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Increasing evidence reveals the damaging impact of having one's chronic pain symptoms invalidated through disbelief, discrediting, and critical judgement. In other instances, a caregiver's over-attentiveness to the daily tasks of individuals with pain can be problematic, potentially undermining rehabilitation. The aim of this study was to develop an instrument to measure different aspects of invalidation perceived by people with chronic pain. Item generation was informed through literature review and a thematic analysis of narratives from 431 peer-reviewed articles. The crowdsourcing platform Prolific was used to distribute survey items to participants. In Study 1A, Principal Component Analysis was performed on data from 302 respondents, giving rise to 4 subscales, including: Invalidation by the Self, Invalidation by Immediate Others, Invalidation by Healthcare Professionals, and Invalidation by Over-attentive Others. Confirmatory Factor Analysis of data collected from another 308 individuals in Study 1B supported the 4-factor model of the Pain-Invalidation Scale (Pain-IS) and identified a best-fit model with 24 items. The Pain-IS was further validated in another 300 individuals in Study 2. The Pain-IS demonstrates sound psychometric properties and may serve as a valuable tool for use by clinicians in the detection of pain-invalidation issues, as a first step in patient pain management. PERSPECTIVE: Links between pain-invalidation and pain levels, as well as functional detriment, highlight the importance of having one's chronic pain experience heard, believed, and accepted. The Pain-Invalidation Scale is designed to identify domains where invalidation of the patient's pain should be addressed to promote emotional processing, treatment adherence, and improved outcomes.

It is commonly assumed that women blush more strongly than men, but sex differences in blushing have been identified in only a few studies and what underlies these differences has not been explored. Hence, the aim of this study was to investigate factors that might underlie sex differences in blushing. To monitor blushing, changes in pulse amplitude in the forehead skin were measured in 40 male and 40 female participants during stressful laboratory tasks (serial subtractions and singing). A male or female experimenter interacted with participants during these tasks in a critical or friendly manner. In addition to blushing, the effect of these manipulations on gaze aversion (a nonverbal cue of embarrassment) was explored. Blushing was greater in women than men and was greater in participants tested by a male than female experimenter. However, neither the sex-composition of experimenter-participant dyads nor the interpersonal style of the experimenter modified blushing intensity, despite effects on eye contact. These findings suggest that sex-linked influences on autonomic reactivity rather than embarrassment moderate blushing during social interactions. These sex-linked influences may be important during cognitive-behavioural treatments for social anxiety associated with fear of blushing.

Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue pretreatment in frozen samples. Here, we characterized the chemical composition of molecular subtypes of breast cancer with DESI-MSI. Regions of interest were identified, including invasive breast cancer (IBC), ductal carcinoma in situ (DCIS), and adjacent benign tissue (ABT), and metabolomic profiles at 200 μm elaborated using Biomap software and the Lasso method. Top ions identified in IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids, and sphingolipids. Highly saturated lipids, as well as antioxidant molecules [taurine (m/z 124.0068), uric acid (m/z 167.0210), ascorbic acid (m/z 175.0241), and glutathione (m/z 306.0765)], were able to distinguish IBC from ABT. Moreover, luminal B and triple-negative subtypes showed more complex lipid profiles compared with luminal A and HER2 subtypes. DCIS and IBC were distinguished on the basis of cell signaling and apoptosis-related ions [fatty acids (341.2100 and 382.3736 m/z) and glycerophospholipids (PE (P-16:0/22:6, m/z 746.5099, and PS (38:3), m/z 812.5440)]. In summary, DESI-MSI identified distinct lipid composition between DCIS and IBC and across molecular subtypes of breast cancer, with potential implications for breast cancer pathogenesis.Significance:These findings present the first in situ metabolomic findings of the four molecular subtypes of breast cancer, DCIS, and normal tissue, and add to the understanding of their pathogenesis.

Samples classifications, ions identified based on visual inspection and statistical analysis, different representative molecular images and mass spectra for each tumor type and tandem mass spectrometry data for metabolite identification.

