Biological and Procedural Predictors of Outcome in the Stroke Preclinical Assessment Network (SPAN) Trial.

BACKGROUND: The SPAN trial (Stroke Preclinical Assessment Network) is the largest preclinical study testing acute stroke interventions in experimental focal cerebral ischemia using endovascular filament middle cerebral artery occlusion (MCAo). Besides testing interventions against controls, the prospective design captured numerous biological and procedural variables, highlighting the enormous heterogeneity introduced by the multicenter structure that might influence stroke outcomes. Here, we leveraged the unprecedented sample size achieved by the SPAN trial and the prospective design to identify the biological and procedural variables that affect experimental stroke outcomes in transient endovascular filament MCAo. METHODS: The study cohort included all mice enrolled and randomized in the SPAN trial (N=1789). Mice were subjected to 60-minute MCAo and followed for a month. Thirteen biological and procedural independent variables and 4 functional (weight loss and 4-point neuroscore on days 1 and 2, corner test on days 7 and 28, and mortality) and 3 tissue (day 2, magnetic resonance imaging infarct volumes and swelling; day 30, magnetic resonance imaging tissue loss) outcome variables were prospectively captured. Multivariable regression with stepwise elimination was used to identify the predictors and their effect sizes. RESULTS: Older age, active circadian stage at MCAo, and thinner and longer filament silicone tips predicted higher mortality. Older age, larger body weight, longer anesthesia duration, and longer filament tips predicted worse neuroscores, while high-fat diet and blood flow monitoring predicted milder neuroscores. Older age and a high-fat diet predicted worse corner test performance. While shorter filament tips predicted more ipsiversive turning, longer filament tips appeared to predict contraversive turning. Age, sex, and weight interacted when predicting the infarct volume. Older age was associated with smaller infarcts on day 2 magnetic resonance imaging, especially in animals with larger body weights; this association was most conspicuous in females. High-fat diet also predicted smaller infarcts. In contrast, the use of cerebral blood flow monitoring and more severe cerebral blood flow drop during MCAo, longer anesthesia, and longer filament tips all predicted larger infarcts. Bivariate analyses among the dependent variables highlighted a disconnect between tissue and functional outcomes. CONCLUSIONS: Our analyses identified variables affecting endovascular filament MCAo outcome, an experimental stroke model used worldwide. Multiple regression refuted some commonly reported predictors and revealed previously unrecognized associations. Given the multicenter prospective design that represents a sampling of real-world conditions, the degree of heterogeneity mimicking clinical trials, the large number of predictors adjusted for in the multivariable model, and the large sample size, we think this is the most definitive analysis of the predictors of preclinical stroke outcome to date. Future multicenter experimental stroke trials should standardize or at least ensure a balanced representation of the biological and procedural variables identified herein as potential confounders.

Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury.

Traumatic brain injury (TBI) is associated with mortality and morbidity worldwide. Accumulating pre-clinical and clinical data suggests TBI is the leading extrinsic cause of progressive neurodegeneration. Neurological deterioration after either a single moderate-severe TBI or repetitive mild TBI often resembles dementia in aged populations; however, no currently approved therapies adequately mitigate neurodegeneration. Inflammation correlates with neurodegenerative changes and cognitive dysfunction for years post-TBI, suggesting a potential association between immune activation and both age- and TBI-induced cognitive decline. Inflammaging, a chronic, low-grade sterile inflammation associated with natural aging, promotes cognitive decline. Cellular senescence and the subsequent development of a senescence associated secretory phenotype (SASP) promotes inflammaging and cognitive aging, although the functional association between senescent cells and neurodegeneration is poorly defined after TBI. In this mini-review, we provide an overview of the pre-clinical and clinical evidence linking cellular senescence with poor TBI outcomes. We also discuss the current knowledge and future potential for senotherapeutics, including senolytics and senomorphics, which kill and/or modulate senescent cells, as potential therapeutics after TBI.

Covid-19 Opens up domestic market for Indian shrimp.

COVID-19 pandemic presents both a challenge and an opportunity to the Indian shrimp sector. With revitalizing the institutional arrangements and redirecting the focus, the Indian shrimp industry can flourish just by adapting to the needs of the local demand, even when the export prospects are uncertain. This paper takes a historical perspective of Indian shrimp farming and exports and suggests a domestic alternative/supplementary market for Indian farmed shrimp, resulting from COVID-19.

Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus.

