Dendritic Spine Shape Analysis: A Clustering Perspective

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201

MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Geometric modeling of 3D woven preforms in composite T-joints

A common method to fabricate net-shaped three-dimensional (3D) woven preforms for composite T-joints is to weave flat 3D preforms via a standard weaving machine with variation in binder yarn path and then separate the preform in the form of a bifurcation. Folding introduces fiber architecture deformation at the 3D woven bifurcation area. In this paper, a geometric modeling approach is proposed to represent the realistic fiber architecture, as a preprocessor for finite element analyses to predict composite structural performance. Supported by X-ray micro-computed tomography (mCT), three important deformation mechanisms are observed including yarn stack shifting, cross-section bending, and cross-section flattening resulting from the folding process. Furthermore, a set of mathematical formulae for simulation of the deformations in the junction region are developed and satisfactory agreement is observed when compared with mCT scan results

Determinants of Glycan Receptor Specificity of H2N2 Influenza A Virus Hemagglutinin

The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA). The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004) that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant) comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58) HA.National Institute of General Medical Sciences (U.S.) (GM57073)National Institute of General Medical Sciences (U.S.) (U54 GM62116)Singapore. Agency for Science, Technology and ResearchSingapore-MIT Alliance for Research and Technolog

Acceptability of the 6-PACK falls prevention program: A pre-implementation study in hospitals participating in a cluster randomized controlled trial

There is limited evidence to support the effectiveness of falls prevention interventions in the acute hospital setting. The 6-PACK falls prevention program includes a fall-risk tool; 'falls alert' signs; supervision of patients in the bathroom; ensuring patients' walking AIDS are within reach; toileting regimes; low-low beds; and bed/chair alarms. This study explored the acceptability of the 6-PACK program from the perspective of nurses and senior staff prior to its implementation in a randomised controlled trial. A mixed-methods approach was applied involving 24 acute wards from six Australian hospitals. Participants were nurses working on participating wards and senior hospital staff including: Nurse Unit Managers; senior physicians; Directors of Nursing; and senior personnel involved in quality and safety or falls prevention. Information on program acceptability (suitability, practicality and benefits) was obtained by surveys, focus groups and interviews. Survey data were analysed descriptively, and focus group and interview data thematically. The survey response rate was 60%. Twelve focus groups (n = 96 nurses) and 24 interviews with senior staff were conducted. Falls were identified as a priority patient safety issue and nurses as key players in falls prevention. The 6-PACK program was perceived to offer practical benefits compared to current practice. Nurses agreed fall-risk tools, low-low beds and alert signs were useful for preventing falls (>70%). Views were mixed regarding positioning patients' walking aid within reach. Practical issues raised included access to equipment; and risk of staff injury with low-low bed use. Bathroom supervision was seen to be beneficial, however not always practical. Views on the program appropriateness and benefits were consistent across nurses and senior staff. Staff perceived the 6-PACK program as suitable, practical and beneficial, and were open to adopting the program. Some practical concerns were raised highlighting issues to be addressed by the implementation plan

Expression of Stretch-Activated Two-Pore Potassium Channels in Human Myometrium in Pregnancy and Labor

Background: We tested the hypothesis that the stretch-activated, four-transmembrane domain, two pore potassium channels (K2P), TREK-1 and TRAAK are gestationally-regulated in human myometrium and contribute to uterine relaxation during pregnancy until labor. Methodology: We determined the gene and protein expression of K2P channels in non-pregnant, pregnant term and preterm laboring myometrium. We employed both molecular biological and functional studies of K2P channels in myometrial samples taken from women undergoing cesarean delivery of a fetus. Principal Findings: TREK-1, but not TREK-2, channels are expressed in human myometrium and significantly up-regulated during pregnancy. Down-regulation of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel was unregulated in the same women. Blockade of stretch-activated channels with a channel non-specific tarantula toxin (GsMTx-4) or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose-dependent manner in pregnant myometrium. Arachidonic acid treatment lowered contractile tension an effect blocked by fluphenazine. Functional studies are consistent with a role for TREK-1 in uterine quiescence. Conclusions: We provide evidence supporting a role for TREK-1 in contributing to uterine quiescence during gestation an

From wing to wing: the persistence of long ecological interaction chains in less-disturbed ecosystems

Human impact on biodiversity usually is measured by reduction in species abundance or richness. Just as important, but much more difficult to discern, is the anthropogenic elimination of ecological interactions. Here we report on the persistence of a long ecological interaction chain linking diverse food webs and habitats in the near-pristine portions of a remote Pacific atoll. Using biogeochemical assays, animal tracking, and field surveys we show that seabirds roosting on native trees fertilize soils, increasing coastal nutrients and the abundance of plankton, thus attracting manta rays to native forest coastlines. Partnered observations conducted in regions of this atoll where native trees have been replaced by human propagated palms reveal that this complex interaction chain linking trees to mantas readily breaks down. Taken together these findings provide a compelling example of how anthropogenic disturbance may be contributing to widespread reductions in ecological interaction chain length, thereby isolating and simplifying ecosystems