Interventional Neurorehabilitation for Promoting Functional Recovery Post-Craniotomy: A Proof-of-Concept

Purpose: The human brain is a highly plastic complex network -it is highly resilient to damage and capable of self-reorganisation after a large perturbation. Clinically, neurological deficits secondary to iatrogenic injury have very few active treatments. New imaging and stimulation technologies, though, offer promising therapeutic avenues to accelerate post-operative recovery trajectories. In this study, we sought to establish the safety profile for interventional neurorehabilitation: connectome-based therapeutic brain stimulation to drive cortical reorganisation and promote functional recovery post-craniotomy. Methods: In n=34 glioma patients who experienced post-operative motor or language deficits, we used connectomics to construct single-subject cortical networks. Based on their clinical and connectivity deficit, patients underwent network-specific Transcranial Magnetic Stimulation (TMS) sessions daily over five consecutive days. Patients were then assessed for TMS-related side effects and improvements. Results: 31/34 (91%) patients were successfully recruited and enrolled for TMS treatment within two weeks of glioma surgery. No seizures or serious complications occurred during TMS rehabilitation and one-week post-stimulation. Transient headaches were reported in 4/31 patients but improved after a single session. No neurological worsening was observed while a benefit was noted in 28/31 patients post-TMS. We present two clinical vignettes and a video demonstration of interventional neurorehabilitation. Conclusions: For the first time, we demonstrate the safety profile and ability to recruit, enrol, and complete TMS acutely post-craniotomy in a high seizure risk population. Given the lack of randomisation and controls in this study, prospective randomised sham-controlled stimulation trials are now warranted to establish the efficacy of interventional neurorehabilitation following craniotomy.

Application of Modular Response Analysis to Medium- to Large-Size Biological Systems

The development of high-throughput genomic technologies associated with recent genetic perturbation techniques such as short hairpin RNA (shRNA), gene trapping, or gene editing (CRISPR/Cas9) has made it possible to obtain large perturbation data sets. These data sets are invaluable sources of information regarding the function of genes, and they offer unique opportunities to reverse engineer gene regulatory networks in specific cell types. Modular response analysis (MRA) is a well-accepted mathematical modeling method that is precisely aimed at such network inference tasks, but its use has been limited to rather small biological systems so far. In this study, we show that MRA can be employed on large systems with almost 1,000 network components. In particular, we show that MRA performance surpasses general-purpose mutual information-based algorithms. Part of these competitive results was obtained by the application of a novel heuristic that pruned MRA-inferred interactions a posteriori. We also exploited a block structure in MRA linear algebra to parallelize large system resolutions.

Uncovering the fragility of large-scale engineering projects

Engineering projects are notoriously hard to complete on-time, with project delays often theorised to propagate across interdependent activities. Here, we use a novel dataset consisting of activity networks from 14 diverse, large-scale engineering projects to uncover network properties that impact timely project completion. We provide empirical evidence of perturbation cascades, where perturbations in the delivery of a single activity can impact the delivery of up to 4 activities downstream, leading to large perturbation cascades. We further show that perturbation clustering significantly affects project overall delays. Finally, we find that poorly performing projects have their highest perturbations in high reach nodes, which can lead to largest cascades, while well performing projects have perturbations in low reach nodes, resulting in localised cascades. Altogether, these findings pave the way for a network-science framework that can materially enhance the delivery of large-scale engineering projects.

Feedback Between Carbon and Nitrogen Cycles During the Ediacaran Shuram Excursion

The middle Ediacaran Period records one of the deepest negative carbonate carbon isotope (δ13Ccarb) excursions in Earth history (termed the Shuram excursion). This excursion is argued by many to represent a large perturbation of the global carbon cycle. If true, this event may also have induced significant changes in the nitrogen cycle, because carbon and nitrogen are intimately coupled in the global ocean. However, the response of the nitrogen cycle to the Shuram excursion remains ambiguous. Here, we reported high resolution bulk nitrogen isotope (δ15N) and organic carbon isotope (δ13Corg) data from the upper Doushantuo Formation in two well-preserved sections (Jiulongwan and Xiangerwan) in South China. The Shuram-equivalent excursion is well developed in both localities, and our results show a synchronous decrease in δ15N across the event. This observation is further supported by bootstrapping simulations taking into account all published δ15N data from the Doushantuo Formation. Isotopic mass balance calculations suggest that the decrease in δ15N during the Shuram excursion is best explained by the reduction of isotopic fractionation associated with water column denitrification (εwd) in response to feedbacks between carbon and nitrogen cycling, which were modulated by changes in primary productivity and recycled nutrient elements through remineralization of organic matter. The study presented here thus offers a new perspective for coupled variations in carbon and nitrogen cycles and sheds new light on this critical time in Earth history.

