narrative on stigma and suicidality, and information on support as helpful elements. The current online program can increase suicide literacy and self-efficacy expectations to seek support and reduce self-stigma. We recommend a larger randomized controlled trial with longer follow-up to confirm these findings.

Fabry–Pérot-based refractometry has demonstrated the ability to assess gas pressure with high accuracy and has been prophesized to be able to realize the SI unit for pressure, the pascal, based on quantum calculations of the molar polarizabilities of gases. So far, the technology has mostly been limited to well-controlled laboratories. However, recently, an easy-to-use transportable refractometer has been constructed. Although its performance has previously been assessed under well-controlled laboratory conditions, to assess its ability to serve as an actually transportable system, a ring-type comparison addressing various well-characterized pressure balances in the 10–90 kPa range at several European national metrology institutes is presented in this work. It was found that the transportable refractometer is capable of being transported and swiftly set up to be operational with retained performance in a variety of environments. The system could also verify that the pressure balances used within the ring-type comparison agree with each other. These results constitute an important step toward broadening the application areas of FP-based refractometry technology and bringing it within reach of various types of stakeholders, not least within industry.

The rising global energy demand has made it essential to reduce energy consumption in the residential building stock. Adding a new insulating envelope with Renewable Energy Sources (RESs) onto the existing buildings’ facade is one way to achieve zero energy consumption in residential buildings. The ENSNARE project aims to semi-automate this process by using prefabricated facade modules and developing new building data acquisition techniques. Prior to this research project, an analysis was carried out and several research gaps were identified. One of the obstacles to using prefabricated modules with RES is that the layout needs to be drawn and adjusted during different phases of the project. That is time-consuming. For this reason, this article describes two new solutions: (1) automated drafting of the optimized layout of prefabricated modules of the facade and the number of solar panels based on the existing residential building model, and (2) automated adjustment of the layout depending on the phase of the renovation project and the accuracy of the measurements in each step. The proposed semi-automated approach has the potential to significantly reduce the time used in drafting the layout of the prefabricated modules, which benefits the whole renovation process, contributing to a more sustainable future for the residential building stock.

Plain English summary A team of persons with a lived experience of suicide and researchers jointly developed an online suicide prevention program. This online program addresses the taboo and stigmatized topic of suicidality from the perspective of people with lived experience. In our team are people who tried to take their own lives, thought about suicide, and people who lost a close person by suicide. For the program we wrote texts on suicidality and suicide on a scientific basis. In videos the team shared their experiences with suicide. The team told what helped them to continue living and gave them hope. Online program participants can read these texts and watch these videos. Participants can learn about suicidality and are encouraged to seek help if needed. During the development of the program, the researchers created a working atmosphere characterized by respect, empathy, transparency, and openness. Dealing with suicidality can be emotionally stressful. The team felt comfortable and safe. The team was proud of the developed online program. We describe strengths and weaknesses of the program development. We did not evaluate the involvement during the program development. If one wants to do this, the purpose should be explained to the team. The team should have a say in the design, such as what questions are asked. Our program gained enormously from involvement of people with a lived experience of suicide. Involvement is possible and necessary even with complex and sensitive topics such as suicidality. Antistigma work should involve those affected. Involvement is important to create a credible program.

In order to reach a Zero-Energy-consuming building stock, it is necessary to insulate and add renewable energy sources on top of existing building envelopes. Off-site prefabricated modules have been used for covering building facades, but manual on-site installation procedures are still more competitive than prefabricated ones. Renovation with prefabricated modules requires high precision in order to obtain airtight and waterproof conditions. For that, an accurate installation of the anchors on top of the facade is crucial. With current techniques, this is a time-consuming operation. One of the attempts to solve the above-mentioned issue was to place the part of the anchor on top of a building facade with high tolerances and to use an interface to correct the deviations. In previous research, this concept, named Matching Kit, was validated, but improvements needed to be made to make it more competitive. In this paper, thanks to novel algorithms and the use of Point Clouds, an improved version is presented. The results show a reduction in working time and an increase in precision. With this research, the interface is closer to being used in the construction industry.