BackgroundPolyphenols are naturally occurring organic compounds found in plants. Research suggests that their intake reduces the risk of cognitive decline and related dementias. Grapes and blueberries are polyphenol-rich foods that have attracted attention for their potential cognitive-enhancing effects.PurposeExamine the effects of supplementation with a standardized and patented polyphenol-rich grape and blueberry extract (Memophenol™) on cognitive function in older adults with mild cognitive impairment.Study designTwo-arm, 6 month, parallel-group, randomized, double-blind, placebo-controlled trial.MethodsOne hundred and forty-three volunteers aged 60 to 80 years with mild cognitive impairment were supplemented with either 150 mg of Memophenol™, twice daily or a placebo. Outcome measures included computer-based cognitive tasks, the Behavior Rating Inventory of Executive Function (BRIEF-A), the Cognitive Failures Questionnaire, and the CASP-19.ResultsCompared to the placebo, Memophenol™ supplementation was associated with greater improvements in the speed of information processing (p = 0.020), visuospatial learning (p = 0.012), and the BRIEF-A global score (p = 0.046). However, there were no other statistically significant between-group differences in the performance of other assessed cognitive tests or self-report questionnaires. Memophenol™ supplementation was well-tolerated with no reports of significant adverse reactions.ConclusionThe promising results from this trial suggest that 6-months of supplementation with Memophenol™ may improve aspects of cognitive function in adults with mild cognitive impairment. Further research will be important to expand on the current findings and identify the potential mechanisms of action associated with the intake of this polyphenol-rich extract.

The variational and diffusion quantum Monte Carlo methods are used to calculate the correlation energy of the paramagnetic three-dimensional homogeneous electron gas at intermediate to high density. Ground state energies in finite cells are determined using Slater-Jastrow-backflow trial wave functions, and finite-size errors are removed using twist-averaged boundary conditions and extrapolation of the energy per particle to the thermodynamic limit of infinite system size. Our correlation energies in the thermodynamic limit are more accurate than previous results. The present diffusion quantum Monte Carlo energies, together with our recently reported [Phys. Rev. B 105, 245135 (2022)] results at low density, are used to parameterize the correlation energy of the electron gas using a functional form that satisfies the exact asymptotic behavior at high density.

ObjectiveTo investigate the diagnostic and prognostic role of gastric fluid DNA (gfDNA) in gasric cancer (GC) patients and controls submitted to upper digestive endoscopy.DesignThe concentration of gfDNA was evaluated in 941 samples, including subjects with normal gastric mucosa (n = 10), peptic diseases (n = 596), pre-neoplastic conditions (n = 99), and cancer (n = 236). gfDNA levels were evaluated according to age, gender, BMI, gastric fluid’s pH, use of proton-pump inhibitors, GC tumor subtypes, histological grades, clinical stages, and disease progression/outcome.ResultsIn the non-cancer group, we observed that gfDNA levels are increased in women as compared to men (p=7.44e-4). Remarkably, gfDNA levels are increased in GC patients as compared to non-GC (normal + peptic diseases, p=5.67e-13) and in GC versus pre-neoplastic disease (p=1.53e-6). Similar differences were also seen when more advanced tumors (T3) were compared to early stages (T2 and below) (p=5.97-4). Moreover, our results suggest the prognostic value of gfDNA as GC-patients with higher gfDNA concentrations (-3), which parallels with better disease-free survival (p= 0.014).ConclusionThese findings highlight the significance of collecting and studying stomach fluids from gastric cancer patients and reveals the potential impact of this approach as well as its diagnostic and prognostic value for disease management.What is already known on this topic-The DNA contained in biofluids that are in direct contact with tumor lesions is a valuable source of information for cancer diagnosis treatment.-Gastric fluids are in direct contact with gastric cancer (GC) lesions and immune cell infiltrates and may be a reliable source of biomarkers with multiple applications.-Liquid biopsies are usually based on the detection and analysis of cell-free DNA found in the plasma, urine or saliva.-Studies of the DNA present in the gastric fluids of patients (gfDNA), collected during routine endoscopy, are scarce and limited to assessing mutation profiles. It’s diagnostic and prognostic potential has not been studied so far.What this study adds-An analysis of gfDNA concentrations in 941 samples revealed increased DNA levels in GC patients as compared to non-GC individuals.-When tumor stages were compared, gfDNA levels are elevated in more advanced disease.-For GC subjects, increased gfDNA was positively associated with immune cell infiltrates and reduced tumor recurrence, suggesting this to be an informative and very low-cost prognostic marker.How this study might affect research, practice or policy-gfDNA collected during routine upper digestive diagnostic endoscopy can be used as an additional and very simple biomarker useful during patient follow-up and to determine cancer prognosis.-In the future gfDNA assessment has the potential to contribute to a range of applications, such as monitoring treatment response, indicating immune cell infiltration and may potentially indicate cases with progressive disease non-responsive to chemotherapy.

