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Engineering human nasal chondrocyte spheroids, towards regeneration of the intervertebral disc
Get PDFChronic low back pain (LBP) is a leading cause of disability worldwide and is strongly associated with degeneration of the intervertebral disc (IVD) [1, 2]. Current therapies for the treatment of discogenic LBP (termed degenerative disc disease, DDD) include conservative or surgical methods which have their limitations and drawbacks. These may include discectomy, fusion surgery and disc arthroplasty [3]. Nevertheless, in recent years, scientific knowledge on human physiology and cell biology as well as interactions has greatly increased creating a tremendous impact in the advancement of tissue engineering and prominently regenerative techniques for IVD repair [4]. Cell therapy has shown promising results for IVD regeneration.
Regenerative IVD therapies target minimal-invasive application of autologous cells amongst others that should ideally differentiate to IVD-like cells and/or secrete trophic and anti-inflammatory factors with the aim to repair the IVD [3, 5-7]. A typical approach taken is to combine cell suspension with biocompatible materials which are supposed to provide mechanical stability and protection of the cells after implantation. Nevertheless, none of these strategies have been widely accepted for clinical implementation. Several publications have indicated that therapeutic cells suffer within the harsh microenvironment of the DDD [5, 8-12]. Human nasal chondrocytes (NC) are a promising cell source for the treatment of DDD. NC can be harvested from nasoseptal cartilage biopsy obtained under local anaesthesia and with minimal donor site morbidity [13-15]. They were shown to possess high proliferation and post-expansion differentiation capacity and can adapt to the heterotopic transplantation sites [16]. Moreover, they showed superior viability over articular chondrocytes (AC) and mesenchymal stromal/stem cells (MSC) in simulated DDD microenvironment thus represent a robust cell population with the potential of survival in the IVD post injection [17].
Within other tissue engineering fields, it has been demonstrated that spheroid-based strategies might help to overcome hurdles associated with DDD due to their superior regenerative performance and/or resistance compared to single cells [18, 19]. Spheroids can self-assemble by forming intercellular contacts on non-adhesive substrates [20-23]. Their 3D organization mimics closer the physiological conditions and allows the cells to differentiate toward target tissue. The 3D structure allows the cells to accumulate ECM that might protect them from a surrounding harsh micromilieu [1, 24]. Furthermore, by priming the spheroids using biomimetic environment [25-27], genetically modifying the cells [28, 29], and/or combining the spheroids with an instructive biomaterial [30] is hypothesized to further increase their performance within a harsh microenvironment. Therefore, taking a spheroid-based therapeutic approach for IVD repair could be a promising strategy.
Currently applied in vitro models to study cell treatment strategies for IVD repair use 2D and 3D culture systems among others [31]. The use of an in vitro 3D model mimicking the degenerated IVD environment, would allow to study the regenerative performance of the therapeutic cells. The harsh IVD microenvironment is characterized by avascular, hypoxia, low glucose level, acidic, inflamed, high osmolality and non-physiological biomechanics [32]. However, it has been shown that less than 15% of the in vitro studies include either one of these parameters thus not mimic the harsh IVD microenvironment properly [31].
In my PhD thesis I give an introduction into the field of my research (Chapter 1: Introduction) and highlight the areas of future research in spheroid-based regeneration of IVD in the form of a review (Chapter 2: Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc). I discuss cell sources and methods for spheroid fabrication and characterization, mechanisms related to spheroid fusion, as well as enhancement of spheroid performance in the context of the IVD microenvironment.
I report my findings on the suitability of nasal chondrocyte derived spheroids (NCS) for use as grafts in cell-based and scaffold-free regeneration of the NP. In particular, I investigate whether human NCS (1) can be generated in a feasible and reproducible way (2) possess the biomechanical and biochemical properties relevant for the target NP tissue, and (3) can be injected into the IVD via a spinal needle and engraft within a DDD-mimicking microenvironment (Chapter 3: Nose to Spine: spheroids generated by human nasal chondrocytes for scaffold-free nucleus pulposus augmentation).