Abstract Aims Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported. SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. Methods and results Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS‐CoV‐2 genomes by real‐time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS‐CoV‐2 infected by reverse real‐time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. Conclusions This is the first report that established the evidence of SARS‐CoV‐2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB‐based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS‐CoV‐2‐infection and to design future specific and personalized treatment strategies.

Loss of function mutations of NSD1 occur in blood cancers. Here, the authors report that NSD1 loss blocks erythroid differentiation which leads to an erythroleukemia-like disease in mice by impairing GATA1-induced target gene activation.

A novel ionization gauge was developed where the electron beam is guided through the ionization space in a straight path. This design was chosen in order to develop a more stable ionization vacuum gauge suitable as reference standard in the range of 10−6 Pa to 10−2 Pa. The design requires a low electron current resulting in even lower ion currents. For the purpose of a reference standard, these ultra-low currents in the range 1 pA–100 nA need to be measured in a traceable manner. For the first time, an ultrastable low-noise current amplifier was used for this purpose.

The autophagic and Hippo pathways are both well characterized contributors to cancer. Here, Tang et al show that LATS1, but not LATS2, negatively regulates autophagy by promoting Beclin1 ubiquitination, which restricts lethal autophagy induced by sorafenib treatment in cancer cells.

Abstract Background Worldwide, approximately 800,000 persons die by suicide every year; with rates of suicide attempts estimated to be much higher. Suicidal persons often suffer from a mental disorder but stigma, lack of available and suitable support, and insufficient information on mental health limit help seeking. The use of internet-based applications can help individuals inform themselves about mental disorders, assess the extent of their own concerns, find local treatment options, and prepare for contact with health care professionals. This project aims to develop and evaluate e-mental health interventions to improve knowledge about suicidality and to reduce stigmatization of those affected. In developing these interventions, a representative telephone survey was conducted to detect knowledge gaps and stigmatizing attitudes in the general population. Methods First, a national representative telephone survey with N = 2000 participants in Germany was conducted. Second, e-mental health interventions are developed to address knowledge gaps and public stigma detected in the survey. These comprise an evidence-based health information package about suicidality, information on regional support services, a self-administered depression test—including suicidality—and an interactive online intervention including personal stories. The development is based on a trialogical exchange of experience between persons affected by suicidality, relatives of affected persons, and clinical experts. Australian researchers who developed an e-mental health intervention for individuals affected by rural suicide were invited to a workshop in order to contribute their knowledge and expertise. Third, the online intervention will be evaluated by a mixed methods design. Discussion From representative telephone survey data, content can be developed to address specific attitudes and knowledge via the e-mental health interventions. These interventions will be easily accessed and provide an opportunity to reach people who tend not to seek professional services, prefer to inform themselves in advance and/or wish to remain anonymous. Evaluation of the online intervention will provide information on any changes in participants’ self-stigma and perceived-stigma of suicidality, and any increase in participants’ knowledge on suicidality or self-efficacy expectations. Trial registration German Clinical Trial Register DRKS00015071 on August 6, 2018.

Mit der curricularen Implementation Forschenden Lernens in die Praxissemester der meisten Bundesländer ist die Erwartung verbunden, dass Lehramtsstudierende Forschungskompetenzen und eine forschende Grundhaltung entwickeln (Fichten & Weyland, 2018). Die Doppelaufgabe des Unterrichtens und Forschens im Praxissemester wird jedoch von den Studierenden häufig als eine belastend wahrgenommene Antinomie beschrieben (Fichten & Weyland, 2018). Eine Möglichkeit des Forschenden Lernens außerhalb der Lehramtspraktika ist die Umsetzung von empirischen Projekten im Rahmen von Abschlussarbeiten (Kamm & Bieri, 2008; Vetter, Staub & Ingrisani, 2014). Die Masterarbeit bietet dabei die Möglichkeit, in einer zeitlich längeren Phase fokussiert einen distanzierten Blick auf Schule und Unterricht einzunehmen. Jedoch existiert auch bei dieser Form Forschenden Lernens die Herausforderung einer guten methodischen Betreuung, damit das Forschende Lernen als sinnvoll erachtet wird (Weyland, 2014). Es kann also zielführend sein, Lehramtsstudierende am Ende ihres Bachelor- oder Masterstudiums beim wissenschaftlichen Arbeiten sowie beim Erlernen forschungsmethodischer Kenntnisse zu unterstützen, um den Nutzen Forschenden Lernens für die spätere Berufspraxis zu verdeutlichen. Dieser Herausforderung begegnet das vom BMBF geförderte Qualitätsoffensive-Lehrerbildung-Projekt QUALITEACH mit dem Teilprojekt „Forschungslabor MasterMind“ mit einer individuellen Methodenberatung für Lehramtsstudierende in der Phase ihrer Abschlussarbeit. Im vorliegenden Beitrag wird die Methodenberatung zunächst erläutert, anschließend werden die thematischen Unterstützungsanliegen der Lehramtsstudierenden skizziert und erste Evaluationsdaten präsentiert.

