The effect of physical fatigue on oscillatory dynamics of the sensorimotor cortex

AIM: While physical fatigue is known to arise in part from supraspinal mechanisms within the brain exactly how brain activity is modulated during fatigue is not well understood. Therefore, this study examined how typical neural oscillatory responses to voluntary muscle contractions were affected by fatigue. METHODS: Eleven healthy adults (age 27±4 years) completed two experimental sessions in a randomised crossover design. Both sessions first assessed baseline maximal voluntary isometric wrist-flexion force (MVFb ). Participants then performed an identical series of fourteen test contractions (2 × 100%MVFb , 10 × 40%MVFb , 2 × 100%MVFb ) both before and after one of two interventions: forty 12-s contractions at 55%MVFb (fatigue intervention) or 5%MVFb (control intervention). Magnetoencephalography (MEG) was used to characterise both the movement-related mu and beta decrease (MRMD and MRBD) and the post-movement beta rebound (PMBR) within the contralateral sensorimotor cortex during the 40%MVFb test contractions, while the 100%MVFb test contractions were used to monitor physical fatigue. RESULTS: The fatigue intervention induced a substantial physical fatigue that endured throughout the post-intervention measurements (28.9-29.5% decrease in MVF, P<0.001). Fatigue had a significant effect on both PMBR (ANOVA, session × time-point interaction: P=0.018) and MRBD (P=0.021): the magnitude of PMBR increased following the fatigue but not the control interventions, whereas MRBD was decreased post-control but not post-fatigue. Mu oscillations were unchanged throughout both sessions. CONCLUSION: Physical fatigue resulted in an increased PMBR, and offset attenuations in MRBD associated with task habituation. This article is protected by copyright. All rights reserved

Improved Performance of Near infrared Excitation Raman Spectroscopy Using Reflective Thin-film Gold on Glass Substrates for Cytology Samples

Confocal near-infrared Raman spectroscopy has been shown to have applications in the area of clinical biology. A source wavelength in the near infrared is preferred over visible wavelengths for inspecting biological samples due to superior wave number resolution and reduced photo damage. However, these excitation sources have a number of drawbacks when compared to lasers in the visible wavelength region, including the requirement to use expensive highly pure crystal substrates such as Raman grade calcium fluoride as well as long acquisition times due to the lower Raman scattering efficiency. This paper investigates the use of a reflective substrate comprising a low cost 100 nm thin-film gold on glass substrate, as an alternative. Similar to recent work that used stainless steel substrates, it is demonstrated that the thin-film gold coated substrates, which are relatively inexpensive, produce cell spectra with 1.65 times the signal to noise ratio when compared with spectra obtained from calcium fluoride under identical conditions, with no apparent background signal in the fingerprint region. Two prostate cell lines are examined having been deposited on glass, calcium fluoride, and thin-film gold on glass substrates using the Thin Prep standard. Background spectra from, and cell adhesion on, these three substrates are compared. A comparison of the intensities and signal to noise ratios of the resulting spectra, and their viability for classification using principle components analysis is performed, which further demonstrates the benefit of reflective substrates

Caval-Aortic Access to Allow Transcatheter Aortic Valve Replacement in Otherwise Ineligible Patients Initial Human Experience