Furthermore, I introduce a novel 3D in vitro degenerative NP micro-tissue (NPµT) model that allows researchers to study the reaction of NCS to the harsh DDD microenvironment. I investigate how pre-conditioning of the NCS with FDA approved drugs could enhance their performance within DDD microenvironment (Chapter 4: Human 3D nucleus pulposus micro-tissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc)
Round the clock protection from outdoors vector exposure in dengue, leishmaniasis and malaria endemic regions
No full textMalaria is an ancient disease with a long and rich history. It has had a profound impact on
human populations over the centuries, and it is likely to have played a significant role in shaping
our evolution. Malaria is one of the oldest infectious diseases known to humanity, and it continues to have a significant impact on global health today. Here we attempt to trace the forms and impacts of malaria from a distant past through historical times to the present. In the last sections, we review the current burdens of malaria across the world and discuss present-day approaches to its management. Only by following, or attempting to follow, malaria throughout its evolution and history can we understand its character and so be better prepared for our future
management of this ancient ill.
We will also discuss another infectious disease spread by Aedes mosquitoes’ dengue. Dengue fever has a long history dating back to the 18th century, primarily affecting tropical and subtropical regions. It has had a significant impact on human health, causing widespread illness and death, as well as resulting in lower productivity and higher healthcare costs. Dengue fever has recently increased in number due to the globalization of travel and trade, making it a rapidly
growing public health issue. Dengue's history emphasizes the significance of efforts to prevent and control the spread of infectious diseases.
Leishmaniasis is a tropical disease that is spread by infected sandflies and is found in many parts of the world resulting in decreased productivity and quality of life. New diagnostic tools, improved treatment, and vector control measures are being used to combat the spread of leishmaniasis. Despite these efforts, leishmaniasis continues to be a neglected public health concern, particularly in resource-limited areas. The history of leishmaniasis demonstrates the impact of neglected tropical diseases and the significance of ongoing prevention efforts.
The thesis studies the outdoor transmission of dengue, leishmaniasis, and malaria and how they affect human outdoor activities. The aim is to understand the preparedness of people for increases in transmission of dengue fever and identify any gaps in knowledge or instruction.
The thesis will also compare different vector control technologies and recommend interventions for controlling the diseases in outdoor settings. The goal is to contribute to the field of vector disease control outdoors and offer insights into the relationship between human behaviour, disease transmission, that may aid in the design of and implementation of optimal packages of intervention strategies
Synthetic reagents for in vitro enzymatic and protein alkylation
No full textDeveloping novel methods for selective bond formation is a persistent pursuit in organic chemistry. Alkylation is the chemical process that introduces sp3 C-X bonds into organic compounds to synthesize complex molecules from simple fragments. With excellent efficiency and selectivity, enzymatic alkylation has emerged as an alternative strategy in organic synthesis. In particular, S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTs) catalyze alkylation reactions using SAM and its derivatives as alkyl donors. Besides being a methyl donor, SAM is also a multifunctional compound that donates methylene, aminocarboxypropyl, adenosyl, and amino moieties during natural product biosynthetic reactions. Thus, the production and utilization of SAM and its derivatives have gained increased importance and attention, which are the focus of this thesis.
As SAM is relatively unstable and expensive for stoichiometric use as a methyl donor, regenerating SAM in situ is a feasible solution to overcome the impediment for large-scale biocatalysis applications of SAM-dependent MTs. The initial design of halide methyltransferase (HMT)-catalyzed SAH methylation for SAM regeneration depended on a volatile, highly toxic, and comparatively high-cost reagent methyl iodide (MeI). In this thesis, we have exploited several non-volatile sulfate- and sulfonate-based methylation reagents for SAH methylation by different promiscuous thiopurine methyltransferase (TPMT) homologs. A simple method combining a TPMT homolog and a synthetic methylation reagent for in vitro SAM regeneration from SAH shows similar efficiency to the MeI-dependent process.
SAH as the precursor of SAM comes with a hefty price tag, especially for preparative-scale production. We have developed a three-enzyme cascade for in vitro stereoselective synthesis of SAH from two low-priced reagents. The production of SAH at a hundred-milligram scale has been achieved with a high isolated yield, showing great potential for industrial applications. Moreover, we describe an all-enzymatic strategy for synthesizing a methyl-edited SAM derivative, β-methyl SAM. An unnatural methylated amino acid has been generated enzymatically from β-methyl SAM, indicating the feasibility of using biocatalysts for methyl-editing diverse bioactive compounds.