Introduction Healthcare systems around the world are looking for solutions to the growing problem of mental disorders. RECOVER is the synonym for an evidence-based, stepped and cross-sectoral coordinated care service model for mental disorders. RECOVER implements a cross-sectoral network with managed care, comprehensive psychological, somatic and social diagnostics, crisis resolution and a general structure of four severity levels, each with assigned evidence-based therapy models (eg, assertive community treatment) and therapies (eg, psychotherapy). The study rationale is the investigation of the effectiveness and efficiency of stepped and integrated care in comparison to standard care.Methods and analysis The trial is conducted in accordance to the Standard Protocol Items: Recommendations for Interventional Trials Statement. The study aims to compare the RECOVER model with treatment as usual (TAU). The following questions are examined: Does RECOVER reduce healthcare costs compared with TAU? Does RECOVER improve patient-relevant outcomes? Is RECOVER cost-effective compared with TAU? A total sample of 890 patients with mental disorders will be assessed at baseline and individually randomised into RECOVER or TAU. Follow-up assessments are conducted after 6 and 12 months. As primary outcomes, cost reduction, improvement in symptoms, daily functioning and quality of life as well as cost-effectiveness ratios will be measured. In addition, several secondary outcomes will be assessed. Primary and secondary outcomes are evaluated according to the intention-to-treat principle. Mixed linear or logistic regression models are used with the direct maximum likelihood estimation procedure which results in unbiassed estimators under the missing-at-random assumption. Costs due to healthcare utilisation and productivity losses are evaluated using difference-in-difference regressions.Ethics and dissemination Ethical approval from the ethics committee of the Hamburg Medical Association has been obtained (PV5672). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications.Trial registration number and registry name ClinicalTrials.gov (NCT03459664), RECOVERProtocol version 19 March 2020 (V.3.0)

The German concept of a trialogue in medicine is at its best a cooperation between patients, relatives, and professionals as partners on equal footing. Prerequisites, and also the aim of the trialogue, are mutual respect, an open attitude from professionals, and self-confidence from patients and relatives. The expertise of each of these groups is to be strengthened through the trialogue and should benefit all. Trialogue cooperation brings about a change of perspective and promotes mutual understanding. By establishing a therapeutic relationship on equal footing with the patient with involvement of their relatives, individual and family resources can be better utilized, professional assistance can be designed to better meet the patient’s needs, and acceptance of and commitment to treatment can be increased. In addition, early symptoms and new phases of the disease can be recognized earlier and adequate treatment can be initiated more quickly. A favorable course of the disease is thus more likely, and relapses are less likely to present. The use of peers has proven to be quite helpful. The consistently trialogue structure within the German Society for Bipolar Disorder (Deutsche Gesellschaft für Bipolare Störungen e.V./DGBS: Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main) as a medical society enables further development of the trialogue on many levels, for example, the drafting and updating of the German guidelines for bipolar disorder with the trialogue in mind.