Converging lines of evidence suggest that autonomic and nociceptive pathways linked with the locus coeruleus are disrupted in complex regional pain syndrome (CRPS). To investigate this, pupillary dilatation to arousal stimuli (which reflects neural activity in the locus coeruleus) and pupillary reflexes to light were assessed in a cross-sectional study of 33 patients with CRPS. Moderately painful electrical shocks were delivered to the affected or contralateral limb and unilateral 110 dB SPL acoustic startle stimuli were delivered via headphones. To determine whether the acoustic startle stimuli inhibited shock-induced pain, startle stimuli were also administered bilaterally 200 ms before or after the electric shock. The pupils constricted briskly and symmetrically to bright light (500 lux) and dilated symmetrically in dim light (5 lux). However, the pupil on the CRPS-affected side was smaller than the contralateral pupil before and after the delivery of painless and painful arousal stimuli. Auditory sensitivity was greater on the affected than unaffected side but acoustic startle stimuli failed to inhibit shock-induced pain. Together, these findings suggest that neural activity in pathways linked with the locus coeruleus is compromised on the affected side in patients with CRPS. This may contribute to autonomic disturbances, auditory discomfort and pain. Perspective: The locus coeruleus is involved not only in modulation of pain but also regulates sensory traffic more broadly. Hence, fatigue of neural activity in the ipsilateral locus coeruleus might not only exacerbate pain and hyperalgesia in CRPS but could also contribute more generally to hemilateral disturbances in sensory processing.

Objective Complex regional pain syndrome (CRPS) is associated with a range of sensory disturbances on the symptomatic side of the body but whether this includes olfaction is uncertain. To clarify this, the aims of this study were to compare ratings of intensity and hedonic appeal of household odorants in CRPS patients and controls, and to determine whether ratings differed between the symptomatic and contralateral sides within the sample of patients. Methods Six odorants (vanilla, fish sauce, vinegar, eucalyptus, almond essence and acetone) were presented sequentially in random order on cottonwool buds held in the midline approximately 1 cm from both nostrils in 37 CRPS patients and 21 pain-free controls. Each odor was rated for intensity and hedonic appeal, and participants reported whether the odor was stronger and/or smelt different on one side than the other. Results The odorants smelt worse for patients than controls (P Conclusions These findings suggest that the trigeminal component of olfaction interacts bilaterally with pain-sensitized circuits in the thalamus or higher cortical centers to distort odor perception in patients with CRPS. This aberrant process appears to differ from the mechanism that underlies hemilateral hyperalgesia in other sensory modalities.

Purpose Several articles have claimed that complex regional pain syndrome (CRPS) does not exist. Although a minority view, it is important to understand the arguments presented in these articles. We conducted a systematic literature search to evaluate the methodological quality of articles that claim CRPS does not exist. We then examined and refuted the arguments supporting this claim using up-to-date scientific literature on CRPS. Methods A systematic search was conducted in MEDLINE, EMBASE and Cochrane CENTRAL databases. Inclusion criteria for articles were (a) a claim made that CRPS does not exist or that CRPS is not a distinct diagnostic entity and (b) support of these claims with subsequent argument(s). The methodological quality of articles was assessed if possible. Results Nine articles were included for analysis: 4 narrative reviews, 2 personal views, 1 letter, 1 editorial and 1 case report. Seven points of controversy were used in these articles to argue that CRPS does not exist: 1) disagreement with the label "CRPS"; 2) the "unclear" pathophysiology; 3) the validity of the diagnostic criteria; 4) CRPS as a normal consequence of immobilization; 5) the role of psychological factors; 6) other identifiable causes for CRPS symptoms; and 7) the methodological quality of CRPS research. Conclusion The level of evidence for the claim that CRPS does not exist is very weak. Published accounts concluding that CRPS does not exist, in the absence of primary evidence to underpin them, can harm patients by encouraging dismissal of patients' signs and symptoms.

