UNASSIGNED: Vertigo, dizziness, gaze instability and disequilibrium are highly prevalent in people with MS (PwMS) and head movement induced dizziness is commonly reported. Vestibular physical therapy (VPT) is a specialised, non-invasive and effective therapy for these problems but usually involves travel for the person to a specialist center with both personal and carbon costs. The use of wearable sensors to track head movement and smartphone applications to deliver and track programs has potential to improve VPT in MS.
UNASSIGNED: This study investigated the usability and effects of a commercially available digital VPT system (wearable head sensor, smartphone app and clinician software) to deliver VPT to PwMS. A pre/post treatment design was employed and the primary outcome was the System Usability Scale (SUS). Other patient reported outcomes were the Service User Acceptability Questionnaire (SUTAQ), the Patient Enablement Instrument (PEI) and the Dizziness Handicap Inventory (DHI). Physical outcomes measurements included Mini-BESTest (MB), Modified Dynamic Gait Index (mDGI), Gait Speed (GS), Dynamic Visual Acuity (DVA) and head kinematics and symptoms during exercise.
UNASSIGNED: Sixteen PwMS (14 female), mean age 44(±14) years were recruited to the study and twelve completed VPT. Mean adherence to exercise, measured digitally was 60% (±18.4). SUS scores were high at 81 (±14) and SUTAQ scores also demonstrated high levels of satisfaction and acceptability of the system. Statistically significant improvements in MB (mean change 2.25; p = 0.004), mDGI (median change 1.00; p = 0.008), DVA (median change -1.00; p = 0.004) were found. Head frequencies significantly improved with concurrent decreased intensity of dizziness during head movements (mean change across 4 gaze stabilization exercises was 23 beats per minute; p < 0.05). Non-significant improvements were seen in DHI (p = 0.07) and GS (p = 0.15). 64.5% of follow up visits were conducted remotely (video or phone), facilitated by the system.
UNASSIGNED: This study had two main outcomes and benefits for PwMS. Firstly, we showed that the system used was both acceptable and could be used by PwMS. Secondly, we demonstrated an improvement in a range of dizziness, balance and gait metrics with remotely delivered care. This system has the potential to positively impact on MS physiotherapy service provision with the potential to deliver effective remote care.

Dizziness is one of the most common chief complaints in both the ambulatory care setting and the emergency department. These symptoms may be representative of a broad range of entities. Therefore, any attempt at treatment must first start with determining the etiology. In this current perspective, we focus specifically on the diagnosis of and treatment of vestibular migraine, which is common and overlaps clinically with a variety of other diagnoses. We discuss the traditional treatments for vestibular migraine in addition to the recent explosion of novel migraine therapeutics. Because vestibular migraine can mimic, or co-exist with, a variety of other vestibular diseases, we discuss several of these disorders including persistent postural-perceptual dizziness, benign paroxysmal positional vertigo, post-concussive syndrome, Ménière\'s disease, and cerebrovascular etiologies. We discuss the diagnosis of each, as well as overlapping and distinguishing clinical features of which the reader should be aware. Finally, we conclude with evidence based as well as expert commentary on management, with a particular emphasis on vestibular migraine.

Diagnostic evaluation of a patient with dizziness or vertigo is complicated by a lack of standardized nomenclature, significant overlap in symptom descriptions, and the subjective nature of the patient\'s symptoms. Although dizziness is an imprecise term often used by patients to describe a feeling of being off-balance, in many cases dizziness can be subcategorized based on symptomatology as vertigo (false sense of motion or spinning), disequilibrium (imbalance with gait instability), presyncope (nearly fainting or blacking out), or lightheadedness (nonspecific). As such, current diagnostic paradigms focus on timing, triggers, and associated symptoms rather than subjective descriptions of dizziness type. Regardless, these factors complicate the selection of appropriate diagnostic imaging in patients presenting with dizziness or vertigo. This document serves to aid providers in this selection by using a framework of definable clinical variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

UNASSIGNED: An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES).
UNASSIGNED: Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms.
UNASSIGNED: Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively.
UNASSIGNED: A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms.