Enhanced volcanism associated to the emplacement of the North Atlantic Igneous Province during the PETM evidenced by mercury anomalies in Pyrenean foreland sections

<p>The Paleocene-Eocene thermal maximum (PETM; ~55.6 Ma) is one of the most pronounced and the best known of the transient hyperthermal events of the Paleogene. The PETM is characterized by global warming, a significant perturbation of the carbon cycle, and a large perturbation of the biosphere. This extraordinary event is recorded by sharp negative carbon excursions (NCIE) in both oceanic and terrestrial carbonates. The sequence of events triggering this disturbance and the source of the <sup>13</sup>C-depleted carbon for the NCIE remains controversial. External perturbation such as volcanism, associated with the setup of the North Atlantic Igneous Province (NAIP), is suspected to be one of the mechanisms responsible for this abrupt climate upheaval. One proxy for investigating the possible link between the establishment of the NAIP and perturbation associated with the PETM is to study mercury (Hg) concentrations record in marine and continental sedimentary successions.</p><p>In this study, we present new high-resolution mercury and stable isotopic records from peripheral basins of the Pyrenean orogen across the PETM. The four studies sections vary from continental to bathyal deposit environment and offer the potential to evaluate how major climatic disturbances are associated with the PETM record through a continental to marine transect.</p><p>The data obtained reveal the occurrence of two main NCIEs. Based on biostratigraphy and similarity of shape and amplitude of the isotopic excursions with global records, the largest NCIE is interpreted as the PETM. This sharp excursion is preceded by another one that we interpreted as the Pre-Onset Excursion (POE), founded in some other profiles worldwide. These two NCIEs are systematically associated with important mercury anomalies, whatever the environment considered. Increase in Hg contents shows no correlation with clay or total organic carbon contents, suggesting that the influences of local processes or Hg scavenging by organic matter appear to be insignificant. These results show that multiple pulses of volcanism, probably associated with the emplacement of the NAIP, contributed to the onset and the long duration of the PETM. In addition, our study highlights the possibility to get reliable information about past extreme climate events from sedimentary successions even if deposited within active tectonic domains.</p><p>This work is financed and carried out within the framework of the BRGM-TOTAL Source-to-Sink project.</p>

The precessing jets of classical nova YZ Reticuli

ABSTRACT The classical nova YZ Reticuli was discovered in 2020 July. Shortly after this, we commenced a sustained, highly time-sampled coverage of its subsequent rapid evolution with time-resolved spectroscopy from the Global Jet Watch observatories. Its H-alpha complex exhibited qualitatively different spectral signatures in the following weeks and months. We find that these H-alpha complexes are well described by the same five Gaussian emission components throughout the six months following eruption. These five components appear to constitute two pairs of lines, from jet outflows and an accretion disc, together with an additional central component. The correlated, symmetric patterns that these jet/accretion disc pairs exhibit suggest precession, probably in response to the large perturbation caused by the nova eruption. The jet and accretion disc signatures persist from the first 10 d after brightening – evidence that the accretion disc survived the disruption. We also compare another classical nova (V6568 Sgr) that erupted in 2020 July whose H-alpha complex can be described analogously, but with faster line-of-sight jet speeds exceeding 4000 km s−1. We suggest that classical novae with higher mass white dwarfs bridge the gap between recurrent novae and classical novae such as YZ Reticuli.