Objective/background To validate and extend on previous positive findings of the sleep-enhancing effects of saffron supplementation in adults with unsatisfactory sleep. Patients/methods In this 28-day, 3-arm, parallel-group, double-blind, randomised controlled trial, 120 adults with unsatisfactory sleep received either a placebo, 14 mg, or 28 mg of a standardised saffron extract (affron®), 1 h before bed. Outcome measures included the Pittsburgh Sleep Diary (with sleep quality ratings as the primary outcome measure), Insomnia Symptom Questionnaire (ISQ), Profile of Mood States, Restorative Sleep Questionnaire, the Functional Outcomes of Sleep Questionnaire, and evening salivary melatonin and cortisol concentrations. Results Compared to the placebo, saffron supplementation was associated with greater improvements in sleep quality ratings (primary outcome measure), mood ratings after awakening, the ISQ total score, and ISQ-insomnia classifications. However, there were no significant differences between the saffron and placebo groups in other questionnaire and sleep diary outcome measures. Sleep improvements were similar for the two administered saffron doses. Compared to the placebo, saffron supplementation was associated with increases in evening melatonin concentrations but did not affect evening cortisol. Saffron supplementation was well-tolerated with no reported significant adverse effects. Conclusions These results provide further validation of the sleep-enhancing effects of 28-days of saffron supplementation in adults with unsatisfactory sleep. Further research is required to examine the efficacy and safety of saffron supplementation using objective sleep measures, over a longer duration, in people presenting with a diagnosed insomnia disorder and other psychogenic and demographic characteristics, and into its potential sleep-enhancing mechanisms of action.

Electrical capacitance tomography is employed for various process tomography applications, typically with circular imaging regions (e.g., to estimate fluid levels in plastic pipes). Typical state-of-the-art implementations focus on circular or cylindrical sensor arrays. In contrast, this research explores using a planar 2D array of electric-field sensors to image volumes composed of various dielectric materials. The array is designed to be used with very-low-frequency electric fields, which are desirable due to their ability to differentiate between various non-conducting objects. D-dot sensors (i.e., charge induction sensors) are used as the electric-field sensing element. In this research, imaging regions of interest are modeled as a composition of (25 cm)3 voxels of dielectric material with randomized relative permittivities. Neural networks are utilized as the inversion algorithm to map measured E-field distortions to the voxels’ relative permittivities. Three applications are explored in a simulated environment: 1) predicting relative permittivities of the entire (pseudo-3D) imaging region from one measurement of electric-field distortions (modeled in free space), 2) imaging regions arbitrarily large (in two dimensions) using the planar array as an imaging kernel, and 3) repeating application (1) in a model of a practical, real-world imaging scenario both with and without interfering material. Application (3) is performed with a real-world experimental setup using a room-sized “E-field Cage” meant to generate a uniform electric field. This work showcases a new electric-field imaging modality using a planar 2D D-dot sensor array paired with a DNN-based inversion algorithm.

Applying an ice cube to the temple (the conditioning stimulus) inhibits electrically evoked pain in the forearm. The present study aimed to determine whether temple cooling also inhibits pressure- and heat-pain test stimuli in the upper limb and, if so, to investigate the intra-session test-retest reliability of this response. Additional aims were to establish whether pain inhibition evoked by temple cooling was associated with parasympathetic activity; and to explore sex differences in response.The sample consisted of 40 healthy adults (24 females). Heart rate was recorded continuously throughout the session. An ice cube (3 × 4 cm contact area) was applied for 1 min to the temple on the dominant side. Before and immediately afterwards, the pressure pain threshold was measured from the dorsal hand and sensitivity to heat (individually adjusted at baseline to elicit moderate pain) was measured from the ventral forearm. The procedures were repeated 15 min later.Temple cooling inhibited pressure pain on the hand but not heat pain on the forearm. However, test-retest reliability of pressure pain inhibition was poor. Heart rate decreased during temple cooling, consistent with a "diving" reflex. Males had stronger pressure pain inhibition, lower heart rate and higher overall autonomic activity than females. However, cardiac parasympathetic activation during temple cooling was comparable in both sexes and was unrelated to pain inhibition.These findings indicate that temple cooling evokes pain inhibition that is stronger in males than in females. Cardiac parasympathetic activity does not appear to mediate this response.The conditioning stimulus in the conditioned pain modulation paradigm is often applied to the upper or lower limbs. This may confound pain-inhibitory effects in people with peripheral neuropathy who typically have enhanced or diminished sensation in the extremities. Applying an ice cube at the temple area induces pain-inhibitory effects on the upper limb after the ice is removed. Future research examining pain modulation in people with peripheral neuropathy may consider adopting temple cooling as the conditioning stimulus.

