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ICDP workshop on the Lake Victoria Drilling Project (LVDP): scientific drilling of the world's largest tropical lake
Lake Victoria, which is bordered by Uganda, Tanzania, Kenya, and has a catchment that extends to Rwanda and Burundi, is home to the largest human population surrounding any lake in the world and provides critical resources across eastern Africa. Lake Victoria is also the world's largest tropical lake by surface area, but it is relatively shallow and without a major inlet, making it very sensitive to changes in climate, and especially hydroclimate. Furthermore, its size creates abundant habitats for aquatic fauna, including the iconic hyper-diverse cichlids, and serves as a major geographic barrier to terrestrial fauna across equatorial Africa. Given Lake Victoria's importance to the eastern African region, its sensitivity to climate, and its influences on terrestrial and aquatic faunal evolution and dispersal, it is vital to understand the connection between the lake and regional climate and how the lake size, shape, and depth have changed through its depositional history. This information can only be ascertained by collecting a complete archive of Lake Victoria's sedimentary record. To evaluate the Lake Victoria basin as a potential drilling target, ∼ 50 scientists from 10 countries met in Dar es Salaam, Tanzania, in July 2022 for the International Continental Scientific Drilling Program (ICDP)-sponsored Lake Victoria Drilling Project (LVDP) workshop. Discussions of the main scientific objectives for a future drilling project included (1) recovering the Pleistocene and Holocene sedimentary records of Lake Victoria that document the dynamic nature of the lake, including multiple lacustrine and paleosol sequences; (2) establishing the chronology of recovered sediments, including using extensive tephra fingerprinting and other techniques from deposits in the region; (3) reconstructing past climate, environment, lacustrine conditions, and aquatic fauna, using an integrated multi-proxy approach, combined with climate and hydrologic modeling; and (4) connecting new records with existing sedimentary snapshots and fossils exposed in deposits around the lake, tying archaeological, paleontological, sedimentological, tectonic, and volcanic findings to new drilling results. The LVDP provides an innovative way to address critical geological, paleontological, climatological, and evolutionary biological questions about Quaternary to modern landscapes and ecosystems in eastern Africa. Importantly, this project affords an excellent opportunity to help develop conservation and management strategies for regional responses to current and future changes in climate, land use, fisheries, and resiliency of at-risk communities in equatorial Africa
Prostate Cancer Theranostics With 177Lu-PSMA.
This review paper highlights the transformative role of PSMA-targeted diagnostics and therapy in prostate cancer management, particularly focusing on 177Lu-PSMA-617, approved by the FDA and EMA for metastatic castration-resistant prostate cancer (mCRPC) patients post-chemotherapy and ARPI treatment. Originating from the VISION trial's success, this paper navigates the current radioligand therapy (RLT) indications, emphasizing practical patient selection, planning, and treatment execution. It critically examines Lu-PSMA's comparative effectiveness against cabazitaxel and Ra-223, addressing decision-making dilemmas for mCRPC treatments. Furthermore, the paper discusses Lu-PSMA in chemotherapy-naïve patients and its application in hormone-sensitive prostate cancer, underlined by ongoing global studies. A significant concern is Lu-PSMA's long-term safety profile, particularly nephrotoxicity risks, necessitating further investigation. The possibility of Lu-PSMA rechallenge in responsive patients is explored, stressing the need for comprehensive analyses and real-world data to refine treatment protocols. Conclusively, PSMA-targeted therapy marks a significant advance in prostate cancer therapy, advocating for its integration into a multimodal, patient-centric treatment approach. The review underscores the imperative for additional comparative studies to optimize treatment sequences and outcomes, ultimately enhancing long-term prognosis and disease control in prostate cancer management
Effects of a co-designed exercise and sport intervention on cardiorespiratory fitness and metabolic syndrome components among individuals living in a refugee camp in Greece: A randomized controlled trial.
BACKGROUND
The metabolic syndrome epidemic, including in forcibly displaced individuals, requires cost-effective prevention and treatment strategies. Yet, the health needs of forcibly displaced individuals often remain underserved. Our study evaluated the effect of a co-designed exercise and sport intervention on cardiorespiratory fitness and metabolic syndrome components among individuals in a refugee camp in Greece and examined the indirect effect through cardiorespiratory fitness on metabolic syndrome components.
METHODS
We conducted a randomized controlled trial involving an intervention and a wait-list control group with n = 142 (52.8 % women) forcibly displaced Southwest Asians and Sub-Saharan Africans. The intervention group participated for 10 weeks in exercise and sport activities. Outcomes were cardiorespiratory fitness and single metabolic syndrome components. Effects were analyzed with structural equation modeling.
