Global excitability and network structure in the human brain

We utilize a model of Wilson-Cowan oscillators to investigate structure-function relationships in the human brain by means of simulations of the spontaneous dynamics of brain networks generated through human connectome data. This allows us to establish relationships between the global excitability of such networks and global structural network quantities for connectomes of two different sizes for a number of individual subjects. We compare the qualitative behavior of such correlations between biological networks and shuffled networks, the latter generated by shuffling the pairwise connectivities of the former while preserving their distribution. Our results point towards a remarkable propensity of the brain's to achieve a trade-off between low network wiring cost and strong functionality, and highlight the unique capacity of brain network topologies to exhibit a strong transition from an inactive state to a globally excited one.Comment: 12 pages, 10 figure

Network analysis of the human structural connectome including the brainstem: a new perspective on consciousness

The underlying anatomical structure is fundamental to the study of brain networks and is likely to play a key role in the generation of conscious experience. We conduct a computational and graph-theoretical study of the human structural connectome incorporating a variety of subcortical structures including the brainstem, which is typically not considered in similar studies. Our computational scheme involves the use of Python DIPY and Nibabel libraries to develop an averaged structural connectome comprised of 100 healthy adult subjects. We then compute degree, eigenvector, and betweenness centralities to identify several highly connected structures and find that the brainstem ranks highest across all examined metrics. Our results highlight the importance of including the brainstem in structural network analyses. We suggest that structural network-based methods can inform theories of consciousness, such as global workspace theory (GWT), integrated information theory (IIT), and the thalamocortical loop theory.Comment: 23 pages, 5 figure

Atmospheric Reconnaissance of TRAPPIST-1 b with JWST/NIRISS: Evidence for Strong Stellar Contamination in the Transmission Spectra

TRAPPIST-1 is a nearby system of seven Earth-sized, temperate, rocky exoplanets transiting a Jupiter-sized M8.5V star, ideally suited for in-depth atmospheric studies. Each TRAPPIST-1 planet has been observed in transmission both from space and from the ground, confidently rejecting cloud-free, hydrogen-rich atmospheres. Secondary eclipse observations of TRAPPIST-1 b with JWST/MIRI are consistent with little to no atmosphere given the lack of heat redistribution. Here we present the first transmission spectra of TRAPPIST-1 b obtained with JWST/NIRISS over two visits. The two transmission spectra show moderate to strong evidence of contamination from unocculted stellar heterogeneities, which dominates the signal in both visits. The transmission spectrum of the first visit is consistent with unocculted starspots and the second visit exhibits signatures of unocculted faculae. Fitting the stellar contamination and planetary atmosphere either sequentially or simultaneously, we confirm the absence of cloud-free hydrogen-rich atmospheres, but cannot assess the presence of secondary atmospheres. We find that the uncertainties associated with the lack of stellar model fidelity are one order of magnitude above the observation precision of 89 ppm (combining the two visits). Without affecting the conclusion regarding the atmosphere of TRAPPIST-1 b, this highlights an important caveat for future explorations, which calls for additional observations to characterize stellar heterogeneities empirically and/or theoretical works to improve model fidelity for such cool stars. This need is all the more justified as stellar contamination can affect the search for atmospheres around the outer, cooler TRAPPIST-1 planets for which transmission spectroscopy is currently the most efficient technique.Comment: 26 pages, 11 figures, accepted for publication in The Astrophysical Journal Letter

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Network analysis of the human structural connectome including the brainstem

The underlying anatomical structure is fundamental to the study of brain networks, but the role of brainstem from a structural perspective is not very well understood. We conduct a computational and graph-theoretical study of the human structural connectome incorporating a variety of subcortical structures including the brainstem. Our computational scheme involves the use of Python DIPY and Nibabel libraries to develop structural connectomes using 100 healthy adult subjects. We then compute degree, eigenvector, and betweenness centralities to identify several highly connected structures and find that the brainstem ranks highest across all examined metrics, a result that holds even when the connectivity matrix is normalized by volume. We also investigated some global topological features in the connectomes, such as the balance of integration and segregation, and found that the domination of the brainstem generally causes networks to become less integrated and segregated. Our results highlight the importance of including the brainstem in structural network analyses

Screening for fecal presence of colistin-resistant Escherichia coli and mcr-1 and mcr-2 genes in camel-calves in southern Tunisia