ObjectivesThis study describes the first use of caval-aortic access and closure to enable transcatheter aortic valve replacement (TAVR) in patients who lacked other access options. Caval-aortic access refers to percutaneous entry into the abdominal aorta from the femoral vein through the adjoining inferior vena cava.BackgroundTAVR is attractive in high-risk or inoperable patients with severe aortic stenosis. Available transcatheter valves require large introducer sheaths, which are a risk for major vascular complications or preclude TAVR altogether. Caval-aortic access has been successful in animals.MethodsWe performed a single-center retrospective review of procedural and 30-day outcomes of prohibitive-risk patients who underwent TAVR via caval-aortic access.ResultsBetween July 2013 and January 2014, 19 patients underwent TAVR via caval-aortic access; 79% were women. Caval-aortic access and tract closure were successful in all 19 patients; TAVR was successful in 17 patients. Six patients experienced modified VARC-2 major vascular complications, 2 (11%) of whom required intervention. Most (79%) required blood transfusion. There were no deaths attributable to caval-aortic access. Throughout the 111 (range 39 to 229) days of follow up, there were no post-discharge complications related to tract creation or closure. All patients had persistent aorto-caval flow immediately post-procedure. Of the 16 patients who underwent repeat imaging after the first week, 15 (94%) had complete closure of the residual aorto-caval tract.ConclusionsPercutaneous transcaval venous access to the aorta allows TAVR in otherwise ineligible patients, and may offer a new access strategy for other applications requiring large transcatheter implants

The effect of physical fatigue on oscillatory dynamics of the sensorimotor cortex

Aim: While physical fatigue is known to arise in part from supraspinal mechanisms within the brain exactly how brain activity is modulated during fatigue is not well understood. Therefore, this study examined how typical neural oscillatory responses to voluntary muscle contractions were affected by fatigue. Methods: Eleven healthy adults (age 27±4 years) completed two experimental sessions in a randomised crossover design. Both sessions first assessed baseline maximal voluntary isometric wrist-flexion force (MVFb). Participants then performed an identical series of fourteen test contractions (2 × 100%MVFb, 10 × 40%MVFb, 2 × 100%MVFb) both before and after one of two interventions: forty 12-s contractions at 55%MVFb (fatigue intervention) or 5%MVFb (control intervention). Magnetoencephalography (MEG) was used to characterise both the movement-related mu and beta decrease (MRMD and MRBD) and the post-movement beta rebound (PMBR) within the contralateral sensorimotor cortex during the 40%MVFb test contractions, while the 100%MVFb test contractions were used to monitor physical fatigue. Results: The fatigue intervention induced a substantial physical fatigue that endured throughout the post-intervention measurements (28.9-29.5% decrease in MVF, P<0.001). Fatigue had a significant effect on both PMBR (ANOVA, session × time-point interaction: P=0.018) and MRBD (P=0.021): the magnitude of PMBR increased following the fatigue but not the control interventions, whereas MRBD was decreased post-control but not post-fatigue. Mu oscillations were unchanged throughout both sessions. Conclusion: Physical fatigue resulted in an increased PMBR, and offset attenuations in MRBD associated with task habituation

Improved performance of near infrared excitation Raman spectroscopy using reflective thin-film gold on glass substrates for cytology samples

Confocal near-infrared Raman spectroscopy has been shown to have applications in the area of clinical biology. A source wavelength in the near infrared is preferred over visible wavelengths for inspecting biological samples due to superior wavenumber resolution and reduced photodamage. However, these excitation sources have a number of drawbacks when compared to lasers in the visible wavelength region, including the requirement to use expensive highly pure crystal substrates such as Raman grade calcium fluoride as well as long acquisition times due to the lower Raman scattering efficiency. This paper investigates the use of a reflective substrate comprising a low cost 100 nm thin-film gold on glass substrate, as an alternative. Similar to recent work that used stainless steel substrates, it is demonstrated that the thin-film gold coated substrates, which are relatively inexpensive, produce cell spectra with 1.65 times the signal to noise ratio when compared with spectra obtained from calcium fluoride under identical conditions, with no apparent background signal in the fingerprint region. Two prostate cell lines are examined having been deposited on glass, calcium fluoride, and thin-film gold on glass substrates using the ThinPrep standard. Background spectra from, and cell adhesion on, these three substrates are compared. A comparison of the intensities and signal to noise ratios of the resulting spectra, and their viability for classification using principle components analysis is performed, which further demonstrates the benefit of reflective substrates

Quality control for multiple breath washout tests in multicentre bronchiectasis studies:Experiences from the BRONCH-UK clinimetrics study

Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or “over-reading” is resource intensive and the impact is unclear. Objectives: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. Methods: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. Results: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. Conclusion: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW

Modulation of post-movement beta rebound by contraction force and rate of force development

Movement induced modulation of the beta rhythm is one of the most robust neural oscillatory phenomena in the brain. In the preparation and execution phases of movement, a loss in beta amplitude is observed (movement related beta decrease (MRBD)). This is followed by a rebound above baseline on movement cessation (post movement beta rebound (PMBR)). These effects have been measured widely, and recentwork suggests that they may have significant importance. Specifically, they have potential to form the basis of biomarkers for disease, and have been used in neuroscience applications ranging from brain computer interfaces to markers of neural plasticity. However, despite the robust nature of both MRBD and PMBR, the phenomena themselves are poorly understood. In this study, we characterise MRBD and PMBR during a carefully controlled isometric wrist flexion paradigm, isolating two fundamental movement parameters;force output, and the rate of force development (RFD). Our results show that neither altered force output nor RFD has a significant effect on MRBD. In contrast, PMBR was altered by both parameters. Higher force output results in greater PMBR amplitude, and greater RFD results in a PMBR which is higher in amplitude and shorter in duration. These findings demonstrate that careful control of movement parameters cansystematically change PMBR. Further, for temporally protracted movements, the PMBR can be over 7 s in duration. This means accurate control of movement and judicious selection of paradigm parameters are critical in future clinical and basic neuroscientific studies of sensorimotor beta oscillations

UK national observational cohort study investigating Tolerance of Anti-cancer Systemic Therapy in the Elderly:the TOASTIE study

Objective: The Cancer Aging Research Group (CARG) score was developed to predict severe chemotherapy-induced toxicity risk in older adults; validation studies results have varied. The TOASTIE study sought to evaluate the CARG score prospectively in a chemotherapy-naïve United Kingdom (UK) population.Methods and Analysis: This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line chemotherapy for any solid organ malignancy or setting. Baseline demographics and established frailty measures were recorded. Follow-up data including toxicity and hospital admissions were collected retrospectively. Baseline CARG score predictive ability was assessed.Results: 339 patients were recruited from 19 centres; median age 73 years (range 65-92), 51.9% male and 54.9% gastrointestinal primary. At baseline, 85% of patients were ECOG PS 0-1, with median Rockwood Clinical Frailty Scale (CFS) 3 (range 0-8). 314 (92.6%) patients had follow-up data; 69 (22.3%) patients experienced CTCAE grade ≥3 toxicity and 84 (27%) required hospital admission during treatment.Increasing CARG risk groups had increased grade 3 toxicity (low 19.6%, medium 22.2%, high 28.2%) however, this was non-significant with no evidence of robust predictive performance. Predictive performance of CFS and ECOG PS was superior to CARG. Importantly, patient and clinician perceptions of toxicity risk differed significantly.Conclusions: In older UK patients with cancer commencing chemotherapy, baseline frailty was prevalent. CARG score did not robustly discriminate or predict high-grade toxicity risk. ECOG and CFS showed superior, albeit limited, ability to predict and discriminate. This study highlights the need for the development of tools that better predict toxicity in this population

Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge

BACKGROUND: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile. METHODS: We compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [18F]DPA-714 PET/MRI scans to assess TSPO signal, indicative of microglial activation, before and after receiving the seasonal influenza vaccination, which was used as an immune stimulant. Participants also underwent [18F]florbetapir and [18F]AV1451 PET scans to assess amyloid and tau burden, respectively. Regional tau and TSPO signal were calculated for regions of interest linked to Braak stage. An additional comparison imaging healthy control group (n = 8; median age = 45.5) had a single [18F]DPA-714 PET/MRI. An expanded group of participants underwent neuropsychological testing, to determine if TREM2 status influenced clinical phenotype. RESULTS: Compared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores. CONCLUSIONS: TREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer's disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer's disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer's disease should aim to enhance protective microglial actions