A Total Cost of Ownership Model for Cloud Computing Infrastructure

A holistic cost assessment of cloud computing ar-chitectures is currently hampered by the lack of assessment methods and the absence of a standardized and comprehensive total cost model. This creates uncertainty about cost developments of concrete scenarios and architectural changes. This article proposes a total cost of ownership model for cloud computing, covering the cost of adoption, procurement, migration, operation, usage, and exit. We evaluated our model in multiple application scenarios and against other models. Our model has shown to be substantially more comprehensive and applicable than other available models for cloud computing. Thus, our model can be useful both in practice and in research. We will demonstrate that our model can increase cost transparency and improve decision support

New Topoisomerase Inhibitors:Evaluating the Potency of Gepotidacin and Zoliflodacin in Fluoroquinolone-Resistant Escherichia coli upon tolC Inactivation and Differentiating Their Efflux Pump Substrate Nature

Inactivating tolC in multidrug-resistant Escherichia coli with differing sequence types and quinolone resistance-determining mutations reveals remarkably potentiated activity of the first-in-class topoisomerase inhibitors gepotidacin and zoliflodacin. Differences between both structurally unrelated compounds in comparison to fluoroquinolones regarding the selectivity of E. coli RND (resistance-nodulation-cell division)-type transporters, efflux inhibitors, and AcrB porter domain mutations were demonstrated. The findings should reinforce efforts to develop efflux-bypassing drugs and provide AcrB targets with critical relevance for this purpose

Internet Interventions / Exploring blended group interventions for depression : randomised controlled feasibility study of a blended computer- and multimedia-supported psychoeducational group intervention for adults with depressive symptoms

Background: Blended interventions aim to capitalise on the strengths of both computer-based and face-to-face therapy. Studies on this innovative treatment format remain scare. This especially accounts for the group treatment of depression. Method: The present study applied eclectic psychotherapy methods to an adult sample exhibiting a variety of depressive symptoms (N = 46). Participants were recruited by a newspaper inlet and randomised either to a treatment or a waiting list condition. Computer supported components were multimedia group sessions, e-learning, online videos and worksheets, remote therapist-patient communication and online pre-post-assessment. Results: Large between-group effect sizes on primary outcome depressiveness (CES-D) (F (1,44) = 4.88, p = 0.032; d = 0.87) and secondary outcome personal resources (resource scales) (F (1,44) = 9.04, p = 0.004; d = 0.73 to F (1,44) = 8.82 p = 0.005, d = 1.15) were found in the intention to treat analysis (ANOVA). Subjective evaluation of the intervention revealed high treatment adherence (91%) and high perceived relevance of supportive computer and multimedia components. Participants rated computer and multimedia components comparable to treatment elements such as group interaction or specific cognitive behavioural exercises, and 25% associated the utilisation of those components with treatment success. Depressiveness and age did not predict the utilisation and the appraisal of computer and multimedia components. Discussion: Results provide preliminary support for the acceptability and feasibility of the investigated blended treatment in a group with non-specific depressive symptoms. However, small sample size and lack of diagnostics restrict generalizability. Additional research in clinical settings is needed.(VLID)216526

Preparation of high-yield and ultra-pure Au25 nanoclusters: towards their implementation in real-world applications

Colloidal approaches allow for the synthesis of Au nanoclusters (NCs) with atomic precision and sizes ranging from a few to hundreds of atoms. In most of the cases, these processes involve a common strategy of thiol etching of initially polydisperse Au nanoparticles into atomically precise NCs, resulting in the release of Au-thiolate complexes as byproducts. To the best of our knowledge, neither the removal of these byproducts nor the mass spectra in the relevant mass region were shown in previous studies. A thorough analysis of inorganic byproducts in the synthesis of Au25 NCs reveals that published protocols lead to Au25 NCs in vanishingly small quantities compared to their byproducts. Three purification methods are presented to separate byproducts from the desired Au25 NCs which are proposed to be applicable to other promising Au NC systems. Additionally, critical factors for a successful synthesis of Au25 NCs are identified and discussed including the role of residual water. An important finding is that the etching duration is very critical and must be monitored by UV-Vis spectroscopy resulting in synthetic yields as high as 40%.Comment: 19 pages, 4 figure

Feasibility of a blended group treatment (bGT) for major depression : uncontrolled interventional study in a university setting

