Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

Extracting Relevance and Affect Information from Physiological Text Annotation

We present physiological text annotation, which refers to the practice of associating physiological responses to text content in order to infer characteristics of the user information needs and affective responses. Text annotation is a laborious task, and implicit feedback has been studied as a way to collect annotations without requiring any explicit action from the user. Previous work has explored behavioral signals, such as clicks or dwell time to automatically infer annotations, and physiological signals have mostly been explored for image or video content. We report on two experiments in which physiological text annotation is studied first to 1) indicate perceived relevance and then to 2) indicate affective responses of the users. The first experiment tackles the user’s perception of relevance of an information item, which is fundamental towards revealing the user’s information needs. The second experiment is then aimed at revealing the user’s affective responses towards a -relevant- text document. Results show that physiological user signals are associated with relevance and affect. In particular, electrodermal activity (EDA) was found to be different when users read relevant content than when they read irrelevant content and was found to be lower when reading texts with negative emotional content than when reading texts with neutral content. Together, the experiments show that physiological text annotation can provide valuable implicit inputs for personalized systems. We discuss how our findings help design personalized systems that can annotate digital content using human physiology without the need for any explicit user interaction

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Effect of low tidal volume ventilation on lung function and inflammation in mice

<p>Abstract</p> <p>Background</p> <p>A large number of studies have investigated the effects of high tidal volume ventilation in mouse models. In contrast data on very short term effects of low tidal volume ventilation are sparse. Therefore we investigated the functional and structural effects of low tidal volume ventilation in mice.</p> <p>Methods</p> <p>38 Male C57/Bl6 mice were ventilated with different tidal volumes (Vt 5, 7, and 10 ml/kg) without or with application of PEEP (2 cm H₂O). Four spontaneously breathing animals served as controls. Oxygen saturation and pulse rate were monitored. Lung function was measured every 5 min for at least 30 min. Afterwards lungs were removed and histological sections were stained for measurement of infiltration with polymorphonuclear leukocytes (PMN). Moreover, mRNA expression of macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)α in the lungs was quantified using real time PCR.</p> <p>Results</p> <p>Oxygen saturation did not change significantly over time of ventilation in all groups (P > 0.05). Pulse rate dropped in all groups without PEEP during mechanical ventilation. In contrast, in the groups with PEEP pulse rate increased over time. These effects were not statistically significant (P > 0.05). Tissue damping (G) and tissue elastance (H) were significantly increased in all groups after 30 min of ventilation (P < 0.05). Only the group with a Vt of 10 ml/kg and PEEP did not show a significant increase in H (P > 0.05). Mechanical ventilation significantly increased infiltration of the lungs with PMN (P < 0.05). Expression of MIP-2 was significantly induced by mechanical ventilation in all groups (P < 0.05). MIP-2 mRNA expression was lowest in the group with a Vt of 10 ml/kg + PEEP.</p> <p>Conclusions</p> <p>Our data show that very short term mechanical ventilation with lower tidal volumes than 10 ml/kg did not reduce inflammation additionally. Formation of atelectasis and inadequate oxygenation with very low tidal volumes may be important factors. Application of PEEP attenuated inflammation.</p

The Impact of Intermittent Umbilical Cord Occlusions on the Inflammatory Response in Pre-Term Fetal Sheep

Fetal hypoxic episodes may occur antepartum with the potential to induce systemic and cerebral inflammatory responses thereby contributing to brain injury. We hypothesized that intermittent umbilical cord occlusions (UCOs) of sufficient severity but without cumulative acidosis will lead to a fetal inflammatory response. Thirty-one chronically instrumented fetal sheep at ∼0.85 of gestation underwent four consecutive days of hourly UCOs from one to three minutes duration for six hours each day. Maternal and fetal blood samples were taken for blood gases/pH and plasma interleukin (IL)-1β and IL-6 levels. Animals were euthanized at the end of experimental study with brain tissue processed for subsequent counting of microglia and mast cells. Intermittent UCOs resulted in transitory fetal hypoxemia with associated acidemia which progressively worsened the longer umbilical blood flow was occluded, but with no cumulative blood gas or pH changes over the four days of study. Fetal arterial IL-1β and IL-6 values showed no significant change regardless of the severity of the UCOs, nor was there any evident impact on the microglia and mast cell counts for any of the brain regions studied. Accordingly, intermittent UCOs of up to three minutes duration with severe, but limited fetal hypoxemia and no cumulative acidemia, do not result in either a systemic or brain inflammatory response in the pre-term ovine fetus. However, fetal IL-1B and IL-6 values were found to be well correlated with corresponding maternal values supporting the placenta as a primary source for these cytokines with related secretion into both circulations. Female fetuses were also found to have higher IL-1β levels than males, indicating that gender may impact on the fetal inflammatory response to various stimuli