Hemoglobin (Hb) is the oxygen transport protein in erythrocytes. In blood, Hb is a tetramer consisting of two Hb-alpha (Hb-α) chains and two Hb-beta (Hb-ß) chains. A number of studies have also shown that Hb-α is also expressed in neurons in both the rodent and human brain. In the current study, we examined for age-related regulation of neuronal Hb-α and hypoxia in the hippocampus and cerebral cortex of intact male and female mice. In addition, to confirm the role and functions of neuronal Hb-α, we also utilized lentivirus CRISPR interference-based Hb-α knockdown (Hb-α CRISPRi KD) in the non-ischemic and ischemic mouse hippocampus and examined the effect on neuronal oxygenation, as well as induction of hypoxia-inducible factor-1α (HIF-1α) and its downstream pro-apoptotic factors, PUMA and NOXA, and on neuronal survival and neurodegeneration. The results of the study revealed an age-related decrease in neuronal Hb-α levels and correlated increase in hypoxia in the hippocampus and cortex of intact male and female mice. Sex differences were observed with males having higher neuronal Hb-α levels than females in all brain regions at all ages. In vivo Hb-α CRISPRi KD in the mouse hippocampus resulted in increased hypoxia and elevated levels of HIF-1α, PUMA and NOXA in the non-ischemic and ischemic mouse hippocampus, effects that were correlated with a significant decrease in neuronal survival and increased neurodegeneration. As a whole, these findings indicate that neuronal Hb-α decreases with age in mice and has an important role in regulating neuronal oxygenation and neuroprotection.

Ganglioside GD3 is up-regulated in microglia and regulates phagocytosis following global cerebral ischemia.

Gangliosides, the major sialic-acid containing glycosphingolipids in the mammalian brain, play important roles in brain development and neural functions. Here, we show that the b-series ganglioside GD3 and its biosynthetic enzyme, GD3-synthase (GD3S), were up-regulated predominantly in the microglia of mouse hippocampus from 2 to 7 days following global cerebral ischemia (GCI). Interestingly, GD3S knockout (GD3S-KO) mice exhibited decreased hippocampal neuronal loss following GCI, as compared to wild-type (WT) mice. While comparable levels of astrogliosis and microglial proliferation were observed between WT and GD3S-KO mice, the phagocytic capacity of the GD3S-KO microglia was significantly compromised after GCI. At 2 and 4 days following GCI, the GD3S-KO microglia demonstrated decreased amoebic morphology, reduced neuronal material engulfment, and lower expression of the phagolysosome marker CD68, as compared to the WT microglia. Finally, by using a microglia-primary neuron co-culture model, we demonstrated that the GD3S-KO microglia isolated from mouse brains at 2 days after GCI are less neurotoxic to co-cultured hippocampal neurons than the WT-GCI microglia. Moreover, the percentage of microglia with engulfed neuronal elements in the co-cultured wells was also significantly decreased in the GD3S-KO mice after GCI. Interestingly, the impaired phagocytic capacity of GD3S-KO microglia could be partially restored by pre-treatment with exogenous ganglioside GD3. Altogether, this study provides functional evidence that ganglioside GD3 regulates phagocytosis by microglia in an ischemic stroke model. Our data also suggest that the GD3-linked microglial phagocytosis may contribute to the mechanism of delayed neuronal death following ischemic brain injury.

A technique for quantifying the sensitivity of dosimetric tool gamma with 2D detector array in pretreatment IMRT plans by segment deletion method.

OBJECTIVES: Motivation of this study is to check the sensitivity of dosimetric tool gamma with 2D detector array combination when unexpected errors occur while transferring intensity-modulated radiation therapy treatment plans from planning system to treatment unit. METHODS: This study consists of 17 head and neck cancer patient's treatment plans. Nine types of verification plans are created for all 17 clinically approved treatment plans by consecutively deleting different segments (up to eight) one by one from each field of the plan. Decrement factor (χ) is introduced in our study which illustrated the degree of decay of gamma passing rate when intentional errors are introduced. We analyzed the data by two different methods-one without selecting the region of interest (ROI) in dose distributions and the other by selecting the region of interest. RESULTS: By linear regression, the absolute value of slopes is 0.025, 0.024 and 0.015 without ROI and 0.030, 0.027 and 0.015 with ROI for 2%/2 mm, 3%/3 mm and 5%/5 mm criteria, respectively. The higher absolute value of the fitted slope indicates the higher sensitivity of this method to identify erroneous plan in treatment unit. The threshold value for 2%/2 mm equivalent to 95% passing criteria in 3%/3 mm used in clinical practice is obtained as 83.44%. CONCLUSIONS: The 2D detector array with dosimetric tool gamma is less sensitive in detecting errors when unprecedented errors of segment deletion occur within the treatment plans.

Cannabidiol (CBD) modulation of apelin in acute respiratory distress syndrome.

Considering lack of target-specific antiviral treatment and vaccination for COVID-19, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve COVID-19-infected patient outcomes. In a follow-up study to our recent findings indicating the potential of Cannabidiol (CBD) in the treatment of acute respiratory distress syndrome (ARDS), here we show for the first time that CBD may ameliorate the symptoms of ARDS through up-regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system. By administering intranasal Poly (I:C), a synthetic viral dsRNA, while we were able to mimic the symptoms of ARDS in a murine model, interestingly, there was a significant decrease in the expression of apelin in both blood and lung tissues. CBD treatment was able to reverse the symptoms of ARDS towards a normal level. Importantly, CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID-19 and many other pathologic conditions.