In addition to enzymatic alkylation of small molecules, we have ventured towards protein alkylation using novel supramolecular reagents. Selenoimidazolium salts enable selective N-alkylation of native proteins via supramolecular interactions. In contrast to leaving groups of conventional alkylation agents, the selenoimidazole moiety plays a non-innocent role in promoting specific alkylation
Using whole Plasmodium falciparum genomes for monitoring of escape from diagnosis, drug treatment and vaccine-induced immunity in Central-West Africa
Get PDFAs malaria control programs continue to push for local malaria elimination, novel molecular tools embedded into ongoing surveillance systems are needed. Information generated from molecular methods allows for improved monitoring of parasite drug resistance and diagnostic evasion, therefore helping inform and adapt control strategies. The overall aim of this doctoral work is to use molecular monitoring of P. falciparum, the causative parasite of the most pathogenic form of malaria, to identify hidden reservoirs of the parasite, to monitor for rapid diagnostic test evasion, to understand parasite transmission dynamics and to inform on the next generation vaccine development. Whole genome sequencing data was generated from filter paper blood samples collected within the framework of yearly malaria indicator surveys conducted on Bioko Island, Equatorial Guinea to describe the island’s parasite transmission dynamics. The connectiveness of parasite populations within the island and importation from the African continent is delineated for the first time. A novel, portable PCR device together with a ready to use, lyophilized quantitative PCR assay was deployed locally on Bioko Island at larger scale to detect reservoirs of parasite carriers that potentially contribute to transmission, but evade detection by rapid diagnostic tests. Whole genome sequencing was further utilized to conduct the first whole genome sieve analysis with blood samples collected during a field efficacy study evaluating a whole organism malaria vaccine in West Africa. This sieve analysis identified candidate genes that may encode protective immune targets for next generation malaria vaccines. Ultimately, these molecular methods will allow for improved assessment of ongoing control methods and their impact on parasite populations, providing information for enhanced resource allocation, leading to continued progress towards malaria control and potential local elimination
HEAR-BRUX: HEARable for handling BRUXism
Get PDFBruxism is a parafunctional oral behavior that can occur during sleep (sleep bruxism) or wakefulness (awake bruxism). Bruxism is characterized by teeth grinding and jaw clenching. It can lead to various health consequences such as tooth fracture, tooth wear, and muscle fatigue. Several devices have been developed to treat and detect the symptoms of bruxism. Oral splints are the most widely used device to manage sleep bruxism by eliminating tooth contact. Electromyography (EMG) is used to monitor the activity of the masticatory muscles to detect bruxism. However, mouth guards are passive devices that don't necessarily reduce the occurrence of bruxism, and EMG can be cumbersome to wear while sleeping or wakefulness. Haerables are wearable ear devices that can record signals such as sound. Such devices may be advantageous for the detection of bruxism induced events as they are easy to use and socially acceptable. Therefore, the question is whether ear devices - sometimes called hearables - that use sound as a biomarker can be affordable devices to detect bruxism. In a first study, I investigated the effect of the type of ear occlusion on recording and found that complete occlusion of the ear with a moldable earpiece supported recording of the characteristic feature of jaw clenching. For reasons of practicality and hygiene, I fitted an off-the-shelf earpiece with a transducer as part of an experimental setup in a second study to investigate the effect of transducer placement on the recording. The oral behaviors recorded were: jaw clenching, teeth grinding, reading, eating, and drinking. The transducers were placed on the zygomatic bone, frontal bone, temporal bone, and inside the ear. Finally, I investigated the use of 2D sound representations to classify the different oral behaviors recorded from the ears using deep learning. Three classifiers were tested, 2-Class (Grinding and Pause), 4-Class (Eating, Grinding, Pause, and Eeading), and 6-Class (Clenching, Drinking, Eating, Grinding, Pause, Reading). I observed that sounds of bruxism-induced events can be recorded from different parts of the head. From the experiment, I observed that the ear is an ideal location to record bruxism-induced sounds, because it compensates for head movements due to eating or drinking that may affect the recording. I also successfully classified the sounds recorded from the ear, but - as expected - the overall test accuracy of the classifier decreased as the number of classes increased. This result has good practical implications, as my approach demonstrated that bruxism-induced sounds can be recorded and distinguished from other oral behaviors. Finally, this project focused on bruxism from a biomechanical lens with the goal of developing a method to record and distinguish bruxism events from other oral behaviors. This method could be used to activate bio-feedback. Future research directions would be to investigating the causes of bruxism - which were not addressed in this work - and for this, further research is important to address one of its main causes, chronic emotional stress, which requires viewing bruxism through a biopsychosocial lens
Linked Open Usable Data for cultural heritage: perspectives on community practices and semantic interoperability
Get PDFDigital technologies have fundamentally transformed the ways in which Cultural Heritage (CH) collections are accessed and engaged with. Linked Open Usable Data (LOUD) specifications, including the International Image Interoperability Framework (IIIF) Presentation API 3.0, Linked Art, and the Web Annotation Data Model (WADM), have emerged as web standards to facilitate the description and dissemination of these valuable resources. Despite the widespread adoption of IIIF, the implementation of LOUD specifications, especially in combination, remains challenging. This is particularly true in the development and assessment of infrastructures, or sites of assemblage, that support these standards.