Adjoint-Based Calculation of Parametric Thermoacoustic Maps of an Industrial Combustion Chamber

The aim of this study is to efficiently calculate parametric thermoacoustic maps of typical combustion chambers. Two configurations are considered: an academic configuration based on a Rijke tube, and an industrial combustion chamber, which is the core of a recently developed microturbine for power generation. Such maps can be understood as the collection of loci of thermoacoustic eigenfrequencies obtained under systematic variations of some defined parameters, while considering the Helmholtz equation as the thermoacoustic model of interest. In this study we consider variations on two parameters: the gain n and time-delay τ associated with a generic flame response model. We also show the feasibility of the proposed approach when considering more realistic flame responses. A straight-forward way to calculate such a thermoacoustic map is by solving the Helmholtz equation, and, thus, the corresponding nonlinear eigenvalue problem (NLEVP), one time per parameter combination. With that approach, the nonlinear eigenvalue problem needs to be solved hundreds or thousands of times if an adequate resolution of the thermoacoustic map is sought. Such a strategy may be computationally unaffordable. In order to overcome this difficulty, this work utilizes an adjoint-based, high-order perturbation method. The actual eigenvalue problem is only solved once at a baseline point. After applying the perturbation equations at that point, a polynomial rational function—the Padé approximant—is obtained to estimate the eigenfrequency drift that results for a small or large perturbation in the flame response. It is demonstrated, for both academic and industrial test cases, that the obtained maps are accurate. Additionally, it is shown that these maps reveal a large variety of thermoacoustic features, such as stability boundaries, intrinsic thermoacoustic modes, and exceptional points. The numerical costs for such calculations are negligible even for the industrial combustion chamber investigated.

Adjoint-Based Calculation of Parametric Thermoacoustic Maps of an Industrial Combustion Chamber

The aim of the present study is to efficiently calculate parametric thermoacoustic maps of typical combustion chambers. Two configurations are considered: an academic configuration based on a Rijke tube, and an industrial combustion chamber, which is the core of a recently developed micro-turbine for power generation. Such maps can be understood as the collection of loci of thermoacoustic eigen frequencies obtained under systematic variations of some defined parameters, while considering the Helmholtz equation as the thermoacoustic model of interest. In this study we consider variations on two parameters: the gain n and time-delay τ associated with a generic flame response model. We also show the feasibility of the proposed approach when considering more realistic flame responses. A straight-forward way to calculate such a thermoacoustic map is by solving the Helmholtz equation, and, thus, the corresponding non-linear eigenvalue problem, one time per parameter combination. With that approach, the non-linear eigenvalue problem needs to be solved hundreds or thousands of times if an adequate resolution of the thermoacoustic map is sought. Such a strategy may be computationally unaffordable. In order to overcome this difficulty, the present work utilizes an adjoint-based, high-order perturbation method. The actual eigenvalue problem is only solved once at a baseline point. After applying the perturbation equations at that point, a polynomial rational function — the Padé approximant — is obtained to estimate the eigen-frequency drift that results for a small or large perturbation in the flame response. It is demonstrated, for both academic and industrial test cases, that the obtained maps are accurate. Additionally, it is shown that these maps reveal a large variety of thermoacoustic features, such as stability boundaries, intrinsic thermoacoustic modes, and exceptional points. The numerical costs for such calculations are negligible even for the industrial combustion chamber investigated.

Temporal and spatial mediated changes in subsurface microbial community assemblages and functions

Groundwater ecosystems can host different habitats with unique microbial assemblages and functions. Although groundwater microbes are important to subsurface processes, little is known about the drivers of change in these communities. Illumina sequencing and bioinformatic tools were used to examine whether different groundwater zones could have the same patterns of microbial community change over a two-year period. Five different groundwater zones from Hospital Hole, a stratified sinkhole in west-central Florida, were used in this study since they have been previously shown to host distinct microbial communities. Seasonal patterns of microbial community assemblages and potential metabolic functions were not identified in the sinkhole communities. Different physicochemical parameters correlated to microbial community change within each zone. Local hydrogeology appears to play an important role in subsurface microbial community change since Hurricane Irma and seasonal turnover events did not appear to cause a large perturbation in the microbial communities. Nutrient availability and local hydrogeochemistry appear to be important drivers of microbial community change in the subsurface.