Odorant transport in a hagfish.

Odorant transport is of fundamental and applied importance. Using computational simulations, we studied odorant transport in an anatomically accurate model of the nasal passage of a hagfish (probably Eptatretus stoutii). We found that ambient water is sampled widely, with a significant ventral element. Additionally, there is a bilateral element to olfactory flow, which enters the single nostril in two narrow, laminar streams that are then split prior to the nasal chamber by the anterior edge of the central olfactory lamella. An appendage on this lamella directs a small portion (10-14%) of the overall nasal flow to the olfactory sensory channels. Much of the remaining flow is diverted away from the sensory channels by two peripheral channels. The anterior edge of the central olfactory lamella, together with a jet-impingement mechanism, disperses flow over the olfactory surfaces. Diffusion of odorant from bulk water to the olfactory surfaces is facilitated by the large surface area:volume ratio of the sensory channels, and by a resistance-based hydrodynamic mechanism that leads to long residence times (up to 4.5 s) in the sensory channels. With increasing volumetric flow rate, the rate of odorant transfer to the olfactory surfaces increases, but the efficiency of odorant uptake decreases, falling in the range 2-6%. Odorant flux decreases caudally across the olfactory surfaces, suggesting in vivo a preponderance of olfactory sensory neurons on the anterior part of each olfactory surface. We conclude that the hagfish has a subtle anatomy for locating and capturing odorant molecules.

Copernicus for urban resilience in Europe.

The urban community faces a significant obstacle in effectively utilising Earth Observation (EO) intelligence, particularly the Copernicus EO program of the European Union, to address the multifaceted aspects of urban sustainability and bolster urban resilience in the face of climate change challenges. In this context, here we present the efforts of the CURE project, which received funding under the European Union's Horizon 2020 Research and Innovation Framework Programme, to leverage the Copernicus Core Services (CCS) in supporting urban resilience. CURE provides spatially disaggregated environmental intelligence at a local scale, demonstrating that CCS can facilitate urban planning and management strategies to improve the resilience of cities. With a strong emphasis on stakeholder engagement, CURE has identified eleven cross-cutting applications between CCS that correspond to the major dimensions of urban sustainability and align with user needs. These applications have been integrated into a cloud-based platform known as DIAS (Data and Information Access Services), which is capable of delivering reliable, usable and relevant intelligence to support the development of downstream services towards enhancing resilience planning of cities throughout Europe.

A healthy turn in urban climate change policies; European city workshop proposes health indicators as policy integrators.

BACKGROUND: The EU FP6 HENVINET project reviewed the potential relevance of a focus on climate change related health effects for climate change policies at the city region level. This was undertaken by means of a workshop with both scientists, city representatives from several EU-countries, representatives of EU city networks and EU-experts. In this paper we introduce some important health related climate change issues, and discuss the current city policies of the participating cities. METHODS: The workshop used a backcasting format to analyse the future relevance of a health perspective, and the main benefits and challenges this would bring to urban policy making. RESULTS: It was concluded that health issues have an important function as indicators of success for urban climate change policies, given the extent to which climate change policies contribute to public health and as such to quality of life. Simultaneously the health perspective may function as a policy integrator in that it can combine several related policy objectives, such as environmental policies, health policies, urban planning and economic development policies, in one framework for action. Furthermore, the participants to the workshop considered public health to be of strategic importance in organizing public support for climate change policies. One important conclusion of the workshop was the view that the connection of science and policy at the city level is inadequate, and that the integration of scientific knowledge on climate change related health effects and local policy practice is in need of more attention. In conclusion, the workshop was viewed as a constructive advance in the process of integration which hopefully will lead to ongoing cooperation. CONCLUSIONS: The workshop had the ambition to bring together a diversity of actor perspectives for exchange of knowledge and experiences, and joint understanding as a basis for future cooperation. Next to the complementarities in experience and knowledge, the mutual critical reflection was a bonus, as ideas had the opportunity to be scrutinized by others, leading to more robustness and common ground. The structured backcasting approach was helpful in integrating all of this with one common focus, embracing diversity and complexity, and stimulating reflection and new ideas.

The challenge of social networking in the field of environment and health.