The research is guided by two perspectives, namely community practices and semantic interoperability. The former aims to assess how organisations, individuals, and apparatuses engage with and contribute to the consensus-making processes surrounding LOUD. By examining community practices, the social fabrics of the LOUD ecosystem can be better understood. The latter perspective explores how data can be made meaningful to machines in a standardised and interoperable approach that promotes the exchange of well-formed information. This work is grounded as part of the SNSF-funded research project Participatory Knowledge Practices in Analogue and Digital Image Archives (PIA) (2021-2025), which aims to develop a citizen science platform around three photographic collections from the Cultural Anthropology Switzerland (CAS) archives. The theoretical framework is firmly rooted in Actor-Network Theory (ANT), as one of the aims of the thesis is to describe the collaborative structures of the LOUD ecosystem and to highlight the importance of non-human actors.
Beyond the implementation of LOUD standards within the PIA research project, the empirical research includes an analysis of the social fabrics of the IIIF and Linked Art communities, as well as an investigation of LUX, Yale Collections Discovery platform. The research aims to identify the socio-technical requirements for developing specifications consistent with LOUD design principles. It also seeks to understand how the implementation of LOUD standards within PIA contributes to recognising their potential benefits and limitations in terms of facilitating data reuse and wider participation. The thesis further examines the implementation strategies, challenges, and outcomes of Yale University’s large-scale deployment of LOUD standards, focusing on how ensuring the consistency of Linked Art and IIIF resources within the LUX platform contributes to the CH domain.
The core methodology of this thesis is an actor- and practice-centred inquiry, focusing on the detailed examination of specific cosmologies within LOUD-driven communities, PIA, and LUX. This approach aims to unravel the intricate web of cultural processes and constellations through a micro-perspective, rich in empirical evidence.
Key empirical findings indicate that LOUD improves the discoverability and integration of data in CH, which requires community-driven consensus on model interoperability. Significant challenges include engaging marginalised groups, sustaining long-term engagement, and balancing technological and social considerations. The strategic use of technology and the capture of digital materiality are critical, yet LOUD presents challenges in terms of resource investment, data consistency, and the wider implementation of complex patterns.
