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The service environment, particularly the tourism sector, has become increasingly relevant in providing sustainable jobs across the globe. The resort environment consists of any combination of guest experience offerings such as accommodation, restaurants, events, and activities that operate mostly within one geographical environment. Furthermore, through an extensive literature review, it is found that the resort environment lacks practical quality improvement tools to enable continuous improvement (CI) within this remarkably complex and competitive space. This article aims to introduce a novel CI framework aimed at the resort environment to ensure a progressive competitive edge. This article illustrates a framework that builds a Total Productivity Management (TPMan) tool on these three dimensions as a foundation with an adapted quality methodology, which has been tried and tested within the manufacturing environment, providing eight pillars as CI components. The article illustrates the results by means of a case study where TPMan was applied over a period of 8 years within a local high-end resort in South Africa. The article concludes that TPMan is relevant to the resort environment as a practical CI tool.

Both areal and phylogenetic affiliation have been discussed as driving factors of the distribution of word order in the languages of the world. However, disentangling the interaction of these two factors is challenging. Here we take Indo-European as a test case. Word order in this family is largely homogeneous both within areas and within branches, which makes it difficult to assess which factor was more important in shaping the present-day distribution. To break out of this impasse we turn to corpus data and explicit statistical modeling. Building on a parallel corpus of movie subtitles, we investigate word order on the sentence level under stable pragmatic conditions. We measure the similarity of word order variation between pairs of languages with an information-theoretic distance metric. Using cluster analysis and variation partitioning methods these distance metrics show that phylogenetic distance predicts more variation than geographical distance, but the most important predictor is the shared fraction where phylogeny and area overlap. We conclude that word order has evolved along both dimensions and cannot be reduced to a single one.

The proliferation of woody plant species over grassland areas has been reported in different regions of the planet. This phenomenon has caused economic, social and environmental effects in the Brazilian Pantanal. Traditional knowledge based on scientific evidences technically supports the forms of management to control the process of colonization of woody plants in native grasslands, thus promoting the original ecological restoration of these ecosystems. Our study aimed to evaluate three management regimes with prescribed fire for controlling the invasion of Vochysia divergens Pohl. on grassland matrix areas in the Brazilian Pantanal. The results obtained showed that prescribed fire is an efficient tool in controlling V. divergens in the early stages of its establishment, and effectively contributes to ecological restoration processes in the savannah grasslands, aimed at controlling woody tree and shrub species invasions in the grasslands of the Brazilian Pantanal.

Tim Bothe,1 Anne-Katrin Fietz,2 Elke Schaeffner,1 Antonios Douros,3– 5 Anna Pöhlmann,2 Nina Mielke,1 Cédric Villain,1,6 Muhammad Helmi Barghouth,1 Volker Wenning,7 Natalie Ebert1 1Institute of Public Health, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada; 4Institute of Clinical Pharmacology and Toxicology, Charité – Universitätsmedizin Berlin, Berlin, Germany; 5Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada; 6Normandie Univ UNICAEN, INSERM U1075 COMETE, service de Gériatrie, CHU de Caen, Caen, France; 7AOK Nordost – Die Gesundheitskasse, Potsdam, GermanyCorrespondence: Tim Bothe, Charité – Universitätsmedizin Berlin, Institute of Public Health, Charitéplatz 1, Berlin, DE-10117, Germany, Tel +49 30 450 570054, Email tim.bothe@charite.dePurpose: The validity of ICD-10 diagnostic codes for chronic kidney disease (CKD) in health claims data has not been sufficiently studied in the general population and over time.Patients and Methods: We used data from the Berlin Initiative Study (BIS), a prospective longitudinal cohort of community-dwelling individuals aged ≥ 70 years in Berlin, Germany. With estimated glomerular filtration rate (eGFR) as reference, we assessed the diagnostic validity (sensitivity, specificity, positive [PPV], and negative predictive values [NPV]) of different claims-based ICD-10 codes for CKD stages G3-5 (eGFR < 60mL/min/1.73m²: ICD-10 N18.x-N19), G3 (eGFR 30–< 60mL/min/1.73m²: N18.3), and G4-5 (eGFR < 30mL/min/1.73m²: N18.4– 5). We analysed trends over five study visits (2009– 2019).Results: We included data of 2068 participants at baseline (2009– 2011) and 870 at follow-up 4 (2018– 2019), of whom 784 (38.9%) and 440 (50.6%) had CKD G3-5, respectively. At baseline, sensitivity for CKD in claims data ranged from 0.25 (95%-confidence interval [CI] 0.22– 0.28) to 0.51 (95%-CI 0.48– 0.55) for G3-5, depending on the included ICD-10 codes, 0.20 (95%-CI 0.18– 0.24) for G3, and 0.36 (95%-CI 0.25– 0.49) for G4-5. Over the course of 10 years, sensitivity increased by 0.17 to 0.29 in all groups. Specificity, PPVs, and NPVs remained mostly stable over time and ranged from 0.82– 0.99, 0.47– 0.89, and 0.66– 0.98 across all study visits, respectively.Conclusion: German claims data showed overall agreeable performance in identifying older adults with CKD, while differentiation between stages was limited. Our results suggest increasing sensitivity over time possibly attributable to improved CKD diagnosis and awareness.Keywords: CKD, diagnostic validity, health claims data, sensitivity, specificity

