Are we really Bayesian? Probabilistic inference shows sub-optimal knowledge transfer.

Numerous studies have found that the Bayesian framework, which formulates the optimal integration of the knowledge of the world (i.e. prior) and current sensory evidence (i.e. likelihood), captures human behaviours sufficiently well. However, there are debates regarding whether humans use precise but cognitively demanding Bayesian computations for behaviours. Across two studies, we trained participants to estimate hidden locations of a target drawn from priors with different levels of uncertainty. In each trial, scattered dots provided noisy likelihood information about the target location. Participants showed that they learned the priors and combined prior and likelihood information to infer target locations in a Bayes fashion. We then introduced a transfer condition presenting a trained prior and a likelihood that has never been put together during training. How well participants integrate this novel likelihood with their learned prior is an indicator of whether participants perform Bayesian computations. In one study, participants experienced the newly introduced likelihood, which was paired with a different prior, during training. Participants changed likelihood weighting following expected directions although the degrees of change were significantly lower than Bayes-optimal predictions. In another group, the novel likelihoods were never used during training. We found people integrated a new likelihood within (interpolation) better than the one outside (extrapolation) the range of their previous learning experience and they were quantitatively Bayes-suboptimal in both. We replicated the findings of both studies in a validation dataset. Our results showed that Bayesian behaviours may not always be achieved by a full Bayesian computation. Future studies can apply our approach to different tasks to enhance the understanding of decision-making mechanisms.

Feasibility of Using Source-Level Brain Computer Interface for People with Multiple Sclerosis.

This work evaluates the feasibility of using a source level Brain-Computer Interface (BCI) for people with Multiple Sclerosis (MS). Data used was previously collected EEG of eight participants (one participant with MS and seven neurotypical participants) who performed imagined movement of the right and left hand. Equivalent current dipole cluster fitting was used to assess related brain activity at the source level and assessed using dipole location and power spectrum analysis. Dipole clusters were resolved within the motor cortices with some notable spatial difference between the MS and control participants. Neural sources that generate motor imagery originated from similar motor areas in the participant with MS compared to the neurotypical participants. Power spectral analysis indicated a reduced level of alpha power in the participant with MS during imagery tasks compared to neurotypical participants. Power in the beta band may be used to distinguish between left and right imagined movement for users with MS in BCI applications.Clinical Relevance- This paper demonstrates the cortical areas activated during imagined BCI-type tasks in a participant with Multiple Sclerosis (MS), and is a proof of concept for translating BCI research to potential users with MS.

Short duration event related cerebellar TDCS enhances visuomotor adaptation.

BACKGROUND: Transcranial direct current stimulation (TDCS) is typically applied before or during a task, for periods ranging from 5 to 30 min. HYPOTHESIS: We hypothesise that briefer stimulation epochs synchronous with individual task actions may be more effective. METHODS: In two separate experiments, we applied brief bursts of event-related anodal stimulation (erTDCS) to the cerebellum during a visuomotor adaptation task. RESULTS: The first study demonstrated that 1 s duration erTDCS time-locked to the participants' reaching actions enhanced adaptation significantly better than sham. A close replication in the second study demonstrated 0.5 s erTDCS synchronous with the reaching actions again resulted in better adaptation than standard TDCS, significantly better than sham. Stimulation either during the inter-trial intervals between movements or after movement, during assessment of visual feedback, had no significant effect. Because short duration stimulation with rapid onset and offset is more readily perceived by the participants, we additionally show that a non-electrical vibrotactile stimulation of the scalp, presented with the same timing as the erTDCS, had no significant effect. CONCLUSIONS: We conclude that short duration, event related, anodal TDCS targeting the cerebellum enhances motor adaptation compared to the standard model. We discuss possible mechanisms of action and speculate on neural learning processes that may be involved.

Towards a cross-level understanding of Bayesian inference in the brain.

Perception emerges from unconscious probabilistic inference, which guides behaviour in our ubiquitously uncertain environment. Bayesian decision theory is a prominent computational model that describes how people make rational decisions using noisy and ambiguous sensory observations. However, critical questions have been raised about the validity of the Bayesian framework in explaining the mental process of inference. Firstly, some natural behaviours deviate from Bayesian optimum. Secondly, the neural mechanisms that support Bayesian computations in the brain are yet to be understood. Taking Marr's cross level approach, we review the recent progress made in addressing these challenges. We first review studies that combined behavioural paradigms and modelling approaches to explain both optimal and suboptimal behaviours. Next, we evaluate the theoretical advances and the current evidence for ecologically feasible algorithms and neural implementations in the brain, which may enable probabilistic inference. We argue that this cross-level approach is necessary for the worthwhile pursuit to uncover mechanistic accounts of human behaviour.