BACKGROUND: The fields of environment and health are both interdisciplinary and trans-disciplinary, and until recently had little engagement in social networking designed to cross disciplinary boundaries. The EU FP6 project HENVINET aimed to establish integrated social network and networking facilities for multiple stakeholders in environment and health. The underlying assumption is that increased social networking across disciplines and sectors will enhance the quality of both problem knowledge and problem solving, by facilitating interactions. Inter- and trans-disciplinary networks are considered useful for this purpose. This does not mean that such networks are easily organized, as openness to such cooperation and exchange is often difficult to ascertain. METHODS: Different methods may enhance network building. Using a mixed method approach, a diversity of actions were used in order to investigate the main research question: which kind of social networking activities and structures can best support the objective of enhanced inter- and trans-disciplinary cooperation and exchange in the fields of environment and health. HENVINET applied interviews, a role playing session, a personal response system, a stakeholder workshop and a social networking portal as part of the process of building an interdisciplinary and trans-disciplinary network. RESULTS: The interviews provided support for the specification of requirements for an interdisciplinary and trans-disciplinary network. The role playing session, the personal response system and the stakeholder workshop were assessed as useful tools in forming such network, by increasing the awareness by different disciplines of other's positions. The social networking portal was particularly useful in delivering knowledge, but the role of the scientist in social networking is not yet clear. CONCLUSIONS: The main challenge in the field of environment and health is not so much a lack of scientific problem knowledge, but rather the ability to effectively communicate, share and use available knowledge for policy making. Structured social network facilities can be useful by policy makers to engage with the research community. It is beneficial for scientists to be able to integrate the perspective of policy makers in the research agenda, and to assist in co-production of policy-relevant information. A diversity of methods need to be applied for network building: according to the fit-for-purpose-principle. It is useful to know which combination of methods and in which time frame produces the best results.Networking projects such as HENVINET are created not only for the benefit of the network itself, but also because the applying of the different methods is a learning tool for future network building. Finally, it is clear that the importance of specialized professionals in enabling effective communication between different groups should not be underestimated.

PET/CT versus triple endoscopy in initial workup of HPV+ oropharyngeal squamous cell carcinoma.

BACKGROUND: Synchronous primary tumors (SPTs) are detected via triple endoscopy or positron emission tomography/computed tomography (PET/CT). Patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) lack risk factors for SPTs. METHODS: We performed a single institution retrospective review of the efficacy of triple endoscopy and PET/CT in HPV+ OPSCC patients. RESULTS: Sixty-five HPV+ OPSCC patients underwent triple endoscopy and PET/CT. Patients were white (n = 48, 72.7%), male (n = 53, 81.5%), mean 58.7 ± 8.1 years old. SPT was detected in 1 (1.5%) patient via PET/CT. No SPTs were detected on triple endoscopy. PET/CT had 100% and 95.3% sensitivity and specificity, respectively. PET/CT positive predictive value (PPV) and negative predictive value (NPV) were 25.0% and 100%, respectively. Triple endoscopy specificity and NPV was 90.2% and 93.2%, respectively. CONCLUSIONS: PET/CT is superior to triple endoscopy in ruling out SPTs. With negative PET/CT, only direct laryngoscopy with biopsy may be necessary.

250 consecutive unilateral extravesical ureteral reimplantations in an outpatient setting.

PURPOSE: Unilateral extravesical ureteral reimplantation is comparable to intravesical procedures and more effective than subureteral injection to resolve vesicoureteral reflux. Initial reports showed that the procedure could be feasibly done on an outpatient basis. We present further data on a large series of consecutive, planned, outpatient unilateral extravesical ureteral reimplantations. MATERIALS AND METHODS: A total of 250 consecutive patients underwent scheduled outpatient unilateral extravesical ureteral reimplantation. We retrospectively reviewed their records. Patient data were collected on reflux laterality and grade, operative time, hospital stay, complications, need for rehospitalization and resolution rate on radiography 1 month postoperatively. RESULTS: A total of 209 females (84%) and 41 males (16%) underwent planned outpatient extravesical ureteral reimplantation, including on the left side in 158 (63%) and on the right side in 92 (37%). Mean reflux grade was 3.2 with grades II to V in 64 (26%), 96 (38%), 74 (30%) and 16 cases (7%), respectively. Average operative time was 63 minutes and average length of stay, defined as time from initial admission in to discharge home, was 6.2 hours (range 3 to 10 hours). Short-term and late complications occurred in 9 (3.6%) and 8 patients (3.2%), respectively. CONCLUSIONS: Extravesical ureteral reimplantation for unilateral vesicoureteral reflux may be consistently done on an outpatient basis with a reasonable complication rate and a low postoperative hospital admission rate.