Publisher Copyright: © 2022 American Physical Society. We present an analysis of positron lifetimes in solids with unprecedented depth. Instead of modeling correlation effects with density functionals, we study positron-electron wave functions with long-range correlations included. This gives new insight in understanding positron annihilation in metals, insulators, and semiconductors. By using a new quantum Monte Carlo approach for computation of positron lifetimes, an improved accuracy compared to previous computations is obtained for a representative set of materials when compared with experiment. Thus, we present a method without free parameters as a useful alternative to the already existing methods for modeling positrons in solids.

PurposeTo validate an individual's feelings or behaviour is to sanction their thoughts or actions as worthy of social acceptance and support. In contrast, rejection of the individual's communicated experience indicates a denial of social acceptance, representing a potential survival threat. Pain-invalidation, though ill-defined, appears to be a fundamental component of psychosocial stress for people with chronic pain. As such, the aim of this paper was to define pain-validation and outline its importance for those with chronic pain.MethodsThe pain-validation construct was defined using themes inherent in the narratives of those with chronic pain, as identified in a previously published systematic search and thematic analysis, together with examination of additional literature on pain-validation in the clinical context.ResultsWe present a construct definition, proposing that pain-validation must necessarily include: (i) belief that the pain experience is true for the individual, (ii) acceptability of the individual's expressions of pain, and (iii) communication of belief and acceptability to the individual experiencing pain. Further, we outline the importance of pain-validation as a protective factor and means of reducing many of the psychosocial stresses of chronic pain; for example, by indicating social support for pain-coping, buffering negative emotions, and re-enforcing unity and shared identity.ImplicationsThe role of pain-validation in the current era of pain management intervention is discussed. Adhering to interventions that involve cognitive and behavioural change is often difficult. Acknowledging and validating the acceptability of the patient's pain experience in the early stages of pain management may, therefore, be a key component of intervention that encourages compliance to the treatment plan and achieving therapeutic goals.

Objectives Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among people living with HIV, and it is possible that it may also influence the evolution of the HIV infection. We assessed the differences between HIV-positive and -negative people infected with TB. Methods The present study is a cross-sectional retrospective study by electronic record revision. We included patients admitted to a tertiary hospital with a diagnosis of TB between 2011 and 2016, comparing those with HIV coinfection with non-HIV patients, according to demographic and clinical characteristics. Results This study included 591 patients, of whom 32% were HIV-coinfected. HIV-TB patients were younger, with a predominance of male gender. Considering TB risk factors, there was a higher prevalence of homelessness and intravenous drug use in the HIV group. In the non-HIV group, direct contact with other patients with TB and immunosuppression were more prevalent. Relative to TB characteristics, the HIV-coinfected group presents with a higher prevalence of disseminated disease and a higher occurrence of previous TB infection. Cancer was the most frequent cause of immunosuppression in the HIV group and the number testing positive for TB via microbiological culture was lower. Assessment of microbiological resistance and in-hospital mortality showed similar numbers in both groups. Conclusions There are few papers comparing clinical course of TB between HIV-infected and non-infected patients. Our study differs from others in the literature as we focused on a country with middling incidence of TB and further characterized the differences between HIV-infected and non-infected patients which can contribute to the management of these patients.

Variational and diffusion quantum Monte Carlo methods are employed to investigate the zero-temperature phase diagram of the three-dimensional homogeneous electron gas at very low density. Fermi fluid and body-centered cubic Wigner crystal ground state energies are determined using Slater-Jastrow-backflow and Slater-Jastrow many-body wave functions at different densities and spin polarizations in finite simulation cells. Finite-size errors are removed using twist-averaged boundary conditions and extrapolation of the energy per particle to the thermodynamic limit of infinite system size. Unlike previous studies, our results show that the electron gas undergoes a first-order quantum phase transition directly from a paramagnetic fluid to a body-centered cubic crystal at density parameter $r_\text{s} = 86.6(7)$, with no region of stability for an itinerant ferromagnetic fluid. However there is a possible magnetic phase transition from an antiferromagnetic crystal to a ferromagnetic crystal at $r_\text{s}=93(3)$., Comment: accepted for publication