Abstract The arrangement of proteins into complexes is a key organizational principle for many cellular functions. Although the topology of many complexes has been systematically analyzed in isolation, their molecular sociology in situ remains elusive. Here, we show that crude cellular extracts of a eukaryotic thermophile, Chaetomium thermophilum, retain basic principles of cellular organization. Using a structural proteomics approach, we simultaneously characterized the abundance, interactions, and structure of a third of the C. thermophilum proteome within these extracts. We identified 27 distinct protein communities that include 108 interconnected complexes, which dynamically associate with each other and functionally benefit from being in close proximity in the cell. Furthermore, we investigated the structure of fatty acid synthase within these extracts by cryoEM and this revealed multiple, flexible states of the enzyme in adaptation to its association with other complexes, thus exemplifying the need for in situ studies. As the components of the captured protein communities are known—at both the protein and complex levels—this study constitutes another step forward toward a molecular understanding of subcellular organization.

Objective: The ACCESS treatment model offers assertive community treatment (ACT) embedded in an integrated care program to patients with severe psychotic disorders. Compared to standard care, it proved to be more effective in terms of service disengagement and other outcomes in patients with psychotic disorders over 12, 24, and 48 months. Many patients with severe mental disorders experience involuntary admissions which can be potentially traumatic. In this study, we assessed the effect of ACT on reducing involuntary admissions over an observation period of 4 years.Method: One hundred seventy-one patients treated in ACCESS were included in this study. The primary outcome was rate of involuntary admissions during 48 months. Secondary outcomes were differences between those with and without involuntary admissions in the 2 years prior to ACCESS regarding change of psychopathology, severity of illness, psychosocial functioning, quality of life, satisfaction with care, medication non-adherence, and service-disengagement.Results: Of 171 patients, 58 patients (33.9%) were involuntarily admitted to hospital in the past 2 years before entry. During the 4 years of treatment, 16 patients (9.4%) were involuntarily admitted to hospital which was a significantly lower rate compared to the 2 years before inclusion in ACCESS (p < .001). Comparing the two groups, larger improvements in severity of illness (p = .004) and functional status (p = .043) were detected in the group with no history of involuntary admissions. At 4-year follow-up, of the remaining patients, 69.2% (n = 81) were full adherent (p < .001), compared to 18.9% (n = 31) at baseline with no differences between the two groups over the study period (p = .25). Over 4 years, only 13 patients (13.2%) were service-disengaged due to non-practical reasons.Conclusions: In this long-term study, we were able to demonstrate a reduction in involuntary admissions in four treatment years compared to the 2 years prior to admission to the ACCESS model in patients with severe and mostly multiphase schizophrenia spectrum disorders and affective disorders with psychotic features. This may help prevent patients from suffering from a potentially traumatic experience during treatment in the psychiatric system.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01888627.

Single-task construction robots (STCRs) have become a popular research topic for decades. However, there is still a gap in the ubiquitous application of STCRs for onsite construction due to various reasons, such as cost concerns. Therefore, cost–benefit analysis (CBA) can be used to measure the net economic benefit of the STCRs, compared to traditional construction methods, in order to boost the implementation of STCRs. This paper presents a simple and practical framework for the economic evaluation of STCRs and conducts a case study of a cable-driven facade installation robot to verify the method. The results show that the cable-driven robot for facade installation is worth investing in in the UK, as well as in the majority of G20 countries. Furthermore, other socioenvironmental implications of STCRs and the limitations of the study are also discussed. In conclusion, the proposed method is highly adaptable and reproducible. Therefore, researchers, engineers, investors, and policy makers can easily follow and customize this method to assess the economic advantages of any STCR systems, compared to traditional construction technologies.

The installation of façade enclosures is a manual, dangerous, and time-consuming construction task. However, thanks to the capability of automated systems, the application of automation in construction is increasing, and therefore, manual work and risky situations can be avoided. Despite this, only a few robotic systems are capable of spanning such a vast work space, i.e. the façade of a building. Among these systems is the cable driven parallel robot (CDPR). Furthermore, the CDPR could carry heavy loads such as unitised curtain wall modules (CWM). Nevertheless, the tools and devices required for installing the CWM need to be innovated. Firstly, in order to cover that research gap, the current manual procedure was analysed in detail. After that, the development team evaluated several options for performing the tasks. Finally, an optimal solution was chosen: the so-called modular end-effector (MEE). The MEE comprises several tools in order to achieve various tasks. Mainly, these tasks are: drilling the concrete slab, bracket installation, and CWM handling and positioning. In addition to the aforementioned tasks, the MEE should accurately fix all elements with a desired tolerance less than 1 mm. Meanwhile, the MEE should compensate for the perturbation movement due to external forces such as wind that affect the system. As part of the study, a detailed workflow for the automated installation of CWMs was elaborated. The drilling step of the workflow was tested and the result is presented in this paper.