LOUD should clearly lead efforts to improve the accessibility and usability of CH data. The community-driven methodology of IIIF and Linked Art inherently promotes collaboration and transparency, making these standards critical tools in the ongoing evolution of data management. Even for projects and institutions that do not adopt these specifications, LOUD's socio-technical practices provide crucial insights into effective digital stewardship and community engagement strategies
Ecology and fisheries interactions of hammerhead sharks with implications for management in the western north Atlantic
No full textThe widespread human-induced removal of large marine predators as a result of global overfishing requires management strategies that effectively reduce the fisheries-related mortality to prevent species extinctions and the trophic downgrading of marine ecosystems. For my thesis, I primarily focused on advancing our understanding of the ecology of great and scalloped hammerhead sharks, Sphyrna mokarran and Sphyrna lewini, to improve their management in the western North Atlantic, since high at-vessel and post-release mortality of these two overfished species in a variety of fisheries may render management measures that solely limit their harvest insufficient. I first developed a new drill attachment for a faster and safer deployment of fin-mounted satellite-linked transmitters that can be used to generate the movement data imperatively needed to design effective management strategies. The new drill attachment allowed the deployment of four-bolt fin-mounted satellite-linked transmitters consistently in under 90 seconds, which may reduce the stress sharks experience and subsequently minimises the risk for detrimental effects during tagging studies. While opportunistically documenting the wound closure capacity of fin tissue in great hammerheads and the fate of fin-mounted satellite-linked transmitters after deployment, I found that these transmitters show a lateral posterior displacement over time until they are completely shed from the fin. The documented high wound closure capacity may support this process and reduces the risk for long-term trauma through fin-mounted transmitters. Using the newly developed drill attachment, I deployed fin-mounted satellite-linked transmitters on great and scalloped hammerheads and analysed observer data from the U.S. commercial longline fisheries to detail the sharks’ regional movements and their overlap with fisheries in the U.S. Atlantic and the Gulf of Mexico, aiming to suggest potential time area closures that may reduce their fisheries-related mortality. Multiple long-distance movements, a high degree of individual variation in movement behaviours and regional space use patterns highlighted the challenges in finding adequate management strategies for great and scalloped hammerheads. But the importance of waters off Florida and North Carolina for the great and scalloped hammerheads and their high overlap with commercial longline fisheries within, make these regions candidates for the design and implementation of year-round and/or time-area closures for the protection of these two species in the western North Atlantic. Anthropogenic activities altering movements could further complicate the management of hammerheads. I thus used passive acoustic telemetry to explore how long-term tourism-related feeding impacts the local space use of great hammerheads during seasonal residency periods along their movement tracks by changing the spatiotemporal availability of resources. I found that feeding progressively altered the space use of great hammerheads across short- and long-term time scales with persisting effects on fed individuals in Bimini, The Bahamas. How the effects of the continued declines of great and scalloped hammerheads may alter the functionality of marine ecosystems depends in part on how these changes are mediated by mesopredators. Thus, in the last part of my thesis I explored the trophic ecology and the body condition of an abundant marine mesopredator known to be an important prey species to great hammerheads, the southern stingray, Hypanus americanus. I identified southern stingrays in Bimini to be an important mesopredator of reef habitats with a preference for annelids and molluscs and provided baseline data to improve our capability to predict the consequences of possible trophic cascades in marine food webs. With one third of all sharks and rays being fished towards extinction, adequate and data-driven management strategies need to be implemented. My thesis, while focusing on great and scalloped hammerheads, provides methods and insights contributing to this effort for large-bodied and highly mobile sharks
HR analytics: A centralizing or decentralizing force?
Get PDFThis study empirically analyzes the relationship between the application of HR analytics and the assignment of decision-making authority in Swiss establishments. From a theoretical standpoint the direction of this relationship is ex-ante unclear as opposing forces are at work simultaneously. While HR analytics can reduce the local information advantage or even take over decision-making processes, acting as a centralizing force, it can also generate additional local information and dampen the hidden action problem, resulting in the decentralization of decision-making processes. The empirical results, relying on doubly robust ATE estimations, are in line with a decentralizing force of HR analytics. More precisely, a comprehensive measure of decision rights as well as operational and strategic decisions are more decentralized in establishments that apply HR analytics. Overall the findings suggest that Swiss establishment combine the use of HR analytics with employee empowerment and do not use it to create a dystopian work environment as feared by proponents of digital taylorism
Invading the remote?: microplastics in seawater and emperor penguins from the Weddell Sea and Dronning Maud Land, Antarctica
Get PDFThe escalating threat of plastic waste has raised environmental concerns in recent decades. Since their
introduction in the early 20th century, plastics have revolutionized many industries, evolving from a
niche product to a cornerstone of modern manufacturing and consumer products that are an integral part
of everyday life. The characteristics that make plastics so widely used, such as their durability and light
weight, also make them persistent in the environment. Their increasing prevalence in the environment,
particularly the marine environment, and the chemical additives associated with plastics have led to
growing concern in recent decades. Each year, an estimated 11 million tons of plastics enter the oceans,
where they are dispersed by ocean currents and broken down into smaller fragments under the influence
of environmental forces. These fragmented microplastics (MPs) have been detected in marine habitats
around the world, reaching even the most remote areas, including the polar regions.