RESULTS
In total, 62.7 % of participants presented with low cardiorespiratory fitness levels (<40th percentile), and 24.6 % met the criteria for metabolic syndrome. In the intervention group, 73.5 % attended the exercise and sport sessions at least once a week. There was evidence for a direct intervention effect on cardiorespiratory fitness, ßdirect = 0.12, p = 0.022, but not for any of the metabolic syndrome components (p ≥ 0.192). Cardiorespiratory fitness significantly facilitated the intervention's indirect effect on abdominal obesity, ßindirect = -0.03, p = 0.012, high diastolic blood pressure, ßindirect = -0.04, p = 0.011, and elevated triglycerides, ßindirect = -0.03, p = 0.025.
CONCLUSION
Implementing exercise and sport activities in a refugee camp in Greece effectively reaches a wider target population and improves cardiorespiratory fitness among forcibly displaced individuals. The intervention contributes to a decrease in abdominal obesity, high diastolic blood pressure and elevated triglycerides indirectly via improved cardiorespiratory fitness
What are the bottlenecks to health data sharing in Switzerland? An interview study.
BACKGROUND
While health data sharing for research purposes is strongly supported in principle, it can be challenging to implement in practice. Little is known about the actual bottlenecks to health data sharing in Switzerland.
AIMS OF THE STUDY
This study aimed to assess the obstacles to Swiss health data sharing, including legal, ethical and logistical bottlenecks.
METHODS
We identified 37 key stakeholders in data sharing via the Swiss Personalised Health Network ecosystem, defined as being an expert on sharing sensitive health data for research purposes at a Swiss university hospital (or a Swiss disease cohort) or being a stakeholder in data sharing at a public or private institution that uses such data. We conducted semi-structured interviews, which were transcribed, translated when necessary, and de-identified. The entire research team discussed the transcripts and notes taken during each interview before an inductive coding process occurred.
RESULTS
Eleven semi-structured interviews were conducted (primarily in English) with 17 individuals representing lawyers, data protection officers, ethics committee members, scientists, project managers, bioinformaticians, clinical trials unit members, and biobank stakeholders. Most respondents felt that it was not the actual data transfer that was the bottleneck but rather the processes and systems around it, which were considered time-intensive and confusing. The templates developed by the Swiss Personalised Health Network and the Swiss General Consent process were generally felt to have streamlined processes significantly. However, these logistics and data quality issues remain practical bottlenecks in Swiss health data sharing. Areas of legal uncertainty include privacy laws when sharing data internationally, questions of "who owns the data", inconsistencies created because the Swiss general consent is perceived as being implemented differently across different institutions, and definitions and operationalisation of anonymisation and pseudo-anonymisation. Many participants desired to create a "culture of data sharing" and to recognise that data sharing is a process with many steps, not an event, that requires sustainability efforts and personnel. Some participants also stressed a desire to move away from data sharing and the current privacy focus towards processes that facilitate data access.
CONCLUSIONS
Facilitating a data access culture in Switzerland may require legal clarifications, further education about the process and resources to support data sharing, and further investment in sustainable infrastructureby funders and institutions
Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.
OBJECTIVES
Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations.
METHODS
Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%.
RESULTS
A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation.
CONCLUSION
Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported
Lipoprotein(a) as a blood marker for large artery atherosclerosis stroke etiology: validation in a prospective cohort from a swiss stroke center.
BACKGROUND
Lipoprotein (a) [Lp(a)] serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort.
METHODS
This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients [NCT00878813]), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers.
RESULTS
Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 [95% CI 1.03and#x2013;2.09], p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes.
CONCLUSIONS
In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov.
REGISTRATION NUMBER
NCT00878813
Fast-slow traits predict competition network structure and its response to resources and enemies.
Plants interact in complex networks but how network structure depends on resources, natural enemies and species resource-use strategy remains poorly understood. Here, we quantified competition networks among 18 plants varying in fast-slow strategy, by testing how increased nutrient availability and reduced foliar pathogens affected intra- and inter-specific interactions. Our results show that nitrogen and pathogens altered several aspects of network structure, often in unexpected ways due to fast and slow growing species responding differently. Nitrogen addition increased competition asymmetry in slow growing networks, as expected, but decreased it in fast growing networks. Pathogen reduction made networks more even and less skewed because pathogens targeted weaker competitors. Surprisingly, pathogens and nitrogen dampened each other's effect. Our results show that plant growth strategy is key to understand how competition respond to resources and enemies, a prediction from classic theories which has rarely been tested by linking functional traits to competition networks
Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.
Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research
The practice of historical ecology: What, when, where, how and what for.
In recent decades, there has been a growing number of studies exploring the historical dimensions of the interconnectedness of human societies and the environment. A core approach in this field is historical ecology. We analyzed 544 historical-ecological papers to assess patterns and trends in the field. We found a high degree of interdisciplinarity with a focus on local case studies, of periods of fewer than 500 years, analyzing archival sources through quantitative approaches. The proportion of papers containing management recommendations has increased over time. To make historical ecology globally relevant, more effort should be made to utilize studies across languages, borders and worldviews. We call for high standards regarding the use of social scientific methodologies. Lastly, we argue that fostering longer-term studies and assessing the real-life impact of policy recommendations emerging from historical ecology can help the discipline better contribute solutions to the challenges facing humanity in an uncertain future