Objetivo: Evaluación farmacoeconómica de dos tratamientos con drogas de distinto mecanismo de acción: Degarelix y triptorelina en el manejo de pacientes con cáncer de próstata avanzado hormonodependiente. Material y método: Se realizó una revisión de la literatura sobre el tratamiento estándar de estos pacientes, efectos tempranos y tardíos de las terapias existentes y además una valoración de Costo Integral del Tratamiento usando el tarifario de Essalud. Resultados: El Costo Integral del Tratamiento, es S/ 10 793 para un paciente que usa Degarelix y S/ 12 251 para un paciente que usa triptorelina genérica; es decir, la terapia con el antagonista de la GnRH genera un ahorro de S/ 1 458 por paciente. Conclusiones: Este ahorro representa S/ 1 008 017 para el total de pacientes con cáncer de próstata avanzado hormonodependiente que se atienden en Essalud, a nivel nacional, con la ventaja adicional que Degarelix no genera costos adicionales por complicaciones producto del efecto Flare.

ObjectiveAlthough empathy is known to be a strength, recent studies suggest that empathy can be a risk factor for psychopathology under certain conditions in children. This study examines parental mental illness as such a condition. Further, it aims to investigate whether maladaptive emotion regulation (ER) mediates the relationship between empathy and psychopathological symptoms of children.MethodsParticipants were 100 children of parents with a mental illness (55% female) and 87 children of parents without a mental illness (50% female) aged 6 - 16 years and their parents.ResultsGreater cognitive empathy was related to more psychopathological symptoms in COPMI, but not in COPWMI. In addition, in COPMI maladaptive ER mediated this relationship. In contrast, greater affective empathy was associated with more psychopathological symptoms regardless of whether parents had a mental illness.ConclusionOur findings highlight the importance of implementing preventive programs for COPMI that specifically target the reduction of maladaptive ER.

ObjectiveChildren of parents with a mental illness are at heightened risk to develop a mental illness themselves due to genetics and environmental factors. Although parenting stress (PS) is known to be associated with increased psychopathology in parents and children, there is no study investigating PS multimodally in a sample of parents with a mental illness. This study aims to compare PS of parents with and without a mental illness and further to examine the relationship between PS and psychopathology of children.MethodsParticipants were parents with a mental illness and parents without a mental illness and their children aged four to sixteen years. We assessed PS multimodally using a questionnaire, parents’ evaluation of children’s behavior (relational schemas) and psychophysiological arousal of parents during free speech task.ResultsSelf-reported PS was increased, and evaluation of children’s behavior was more negative and less positive in parents with a mental illness compared to parents without a mental illness. Children’s psychopathology was associated with self-reported PS and relational schemas of parents. Regarding psychophysiological arousal, parents with a mental illness showed reduced reactivity in heart rate from baseline to free speech task in comparison to parents without a mental illness.ConclusionsOur findings highlight the importance of implementing intervention programs to reduce PS for parents and children. In particular, parents with a mental illness might benefit from specific intervention programs in order to interrupt the transgenerational transmission of mental disorders.

