Crack roughness and avalanche precursors in the random fuse model

We analyze the scaling of the crack roughness and of avalanche precursors in the two dimensional random fuse model by numerical simulations, employing large system sizes and extensive sample averaging. We find that the crack roughness exhibits anomalous scaling, as recently observed in experiments. The roughness exponents ($\zeta$, $\zeta_{loc}$) and the global width distributions are found to be universal with respect to the lattice geometry. Failure is preceded by avalanche precursors whose distribution follows a power law up to a cutoff size. While the characteristic avalanche size scales as $s_0 \sim L^D$, with a universal fractal dimension $D$, the distribution exponent $\tau$ differs slightly for triangular and diamond lattices and, in both cases, it is larger than the mean-field (fiber bundle) value $\tau=5/2$

COVID-19: Considerations about immune suppression and biologicals at the time of SARS-CoV-2 pandemic

The extent of the profound immunological and nonimmunological responses linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being investigated worldwide due to the large burden associated with death due to SARS-CoV-2 and the short-term consequences of coronavirus disease 2019 (COVID-19). It has been hypothesized that patients on immunosuppressive treatments, including biologics, may have an augmented risk of being infected by SARS-CoV-2; however, there are currently no definitive data about biological drugs and COVID-19 in immune-mediated inflammatory diseases. Current epidemiological models developed to understand how long the COVID-19 epidemic may last are not conclusive and range from sustained epidemics to complete elimination. Nevertheless, even in the best-case scenario of apparent elimination, there is concordance about a possible contagion resurgence as late as 2024. Therefore, knowledge of the impact of SARS-CoV-2 on immune-mediated diseases and among patients treated with biologicals, together with the results of novel and promising COVID-19 treatment strategies targeting the virus and the host immune response (or both), will help us to best manage our patients during this pandemic over the next few years

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin

Case report: Personalized transcatheter approach to mid-aortic syndrome by in vitro simulation on a 3-dimensional printed model

An 8-year-old girl, diagnosed with mid-aortic syndrome (MAS) at the age of 2 months and under antihypertensive therapy, presented with severe systemic hypertension (>200/120 mmHg). Computed tomography (CT) examination revealed aortic aneurysm between severe stenoses at pre- and infra-renal segments, and occlusion of principal splanchnic arteries with peripheral collateral revascularization. Based on CT imaging, preoperative three-dimensional (3D) anatomy was reconstructed to assess aortic dimensions and a dedicated in vitro planning platform was designed to investigate the feasibility of a stenting procedure under fluoroscopic guidance. The in vitro system was designed to incorporate a translucent flexible 3D-printed patient-specific model filled with saline. A covered 8-zig 45-mm-long Cheatham-Platinum (CP) stent and a bare 8-zig, 34-mm-long CP stent were implanted with partial overlap to treat the stenoses (global peak-to-peak pressure gradient > 60 mmHg), excluding the aneurysm and avoiding risk of renal arteries occlusion. Percutaneous procedure was successfully performed with no residual pressure gradient and exactly replicating the strategy tested in vitro. Also, as investigated on the 3D-printed model, additional angioplasty was feasible across the frames of the stent to improve bilateral renal flow. Postoperative systemic pressure significantly reduced (130/70 mmHg) as well as dosage of antihypertensive therapy. This is the first report demonstrating the use of a 3D-printed model to effectively plan percutaneous intervention in a complex pediatric MAS case: taking full advantage of the combined use of a patient-specific 3D model and a dedicated in vitro platform, feasibility of the stenting procedure was successfully tested during pre-procedural assessment. Hence, use of patient-specific 3D-printed models and in vitro dedicated platforms is encouraged to assist pre-procedural planning and personalize treatment, thus enhancing intervention success

Unbalance in Myotonic Dystrophy-1 may follow cervical ataxia and respond to exercise

Patients with myotonic dystrophy-type 1 (DM-1) often fall, due to \u201cintrinsic\u201d mechanisms (eg legs \u201cgiving out\u201d) for unknown reasons (Wiles CM.JNNP 2006;77:393-396). A case is presented, in which neck position sense was impaired. DA was a woman, 57 yrs old, employed. DM-1 was diagnosed at age 35. She had fallen 12 times in 2 months. She felt unsteady (DHIsf inventory 7/13, normal=13/13). Strength was 4/5 at the lower limbs and on the neck extensors, 2 to 4/5 at the upper limbs, 0 to 2/5 on the neck flexors. Neck position sense was tested through a goniometric helmet. The head was placed at target angles of 20% or 70% of the full range of motion, in opposite directions of yaw, pitch or roll, and then replaced to neutral. Repositioning was asked for 6 times for each target, in a balanced design. Overall error (% of target) was +29+45 (normal 70); the capacity to lean around towards the limits of stability,LOS, was also low (Balance Master\uae LOS 57%, normal >85). Eleven 1-hr exercise sessions were held in 6 days, based on hands-on strenghtening of the neck and the shoulder girdle. The DHIsf score rose to 11/13. Head repositioning errors declined to +17+24. The SOT rose to 56 and the LOS rose to 85. During the following 3 months the patient reported no falls. Neck position sense is crucial to balance (Brandt T. JNNP 2001 ;71:8-22) and it relies upon muscle spindles. In DM-1 severe alterations of neck spindles have been demonstrated (Swash M. Clin Neuropathol 1983;2,2:75-783). The case suggests that this may lead to unbalance in DM-1, and that a short program of neck strengthening may be beneficial