The forsterite zone of the Ubehebe Peak contact aureole, Death Valley, USA consists of an outer zone of tabular/jack-straw olivine and an inner zone of subequant polyhedral olivine. Subequant polyhedral forsterite crystals close to the intrusion are small and tabular forsterite crystals farther away are larger. To investigate the formation of the two morphologies, forsterite growth experiments were conducted in cold seal pressure vessels in the CaO-MgO-SiO2-CO2-H2O system. Forsterite precipitation follows a disequilibrium reaction pathway made of three reactions: [1] tabular forsterite growth from quartz and dolomite, [2] forsterite growth from tremolite dissolution, and [3] subequant polyhedral forsterite growth from tabular forsterite dissolution. Initially, quartz reacts with dolomite to simultaneously form twinned tabular forsterite and tremolite. As quartz reacts away, forsterite precipitation continues at a slower rate through tremolite dissolution. A second generation of forsterite then precipitates on top of some tabular forsterite but has different habit and tracht. Once all the tremolite reacts away, subequant polyhedral forsterite precipitation continues at an even slower rate through dissolution of tabular forsterite. The tabular morphology of jack-straw olivine is a consequence of twin-mediated unidirectional growth; the abundance of twins being due to rapid nucleation and growth at initially high reaction affinities. Twin junctions are preferential nucleation centers for steps, so faceted growth is enhanced on {100}. This phenomenon is the twin plane re-entrant effect. Subequant polyhedral forsterite in the Ubehebe Peak inner contact aureole recrystallized and ripened from tabular forsterite. In the outer contact aureole, conditions were not conducive to recrystallization and ripening so well-developed tabular forsterite persists.

Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a genetically and clinically heterogeneous disorder with four described subtypes. Autosomal recessive syndrome of cerebellar ataxia, mental retardation, and disequilibrium type 4 (CAMRQ4) is caused by mutations in the ATP8A2 gene. We report an 8-year-old boy with choreoathetosis, hypotonia, without the ability to keep his head up and profound mental retardation. There was quadrupedal locomotion, as well. MRI of the brain revealed a hypotrophy of the corpus callosum, diffuse white matter reduction, widespread delayed myelination and ventriculomegaly. Trio whole-exome sequencing revealed compound heterozygosity in the ATP8A2 gene consisting of a known variant c.1756C>T (p.Arg586*) inherited from the mother and a novel variant c.691_701delCTGATGAAGTT (p.Leu231fs) inherited from the father. CAMRQ type 4 has been found in about 50 patients. To the best of our knowledge, this is the first reported patient with CAMRQ4 with these gene variants. The clinical presentation is severe.

UNASSIGNED: Central nervous system dysfunction has been postulated to cause debilitating symptoms in patients with myalgic encephalomyelitis (ME) (originally called \"chronic fatigue syndrome\"). Repetitive transcranial magnetic stimulation (rTMS) is a newly developed neuromodulatory procedure and has been suggested to facilitate the cortical neural activity.
UNASSIGNED: This study enrolled 30 patients with ME (7 men and 23 women) with a mean age of 39 ± 12 years, who received rTMS treatment of both the left dorsolateral prefrontal cortex and the left primary motor area in the brain. The performance status score (0-9) for restricting activities of daily living, orthostatic intolerance (OI) during a 10-min standing test, neurologic disequilibrium diagnosed as unstable standing with their feet together and eyes closed, neuropathic pain or fibromyalgia, and muscle weakness were compared before and after treatment.
UNASSIGNED: After therapy, favorable effects were observed with a decrease in performance status score or index for restriction of activities of daily living of ≥ 2 points in 20 patients (67%). OI with the inability to complete the 10-min standing test was resolved in 10 (83%) out of 12 patients, and disequilibrium was resolved in 15 (88%) out of 17 patients. Neuropathic pain or fibromyalgia was attenuated in seven (70%) out of 10 patients. Muscle weakness with grip power of < 10 kg was resolved in two (50%) out of four patients. No untoward effects were encountered in all the study patients.
UNASSIGNED: The treatment with rTMS is effective in alleviating various symptoms, especially OI and disequilibrium, and in improving the activities of daily living in patients with ME.

