Determining the feasibility of a real-time geophysical magnetic and electric measurement system for monitoring strain underground

In deep mining environments, rockbursts can occur in areas of high stress. The unpredictable nature, and sometimes fatal consequences of the rockbursts, makes identifying increases in stress that occur prior to failure events, important for mine safety. The piezoelectric, electrokinetic, and seismo-electric/magnetic effects result in rocks that are stressed emitting electric and magnetic fields that can potentially be measured in (or close to) a rock mass. Electric, magnetic and seismic data were collected during a four-day period at Coleman Mine, Sudbury, Ontario, and later analysed. No signals due to strain were evident in the magnetic or electric data, so a more careful three-part experiment was proposed to see if strain related signals could be identified in magnetic data. In the first part of the experiment thirty-two rocks were stressed until failure. Measurable magnetic signals associated with audible cracking sounds were found for most rock samples, as well as consistent signals across all samples prior to failure. The implementation of real-time monitoring of these signals has the potential to significantly improve deep mine safety by mapping the evolution of strain underground and potentially indicating areas susceptible to failure.Master of Science (MSc) in Geolog

Maternal inheritance of twist and analysis of MAPK activation in embryos of the polychaete Annelid Platynereis dumerilii

In this study, we aimed to identify molecular mechanisms involved in the specification of the 4d (mesentoblast) lineage in Platynereis dumerilii. We employ RT-PCR and in situ hybridization against the Platynereis dumerilii twist homolog (Pdu-twist) to reveal mesodermal specification within this lineage. We show that Pdu-twist mRNA is already maternally distributed. After fertilization, ooplasmatic segregation leads to relocation of Pdu-twist transcripts into the somatoblast (2d) lineage and 4d, indicating that the maternal component of Pdu-twist might be an important prerequisite for further mesoderm specification but does not represent a defining characteristic of the mesentoblast. However, after the primordial germ cells have separated from the 4d lineage, zygotic transcription of Pdu-twist is exclusively observed in the myogenic progenitors, suggesting that mesodermal specification occurs after the 4d stage. Previous studies on spiral cleaving embryos revealed a spatio-temporal correlation between the 4d lineage and the activity of an embryonic organizer that is capable to induce the developmental fates of certain micromeres. This has raised the question if specification of the 4d lineage could be connected to the organizer activity. Therefore, we aimed to reveal the existence of such a proposed conserved organizer in Platynereis employing antibody staining against dpERK. In contrast to former observations in other spiralian embryos, activation of MAPK signaling during 2d and 4d formation cannot be detected which questions the existence of a conserved connection between organizer function and specification of the 4d lineage. However, our experiments unveil robust MAPK activation in the prospective nephroblasts as well as in the macromeres and some micromeres at the blastopore in gastrulating embryos. Inhibition of MAPK activation leads to larvae with a shortened body axis, defects in trunk muscle spreading and improper nervous system condensation, indicating a critical function for MAPK signaling for the reorganization of embryonic tissues during the gastrulation process

Towards advanced understanding of scale-up: From computational fluid dynamics to systems biotechnology approaches

Scale-up of mammalian cell culture processes from development scale to commercial manufacturing scale is routinely performed in biopharmaceutical process development. For this purpose, well established biochemical engineering principles, empirical formula and scale-up criteria were developed. Considering well characterized equipment as well as company specific process and platform knowledge, scale-up typically is successfully achieved. Yet, improved understanding of scale-up phenomena is desirable for various reasons. Since miniaturized systems are increasingly used in biopharmaceutical process development and, at the same time, efforts with respect to resources and timelines to achieve final manufacturing scale are to be minimized, scale-up steps need to cope with larger bioreactor volume changes in the future. From a process science perspective, an integrated analysis of scale-up phenomena considering both the biochemical engineering aspects (e.g. power input, kLa) as well as cell-level data is needed. In order to gain more profound understanding of scale-up, comprehensive characterization of our cultivation systems using computational fluid dynamics (CFD) was achieved (Figure 1). To further improve and integrate the understanding of an antibody producing CHO cell in a bioreactor environment across scales, we performed thorough analysis of metabolic rates and fluxes in different cultivation scales. In addition, gene expression data using NGS were obtained (Figure 2). We designed a new method for preparation of liquid marbles by using hydrophilic particles [1] (Fig.1). Salt-hydrogel marbles were prepared by atomising droplets of hydrogel solution in a cold air column followed by rolling of the collected hydrogel microbeads in a bed of micrometre size salt particles. Evaporation of the water from the resulting salt marbles with a hydrogel core yielded hollow-shell salt microcapsules. The method is not limited to hydrophilic particles and could potentially be also applied to other materials, such as graphite, carbon, silica and others. The structure and morphology of the salt-hydrogel marbles were analysed with SEM and their particle size distributions were measured. We also tested the dissolution times of the dried salt marbles compared them to these for table salt samples at the same conditions. The high accessible surface area of the shell of salt microcrystals allows a faster initial release of salt from the hollow-shell salt capsules upon their dissolution in water than from the same amount of table salt. The results suggest that such hollow-shell particles could find applications as a table salt substitute in dry food products and salt seasoning formulations with reduced salt content without the loss of saltiness. Please click Additional Files below to see the full abstract