Potential barriers and facilitators for implementation of an integrated care pathway for hearing-impaired persons: an exploratory survey among patients and professionals

BACKGROUND: Because of the increasing costs and anticipated shortage of Ear Nose and Throat (ENT) specialists in the care for hearing-impaired persons, an integrated care pathway that includes direct hearing aid provision was developed. While this direct pathway is still under investigation, in a survey we examined expectations and potential barriers and facilitators towards this direct pathway, of patients and professionals involved in the pathway. METHODS: Two study populations were assessed: members of the health professions involved in the care pathway for hearing-impaired persons (general practitioners (GPs), hearing aid dispensers, ENT-specialists and clinical audiologists) and persons with hearing complaints. We developed a comprehensive semi-structured questionnaire for the professionals, regarding expectations, barriers, facilitators and conditions for implementation. We developed two questionnaires for persons with hearing complaints, both regarding evaluations and preferences, and administered them after they had experienced two key elements of the direct pathway: the triage and the hearing aid fitting. RESULTS: On average GPs and hearing aid dispensers had positive expectations towards the direct pathway, while ENT-specialists and clinical audiologists had negative expectations. Professionals stated both barriers and facilitators towards the direct pathway. Most professionals either supported implementation of the direct pathway, provided that a number of conditions were satisfied, or did not support implementation, unless roughly the same conditions were satisfied. Professionals generally agreed on which conditions need to be satisfied. Persons with hearing complaints evaluated the present referral pathway and the new direct pathway equally. Many, especially older, participants stated however that they would still visit the GP and ENT-specialist, even when this would not be necessary for reimbursement of the hearing aid, and found it important that the ENT-specialist or Audiological Centre evaluated their hearing aid. CONCLUSION: This study identified professional concerns about the direct pathway for hearing-impaired persons. Gaps exist in expectations amongst professions. Also gaps exist between users of the pathway, especially between age groups and regions. Professionals are united in the conditions that need to be fulfilled for a successful implementation of the direct pathway. Implementation on a regional level is recommended to best satisfy these conditions

A real-life observational study of the effectiveness of FACT in a Dutch mental health region

<p>Abstract</p> <p>Background</p> <p>ACT is an effective community treatment but causes discontinuity of care between acutely ill and currently stable patient groups. The Dutch variant of ACT, FACT, combines both intensive ACT treatment and care for patients requiring less intensive care at one time point yet likely to need ACT in the future. It may be hypothesised that this case mix is not beneficial for patients requiring intensive care, as other patient groups may "dilute" care provision. The effectiveness of FACT was compared with standard care, with a particular focus on possible moderating effects of patient characteristics within the case mix in FACT.</p> <p>Methods</p> <p>In 2002, three FACT teams were implemented in a Dutch region in which a cumulative routine outcome measurement system was in place. Patients receiving FACT were compared with patients receiving standard treatment, matched on "baseline" symptom severity and age, using propensity score matching. Outcome was the probability of being in symptomatic remission of psychotic symptoms.</p> <p>Results</p> <p>The probability of symptomatic remission was higher for SMI patients receiving FACT than for controls receiving standard treatment, but only when there was an unmet need for care with respect to psychotic symptoms (OR = 6.70, p = 0.002; 95% CI = 1.97 – 22.7).</p> <p>Conclusion</p> <p>Compared to standard care, FACT was more rather than less effective, but only when a need for care with respect to psychotic symptoms is present. This suggests that there is no adverse effect of using broader patient mixes in providing continuity of care for all patients with severe mental illness in a defined geographical area.</p