Objective: This study investigated the feasibility of a novel blended (face-to-face and computer-based) group intervention for the reduction of depressive symptoms in major depression. Design: Patient-centred uncontrolled interventional study. Setting: University setting in a general community sample. A multimodal recruitment strategy (public health centres and public areas) was applied. Participants: Based on independent interviews, 26 participants, diagnosed with major depressive disorder (81% female; 23% comorbidity >1 and 23% comorbidity >2), entered treatment. Intervention: Acceptance and mindfulness based, as well as self-management and resource-oriented psychotherapy principles served as the theoretical basis for the low-threshold intervention. The blended format included face-to-face sessions, complemented with multimedia presentations and a platform featuring videos, online work sheets, an unguided group chat and remote therapistpatient communication. Main outcome measures: The Center for Epidemiological Studies-Depression scale and the 12-item General Health Questionnaire. Results: Large to very large within group effect sizes were found on self-reported depression (F(2, 46.37)=25.69, p<0.001; d=1.80), general health (F(2,46.73)=11.47, p<0.001; d=1.32), personal resources (F(2,43.36)=21.17, p<0.001; d=0.90) and mindfulness (F(2,46.22)=9.40, p<0.001; d=1.12) after a follow-up period of 3 months. Treatment satisfaction was high, and 69% ranked computer and multimedia use as a therapeutic factor. Furthermore, participants described treatment intensification as important advantage of the blended format. Half of the patients (48%) would have preferred more time for personal exchange. Conclusion: The investigated blended group format seems feasible for the reduction of depressive symptoms in major depression. The development of blended interventions can benefit from assuring that highly structured treatments actually meet patients needs. As a next step, the intervention should be tested in comparative trials in routine care.(VLID)249289

Disruption of dopamine D2/D3 system function impairs the human ability to understand the mental states of other people

Difficulties in reasoning about others’ mental states (i.e., mentalising/Theory of Mind) are highly prevalent among disorders featuring dopamine dysfunctions (e.g., Parkinson’s disease) and significantly affect individuals’ quality of life. However, due to multiple confounding factors inherent to existing patient studies, currently little is known about whether these sociocognitive symptoms originate from aberrant dopamine signalling or from psychosocial changes unrelated to dopamine. The present study, therefore, investigated the role of dopamine in modulating mentalising in a sample of healthy volunteers. We used a double-blind, placebo-controlled procedure to test the effect of the D2/D3 antagonist haloperidol on mental state attribution, using an adaptation of the Heider and Simmel (1944) animations task. On 2 separate days, once after receiving 2.5 mg haloperidol and once after receiving placebo, 33 healthy adult participants viewed and labelled short videos of 2 triangles depicting mental state (involving mentalistic interaction wherein 1 triangle intends to cause or act upon a particular mental state in the other, e.g., surprising) and non-mental state (involving reciprocal interaction without the intention to cause/act upon the other triangle’s mental state, e.g., following) interactions. Using Bayesian mixed effects models, we observed that haloperidol decreased accuracy in labelling both mental and non-mental state animations. Our secondary analyses suggest that dopamine modulates inference from mental and non-mental state animations via independent mechanisms, pointing towards 2 putative pathways underlying the dopaminergic modulation of mental state attribution: action representation and a shared mechanism supporting mentalising and emotion recognition. We conclude that dopaminergic pathways impact Theory of Mind, at least indirectly. Our results have implications for the neurochemical basis of sociocognitive difficulties in patients with dopamine dysfunctions and generate new hypotheses about the specific dopamine-mediated mechanisms underlying social cognition

Effectiveness and cost-effectiveness for the treatment of depressive symptoms in refugees and asylum seekers: a multi-centred randomized controlled trial