The anti-inflammatory effect of ε-viniferin by specifically targeting formyl peptide receptor 1 on human neutrophils.

The uncontrol respiratory burst in neutrophils can lead to inflammation and tissue damage. This study investigates the effect and the underlying mechanism of ε-viniferin, a lignan from the root of Vitis thunbergii var. thunbergii, inhibits N-formyl-L-methionyl-L-leucyl-l-phenylalanine (fMLP) induced respiratory burst by antagonizing formyl peptide receptor 1 in human neutrophils. Briefly, ε-viniferin specifically inhibited fMLP (0.1 µM: formyl peptide receptor 1 agonist or 1 µM: formyl peptide receptor 1, 2 agonist)-induced superoxide anion production in a concentration-dependent manner (IC50 = 2.30 ± 0.96 or 9.80 ± 0.21 µM, respectively) without affecting this induced by formyl peptide receptor 2 agonist (WKYMVM). ε-viniferin inhibited fMLP (0.1 µM)-induced phosphorylation of ERK, Akt, Src or intracellular calcium mobilization without affecting these caused by WKYMVM. The synergistic suppression of fMLP (1 µM)-induced superoxide anion production was observed only in the combination of ε-viniferin and formyl peptide receptor 2 antagonist (WRW4) but not in combination of ε-viniferin and formyl peptide receptor 1 antagonist (cyclosporine H). ε-viniferin inhibited FITC-fMLP binding to formyl peptide receptors. Moreover, the synergistic suppression of FITC-fMLP binding was observation only in the combination of ε-viniferin and WRW4 but not in other combinations. ATPγS induced superoxide anion production through formyl peptide receptor 1 in fMLP desensitized neutrophils and this effect was inhibited by ε-viniferin. The concentration-response curve of fMLP-induced superoxide anion was not parallel shifted by ε-viniferin. Furthermore, the inhibiting effect of ε-viniferin on fMLP-induced superoxide anion production was reversible. These results suggest that ε-viniferin is an antagonist of formyl peptide receptor 1 in a reversible and non-competitive manner.

Using optically pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum.

KEY POINTS: The application of conventional cryogenic magnetoencephalography (MEG) to the study of cerebellar functions is highly limited because typical cryogenic sensor arrays are far away from the cerebellum and naturalistic movement is not allowed in the recording. A new generation of MEG using optically pumped magnetometers (OPMs) that can be worn on the head during movement has opened up an opportunity to image the cerebellar electrophysiological activity non-invasively. We use OPMs to record human cerebellar MEG signals elicited by air-puff stimulation to the eye. We demonstrate robust responses in the cerebellum. OPMs pave the way for studying the neurophysiology of the human cerebellum. ABSTRACT: We test the feasibility of an optically pumped magnetometer-based magnetoencephalographic (OP-MEG) system for the measurement of human cerebellar activity. This is to our knowledge the first study investigating the human cerebellar electrophysiology using optically pumped magnetometers. As a proof of principle, we use an air-puff stimulus to the eyeball in order to elicit cerebellar activity that is well characterized in non-human models. In three subjects, we observe an evoked component at approx. 50 ms post-stimulus, followed by a second component at approx. 85-115 ms post-stimulus. Source inversion localizes both components in the cerebellum, while control experiments exclude potential sources elsewhere. We also assess the induced oscillations, with time-frequency decompositions, and identify additional sources in the occipital lobe, a region expected to be active in our paradigm, and in the neck muscles. Neither of these contributes to the stimulus-evoked responses at 50-115 ms. We conclude that OP-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum.

Temperature-Controlled Assembly/Reassembly of Two Dicarboxylate-Based Three-Dimensional Co(II) Coordination Polymers with an Antiferromagnetic Metallic Layer and a Ferromagnetic Metallic Chain.

Two new dicarboxylate-based three-dimensional cobalt coordination polymers, [Co(Me2mal)(bpe)0.5(H2O)]n (1) and [Co(Me2mal)(bpe)0.5]n (2), were synthesized from dimethylmalonic acid (H2-Me2mal) in temperature-controlled solvothermal reactions. Lower temperatures (6080 °C) favored the formation of 1, while higher temperatures (120 °C) favored the production of 2. Compound 1 is comprised of Co(II) corrugated layers linked by syn-anti carboxylate bridges from the Me2mal2- ligands and pillared through bis-monodentate bpe groups. Compound 2 is comprised of a three-dimensional network involving one-dimensional Co-carboxylate chains bonded by antisymmetric µ4-Me2mal2- ligands and aligned parallel to the [001] direction. The solvothermal retreatment of crystalline samples of 1 in a DMF/H2O solvent at 120 °C allowed the structural reassembly, with complete conversion within 2 over 48 h. Magnetic analyses revealed that compound 1 exhibits both spin-orbital coupling and antiferromagnetic interactions through a syn-anti carboxylate (Me2mal2-) bridge exchange pathway [Co-Co separation of 5.478 Å] and compound 2 showed a ferromagnetic interaction resulting from the short Co-Co separation (3.150 Å) and the small Co-O-Co bridging angles (98.5° and 95.3°) exchange pathway which was provided by µ4-Me2mal2- bridging ligand.

