Deglacial upslope shift of NE Atlantic intermediate waters controlled slope erosion and cold-water coral mound formation (Porcupine Seabight, Irish margin)

Highlights • Holocene cold-water coral mound formation started non-synchronous in Belgica province. • Coral mounds and slope sediments record changes in intermediate water mass dynamics. • Increased turbulent bottom currents steered slope erosion and mound formation. • Internal waves at the ENAW-MOW boundary enhance energy supply and particle flux. • Transition zone between the ENAW-MOW shifted 250 m upslope during the last deglacial. Abstract Turbulent bottom currents significantly influence the formation of cold-water coral mounds and sedimentation processes on continental slopes. Combining records from coral mounds and adjacent slope sediments therefore provide an unprecedented palaeo-archive to understand past variations of intermediate water-mass dynamics. Here, we present coral ages from coral mounds of the Belgica province (Porcupine Seabight, NE Atlantic), which indicate a non-synchronous Holocene re-activation in mound formation suggested by a temporal offset of ∼2.7 kyr between the deep (start: ∼11.3 ka BP at 950 m depth) and shallow (start: ∼8.6 ka BP at 700 m depth) mounds. A similar depth-dependent pattern is revealed in the slope sediments close to these mounds that become progressively younger from 22.1 ka BP at 990 m to 12.2 ka BP at 740 m depth (based on core-top ages). We suggest that the observed changes are the consequence of enhanced bottom-water hydrodynamics, caused by internal waves associated to the re-invigoration of the Mediterranean Outflow Water (MOW) and the development of a transition zone (TZ) between the MOW and the overlying Eastern North Atlantic Water (ENAW), which established during the last deglacial. These highly energetic conditions induced erosion adjacent to the Belgica mounds and supported the re-initiation of mound formation by increasing food and sediment fluxes. The striking depth-dependent patterns are likely linked to a shift of the ENAW-MOW-TZ, moving the level of maximum energy ∼250 m upslope since the onset of the last deglaciation

Deglacial upslope shift of NE Atlantic intermediate waters controlled slope erosion and cold-water coral mound formation (Porcupine Seabight, Irish margin)

Highlights • Holocene cold-water coral mound formation started non-synchronous in Belgica province. • Coral mounds and slope sediments record changes in intermediate water mass dynamics. • Increased turbulent bottom currents steered slope erosion and mound formation. • Internal waves at the ENAW-MOW boundary enhance energy supply and particle flux. • Transition zone between the ENAW-MOW shifted 250 m upslope during the last deglacial. Abstract Turbulent bottom currents significantly influence the formation of cold-water coral mounds and sedimentation processes on continental slopes. Combining records from coral mounds and adjacent slope sediments therefore provide an unprecedented palaeo-archive to understand past variations of intermediate water-mass dynamics. Here, we present coral ages from coral mounds of the Belgica province (Porcupine Seabight, NE Atlantic), which indicate a non-synchronous Holocene re-activation in mound formation suggested by a temporal offset of ∼2.7 kyr between the deep (start: ∼11.3 ka BP at 950 m depth) and shallow (start: ∼8.6 ka BP at 700 m depth) mounds. A similar depth-dependent pattern is revealed in the slope sediments close to these mounds that become progressively younger from 22.1 ka BP at 990 m to 12.2 ka BP at 740 m depth (based on core-top ages). We suggest that the observed changes are the consequence of enhanced bottom-water hydrodynamics, caused by internal waves associated to the re-invigoration of the Mediterranean Outflow Water (MOW) and the development of a transition zone (TZ) between the MOW and the overlying Eastern North Atlantic Water (ENAW), which established during the last deglacial. These highly energetic conditions induced erosion adjacent to the Belgica mounds and supported the re-initiation of mound formation by increasing food and sediment fluxes. The striking depth-dependent patterns are likely linked to a shift of the ENAW-MOW-TZ, moving the level of maximum energy ∼250 m upslope since the onset of the last deglaciation

A generalizable deep voxel-guided morphometry algorithm for the detection of subtle lesion dynamics in multiple sclerosis