Often regarded as the last pristine wilderness, Antarctica and the adjacent Southern Ocean are to a
certain extent isolated by the robust Antarctic Circumpolar Current, which limits the influx of water
masses and organisms from the northern oceans. Despite a relatively low human presence compared to
other global regions, increasing tourism and fishing pose emerging challenges to the unique and fragile
local biota, exacerbated by global warming and accelerated ice loss. Evidence of MP contamination in
the Southern Ocean and Antarctica has raised significant concerns as a potential additional stressor to
local ecosystems. Studies of MP contamination in the most accessible and anthropogenically impacted
regions of the Southern Ocean suggest that local human activities contribute to the MP load. Little is
known about the state of MP contamination in regions considered pristine with negligible human
activity. The Weddell Sea and the ocean off Dronning Maud Land (WS/DML) represent the highlatitude
Southern Ocean, characterized by circumpolar currents and deep water formation that contribute
to the global thermohaline circulation, and by a perennial sea ice cover, making the region difficult to
access.
This thesis addresses critical knowledge gaps about MPs in the Southern Ocean by investigating
seawater from the WS/DML for the occurrence and distribution of MPs, including MPs as small as
11 μm that have been overlooked in previous studies, and by evaluating an approach to analyze ship
paint fragments, a challenging MP type that has been commonly encountered in the Southern Ocean. In
addition, the extent to which MPs have already penetrated the local food web is evaluated by
investigating MP uptake in an endemic Antarctic apex predator.
By sampling surface and subsurface waters for MPs (>300 μm), we provided the first evidence of MP
contamination in the pristine WS/DML, with MP concentrations comparable to those reported for
regions significantly more impacted by human activity. The regular occurrence of fragments resembling
paint from the research vessel (RV) Polarstern, from which we have sampled, led us to address the
methodological challenges of analyzing and comparing these complex MP types. By combining two
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forensic methods, ATR-FTIR and micro-XRF, complemented by multivariate statistics, we were able
to trace 89% of these particles back to the RV Polarstern, further demonstrating that the ship emitted
paint fragments into the environment while operating.
With evidence of MP contamination in the seawater of this pristine region, we asked whether the local
biota was affected. Examination of the gizzard contents of emperor penguin chicks from the Atka Bay
colony revealed no evidence of MP (>500 μm) ingestion by chicks fed via regurgitation by their parents
foraging in the study region. This suggests that emperor penguins, and thus the underlying food web,
are still negligibly affected. The precise contamination control in this study further demonstrates the
need for meticulous protocols to avoid sample contamination and overestimation of MP counts.
While the body of scientific literature on MPs contamination in the Southern Ocean has expanded over
the course of this thesis, a critical gap in our knowledge remained: the occurrence of the smallest MPs
in the Southern Ocean, which have been shown to be particularly abundant in other marine regions of
the world, and additionally pose an increased threat to marine biota. We therefore shifted the focus of
our research to small MPs (11–50 μm), a critical size class for understanding the broader ecological
impacts of microplastic pollution. The participation on another expedition to the southern Weddell Sea
allowed us to sample surface water for MPs as small as 11 μm in size, which were subsequently analyzed
by micro-FTIR, revealing surprisingly high concentrations of MPs in this size class found in all samples.
This emphasizes the need for further research targeting these small MPs.
Finally, with three methodologically distinct but related studies, this thesis shows that the WS/DML is
no less affected by MP pollution than other regions in the Southern Ocean with much higher human
activity, suggesting long-range transport from these regions to the study area. While large MPs do not
appear to have a significant impact on the local food web, more research is needed on small MPs. The
high prevalence of small microplastics in the marine abiotic environment and the observed emission of
paint fragments call for mitigation measures to prevent potential impacts on the fragile local ecosystems.