BACKGROUND: Current evidence points towards a high prevalence of psychological distress in refugee populations, contrasting with a scarcity of resources and amplified by linguistic, institutional, financial, and cultural barriers. The objective of the study is to investigate the overall effectiveness and cost-effectiveness of a Stepped Care and Collaborative Model (SCCM) at reducing depressive symptoms in refugees, compared with the overall routine care practices within Germany's mental healthcare system (treatment-as-usual, TAU). METHODS: A multicentre, clinician-blinded, randomised, controlled trial was conducted across seven university sites in Germany. Asylum seekers and refugees with relevant depressive symptoms with a Patient Health Questionnaires score of ≥ 5 and a Refugee Health Screener score of ≥ 12. Participants were randomly allocated to one of two treatment arms (SCCM or TAU) for an intervention period of three months between April 2018 and March 2020. In the SCCM, participants were allocated to interventions tailored to their symptom severity, including watchful waiting, peer-to-peer- or smartphone intervention, psychological group therapies or mental health expert treatment. The primary endpoint was defined as the change in depressive symptoms (Patient Health Questionnaire-9, PHQ-9) after 12 weeks. The secondary outcome was the change in Montgomery Åsberg Depression Rating Scale (MADRS) from baseline to post-intervention. FINDINGS: The intention-to-treat sample included 584 participants who were randomized to the SCCM (n= 294) or TAU (n=290). Using a mixed-effects general linear model with time, and the interaction of time by randomisation group as fixed effects and study site as random effect, we found significant effects for time (p < .001) and time by group interaction (p < .05) for intention-to-treat and per-protocol analysis. Estimated marginal means of the PHQ-9 scores after 12 weeks were significantly lower in SCCM than in TAU (for intention-to-treat: PHQ-9 mean difference at T(1) 1.30, 95% CI 1.12 to 1.48, p < .001; Cohen's d=.23; baseline-adjusted PHQ-9 mean difference at T(1) 0.57, 95% CI 0.40 to 0.74, p < .001). Cost-effectiveness and net monetary benefit analyses provided evidence of cost-effectiveness for the primary outcome and quality-adjusted life years. Robustness of results were confirmed by sensitivity analyses. INTERPRETATION: The SSCM resulted in a more effective and cost-effective reduction of depressive symptoms compared with TAU. Findings suggest a suitable model to provide mental health services in circumstances where resources are limited, particularly in the context of forced migration and pandemics. FUNDING: This project is funded by the Innovationsfond and German Ministry of Health [grant number 01VSF16061]. The present trial is registered under Clinical-Trials.gov under the registration number: NCT03109028. https://clinicaltrials.gov/ct2/show/NCT0310902

TESTES E TRATAMENTOS DA TENOSSINOVITE DE QUERVAIN NA CLÍNICA ORTOPÉDICA DA REABILITAÇÃO FÍSICA: REVISÃO BIBLIOGRÁFICA SISTEMÁTICA

De Quervain's Tenosynovitis (TQ), initially described in 1895 by Swiss physician Fritz de Quervain, is a painful and chronic musculoskeletal condition characterized by thickening of the tendon sheaths in the first dorsal compartment of the hand. The pathophysiological process begins with involvement of the first dorsal compartment of the wrist, where the tendons of the abductor pollicis longus (APL) and extensor pollicis brevis (ECP) are located. Thus, the problem addressed in this article is guided by the following research question: "What is the effectiveness of treatments used for De Quervain's Tenosynovitis (TQ) on the functional capacity of patients affected by this orthopedic clinical condition?" The objective of this article, therefore, was to analyze in the literature the impacts of De Quervain's Tenosynovitis on the functional capacity of affected patients. As a result of this review, 46 studies were found, duplicate articles were eliminated, totaling 25. After careful reading of the titles and abstracts, 13 articles were selected, which were available in full in the databases, met all inclusion criteria, and were relevant to the present study. The review highlights a significant gap in the scientific evidence base for conservative methods in the treatment of TQ. The lack of comprehensive and high-quality studies raises doubts about the effectiveness of these methods compared to Corticosteroid Injections (CIs) and Surgery.A Tenossinovite de Quervain (TQ), descrita inicialmente em 1895 pelo médico suíço Fitz de Quervain, é uma condição musculoesquelética dolorosa e crônica caracterizada pelo espessamento das bainhas tendinosas no primeiro compartimento dorsal da mão. O processo fisiopatológico se inicia com o comprometimento do primeiro compartimento dorsal do punho, onde estão localizados os tendões do ALP e do ECP. Desse modo, a problemática desse artigo é norteada com a seguinte situação problema: "qual é a eficácia dos tratamentos utilizados para Tenossinovite de Quervain (TQ) na capacidade funcional de pacientes acometidos por essa situação clínica ortopédica?". Objetivou-se, portanto, com esse artigo, analisar na literatura os impactos da Tenossinovite de Quervain na capacidade funcional dos pacientes afetados. Como resultados dessa revisão, foram encontrados 46 estudos, eliminaram-se os artigos duplicados, um total de 25. Após a leitura criteriosa dos títulos e resumos, foram selecionados 13 artigos, os quais estavam disponíveis na íntegra nas bases de dados, atenderam todos os critérios de inclusão e mostraram-se relevantes para o presente estudo. A revisão realizada destaca uma lacuna significativa na base de evidências científicas para os métodos conservadores no tratamento da TQ. A falta de estudos abrangentes e de alta qualidade deixa dúvidas sobre a eficácia desses métodos em comparação com as Injeções de Corticosteroides (ICs) e a Cirurgia