An algorithm to classify homologous series within compound datasets

Homologous series are groups of related compounds that share the same core structure attached to a motif that repeats to different degrees. Compounds forming homologous series are of interest in multiple domains, including natural products, environmental chemistry, and drug design. However, many homologous compounds remain unannotated as such in compound datasets, which poses obstacles to understanding chemical diversity and their analytical identification via database matching. To overcome these challenges, an algorithm to detect homologous series within compound datasets was developed and implemented using the RDKit. The algorithm takes a list of molecules as SMILES strings and a monomer (i.e., repeating unit) encoded as SMARTS as its main inputs. In an iterative process, substructure matching of repeating units, molecule fragmentation, and core detection lead to homologous series classification through grouping of identical cores. Three open compound datasets from environmental chemistry (NORMAN Suspect List Exchange, NORMAN-SLE), exposomics (PubChemLite for Exposomics), and natural products (the COlleCtion of Open NatUral producTs, COCONUT) were subject to homologous series classification using the algorithm. Over 2000, 12,000, and 5000 series with CH2 repeating units were classified in the NORMAN-SLE, PubChemLite, and COCONUT respectively. Validation of classified series was performed using published homologous series and structure categories, including a comparison with a similar existing method for categorising PFAS compounds. The OngLai algorithm and its implementation for classifying homologues are openly available at: https://github.com/adelenelai/onglai-classify-homologues

No Talking, Just Writing! Efficacy of an Internet-Based Cognitive Behavioral Therapy with Exposure and Response Prevention in Obsessive Compulsive Disorder

Background: Many patients with obsessive-compulsive disorder (OCD) do not receive first-line treatment according to the current guidelines (cognitive behavioral therapy with exposure and response prevention, CBT with ERP) due to barriers to treatment. Internet-based therapy is designed to overcome these barriers. The present study evaluates the efficacy of an Internet-based writing therapy with therapeutic interaction based on the concept of CBT with ERP for patients with OCD. Methods: Thirty-four volunteers with OCD according to DSM-IV-criteria were included in the trial and randomized according to a waiting-list control design with follow-up measures at 8 weeks and 6 months. The intervention consisted of 14 sessions, either starting directly after randomization or with an 8-week delay. Main outcome measure was the change in the severity of OCD symptoms (Yale-Brown Obsessive Compulsive Scale Self- Rating, Y-BOCS SR, and Obsessive-Compulsive Inventory-Revised, OCI-R). Results: Obsessive-compulsive symptoms were significantly improved in the treatment group compared to the waiting-list control group with large effect sizes of Cohen's d = 0.82 (Y-BOCS SR) and d = 0.87 (OCI-R), using an intention-to-treat analysis. This effect remained stable at 6-month follow-up. Only 4 participants (12%) dropped out prematurely from the study. Of the 30 completers, 90% rated their condition as improved and would recommend the program to their friends. Conclusions: Internet-based writing therapy led to a significant improvement of obsessive-compulsive symptoms. Even though replications with larger sample sizes are needed, the results support the notion that Internet-based approaches have the potential for improving the treatment situation for patients with OCD

Mental health and substance use among elite para-athletes: An cross-sectional survey