Early analysis and diagnosis of breast tumors is essential for either quickly launching a treatment or for seeing the evolution of patients who, for instance, have already undergone chemotherapy treatment. Once tissues are excised, histological analysis is the most frequent tool used to characterize benign or malignant tumors. Dielectric microwave spectroscopy makes use of an open-ended coaxial probe in the 1–8 GHz frequency range to quickly identify the type of tumor (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma). The experiment was undertaken with data from 70 patients who had already undergone chemotherapy treatment, which helped to electrically map the histological tissues with their electric permittivity. Thus, the variations in the permittivity of different types of tumors reveal distinctive patterns: benign tumors have permittivity values lower than 35, while malignant ones range between 40 and 60. For example, at a frequency of 2 GHz, the measured permittivity was 45.6 for ductal carcinoma, 33.1 for lobular carcinoma, 59.5 for mucinous carcinoma, and 27.6 for benign tumors. This differentiation remains consistent in a frequency range of 1 to 4.5 GHz. These results highlight the effectiveness of these measurements in the classification of breast tumors, providing a valuable tool for quick and accurate diagnosis and effective treatment.

Cloudscheduler is a system to manage resources of local and remote compute clouds and makes those resources available to HTCondor pools. It examines the resource needs of idle jobs, then starts virtual machines (VMs), sized accordingly, on allowed clouds with available resources. Using yaml files, cloudscheduler then provisions the VMs during the boot process with all necessary tools needed to register with HTCondor and run the experiment’s jobs. Although we have run cloudscheduler in its first version for ATLAS and Belle-II workloads successfully for more than 10 years, we developed cloudscheduler version 2 (CSV2), a complete overhaul and modernization of cloudscheduler. The new system is used successfully in production for Belle-II, ATLAS, DUNE, and BABAR. In addition to using cloudscheduler version 2 as a WLCG site, we also run it as a service for other WLCG sites, and the Canadian Advanced Network for Astronomical Research (CANFAR) group uses its own instance of CSV2 for their astronomy workloads. In this paper, we report on our experience in operating CSV2 for different experiment’s jobs, running on up to 10,000 cores across all experiments and clouds in North America, Australia, and Europe. We will also report on how to correctly account for the resource usage in the WLCG APEL system, how the monitoring works, as well as on the integration of different clouds and how to use resources opportunistically.

The BABAR experiment collected electron-positron collisions at the SLAC National Accelerator Laboratory (SLAC) from 1999-2008. Although data taking has stopped 15 years ago, the collaboration is still actively doing data analyses, publishing results, and giving presentations at international conferences. Special considerations were needed to do analyses using a computing environment that was developed decades ago. A framework is required that preserves the data, data access, and the capability of doing analyses using a well defined and preserved environment. Also, BABAR’s support by SLAC ended at the beginning of 2021. Fortunately, the High Energy Physics Research Computing group at the University of Victoria (UVic), Canada, offered to provide the new home for the main BABAR computing infrastructure, the Grid Computing Centre Karlsruhe offered to host all data for access by analyses running at UVic, and CERN and the IN2P3 Computing Centre offered to store a backup of all data. This paper presents what was done at BABAR to preserve the data and analysis capabilities and what was needed to move the whole computing infrastructure, including collaboration tools and data files, away from SLAC. It will be shown how BABAR preserved the ability to continue to do data analyses and also have a working collaboration tools infrastructure. This paper will describe on BABAR’s experience with such a big change in its infrastructure and what was learned from it, which may be useful to other experiments which are interested in long term analysis support and data preservation in general.