ABORDAGENS INOVADORAS NO DIAGNÓSTICO PRECOCE DO GLAUCOMA

&nbsp;In the continuous search for advances in the ophthalmological field, innovative approaches to the early diagnosis of glaucoma emerge as a crucial answer. The implementation of advanced imaging technologies and monitoring methods offers a promising prospect for identifying signs of the disease early, enabling more effective interventions. Objectives: Explore innovative approaches to early diagnosis of glaucoma. Methodology:&nbsp; The articles found were read, upon reading the articles were subjected to inclusion and exclusion criteria, within the inclusion criteria original articles were considered, which addressed the topic researched and allowed full access to the content of the study, published in the period of 2015 to 2023, in Portuguese and English, totaling 19 articles for the present study. The research was carried out through online access to the National Library of Medicine (PubMed MEDLINE), Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature in Health Sciences (LILACS) databases in March 2024. Results and Discussions:&nbsp; Innovative approaches to the early diagnosis of glaucoma present promising advances in effective detection of the disease. The application of advanced imaging technologies, such as optical coherence tomography (OCT), has demonstrated remarkable sensitivity in identifying early structural changes, providing a solid foundation for timely interventions. The importance of these approaches in the clinical context, highlighting how early detection can positively influence the course of the disease. Furthermore, the personalization of care, made possible by these technologies, emerges as a determining factor in the approach to glaucoma, adapting to the specific needs of each patient. Conclusion: In summary, the results presented reinforce the positive impact of innovative approaches in the early diagnosis of glaucoma. The enhanced sensitivity provided by advanced imaging technologies highlights their crucial role in early identification of ocular changes. This conclusion highlights the continued importance of research and implementation of these approaches to improve the effectiveness of ophthalmological care, contributing significantly to the preservation of vision and quality of life for patients affected by glaucoma.Na busca contínua por avanços na área oftalmológica, as abordagens inovadoras no diagnóstico precoce do glaucoma emergem como uma resposta crucial. A implementação de tecnologias avançadas de imagem e métodos de monitoramento oferece uma perspectiva promissora para identificar precocemente os sinais da doença, possibilitando intervenções mais eficazes. Objetivos: Explorar abordagens inovadoras para o diagnóstico precoce do glaucoma. Metodologia: &nbsp;Foi realizada a leitura dos artigos encontrados, mediante a leitura, os artigos foram submetidos a critérios de inclusão e de exclusão, dentre os de inclusão foram considerados artigos originais, que abordassem o tema pesquisado e permitissem acesso integral ao conteúdo do estudo, publicados no período de 2015 a 2023, em português e em inglês, totalizando 19 artigos para o presente estudo. A pesquisa foi realizada através do acesso online nas bases de dados National Library of Medicine (PubMed MEDLINE), Scientific Electronic Library Online (SCIELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) no mês de março de 2024. Resultados e Discussões:&nbsp; As abordagens inovadoras no diagnóstico precoce do glaucoma apresentam promissores avanços na detecção eficaz da doença. A aplicação de tecnologias avançadas de imagem, como a tomografia de coerência óptica (OCT), demonstrou uma sensibilidade notável na identificação de alterações estruturais precoces, proporcionando uma base sólida para intervenções tempestivas. A importância dessas abordagens no contexto clínico, ressaltando como a detecção precoce pode influenciar positivamente o curso da doença. Além disso, a personalização dos cuidados, viabilizada por essas tecnologias, emerge como um fator determinante na abordagem do glaucoma, adaptando-se às necessidades específicas de cada paciente. Conclusão: Em síntese, os resultados apresentados reforçam o impacto positivo das abordagens inovadoras no diagnóstico precoce do glaucoma. A sensibilidade aprimorada proporcionada por tecnologias avançadas de imagem destaca seu papel crucial na identificação precoce de alterações oculares. Esta conclusão ressalta a importância contínua da pesquisa e implementação dessas abordagens para melhorar a eficácia dos cuidados oftalmológicos, contribuindo, significativamente, para a preservação da visão e qualidade de vida dos pacientes afetados pelo glaucoma

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years