Perilymph Fistula (PLF), abnormal communication between the fluid-filled space of the inner ear and the air-filled space of the middle ear, is a significant cause of vestibular and auditory symptoms. This is a retrospective study of 22 cases treated with PLF repair surgery, selected based on our surgical indication. We analyzed the characteristics of these 22 cases and evaluated the efficacy of PLF repair surgery in treating vestibular and auditory symptoms. Cases with antecedent events had significantly shorter intervals before surgery. The postoperative recovery from vestibular symptoms following PLF repair surgery was strikingly rapid, with 82% of cases demonstrating marked improvement within a week, even in chronic cases. Despite the notable absence of a control group in the study, the marked improvements in vestibular symptoms and substantial reductions in Dizziness Handicap Inventory (DHI) scores suggest that the observed benefits are attributable to the surgical intervention. Further, timely surgery showed improvements in hearing, with some benefits also seen in late-stage surgeries. Using the perilymph-specific protein Cochlin-tomoprotein (CTP) as a diagnostic biomarker, we could prove that PLF could be responsible for disequilibrium and related auditory disturbances in these patients. A new hypothesis is proposed that the chronic disequilibrium experienced by many PLF patients is due to enhanced mobility of the utricle and not to endolymphatic hydrops. Further research is needed to fully elucidate PLF\'s symptoms and treatment efficacy using the surgical indication we developed.

Potential biosignatures that offer the promise of extraterrestrial life (past or present) are to be expected in the coming years and decades, whether from within our own solar system, from an exoplanet atmosphere, or otherwise. With each such potential biosignature, the degree of our uncertainty will be the first question asked. Have we really identified extraterrestrial life? How sure are we? This paper considers the problem of unconceived alternative explanations. We stress that articulating our uncertainty requires an assessment of the extent to which we have explored the relevant possibility space. It is argued that, for most conceivable potential biosignatures, we currently have not explored the relevant possibility space very thoroughly at all. Not only does this severely limit the circumstances in which we could reasonably be confident in our detection of extraterrestrial life, it also poses a significant challenge to any attempt to quantify our degree of uncertainty. The discussion leads us to the following recommendation: when it comes specifically to an extraterrestrial life-detection claim, the astrobiology community should follow the uncertainty assessment approach adopted by the Intergovernmental Panel on Climate Change (IPCC).

BACKGROUND: In plant water relations research, predawn leaf water potential (Ψpd) is often used as a proxy for soil water potential (Ψsoil), without testing the underlying assumptions that nighttime transpiration is negligible and that enough time has passed for a hydrostatic equilibrium to be established. The goal of this research was to test the assumption Ψpd = Ψsoil for field-grown grapevines.
RESULTS: A field trial was conducted with 30 different cultivars of wine grapes grown in a single vineyard in arid southeastern Washington, USA, for two years. The Ψpd and the volumetric soil water content (θv) under each sampled plant were measured multiple times during several dry-down cycles. The results show that in wet soil (Ψsoil >  - 0.14 MPa or relative extractable water content, θe > 0.36), Ψpd was significantly lower than Ψsoil for all 30 cultivars. Under dry soil conditions (Ψsoil <  - 0.14 MPa or θe < 0.36) Ψpd lined up better with Ψsoil. There were differences between cultivars, but these were not consistent over the years.
CONCLUSIONS: These results suggest that for wet soils Ψpd of grapevines cannot be used as a proxy for Ψsoil, while the Ψpd = Ψsoil assumption may hold for dry soils.