Complex regional pain syndrome (CRPS) is often associated with reduced sound tolerance (hyperacusis) on the affected side, but the mechanism of this symptom is unclear. As compensatory increases in central auditory activity after cochlear injury may trigger hyperacusis, hearing and discomfort thresholds to pure tones (250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz) were assessed in 34 patients with CRPS and 26 pain-free controls. In addition, in 31 patients and 17 controls, auditory-evoked potentials to click stimuli (0.08 ms duration, 6 Hz, 60 dB above the hearing threshold) were averaged across 2000 trials for each ear. Auditory discomfort thresholds were lower at several pitches on the CRPS-affected than contralateral side and lower at all pitches on the affected side than in controls. However, ipsilateral hyperacusis was not associated with psychophysical or physiological signs of cochlear damage. Instead, neural activity in the ipsilateral brainstem and midbrain was greater when repetitive click stimuli were presented on the affected than contralateral side and greater bilaterally than in controls. In addition, click-evoked potentials, reflecting thalamo-cortical signal transfer and early cortical processing, were greater contralaterally in patients than controls. Together, these findings suggest that hyperacusis originates in the ipsilateral brainstem and midbrain rather than the peripheral auditory apparatus of patients with CRPS. Failure of processes that jointly modulate afferent auditory signalling and pain (eg, inhibitory influences stemming from the locus coeruleus) could contribute to ipsilateral hyperacusis in CRPS.

Este artículo contiene 9 páginas, 4 figuras, 1 tabla., The relevance of wastewater treatment plant (WWTP) effluents in fluvial networks is increasing as urbanization grows in catchments. Urban-sourced fine particles from WWTP effluents deposit and accumulate in the streambed sediment of receiving streams over time and can fuel respiration rates, which can thus potentially increase rates of biogeochemical reactions and CO2 emissions to the atmosphere. We aimed to provide a quantitative assessment of the influence of WWTP-sourced fine particles deposited in the streambed sediment on stream metabolic activity for 1 year in an intermittent Mediterranean stream. More nutrientrich and metabolically active fine particle standing stocks were observed downstream of the WWTP, propagating to the end of the 820 m study reach, especially during the dry period (i.e., when the dilution capacity of the stream to WWTP inputs is, This work was supported by an NSF EAR-Postdoctoral Fellowship and a Marie Curie Individual Fellowship (833702MICROPATH) to J.D.D., AEI/FEDER UE and Spanish Office for Research (MINECO) funded MEDSOUL (CGL2014-59977-C3-2-R) and Eco-Reactors (PGC2018- 101975-B-C22) to E.M., and a Ramon y Cajal fellowship (RYC-2017-22643), NICUS (CGL2014-55234-JIN) and CANTERA (RTI2018-094521-B-100) to S.B.

Density functional theory (DFT) is widely used to study defects in monolayer graphene with a view to applications ranging from water filtration to electronics to investigations of radiation damage in graphite moderators. To assess the accuracy of DFT in such applications, we report diffusion quantum Monte Carlo (DMC) calculations of the formation energies of some common and important point defects in monolayer graphene: monovacancies, Stone-Wales defects, and silicon substitutions. We find that standard DFT methods underestimate monovacancy formation energies by around 1 eV. The disagreement between DFT and DMC is somewhat smaller for Stone-Wales defects and silicon substitutions. We examine vibrational contributions to the free energies of formation for these defects, finding that vibrational effects are non-negligible. Finally, we compare the DMC atomization energies of monolayer graphene, monolayer silicene, and bulk silicon, finding that bulk silicon is significantly more stable than monolayer silicene by 0.7522(5) eV per atom.

Dual-site transcranial magnetic stimulation (TMS) can be used to measure the cerebellar inhibitory influence on the primary motor cortex, known as cerebellar brain inhibition (CBI), which is thought to be important for motor control. The aim of this study was to determine whether age-related differences in CBI (measured at rest) were associated with an age-related decline in bilateral motor control measured using the Purdue Pegboard task, the Four Square Step Test, and a 10-m walk. In addition, we examined test re-test reliability of CBI measured using dual-site TMS with a figure-of-eight coil in two sessions. There were three novel findings. First, CBI was less in older than in younger adults, which is likely underpinned by an age-related loss of Purkinje cells. Second, greater CBI was associated with faster 10-m walking performance in older adults, but slower 10-m walking performance in younger adults. Third, moderate intraclass correlation coefficients (ICCs: 0.53) were found for CBI in younger adults; poor ICCs were found for CBI (ICC: 0.40) in older adults. Together, these results have important implications for the use of dual-site TMS to increase our understanding of age- and disease-related changes in cortical motor networks, and the role of functional connectivity in motor control.