In the present study, we examined 30 individuals of introduced African cichlids, Oreochromis niloticus and Coptodon rendalli, collected in a river spring of the Pardo River, Paranapanema River basin, southeastern Brazil. Based on morphological and molecular analyses of the partial LSU rDNA gene, we identified four species of monogeneans, Cichlidogyrus tilapiae, C. thurstonae, C. mbirizei, and Scutogyrus longicornis on the gills of O. niloticus, whereas individuals of C. rendalli were infested only with C. papernastrema. This is the first record of C. mbirizei and C. papernastrema in tilapias from Brazil. The ecological consequences of the introduction of exotic species of tilapia such as O. niloticus and C. rendalli along with their monogenean parasites in a wild environment represented by a river spring are discussed. Our new molecular data on Cichlidogyrus and Scutogyrus contribute to the investigation of the phylogenetic interrelationships of these widely distributed genera of monogeneans since their species composition is still unsettled.

Paula Sagmeister,1,&ast; Jimmy Daza,2,&ast; Andrea Ofner,1 Andreas Ziesch,1 Liangtao Ye,1,3,4 Najib Ben Khaled,1,3 Matthias Ebert,2,5 Julia Mayerle,1 Andreas Teufel,2,5 Enrico N De Toni,1,3 Stefan Munker1,3 1Department of Medicine II, LMU Munich, Munich, Bavaria, Germany; 2Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden Wurttenberg, Germany; 3Liver Center Munich, LMU Munich, Munich, Bavaria, Germany; 4Center of Digestive Disease, Sun Yat-Sen University, Shenzhen, Guangdong, People’s Republic of China; 5Center for Preventive Medicine and Digital Health Baden-Württenberg (CPDBW), Heidelberg University, Mannheim, Baden Wurttenberg, Germany&ast;These authors contributed equally to this workCorrespondence: Paula Sagmeister, Email sagmeister.paula@hotmail.comIntroduction: Although the treatment paradigm for hepatocellular carcinoma (HCC) has recently shifted in favour of checkpoint inhibitor (CPI)-based treatment options, the tyrosine kinase inhibitors (TKI) currently approved for the treatment of HCC are expected to remain the cornerstone of HCC treatment alone or in combination with CPIs. Despite considerable research efforts, no biomarker capable of predicting the response to specific TKIs has been validated. Thus, personalized approaches to HCC may aid in determining optimal treatment lines for 2nd and 3rd lines. To identify new biomarkers, we examined differential sensitivity and investigated potential transcriptomic predictors.Methods: To this aim, the sensitivity of nine HCC cell lines to sorafenib, lenvatinib, regorafenib, and cabozantinib was evaluated by a prolonged treatment scheme to determine their respective growth rate inhibition concentrations (GR50). Subgroups discriminated by GR50 values underwent differential expression and gene set enrichment analysis (GSEA).Results: The nine cell lines showed broadly different sensitivities to different TKIs. GR50 values of sorafenib and regorafenib clustered closer in all cell lines, whereas treatments with lenvatinib and cabozantinib showed diversified GR50 values. GSEA showed the activation of specific pathways in sensitive vs non-sensitive cell lines. A signature consisting of 14 biomarkers (GAGE12H, GJB6, PTCHD3, PRH1-PRR4, C6orf222, HBB, C17orf99, GOLGA6A, CRYAA, CCL23, RP11-347C12.3, RP11-514O12.4, FAM180B, and TMPRSS4) discriminates the cell lines’ response into three distinct treatment profiles: 1) equally sensible to sorafenib, regorafenib and cabozantinib, 2) sensible to lenvatinib, and 3) more sensible to regorafenib than sorafenib.Conclusion: We observed diverse responses to either of the four TKIs. Subgroup analysis of TKI effectiveness showed distinct transcriptomic profiles and signaling pathways associated with responsiveness. This prompts more extensive studies to explore and validate pharmacogenomic and transcriptomic strategies for a personalized treatment approach, particularly after the failure of CPI treatment.Keywords: biomarkers, sorafenib, lenvatinib, regorafenib, cabozantinib