The ACCESS-model offers integrated care including assertive community treatment to patients with psychotic disorders. ACCESS proved more effective compared to standard care (ACCESS-I study) and was successfully implemented into clinical routine (ACCESS-II study). In this article, we report the 4-year outcomes of the ACCESS-II study. Between May 2007 and December 2013, 115 patients received continuous ACCESS-care. We hypothesized that the low 2-year disengagement and hospitalization rates and significant improvements in psychopathology, functioning, and quality of life could be sustained over 4 years. Over 4 years, only 10 patients disengaged from ACCESS. Another 23 left for practical reasons and were successfully transferred to other services. Hospitalization rates remained low (13.0% in year 3; 9.1% in year 4). Involuntary admissions decreased from 35% in the 2 years prior to ACCESS to 8% over 4 years in ACCESS. Outpatient contacts remained stably high at 2.0-2.4 per week. We detected significant improvements in psychopathology (effect size d = 0.79), illness severity (d = 1.29), level of functioning (d = 0.77), quality of life (d = 0.47) and stably high client satisfaction (d = 0.02) over 4 years. Most positive effects were observed within the first 2 years with the exception of illness severity, which further improved from year 2 to 4. Within continuous intensive 4-year ACCESS-care, sustained improvements in psychopathology, functioning, quality of life, low service disengagement and re-hospitalization rates, as well as low rates of involuntary treatment, were observed in contrast to other studies, which reported a decline in these parameters once a specific treatment model was stopped. Yet, stronger evidence to prove these results is required.Clinical Trial Registration Number: NCT01888627.

Properly designed feedback can be highly conducive to students' learning. Therefore, teacher education needs to equip future teachers with research-based knowledge of how to provide effective feedback. The present study reports the implementation and quasi-experimental evaluation (a pre-post control group design; N = 141) of a four-week intervention programme that aimed to enhance student teachers' knowledge of effective feedback and their ability to provide it to students. As a secondary objective, we also tested whether the experience of applying research-based knowledge about feedback improved participants' attitudes towards educational research. The results showed a substantial increase in knowledge about effective feedback. Moreover, in-depth analysis of written feedback indicated an improvement in participants' ability to provide high-quality feedback. However, there was no additional effect on their attitudes towards the usability of knowledge from educational research. We discuss the implications for teacher education and teaching about effective feedback.

Cell surface proteins are major targets of biomedical research due to their utility as cellular markers and their extracellular accessibility for pharmacological intervention. However, information about the cell surface protein repertoire (the surfaceome) of individual cells is only sparsely available. Here, we applied the Cell Surface Capture (CSC) technology to 41 human and 31 mouse cell types to generate a mass-spectrometry derived Cell Surface Protein Atlas (CSPA) providing cellular surfaceome snapshots at high resolution. The CSPA is presented in form of an easy-to-navigate interactive database, a downloadable data matrix and with tools for targeted surfaceome rediscovery (http://wlab.ethz.ch/cspa). The cellular surfaceome snapshots of different cell types, including cancer cells, resulted in a combined dataset of 1492 human and 1296 mouse cell surface glycoproteins, providing experimental evidence for their cell surface expression on different cell types, including 136 G-protein coupled receptors and 75 membrane receptor tyrosine-protein kinases. Integrated analysis of the CSPA reveals that the concerted biological function of individual cell types is mainly guided by quantitative rather than qualitative surfaceome differences. The CSPA will be useful for the evaluation of drug targets, for the improved classification of cell types and for a better understanding of the surfaceome and its concerted biological functions in complex signaling microenvironments.