Abstract Camels (Camelus dromedarius) are known to harbor multidrug resistant Gram-negative bacteria and to be involved in the transmission of various microorganisms to humans. Data on the occurrence of colistin resistant Escherichia coli as well as mobilized colistin resistance (mcr) genes in camels are lacking. We investigated the presence of colistin resistance and mcr (1–2) genes in E. coli from the feces of camels in Tunisia. Presumptive E. coli isolates from camel-calves in southern Tunisia were qualitatively screened for growth on Mueller–Hinton agar supplemented with 2 mg/L of colistin. The minimal inhibitory concentration of colistin was determined for isolates growing on this medium. All isolates were screened for the presence of the mcr-1 and mcr-2 genes by polymerase chain reaction without detecting any of these genes. However, one isolate was confirmed resistant to colistin and further testing of this isolate revealed it to be Enterobacter cloacae. Our study demonstrated absence of colistin resistance and of the mcr-1 and mcr-2 genes in E. coli isolated from camel feces in southern Tunisia. Thus, there is no evidence that camels represent a major source of mcr genes contamination for the local population or for tourists visiting southern Tunisia

Comparative Investigation of Chemical Constituents of Kernels, Leaves, Husk, and Bark of Juglans regia L., Using HPLC-DAD-ESI-MS/MS Analysis and Evaluation of Their Antioxidant, Antidiabetic, and Anti-Inflammatory Activities

Leaves, husk, kernels, and bark methanolic extracts of Juglans regia L. were tested for their in vitro antidiabetic, anti-inflammatory, and antioxidant activities. For these purposes, α-amylase and α-glucosidase were used as the main enzymes to evaluate antidiabetic activities. Moreover, lipoxidase and tyrosinase activities were tested to estimate anti-inflammatory properties. Antioxidant properties of Juglans regia L., extracts were determined using three different assays. Leaves extract has an important radical scavenging activity and a-amylase inhibition. Similarly, husk extracts showed high total phenolic content (306.36 ± 4.74 mg gallic acid equivalent/g dry extract) with an important α-amylase inhibition (IC50 = 75.42 ± 0.99 µg/mL). Kernels exhibit significant tyrosinase (IC50 = 51.38 ± 0.81 µg/mL) correlated with antioxidant activities (p < 0.05). Husk and bark extracts also showed strong anti-lipoxidase activities with IC50 equal to 29.48 ± 0.28 and 28.58 ± 0.35 µg/mL, respectively. HPLC-DAD-ESI-MS/MS analysis highlights the phenolic profile of methanolic extracts of Juglans regia L. plant parts. The identified polyphenols were known for their antioxidant, antidiabetic (dicaffeoyl-quinic acid glycoside in kernels), and anti-inflammatory (3,4-dihydroxybenzoic acid in leaves) activities. Further investigations are needed to determine molecular mechanisms involved in these effects as well as to study the properties of the main identified compounds

Atmospheric Reconnaissance of TRAPPIST-1 b with JWST/NIRISS: Evidence for Strong Stellar Contamination in the Transmission Spectra

TRAPPIST-1 is a nearby system of seven Earth-sized, temperate, rocky exoplanets transiting a Jupiter-sized M8.5V star, ideally suited for in-depth atmospheric studies. Each TRAPPIST-1 planet has been observed in transmission both from space and from the ground, confidently rejecting cloud-free, hydrogen-rich atmospheres. Secondary eclipse observations of TRAPPIST-1 b with JWST/MIRI are consistent with little to no atmosphere given the lack of heat redistribution. Here we present the first transmission spectra of TRAPPIST-1 b obtained with JWST/NIRISS over two visits. The two transmission spectra show moderate to strong evidence of contamination from unocculted stellar heterogeneities, which dominates the signal in both visits. The transmission spectrum of the first visit is consistent with unocculted starspots and the second visit exhibits signatures of unocculted faculae. Fitting the stellar contamination and planetary atmosphere either sequentially or simultaneously, we confirm the absence of cloud-free, hydrogen-rich atmospheres, but cannot assess the presence of secondary atmospheres. We find that the uncertainties associated with the lack of stellar model fidelity are one order of magnitude above the observation precision of 89 ppm (combining the two visits). Without affecting the conclusion regarding the atmosphere of TRAPPIST-1 b, this highlights an important caveat for future explorations, which calls for additional observations to characterize stellar heterogeneities empirically and/or theoretical works to improve model fidelity for such cool stars. This need is all the more justified as stellar contamination can affect the search for atmospheres around the outer, cooler TRAPPIST-1 planets for which transmission spectroscopy is currently the most efficient technique

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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