The distribution pattern of MP concentrations and polymer diversity, similarly observed in both studies
on water samples from the WS/DML, further suggests that MPs are subject to complex environmental
dynamics and pathways in the study region, requiring more systematic sampling and multidisciplinary
studies in the future to provide a comprehensive understanding and support decision makers
Implementation and outcomes of suicide prevention measures in Switzerland
Get PDFBackground
Suicide is a significant public health challenge with wide-ranging impacts, even in politically stable, high-income countries with advanced healthcare systems such as Switzerland. As a multicausal phenomenon, suicidality is linked to various interacting risk factors at both individual and structural levels. Suicide rates vary based on factors such as gender, age, geographical region, occupation, and mental health status. Effective suicide prevention requires a holistic approach that integrates and coordinates measures across universal, selective, and indicated prevention levels, fostering collaboration among various sectors, stakeholders, and professions. In 2016, Switzerland launched a national suicide prevention strategy to strengthen related efforts nationwide and sustainably reduce the suicide rate. Since suicidality is closely linked to mental disorders, effective mental healthcare is a critical component of suicide prevention. The exceptionally high suicide risk during the first weeks and months after discharge from a psychiatric inpatient unit highlights the importance of targeted post-discharge support measures for vulnerable patients. Since 2021, the foundation Health Promotion Switzerland has been co-funding four regional suicide prevention projects focused on supporting patients at suicide risk following hospital discharge.
Objectives
The overarching aim of this PhD thesis was to advance suicide prevention in Switzerland by providing evidence-based insights into contextual conditions and regional prevention measures. Specific objectives included raising awareness of suicide among the elderly, addressing challenges, gaps, and success factors in suicide prevention across Germany, Austria, and Switzerland, assessing the effects of interventions from two regional suicide prevention projects for patients at increased suicide risk, and promoting the sustainability of project-based suicide prevention initiatives.
Methods
To achieve the specific objectives and the overall aim, several research projects using different methods were conducted. First, a qualitative study based on semi-structured interviews examined the experiences and opinions of 36 experts in suicide prevention from Germany, Austria, and Switzerland. Incorporating perspectives from policy, science, and practice allowed for a comprehensive understanding of the current challenges, gaps, and success factors in suicide prevention across the three countries. A cross-sectional survey collected data via a standardized questionnaire to evaluate the utilization and perceived usefulness of measures from a regional suicide prevention project among individuals at increased suicide risk. Additionally, an interrupted time series analysis of administrative patient data from a psychiatric hospital was conducted to assess the effects of this intervention package on psychiatric readmissions. Within a longitudinal observational study, we examined changes in the therapeutic alliance and perceived self-efficacy over the course of a project-based, suicide-specific treatment among patients with suicidal behavior. In addition to this original research, an editorial and a policy brief were developed to support the translation of research findings into policy and practice.
Results
The research identified key aspects to advance suicide prevention in Germany, Austria, and Switzerland. Challenges that need to be addressed include persistent stigmatization of suicidal thoughts and behavior, as well as structural deficiencies in mental healthcare. Significant gaps remain in multilevel collaboration, and there is a lack of targeted programs for older adults and men. Key success factors include the implementation of a national suicide prevention strategy and involving individuals with lived experience in the design, implementation, and evaluation of preventive measures. Notable examples of good practice include regional networks that foster intersectoral and interprofessional collaboration and initiatives promoting responsible media coverage of suicide. Regarding the multicomponent suicide prevention project in Central Switzerland, we found that the different measures were used to varying degrees by the target groups, with around half of the users considering the self-management interventions helpful. In line with this, the secondary data analysis revealed that the intervention package was associated with significant reductions in psychiatric readmissions among individuals at increased suicide risk, with larger reductions observed among women compared to men. The evaluation of the project-based, suicide-specific treatment demonstrated that the therapeutic alliance and perceived self-efficacy improved over the course of therapy for individuals with suicidal behavior. Notably, higher perceived self-efficacy at the beginning of the intervention was associated with less suicidal ideation throughout the treatment.
Conclusion
Switzerland has made considerable progress in suicide prevention, with various stakeholders engaged, a national action plan implemented, and targeted financial investments. Nevertheless, there remain significant areas for improvement, which have been outlined in this PhD thesis. Sustainable progress toward reducing suicide rates can be achieved through consistent multisectoral engagement and efficient allocation of resources, supported by a shift in perspective that frames suicide prevention as a broader societal responsibility. While primary and secondary prevention are essential to reducing the onset of suicidal thoughts and behaviors, it is equally imperative to address the persistent gaps and deficiencies in mental healthcare. The findings from the evaluation of two regional suicide prevention projects underscore the importance and positive effects of structured post-discharge support for vulnerable patients. To strengthen both individual and systemic support mechanisms, multicomponent approaches to suicide prevention that target different groups with integrated interventions have proven particularly valuable