Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology. As more causal and risk genes are identified, it has become apparent that affected individuals can carry multiple disease-associated variants. In light of this observation, we discuss the oligogenic architecture of ALS. To end, we highlight emerging key molecular processes and opportunities for therapy.

The meta-analysis does not show an advantage of staple fixation of mesh over fibrin glue fixation in laparoscopic total extraperitoneal inguinal hernia repair. Because fibrin glue mesh fixation with laparoscopic inguinal hernia repair achieves similar hernia recurrence rates compared with staple/tack fixation, but decreased incidence of chronic inguinal pain, it may be the preferred technique.

In this paper we present some results concerning the stability of flow in a circular pipe to small but finite axisymmetric disturbances. The flow is unstable if the amplitude of a disturbance exceeds a critical value, the equilibrium amplitude, which we have calculated for a wide range of wave-numbers and Reynolds numbers. For large values of the Reynolds number, R, and for a real value of the wave-number, α, we indicate that the energy density of a critical disturbance is of order c2i, where −ααci is the damping rate of the associated infinitesimal disturbance. The energy, per unit length of the pipe, of a critical disturbance which is concentrated near the axis of the pipe is of order R−2, and the wave-number α is of order R1/3 For a critical disturbance which is concentrated near the wall of the pipe the energy is of order $R^{-\frac{3}{2}}$ and α is of order R½. This suggests that non-linear instability is most likely to be caused by a ‘centre’ mode rather than by a ‘wall’ mode. The wall mode solution is also essentially the solution for the problem of plane Couette flow when αR is large. We compare it with the true solution.In an appendix Dr A. E. Gill indicates how some of the results of this paper may be inferred from a simple scale analysis.