Decomposing sensorimotor variability changes in ageing and their connection to falls in older people.

The relationship between sensorimotor variability and falls in older people has not been well investigated. We developed a novel task having shared biomechanics of obstacle negotiation to quantify sensorimotor variability related to locomotion across age. We found that sensorimotor variability in foot placement increases continuously with age. We then applied sensory psychophysics to pinpoint the visual and somatosensory systems associated with sensorimotor variability. We showed increased sensory variability, specifically increased proprioceptive variability, the vital cause of more variable foot placement in older people (greater than 65 years). Notably, older participants relied more on the vision to judge their own foot's height compared to the young, suggesting a shift in multisensory integration strategy to compensate for degenerated proprioception. We further modelled the probability of tripping-over based on the relationship between sensorimotor variability and age and found a correspondence between model prediction and community-based data. We reveal increased sensorimotor variability, modulated by sensation precision, a potentially vital mechanism of raised tripping-over and thus fall events in older people. Analysis of sensorimotor variability and its specific components may have the utility of fall risk and rehabilitation target evaluation.

Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence in situ hybridization methods.

OBJECTIVES: Analysis of the targetable driver mutations is now recommended in all patients with advanced lung adenocarcinoma. Molecular-based methods are usually adopted, however, along with the implementation of highly sensitive and/or mutation-specific antibodies, immunohistochemistry (IHC) has been considered an alternative method for identifying driver mutations in lung adenocarcinomas. MATERIALS AND METHODS: A total of 205 lung adenocarcinomas were examined for EGFR mutations and ALK and ROS1 rearrangements using real-time PCR, fluorescence in situ hybridization (FISH) and IHC in parallel. The performance of different commercially available IHC antibody clones toward targetable driver mutations was evaluated. The association between these driver mutations and clinicopathological characteristics was also analyzed. RESULTS: In 205 cases we studied, 58.5% were found to harbor EGFR mutations, 6.3% ALK rearrangements and 1.0% ROS1 rearrangements. Compared to molecular-based methods, IHC of EGFR mutations showed an excellent specificity but the sensitivity is suboptimal, while IHC of ALK and ROS1 rearrangements demonstrated high sensitivity and specificity. No significant difference regarding the performance of different antibody clones toward these driver mutations was observed, except that clone SP125 showed a higher sensitivity than 43B2 in the detection of p.L858R of EGFR. CONCLUSION: In circumstances such as poor quality of nucleic acids or low content of tumor cells, IHC of EGFR mutation-specific antibodies could be used as an alternative method. Patients negative for EGFR mutations are subjected to further analysis on ALK and ROS1 rearrangements using IHC methods. Herein, we proposed a lung adenocarcinoma testing algorithm for the application of IHC in therapeutic diagnosis.

Clinicopathology of Immunoglobulin G4-Related Chronic Sclerosing Sialadenitis: A Single-Center Study.

OBJECTIVES: To investigate the clinicopathologic characteristics of patients with immunoglobulin G4-related chronic sclerosing sialadenitis (IgG4-RCSS), a recently recognized disease. STUDY DESIGN: Case series with chart review and pathology study. SETTINGS: Tertiary care hospital. SUBJECTS AND METHODS: We evaluated chronic sialadenitis specimens obtained over 11 years using pathologic examination and IgG4 immunohistochemistry staining. The specimens were assigned a revised diagnosis of IgG4-RCSS or chronic sialadenitis not otherwise specified, and clinicopathologic data from each group were compared. RESULTS: Of the 84 patients, 21 were diagnosed with IgG4-RCSS and 63 with chronic sialadenitis not otherwise specified. IgG4-RCSS patients were older (68.2 ± 13.9 vs 54.2 ± 15.8 years, P = .001), predominantly male (85.7% vs 61.9%, P = .036), and more likely to present with painless swelling (75% vs 44.3%, P = .001) and bilateral involvement (52.4% vs 6.3%, P < .001). Ratio of IgG4-positive plasma cells to IgG-positive plasma cells in IgG4-RCSS tissues was 0.81 ± 0.14. The mean value of serum IgG4 in IgG4-RCSS patients was 918.8 mg/dL. CONCLUSION: IgG4-RCSS is more common in older male patients and frequently presents with bilateral involvement. Informing head and neck surgeons of the clinical features of IgG4-RCSS and promoting a combined approach of clinical evaluation, imaging, and biopsy can improve the accuracy of preoperative diagnoses.