Bernhard T Baune,1– 3 Ioana Florea,4 Bjarke Ebert,5 Maëlys Touya,6 Anders Ettrup,5 Monica Hadi,7 Hongye Ren8 1Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany; 2Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia; 3The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia; 4Clinical Development, H. Lundbeck A/S, Valby, Denmark; 5Medical Strategy & Communication, H. Lundbeck A/S, Valby, Denmark; 6Value Evidence, Lundbeck, Deerfield, IL, USA; 7Patient-Centered Research, Evidera, London, UK; 8Value Evidence, H. Lundbeck A/S, Valby, DenmarkCorrespondence: Hongye Ren Email HNRE@lundbeck.comPurpose: This qualitative study explored patient perceptions of the most burdensome symptoms of major depressive disorder (MDD), the impact of symptoms on patients’ daily lives, and patient expectations and experiences regarding the timing of onset of antidepressant pharmacotherapy.Patients and Methods: Data were collected through facilitated, patient focus-group sessions in the USA between May and June 2019. Participants were adults with confirmed MDD who reported a major depressive episode within the past 2 years, for which they had received pharmacologic treatment for ≥ 6 weeks. The semi-structured discussion focused on the key topics of bothersome symptoms of MDD, the impact of symptoms on quality of life, and the effects of antidepressant treatment. Interviews were audio-recorded; findings were summarized using a content-analysis approach.Results: Five focus-group sessions were undertaken, involving a total of 29 patients (each attended one session; mean age, 43.4 years; 72.4% female). Mean time since confirmed diagnosis of MDD was 13.1 years. The most commonly prescribed antidepressants received were bupropion (41.4% of participants), escitalopram (34.5%), and sertraline (34.5%). The most frequently reported bothersome MDD symptoms were fatigue (mentioned by 58.6% of participants), lack of motivation/loss of interest (51.7%), anxiety/panic (44.8%), sadness (41.4%), and lack of concentration/brain fog (41.4%). Socialization, family life, and work were the areas in which quality of life was most impacted. Participants expressed dissatisfaction with their antidepressant treatment. Fast symptom resolution was mentioned as a priority (defined as < 1 week by 38.5% of participants and ≤ 1 month by 65.4%). Most participants had not experienced fast relief from their symptoms with current or previous antidepressant medications.Conclusion: Results of this qualitative study suggest that fatigue, anhedonia, cognitive symptoms, and anxiety are some of the most bothersome symptoms for patients with MDD and highlight the importance of obtaining rapid relief from these symptoms in order to improve outcomes and patient satisfaction with antidepressant medication.Keywords: antidepressant therapy, major depressive disorder, onset of treatment effect, patient experience, symptoms, quality of life

Sperm is the most fundamental male reproductive feature. It serves the fertilization of eggs and evolves under sexual selection. Two components of sperm are of particular interest, their number and their morphology. Mode of fertilization is believed to be a key determinant of sperm length across the animal kingdom. External fertilization, unlike internal, favors small and numerous sperm, since sperm density is thinned out in the environment. Here, we study the evolution of sperm morphology in the genus Daphnia, where fertilization occurs in a receptacle, the brood pouch, where sperm can constantly be flushed out by a water current. Based on microscopic observations of sperm morphologies mapped on a phylogeny with 15 Daphnia and 2 outgroup species, we found that despite the internal fertilization mode, Daphnia have among the smallest sperm recorded, as would be expected with external fertilization. Despite being all relatively small compared to other arthropods, sperm length diverged at least twice, once within each of the Daphnia subgenera Ctenodaphnia and Daphnia. Furthermore, species in the latter subgenus also lost the ability of cell compaction by extracellular encapsulation and have very polymorphic sperm with long, and often numerous, filopodia. We discuss the different strategies that Daphnia evolved to achieve fertilization success in the females’ brood pouch.