Selective stimulation of human intrinsic laryngeal muscles: Analysis in a mathematical three-dimensional space.

OBJECTIVES/HYPOTHESIS: Standard stimulating methods using square waves do not appropriately restore physiological control of individual intrinsic laryngeal muscles (ILMs). To further explore our earlier study of evoked orderly recruitment by quasitrapezoidal (QT) currents, we integrated the contribution of the cricothyroideus (CT) with attention to mutual activation in an additional patient, based on recent studies of appropriate responses via strict recurrent laryngeal nerve (RLN) stimulation. STUDY DESIGN: Basic science study. METHODS: The patient received functional electrical stimulation (FES) with QT pulses at 5 Hz, 60 to 2,000 µAmp, 100 to 500 µs pulse width, 0 to 500 µs decay. Ipsilateral electromyography (EMG) responses were calculated using the average maximum amplitude, area under the curve, and the root mean square of the rectified amplitude waveforms. The thyroarytenoideus (TA), posterior cricoarytenoideus (PCA), lateral cricothyroideus (LCA), and the CT were each interrogated via two monopolar electrodes, values were recorded in MATLAB, exported to Excel, and analyzed. Individual and mutual recruitment configurations and activation delays with stimulation were explored using multiple regression and exploration factor analyses. RESULTS: A total of 868 EMG data points based on 18 trials and up to 11 subtrials were captured from each of the four ILMs. Various combinations of pulse amplitude, pulse width, and exponential decay were found to produce significant (P ≤ .001) individual ILM responses. CT mirrored the LCA, whereas the TA and PCA exhibited separate interactions along shared trajectories in a three-dimensional space. CONCLUSIONS: FES calibrated to individual and coupled ILMs offers promise for restoring normal and pathological contraction patterns via strict RLN stimulation. LEVEL OF EVIDENCE: 5 Laryngoscope, 130:967-973, 2020.

In-Office vs Operating Room Time to Treatment of Oropharyngeal Biopsies.

This cohort study evaluates whether in-office biopsies significantly improve time to biopsy and time to treatment compared with operating room biopsies.

Predicting feeding tube and tracheotomy dependence in laryngeal cancer patients.

CONCLUSIONS: The two scales reliably measure laryngeal edema and dysfunction in laryngeal cancer patients. The eight categories from these scales, and abnormal pharyngeal squeeze, can be used to form a new rating scale intended to help clinicians identify and circumvent swallowing complications after chemo-irradiation. OBJECTIVES: The objectives were to compare two laryngeal edema rating scales in laryngeal cancer patients and determine if post-radiation +/- chemotherapy edema predicts dependence on a feeding tube and/or tracheostomy. METHODS: A retrospective chart review between 2005-2008 revealed 28 laryngeal cancer patients status post-radiation +/- chemotherapy, with video laryngoscopies performed within 6 months after treatment. Four raters evaluated videos based on the Laryngopharyngeal Edema Scale (LES) and the Reflux Finding Score (RFS). Tracheostomy and feeding tube outcomes were then correlated with the two scales. RESULTS: Feeding tube and tracheostomy dependence were associated with pre-treatment vocal cord paralysis, advanced T stage, and chemoradiation. Eight categories from the LES and RFS scales were significantly associated with the need for a feeding tube.

Neural correlates of individual differences in pain-related fear and anxiety.