IntroductionMultiple sclerosis (MS) is a chronic neurological disorder characterized by the progressive loss of myelin and axonal structures in the central nervous system. Accurate detection and monitoring of MS-related changes in brain structures are crucial for disease management and treatment evaluation. We propose a deep learning algorithm for creating Voxel-Guided Morphometry (VGM) maps from longitudinal MRI brain volumes for analyzing MS disease activity. Our approach focuses on developing a generalizable model that can effectively be applied to unseen datasets.MethodsLongitudinal MS patient high-resolution 3D T1-weighted follow-up imaging from three different MRI systems were analyzed. We employed a 3D residual U-Net architecture with attention mechanisms. The U-Net serves as the backbone, enabling spatial feature extraction from MRI volumes. Attention mechanisms are integrated to enhance the model's ability to capture relevant information and highlight salient regions. Furthermore, we incorporate image normalization by histogram matching and resampling techniques to improve the networks' ability to generalize to unseen datasets from different MRI systems across imaging centers. This ensures robust performance across diverse data sources.ResultsNumerous experiments were conducted using a dataset of 71 longitudinal MRI brain volumes of MS patients. Our approach demonstrated a significant improvement of 4.3% in mean absolute error (MAE) against the state-of-the-art (SOTA) method. Furthermore, the algorithm's generalizability was evaluated on two unseen datasets (n = 116) with an average improvement of 4.2% in MAE over the SOTA approach.DiscussionResults confirm that the proposed approach is fast and robust and has the potential for broader clinical applicability

Survival analysis for AdVerse events with VarYing follow-up times (SAVVY) -- estimation of adverse event risks

The SAVVY project aims to improve the analyses of adverse event (AE) data in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). Although statistical methodologies have advanced, in AE analyses often the incidence proportion, the incidence density, or a non-parametric Kaplan-Meier estimator (KME) are used, which either ignore censoring or CEs. In an empirical study including randomized clinical trials from several sponsor organisations, these potential sources of bias are investigated. The main aim is to compare the estimators that are typically used in AE analysis to the Aalen-Johansen estimator (AJE) as the gold-standard. Here, one-sample findings are reported, while a companion paper considers consequences when comparing treatment groups. Estimators are compared with descriptive statistics, graphical displays and with a random effects meta-analysis. The influence of different factors on the size of the bias is investigated in a meta-regression. Comparisons are conducted at the maximum follow-up time and at earlier evaluation time points. CEs definition does not only include death before AE but also end of follow-up for AEs due to events possibly related to the disease course or the treatment. Ten sponsor organisations provided 17 trials including 186 types of AEs. The one minus KME was on average about 1.2-fold larger than the AJE. Leading forces influencing bias were the amount of censoring and of CEs. As a consequence, the average bias using the incidence proportion was less than 5%. Assuming constant hazards using incidence densities was hardly an issue provided that CEs were accounted for. There is a need to improve the guidelines of reporting risks of AEs so that the KME and the incidence proportion are replaced by the AJE with an appropriate definition of CEs

Programmatic options for monitoring malaria in elimination settings: easy access group surveys to investigate Plasmodium falciparum epidemiology in two regions with differing endemicity in Haiti.

BACKGROUND: As in most eliminating countries, malaria transmission is highly focal in Haiti. More granular information, including identifying asymptomatic infections, is needed to inform programmatic efforts, monitor intervention effectiveness, and identify remaining foci. Easy access group (EAG) surveys can supplement routine surveillance with more granular information on malaria in a programmatically tractable way. This study assessed how and which type of venue for EAG surveys can improve understanding malaria epidemiology in two regions with different transmission profiles. METHODS: EAG surveys were conducted within the departments of Artibonite and Grand'Anse (Haiti), in regions with different levels of transmission intensity. Surveys were conducted in three venue types: primary schools, health facilities, and churches. The sampling approach varied accordingly. Individuals present at the venues at the time of the survey were eligible whether they presented malaria symptoms or not. The participants completed a questionnaire and were tested for Plasmodium falciparum by a highly sensitive rapid diagnostic test (hsRDT). Factors associated with hsRDT positivity were assessed by negative binomial random-effects regression models. RESULTS: Overall, 11,029 individuals were sampled across 39 venues in Artibonite and 41 in Grand'Anse. The targeted sample size per venue type (2100 in Artibonite and 2500 in Grand'Anse) was reached except for the churches in Artibonite, where some attendees left the venue before they could be approached or enrolled. Refusal rate and drop-out rate were < 1%. In total, 50/6003 (0.8%) and 355/5026 (7.1%) sampled individuals were hsRDT positive in Artibonite and Grand'Anse, respectively. Over half of all infections in both regions were identified at health facilities. Being male and having a current or reported fever in the previous 2 weeks were consistently identified with increased odds of being hsRDT positive. CONCLUSIONS: Surveys in churches were problematic because of logistical and recruitment issues. However, EAG surveys in health facilities and primary schools provided granular information about malaria burden within two departments in Haiti. The EAG surveys were able to identify residual foci of transmission that were missed by recent national surveys. Non-care seeking and/or asymptomatic malaria infections can be identified in this alternative surveillance tool, facilitating data-driven decision-making for improved targeting of interventions