Robotic psychophysics system for assessment, diagnosis and rehabilitation of the neurological causes of falls in the elderly.

Falls are the leading causes of unintentional injuries in the elderly and thus a pose a major hazard to our ageing society. We present the FOHEPO (FOot HEight POsitioning) system to measure, diagnose and eventually rehabilitate ageing-related neurological causes of falls. We hypothesise that both perceptual and motor variability is likely to increase with age and may lead to imprecise perception and movements causing trip overs, the major triggers of falls. Our robotic experimental system automatically measures and tracks different sources of noise in the nervous system: visual perception noise of obstacle height, proprioceptive noise of localising raising one's foot to a desired height, noise in the visual feedback of the foot movements. We developed age-appropriate psychophysical measurement protocols shorter than standard protocols for perceptual and motor accuracy. These quantify individual subjects perceptual and movement accuracy thresholds through their psychometric curves. Therefore, these platform measurements will enable us to estimate fall probabilities quantitatively, i.e. the chance that a foot will clip an obstacle because subjects did not add a sufficient safety factor when clearing it. Potentially, we can use our FOHEPO system in a game-ified setting to rehabilitate elderly users to move with larger safety factors so as to reduce their risks of trip-over.

Malignant hepatic epithelioid hemangioendothelioma with high-output heart failure: successful management of heart failure with transcatheter arterial chemoembolization.

A 73-year-old woman was admitted to hospital because of progressive dyspnea on exertion. Computed tomography revealed a large hepatic tumor, which was proved to be a hepatic epithelioid hemangioendothelioma (EHE). Echocardiography demonstrated high cardiac output, for which the tumor was considered to be the leading cause. A transcatheter arterial chemoembolization (TACE) was performed sequentially at 1-month intervals to reduce the size of the hepatic tumor, and this temporarily improved the patient's cardiac condition and quality of life. In this case, we successfully used TACE in the treatment of hepatic EHE with high-output heart failure. TACE is a reasonable choice of treatment both for managing malignant hepatic tumors and resolving low systemic vascular resistance by embolization of the abnormal neoangiogenic vessels. Nevertheless, clinicians should be aware of the potential adverse effect of hepatic decompensation induced by TACE, especially when the tumor involvement is widespread and poorly preserved hepatic function is encountered.

Lacrimal gland pleomorphic adenoma masquerading as thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy is the most common cause of proptosis in adult female, especially those with positive thyroid antibody. Sometimes, other diagnoses should be considered. A 45-year-old female presented with progressive right proptosis and mild diplopia for 2 years. One year earlier, she had been diagnosed with thyroid-associated ophthalmopathy because of abnormal thyroid autoantibody. Computed tomography scan showed a 2.4- × 1.9- × 1.6-mm heterogeneous soft-tissue density lying above the left eye. Excisional biopsy of this mass revealed the histopathologic diagnosis of pleomorphic adenoma. This case highlights the need for including other diagnoses such as pleomorphic adenoma in the differential diagnosis of patients with proptosis, diplopia and abnormal thyroid antibody.

Primary congenital pulmonary hypoplasia of a neonate.

Pulmonary hypoplasia is a rare but usually lethal disease. We report a full-term male neonate who presented with respiratory failure immediately after birth. Chest X-ray revealed a small lung volume despite advanced ventilator support. Respiratory failure persisted and this baby died at 40.5 hours of age. The autopsy showed a lung-to-birth weight ratio of 0.69% and a radial alveoli count of 2.97. All this information confirmed the diagnosis of primary congenital pulmonary hypoplasia.

Nephrogenic systemic fibrosis associated with gadolinium use.

Nephrogenic systemic fibrosis (NSF) is an idiopathic, progressive, systemic fibrosis that occurs in patients with renal diseases. Recently, gadolinium-containing contrast (Gd-contrast) has become a suspected causal factor for NFS. This report discusses two female patients with end-stage renal disease, aged 70 and 51 years, respectively, who developed histologically proven NSF after exposure to Gd-contrast. Clinically, both patients were characterized by fibrosis and induration of skin and muscle mainly in the limbs with joint contracture. In the first case, NSF developed gradually after undergoing evaluation by Gd-contrast magnetic resonance imaging (MRI) and subsequent surgery for her urothelial carcinoma. In the second patient, NSF developed after undergoing evaluation by Gd-contrast MRI for her right shoulder bursitis with calcification, and the conditions of NSF continued to worsen after the surgical treatment of this right shoulder lesion. Although the role of Gd-contrast in NSF is still not well known, the correlation in our cases strongly suggests that it should be used with cautioned in patients with end-stage renal disease. Both of our patients underwent surgery before or during the development of NSF, indicating that the surgical procedure may be a contributing factor.