Objective The scientific studies on the mental health and substance use among elite para-athletes are rare (Lardi et al., in preparation; Lüdi et al., 2023). However, the shows similarities as well as differences to the regular elite athletes’ populations (Rice et al., 2016; Swartz et al., 2019). The aim of this study was to investigate the mental health and substance use of para-athletes (PAs) from their perspective, in order to gain an overview of the situation in elite para-sport and to potentially create a basis for prevention campaigns and, if necessary, interventions. Methodology An online survey (SoSciSurvey) was used to create a questionnaire, which was translated into eight languages to reach PAs internationally. In addition to socio-demographic and sports-specific (Para-Sport, PS) variables, psychological and physical factors, as well as substance use, were assessed using standardized instruments. Results (CAVE: at the time at submission preliminary since the survey ends by the end of November/The final results will be presented at the congress): The PAs (N = 82) showed different prevalences regarding mental disorders compared to data from the general population and regular elite athletes, with disorder-specific deviations. There were significant gender differences in psychological distress (K-10, p .05), but there was a significant correlation (p .05), and there was no significant gender difference (AUDIT-C, p > .05). Conclusions Based on the results, prevention should occur in the disorder-specific area and refer to the professional services, social support, focusing more on discrimination, and include substance use (alcohol and cannabis). It is important to consider that PAs are a vulnerable population and research gaps still exist. References Lardi, M., Kiselev, N., Imboden, C., Stoffel, O., Heiniger, A., & Schaub, M. (in preparation). Unveiling the shadows - Substance use among para-athletes: A qualitative study with Swiss elite para-athletes. Lüdi, L., Pfarrwaller, G., Imboden, C., Stoffel, O., Schlüssel, M., Heiniger, A., Kleim, B., & Kiselev, N. (2023). Perspectives on mental health and well-being: Voices of Swiss paralympic athletes. Sports Psychiatry: Journal of Sports and Exercise Psychiatry. Advance online publication. https://doi.org/10.1024/2674-0052/a000057 Rice, S. M., Purcell, R., De Silva, S., Mawren, D., McGorry, P. D., & Parker, A. G. (2016). The mental health of elite athletes: A narrative systematic review. Sports Medicine, 46, 1333-1353. https://doi.org/10.1007/s40279-016-0492-2 Swartz, L., Hunt, X., Bantjes, J., Hainline, B., & Reardon, C. L. (2019). Mental health symptoms and disorders in Paralympic athletes: A narrative review. British Journal of Sports Medicine, 53(12), 737-740. https://doi.org/10.1136/bjsports-2019-10073

Current and future workforce of general internal medicine in Switzerland: a cross-sectional study.

AIM OF THIS STUDY General internal medicine is a crucial element in healthcare systems. Understanding how many people are and will be working in this field is important to maintain and improve quality for patients in healthcare systems. This can provide a basis for political decisions. METHODS We conducted a cross-sectional study to analyse the current and future workforce of generalists (general practitioners and internists in hospitals) in Switzerland. The Swiss Society of General Internal Medicine (SSGIM) distributed a survey to all members. Respondents were asked about their current average workload in 2023 and planned workload in 2033. The responses were used to calculate full-time equivalent (FTE) for the current and future workforce of generalists and to extrapolate FTE for all active SSGIM members. To model the demand by 2033, we derived different scenarios. RESULTS Of all 6,232 active SSGIM members, 2,030 (33%) participated: 46% female, 25% (largest age group) 56-65 years old, 19% still in postgraduate training. The average workload in 2023 was 78% for female and 87% for male generalists; the FTE extrapolated to all active SSGIM members in 2023 was 5,246. By 2033, 1,935 FTEs (36%) will retire, 502 FTEs (10%) will reduce their workload, 116 FTEs (2%) will increase their workload and 2,800 FTEs (53%) will remain in the workforce with the same workload as in 2023. To maintain the same workforce as in 2023, 2,321 new FTEs (44%) will be needed by 2033. To fill this gap of 232 FTE new generalists per year, we modelled different scenarios with assumptions of interest, workload, migration and dropouts. CONCLUSIONS Within only one decade, 44% of the current workforce of generalists will disappear, mainly due to retirement and decreased workload. To fill this gap, various scenarios need to be incorporated. Politicians are called upon to create the political framework to create attractive training and working conditions for generalists to address the future demand for healthcare services

The continuum of Drosophila embryonic development at single-cell resolution.

Drosophila melanogaster is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million and gene expression in half a million nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer the age of each nucleus, resulting in continuous, multimodal views of molecular and cellular transitions in absolute time. We identify cell lineages; infer their developmental relationships; and link dynamic changes in enhancer usage, transcription factor (TF) expression, and the accessibility of TFs cognate motifs. With these data, the dynamics of enhancer usage and gene expression can be explored within and across lineages at the scale of minutes, including for precise transitions like zygotic genome activation