Brain Potentials Highlight Stronger Implicit Food Memory for Taste than Health and Context Associations

Increasingly consumption of healthy foods is advised to improve population health. Reasons people give for choosing one food over another suggest that non-sensory features like health aspects are appreciated as of lower importance than taste. However, many food choices are made in the absence of the actual perception of a food's sensory properties, and therefore highly rely on previous experiences of similar consumptions stored in memory. In this study we assessed the differential strength of food associations implicitly stored in memory, using an associative priming paradigm. Participants (N = 30) were exposed to a forced-choice picture-categorization task, in which the food or non-food target images were primed with either non-sensory or sensory related words. We observed a smaller N400 amplitude at the parietal electrodes when categorizing food as compared to non-food images. While this effect was enhanced by the presentation of a food-related word prime during food trials, the primes had no effect in the non-food trials. More specifically, we found that sensory associations are stronger implicitly represented in memory as compared to non-sensory associations. Thus, this study highlights the neuronal mechanisms underlying previous observations that sensory associations are important features of food memory, and therefore a primary motive in food choice.</p

Brace technology thematic series - The Sforzesco and Sibilla braces, and the SPoRT (Symmetric, Patient oriented, Rigid, Three-dimensional, active) concept

<p>Abstract</p> <p>Background</p> <p>Bracing is an effective strategy for scoliosis treatment, but there is no consensus on the best type of brace, nor on the way in which it should act on the spine to achieve good correction. The aim of this paper is to present the family of SPoRT (Symmetric, Patient-oriented, Rigid, Three-dimensional, active) braces: Sforzesco (the first introduced), Sibilla and Lapadula.</p> <p>Methods</p> <p>The Sforzesco brace was developed following specific principles of correction. Due to its overall symmetry, the brace provides space over pathological depressions and pushes over elevations. Correction is reached through construction of the envelope, pushes, escapes, stops, and drivers. The real novelty is the drivers, introduced for the first time with the Sforzesco brace; they allow to achieve the main action of the brace: a three-dimensional elongation pushing the spine in a down-up direction.</p> <p>Brace prescription is made plane by plane: frontal (on the "slopes", another novelty of this concept, i.e. the laterally flexed sections of the spine), horizontal, and sagittal. The brace is built modelling the trunk shape obtained either by a plaster cast mould or by CAD-CAM construction. Brace checking is essential, since SPoRT braces are adjustable and customisable according to each individual curve pattern.</p> <p>Treatment time and duration is individually tailored (18-23 hours per day until Risser 3, then gradual reduction). SEAS (Scientific Exercises Approach to Scoliosis) exercises are a key factor to achieve success.</p> <p>Results</p> <p>The Sforzesco brace has shown to be more effective than the Lyon brace (matched case/control), equally effective as the Risser plaster cast (prospective cohort with retrospective controls), more effective than the Risser cast + Lyon brace in treating curves over 45 degrees Cobb (prospective cohort), and is able to improve aesthetic appearance (prospective cohort).</p> <p>Conclusions</p> <p>The SPoRT concept of bracing (three-dimensional elongation pushing in a down-up direction) is different from the other corrective systems: 3-point, traction, postural, and movement-based. The Sforzesco brace, being comparable to casting, may be the best brace for the worst cases.</p

A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages. Depletion of folylpolyglutamate synthetase (FPGS), which normally promotes intracellular accumulation and activity of natural folates and methotrexate, is linked to methotrexate and 5-fluorouracil resistance and its association with relapse illustrates the need for improved intervention strategies. Here, we describe a novel antifolate (C1) that, like methotrexate, potently inhibits dihydrofolate reductase and downstream one-carbon metabolism. Contrary to methotrexate, C1 displays optimal efficacy in FPGS-deficient contexts, due to decreased competition with intracellular folates for interaction with dihydrofolate reductase. We show that FPGS-deficient patient-derived CRC organoids display enhanced sensitivity to C1, whereas FPGS-high CRC organoids are more sensitive to methotrexate. Our results argue that polyglutamylation-independent antifolates can be applied to exert selective pressure on FPGS-deficient cells during chemotherapy, using a vulnerability created by polyglutamylation deficiency