Neurophysiology of vestibular rehabilitation

The vestibular system is a sophisticated human control system. Accurate processing of sensory input about rapid head and postural motion is critical. Not surprisingly, the body uses multiple, partially redundant sensory inputs and motor outputs, combined with a very competent central repair capability. The system as a whole can adapt to substantial peripheral vestibular dysfunction. The Achilles' heel of the vestibular system is a relative inability to repair central vestibular dysfunction

A mathematical model for top-shelf vertigo: the role of sedimenting otoconia in BPPV

Benign Paroxysmal Positional Vertigo (BPPV) is a mechanical disorder of the vestibular system in which calcite particles called otoconia interfere with the mechanical functioning of the fluid-filled semicircular canals normally used to sense rotation. Using hydrodynamic models, we examine the two mechanisms proposed by the medical community for BPPV: cupulolithiasis, in which otoconia attach directly to the cupula (a sensory membrane), and canalithiasis, in which otoconia settle through the canals and exert a fluid pressure across the cupula. We utilize known hydrodynamic calculations and make reasonable geometric and physical approximations to derive an expression for the transcupular pressure $\Delta P_c$ exerted by a settling solid particle in canalithiasis. By tracking settling otoconia in a two-dimensional model geometry, the cupular volume displacement and associated eye response (nystagmus) can be calculated quantitatively. Several important features emerge: 1) A pressure amplification occurs as otoconia enter a narrowing duct; 2) An average-sized otoconium requires approximately five seconds to settle through the wide ampulla, where $\Delta P_c$ is not amplified, which suggests a mechanism for the observed latency of BPPV; and 3) An average-sized otoconium beginning below the center of the cupula can cause a volumetric cupular displacement on the order of 30 pL, with nystagmus of order $2^\circ$/s, which is approximately the threshold for sensation. Larger cupular volume displacement and nystagmus could result from larger and/or multiple otoconia.Comment: 15 pages, 5 Figures updated, to be published in J. Biomechanic

Robust estimates of soil moisture and latent heat flux coupling strength obtained from triple collocation

Land surface models (LSMs) are often applied to predict the one-way coupling strength between surface soil moisture (SM) and latent heat (LH) flux. However, the ability of LSMs to accurately represent such coupling has not been adequately established. Likewise, the estimation of SM/LH coupling strength using ground-based observational data is potentially compromised by the impact of independent SM and LH measurements errors. Here we apply a new statistical technique to acquire estimates of one-way SM/LH coupling strength which are nonbiased in the presence of random error using a triple collocation approach based on leveraging the simultaneous availability of independent SM and LH estimates acquired from (1) LSMs, (2) satellite remote sensing, and (3) ground-based observations. Results suggest that LSMs do not generally overestimate the strength of one-way surface SM/LH coupling

ECOSTRESS: NASA's next generation mission to measure evapotranspiration from the International Space Station

The ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station ECOSTRESS) was launched to the International Space Station on June 29, 2018. The primary science focus of ECOSTRESS is centered on evapotranspiration (ET), which is produced as level‐3 (L3) latent heat flux (LE) data products. These data are generated from the level‐2 land surface temperature and emissivity product (L2_LSTE), in conjunction with ancillary surface and atmospheric data. Here, we provide the first validation (Stage 1, preliminary) of the global ECOSTRESS clear‐sky ET product (L3_ET_PT‐JPL, version 6.0) against LE measurements at 82 eddy covariance sites around the world. Overall, the ECOSTRESS ET product performs well against the site measurements (clear‐sky instantaneous/time of overpass: r2 = 0.88; overall bias = 8%; normalized RMSE = 6%). ET uncertainty was generally consistent across climate zones, biome types, and times of day (ECOSTRESS samples the diurnal cycle), though temperate sites are over‐represented. The 70 m high spatial resolution of ECOSTRESS improved correlations by 85%, and RMSE by 62%, relative to 1 km pixels. This paper serves as a reference for the ECOSTRESS L3 ET accuracy and Stage 1 validation status for subsequent science that follows using these data

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario

Bilateral Vestibular Weakness

Bilateral vestibular weakness (BVW) is a rare cause of imbalance. Patients with BVW complain of oscillopsia. In approximately half of the patients with BVW, the cause remains undetermined; in the remainder, the most common etiology by far is gentamicin ototoxicity, followed by much rarer entities such as autoimmune inner ear disease, meningitis, bilateral Ménière’s disease, bilateral vestibular neuritis, and bilateral vestibular schwannomas. While a number of bedside tests may raise the suspicion of BVW, the diagnosis should be confirmed by rotatory chair testing. Treatment of BVW is largely supportive. Medications with the unintended effect of vestibular suppression should be avoided

The Gain-Time Constant Product Quantifies Total Vestibular Output in Bilateral Vestibular Loss

Patients with inner ear damage associated with bilateral vestibular impairment often ask “how much damage do I have.” Although there are presently three clinical methods of measuring semicircular canal vestibular function; electronystagmography (ENG or VENG), rotatory chair and video head-impulse (VHIT) testing; none of these methods provides a method of measuring total vestibular output. Theory suggests that the slow cumulative eye position can be derived from the rotatory chair test by multiplying the high frequency gain by the time constant, or the “GainTc product.” In this retrospective study, we compared the GainTc in three groups, 30 normal subjects, 25 patients with surgically induced unilateral vestibular loss, and 24 patients with absent or nearly absent vestibular responses due to gentamicin exposure. We found that the GainTc product correlated better with remaining vestibular function than either the gain or the time constant alone. The fraction of remaining vestibular function was predicted by the equation R = (GainTc/11.3) – 0.6. We suggest that the GainTc product answers the question “how much damage do I have,” and is a better measure than other clinical tests of vestibular function

The Gain-Time Constant Product Quantifies Total Vestibular Output in Bilateral Vestibular Loss

Patients with inner ear damage associated with bilateral vestibular impairment often ask “how much damage do I have.” Although there are presently three clinical methods of measuring semicircular canal vestibular function; electronystagmography (ENG or VENG), rotatory chair and video head-impulse (VHIT) testing; none of these methods provides a method of measuring total vestibular output. Theory suggests that the slow cumulative eye position can be derived from the rotatory chair test by multiplying the high frequency gain by the time constant, or the “GainTc product.” In this retrospective study, we compared the GainTc in three groups, 30 normal subjects, 25 patients with surgically induced unilateral vestibular loss, and 24 patients with absent or nearly absent vestibular responses due to gentamicin exposure. We found that the GainTc product correlated better with remaining vestibular function than either the gain or the time constant alone. The fraction of remaining vestibular function was predicted by the equation R = (GainTc/11.3) – 0.6. We suggest that the GainTc product answers the question “how much damage do I have,” and is a better measure than other clinical tests of vestibular function