Although individual differences in fear and anxiety modulate the pain response and may even cause more suffering than the initiating physical stimulus, little is known about the neural systems mediating this relationship. The present study provided the first examination of the neural correlates of individual differences in the tendency to (1) feel anxious about the potentially negative implications of physical sensations, as measured by the anxiety sensitivity index (ASI), and (2) fear various types of physical pain, as indexed by the fear of pain questionnaire (FPQ). In separate sessions, participants completed these questionnaires and experienced alternating blocks of noxious thermal stimulation (45-50 degrees C) and neutral thermal stimulation (38 degrees C) during the collection of whole-brain fMRI data. Regression analyses demonstrated that during the experience of pain, ASI scores predicted activation of a medial prefrontal region associated with self-focused attention, whereas FPQ scores predicted activation of a ventral lateral frontal region associated with response regulation and anterior and posterior cingulate regions associated with monitoring and evaluation of affective responses. These functional relationships cannot be wholly explained by generalized anxiety (indexed by STAI-T scores), which did not significantly correlate with activation of any regions. The present findings may help clarify both the impact of individual differences in emotion on the neural correlates of pain, and the roles in anxiety, fear, and pain processing played by medial and orbitofrontal systems.

Improved wound healing of postischemic cutaneous flaps with the use of bone marrow-derived stem cells.

OBJECTIVES/HYPOTHESIS: To determine if the intravascular delivery of mesenchymal stem cells improves wound healing and blood perfusion to postischemic cutaneous flap tissues. STUDY DESIGN: Randomized controlled study. METHODS: A murine model of a cutaneous flap was created based on the inferior epigastric vessels. Mice (n = 14) underwent 3.5 hours of ischemia followed by reperfusion. Bone marrow stromal cells (BMSCs) 1 × 10(6) were injected intravenously. Wound healing was then assessed measuring percent flap necrosis, flap perfusion, and tensile strength of the flap after a period of 14 days. Localization of BMSCs was determined with radiolabeled and fluorescent labeled BMSCs. RESULTS: Postischemic cutaneous flap tissues treated with BMSCs demonstrated significantly less necrosis than control flaps (P <0.01). Beginning on postoperative day 5, BMSC-treated flaps demonstrated greater blood perfusion than untreated flaps (P <0.01). Tensile strength of BMSC-treated cutaneous flaps was significantly higher (P <0.01), with a mean strength of 283.4 ± 28.4 N/m than control flaps with a mean of 122.4 ± 23.5 N/m. Radiolabeled BMSCs localized to postischemic flaps compared to untreated tissues (P = 0.001). Fluorescent microscopy revealed incorporation of BMSCs into endothelial and epithelial tissues of postischemic flaps. CONCLUSIONS: This study demonstrates that the intravascular delivery of BMSCs increases wound healing and promotes flap survival following ischemia-reperfusion injury of cutaneous tissue flaps.

Evaluating a collaborative IT based research and development project.

In common with all projects, evaluating an Information Technology (IT) based research and development project is necessary in order to discover whether or not the outcomes of the project are successful. However, evaluating large-scale collaborative projects is especially difficult as: (i) stakeholders from different countries are involved who, almost inevitably, have diverse technological and/or application domain backgrounds and objectives; (ii) multiple and sometimes conflicting application specific and user-defined requirements exist; and (iii) multiple and often conflicting technological research and development objectives are apparent. In this paper, we share our experiences based on the large-scale integrated research project - The HUMBOLDT project - with project duration of 54 months, involving contributions from 27 partner organisations, plus 4 sub-contractors from 14 different European countries. In the HUMBOLDT project, a specific evaluation methodology was defined and utilised for the user evaluation of the project outcomes. The user evaluation performed on the HUMBOLDT Framework and its associated nine application scenarios from various application domains, resulted in not only an evaluation of the integrated project, but also revealed the benefits and disadvantages of the evaluation methodology. This paper presents the evaluation methodology, discusses in detail the process of applying it to the HUMBOLDT project and provides an in-depth analysis of the results, which can be usefully applied to other collaborative research projects in a variety of domains.

Functional magnetic resonance imaging identifies somatotopic organization of nociception in the human spinal cord.