INTRODUÇÃO: No final de 2019, foi relatado o surgimento de uma nova doença causada pelo SARS- CoV-2, originário de Wuhan, China, responsável por causar uma síndrome respiratória aguda grave. Causando-se, assim, uma crise de saúde sem precedentes, lotando os hospitais e causando cancelamento dos atendimentos médicos não urgentes. O impacto da implementação de protocolos de priorização cirúrgica estão sendo um dos maiores desafios para os urologistas nessa npandemia, devido ao aumento de cirurgias oncológicas adiadas. MATERIAIS E MÉTODOS: O presente estudo consiste em uma revisão de literatura, na qual os dados apresentados provêm de artigos científicos publicados no ano de 2020. A busca desses artigos foi realizada nos bancos de dados SCIELO e PUBMED. DISCUSSÃO: O trabalho buscou relatar os efeitos globais da pandemia do COVID-19 na prática clínica cirúrgica e oncológica em urologia, mostrando que o adiamento de certas cirurgias pode causar progressão clínica de curto prazo do câncer, aumento da mortali- dade específica por câncer e alguns danos psicológicos, tais como ansiedade e depressão . CONCLUSÃO: Como explanado na maioria dos artigos sobre o tema, o médico tem papel fundamental na classificação dos pacientes quanto aos riscos de sua doença e risco de internação, além da grande importância do desenvolvimento de protocolos por equipes multidisciplinares para melhor categorizar as prioridades e minimizar os prejuízos desses adiamentos cirúrgicos para os pacientes.

Purpose: Treatment response is the degree to which an individual benefits from a treatment. This systematic review sought to identify and synthesize research evidence regarding individual characteristics that predict language treatment response among children with developmental language disorder (DLD). Method: To be eligible for inclusion, articles needed to report results of an oral language treatment program in a group of children aged 4-10 years with identified DLD and also include a quantitative analysis of the relation between one or more pretreatment child characteristics and the outcome of language treatment. Seven databases (Cumulated Index to Nursing and Allied Health Literature, Dissertations and Theses Global, Education Resources Information Center, Linguistics and Language Behavior Abstracts, PsycINFO, Medline, and Web of Science) were searched for articles in June and July 2021, with search updates conducted in May 2023. Studies were categorized by the type of treatment provided, and results were synthesized qualitatively. Results: The review included 31 studies, 1,551 participants with DLD, and over 300 statistical tests of a predictor's effect on language treatment response. Most studies (n = 21) included only monolingual speakers of English, with five studies including bilinguals and five including monolingual speakers of non-English languages. Language treatments targeted word learning in controlled or clinical conditions, grammatical learning in controlled or clinical conditions, or multiple language targets in clinical conditions. Predictors of treatment response are summarized across four categories: cognitive, demographic, pretreatment language levels, and other. Conclusions: There were relatively few significant tests of the predictors of language treatment response. A central limitation of the evidence is that most included studies were designed to consider language treatment efficacy, not predictors of treatment response. Increasing research attention to the question of predictors of language treatment response in children with DLD is needed to enhance treatment and optimize outcomes for individual children.

Weeds of the umbelliferous family (Apiaceae) are gaining importance in several crops and regions and are often difficult to control chemically. For example, the occurrence of bur chervil (Anthriscus caucalis M. Bieb.) is not only increasing as a ruderal plant, but is also establishing as an arable weed in winter crops. There, it is often not sufficiently controlled by standard measures and beyond that frequently confused with other weedy umbellifers. In addition, the first A. caucalis populations with resistance to inhibitors of the acetolactate synthase (ALS) have been described. For this reason, we sequenced the ALS gene of a sensitive and a resistant A. caucalis population and found a mutation at position Pro197. This population was compared with a sensitive one, as well as other umbellifers such as hedge parsley (Torilis arvensis (Huds.) Link), wild carrot (Daucus carota L.) and hemlock (Conium maculatum L.) in a greenhouse trial with 14 herbicides. There were clear differences between the treatments of sensitive and resistant A. caucalis and the other umbellifers. The sensitive A. caucalis population was effectively controlled by the ALS inhibitors thifensulfuron, tribenuron and metsulfuron, but not by florasulam. Of these herbicides, only metsulfuron had a partial efficacy on the resistant population with 71.8% freshwater reduction. Notably, the efficacy profiles of ALS inhibitors differed significantly between species, while several synthetic auxins and chlortoluron effectively controlled most populations tested. Finally, the correct identification of the umbellifer species, as well as the resistance status, is necessary to carry out targeted chemical control.