Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient's circumstances. Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management. The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies. Innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.

Animal locomotion causes head rotations, which are detected by the semicircular canals of the inner ear. Morphologic features of the canals influence rotational sensitivity, and so it is hypothesized that locomotion and canal morphology are functionally related. Most prior research has compared subjective assessments of animal "agility" with a single determinant of rotational sensitivity: the mean canal radius of curvature (R). In fact, the paired variables of R and body mass are correlated with agility and have been used to infer locomotion in extinct species. To refine models of canal functional morphology and to improve locomotor inferences for extinct species, we compare 3D vector measurements of head rotation during locomotion with 3D vector measures of canal sensitivity. Contrary to the predictions of conventional models that are based upon R, we find that axes of rapid head rotation are not aligned with axes of either high or low sensitivity. Instead, animals with fast head rotations have similar sensitivities in all directions, which they achieve by orienting the three canals of each ear orthogonally (i.e., along planes at 90°angles to one another). The extent to which the canal configuration approaches orthogonality is correlated with rotational head speed independent of body mass and phylogeny, whereas R is not.angular velocity | vestibular T he inner ear contains three bony semicircular canals, each of which encloses an endolymph-filled duct. Head rotations during locomotion cause inertial endolymph movements that are communicated to the brain. Canal morphology affects endolymph flow and thus influences an animal's sensitivity to rotation; if an animal is more sensitive to rotations about some axes than others, and if different patterns of head rotation are produced by different locomotor behaviors, then canal morphology and locomotion could be functionally related. By this reasoning, differences in canal morphology in living and extinct animals have been attributed to interspecific differences in locomotion (1-10), but characterization of any functional relationship between canal morphology and locomotion has been limited by the use of simplified models of canal sensitivity and the absence of in vivo data about how the head actually moves (11).The relevant variables for comparing canal sensitivity with head movement are angular velocity vectors and vestibular sensitivity vectors, respectively. (Although the direct stimulus to the canal is angular acceleration, the canal response is proportional to angular velocity within a range of head movement frequencies. Angular velocity was used here for a variety of reasons, as described in SI Materials and Methods.) Angular velocity vectors characterize instantaneous head rotations about different axes and can be experimentally measured in moving animals. Vestibular sensitivity vectors characterize the extent to which an animal is more sensitive to rotations about some axes than other axes. Although vestibular sensitivity vectors cannot be measured directly, t...

SIH is an important cause of headaches caused by spinal cerebrospinal fluid (CSF) leaks, with an increasingly broad spectrum of clinical presentations and diagnostic findings. A simple conception of the condition as being defined by the presence of low CSF pressure is no longer sufficient or accurate. A number of etiologies for spinal CSF leaks have been identified, including the recent discovery of CSF-venous fistulas, and these various etiologies may require different diagnostic and therapeutic pathways in order to affect a cure. Familiarity with the spectrum of presentations and causes of SIH is critical to accurate and timely diagnosis and management. Challenges exist in both diagnosis and treatment, and require understanding of the underlying pathogenesis of the condition in order to appropriately select testing and treatment. Prospective studies are needed going forward in order to inform workup and guide treatment decisions.