Functional magnetic resonance imaging (fMRI) is a technique that uses blood oxygen-level-dependent (BOLD) signals to elucidate discrete areas of neuronal activity. Despite the significant number of fMRI human brain studies, few researchers have applied fMRI technology to investigating neuronal activity within the human spinal cord. Our study goals were to demonstrate that fMRI could reveal the following: (i) appropriate somatotopic activations in response to noxious stimuli in the deep and superficial dorsal horn of the human cervical spinal cord, and (ii) lateralization of fMRI activations in response to noxious stimulation in the right and left upper extremity. We subjected healthy participants to noxious stimulation during fMRI scans. Using a spiral in-out image sequence and retrospective correction for physiologic noise, we demonstrated that fMRI can create high-resolution, neuronal activation maps of the human cervical spinal cord. During nociceptive stimulation of all 4 sites (left deltoid, right deltoid, left thenar eminence and right thenar eminence), we found ipsilateral dorsal horn activation. Stimulation of the deltoid activated C5, whereas stimulation of the thenar eminence activated C6. Our study contributes to creating an objective analysis of pain transmission; other investigators can use these results to further study central nervous system changes that occur in patients with acute and chronic pain.

Your pain or mine? Common and distinct neural systems supporting the perception of pain in self and other.

Humans possess a remarkable capacity to understand the suffering of others. Cognitive neuroscience theories of empathy suggest that this capacity is supported by 'shared representations' of self and other. Consistent with this notion, a number of studies have found that perceiving others in pain and experiencing pain oneself recruit overlapping neural systems. Perception of pain in each of these conditions, however, may also cause unique patterns of activation, that may reveal more about the processing steps involved in each type of pain. To address this issue, we examined neural activity while participants experienced heat pain and watched videos of other individuals experiencing injuries. Results demonstrated (i) that both tasks activated anterior cingulate cortex and anterior insula, consistent with prior work; (ii) whereas self-pain activated anterior and mid insula regions implicated in interoception and nociception, other pain activated frontal, premotor, parietal and amygdala regions implicated in emotional learning and processing social cues; and (iii) that levels of trait anxiety correlated with activity in rostral lateral prefrontal cortex during perception of other pain but not during self-pain. Taken together, these data support the hypothesis that perception of pain in self and other, while sharing some neural commonalities, differ in their recruitment of systems specifically associated with decoding and learning about internal or external cues.

Control over brain activation and pain learned by using real-time functional MRI.

If an individual can learn to directly control activation of localized regions within the brain, this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease. Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain. Here, we found that by using real-time functional MRI (rtfMRI) to guide training, subjects were able to learn to control activation in the rostral anterior cingulate cortex (rACC), a region putatively involved in pain perception and regulation. When subjects deliberately induced increases or decreases in rACC fMRI activation, there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus. Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information, or using rtfMRI information derived from a different brain region, or sham rtfMRI information derived previously from a different subject. Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training. These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training, that voluntary control over activation in rACC leads to control over pain perception, and that these effects were powerful enough to impact severe, chronic clinical pain.

Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other.

Understanding one's own and other individual's emotional states is essential for maintaining emotional equilibrium and strong social bonds. Although the neural substrates supporting ref lection upon one's own feelings have been investigated, no studies have directly examined attributions about the internal emotional states of others to determine whether common or distinct neural systems support these abilities. The present study sought to directly compare brain regions involved in judging one's own, as compared to another individual's, emotional state. Thirteen participants viewed mixed valence blocks of photos drawn from the International Affective Picture System while whole-brain fMRI data were collected. Preblock cues instructed participants to evaluate either their emotional response to each photo, the emotional state of the central figure in each photo, or (in a baseline condition) whether the photo was taken indoors or outdoors. Contrasts indicated (1) that both self and other judgments activated the medial prefrontal cortex (MPFC), the superior temporal gyrus, and the posterior cingulate/precuneus, (2) that self judgments selectively activated subregions of the MPFC and the left temporal cortex, whereas (3) other judgments selectively activated the left lateral prefrontal cortex (including Broca's area) and the medial occipital cortex. These results suggest (1) that self and other evaluation of emotion rely on a network of common mechanisms centered on the MPFC, which has been hypothesized to support mental state attributions in general, and (2) that medial and lateral PFC regions selectively recruited by self or other judgments may be involved in attention to, and elaboration of, internally as opposed to externally generated information.