Duchenne muscular dystrophy (DMD) is a degenerative genetic myopathy characterized by complete absence of dystrophin. Although the mdx mouse lacks dystrophin, its phenotype is milder compared to DMD patients. The incorporation of a null mutation in the Cmah gene led to a more DMD-like phenotype (i.e., more fibrosis). Although fibrosis is thought to be the major determinant of 'structural weakness', intracellular remodeling of myofibrillar geometry was shown to be a major cellular determinant thereof. To dissect the respective contribution to muscle weakness, we assessed biomechanics and extra- and intracellular architecture of whole muscle and single fibers from extensor digitorum longus (EDL) and diaphragm. Despite increased collagen contents in both muscles, passive stiffness in mdx Cmah-/- diaphragm was similar to wt mice (EDL muscles were twice as stiff). Isometric twitch and tetanic stresses were 50% reduced in mdx Cmah-/- diaphragm (15% in EDL). Myofibrillar architecture was severely compromised in mdx Cmah-/- single fibers of both muscle types, but more pronounced in diaphragm. Our results show that the mdx Cmah-/- genotype reproduces DMD-like fibrosis but is not associated with changes in passive visco-elastic muscle stiffness. Furthermore, detriments in active isometric force are compatible with the pronounced myofibrillar disarray of the dystrophic background.

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism.

Our current understanding of the Universe is established through the pristine measurements of structure in the cosmic microwave background (CMB) and the distribution and shapes of galaxies tracing the large scale structure (LSS) of the Universe. One key ingredient that underlies cosmological observables is that the field that sources the observed structure is assumed to be initially Gaussian with high precision. Nevertheless, a minimal deviation from Gaussianityis perhaps the most robust theoretical prediction of models that explain the observed Universe; itis necessarily present even in the simplest scenarios. In addition, most inflationary models produce far higher levels of non-Gaussianity. Since non-Gaussianity directly probes the dynamics in the early Universe, a detection would present a monumental discovery in cosmology, providing clues about physics at energy scales as high as the GUT scale.

Astrophysical observations currently provide the only robust, empirical measurements of dark matter. In the coming decade, astrophysical observations will guide other experimental efforts, while simultaneously probing unique regions of dark matter parameter space. This white paper summarizes astrophysical observations that can constrain the fundamental physics of dark matter in the era of LSST. We describe how astrophysical observations will inform our understanding of the fundamental properties of dark matter, such as particle mass, self-interaction strength, non-gravitational interactions with the Standard Model, and compact object abundances. Additionally, we highlight theoretical work and experimental/observational facilities that will complement LSST to strengthen our understanding of the fundamental characteristics of dark matter.

This online structured survey has demonstrated the global impact of the COVID-19 pandemic on vascular services. The majority of centres have documented marked reductions in operating and services provided to vascular patients. In the months during recovery from the resource restrictions imposed during the pandemic peaks, there will be a significant vascular disease burden awaiting surgeons. One of the most affected specialties.

Objective

To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak.

Methods

An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume.

Results

The impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence.

Conclusion

Centres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.