Neurological consequences of COVID-19: what have we learned and where do we go from here?

The coronavirus disease-19 (COVID-19) pandemic is an unprecedented worldwide health crisis. COVID-19 is caused by SARS-CoV-2, a highly infectious pathogen that is genetically similar to SARS-CoV. Similar to other recent coronavirus outbreaks, including SARS and MERS, SARS-CoV-2 infected patients typically present with fever, dry cough, fatigue, and lower respiratory system dysfunction, including high rates of pneumonia and acute respiratory distress syndrome (ARDS); however, a rapidly accumulating set of clinical studies revealed atypical symptoms of COVID-19 that involve neurological signs, including headaches, anosmia, nausea, dysgeusia, damage to respiratory centers, and cerebral infarction. These unexpected findings may provide important clues regarding the pathological sequela of SARS-CoV-2 infection. Moreover, no efficacious therapies or vaccines are currently available, complicating the clinical management of COVID-19 patients and emphasizing the public health need for controlled, hypothesis-driven experimental studies to provide a framework for therapeutic development. In this mini-review, we summarize the current body of literature regarding the central nervous system (CNS) effects of SARS-CoV-2 and discuss several potential targets for therapeutic development to reduce neurological consequences in COVID-19 patients.

Cell-free soluble expression of the membrane protein PsbS.

Photosystem II subunit S (PsbS) is a membrane protein that plays an exclusive role in non-photochemical quenching for photoprotection of plants under high-light conditions. The activation mechanism of PsbS and its pH-induced conformational changes are currently unknown. For structural investigation of PsbS, effective synthesis of PsbS with selective isotope or electron-spin labels or non-natural amino acids incorporated would be a great asset. Here we present cell-free (CF) expression as a successful method for in vitro production of PsbS that would allow such incorporation. The addition of several detergents, liposomes and lipid nanodiscs was tested for achieving soluble CF expression of PsbS. We have optimized the CF method to yield soluble PsbS of ∼500 ng/µl using a continuous-exchange method at 30 °C, along with a successful purification and refolding of PsbS in n-Dodecyl ß-D-maltoside (ß-DM) detergent. We expect that the presented protocols are transferrable for in vitro expression of other membrane proteins of the Light-Harvesting Complex family.

Activation of Myeloid TLR4 Mediates T Lymphocyte Polarization after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naive T lymphocytes, enhanced the polarization of T effector cells (TH1/TH17), and decreased the production of regulatory T cells in an MLR. Similarly, elevated T effector cell polarization within blood and brain tissue was attenuated by myeloid cell depletion after TBI. Functionally, C3H/HeJ (TLR4 mutant) mice reversed M1 macrophage and TH1/TH17 polarization after TBI compared with C3H/OuJ (wild-type) mice. Moreover, brain monocytes isolated from C3H/HeJ mice were less potent stimulators of T lymphocyte proliferation and TH1/TH17 polarization compared with C3H/OuJ monocytes. Taken together, our data implicate TLR4-dependent, M1 macrophage trafficking/polarization into the CNS as a key mechanistic link between acute TBI and long-term, adaptive immune responses.

Validation of Dolphin dosimetry in three dimensional patient-specific quality assurance programme.

AIM: The aim of this study is to commission and validate Dolphin-Compass dosimetry as a patient-specific Quality Assurance (QA) device. BACKGROUND: The advancement of radiation therapy in terms of highly conformal delivery techniques demands a novel method of patient-specific QA. Dolphin-Compass system is a dosimetry solution capable of doing different QA in radiation therapy. MATERIALS AND METHODS: Dolphin, air-vented ionization detector array mounted on Versa-HD Linear Accelerator (LINAC) was used for measurements. The Compass is a dose computation algorithm which requires modelling of LINAC head similar to other Treatment Planning Systems (TPS). The dosimetry system was commissioned after measuring the required beam data. The validation was performed by comparison of treatment plans generated in Monaco TPS against the measurement data. Different types of simple, complex, static and dynamic radiation fields and highly conformal treatment plans of patients were used in this study. RESULTS: For all field sizes, point doses obtained from Dolphin-Compass dosimetry were in good agreement with the corresponding TPS calculated values in most of the regions, except the penumbra, outside field and at build-up depth. The results of gamma passing rates of measurements by using different Multi-leaf Collimator patterns and Intensity Modulated Radiation Therapy fluence were also found to be in good correlation with the corresponding TPS values. CONCLUSIONS: The commissioning and validation of dosimetry was performed with the help of various fields, MLC patterns and complex treatment plans. The present study also evaluated the efficiency of the 3D dosimetry system for the QA of complex treatment plans.

Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization.

Inflammation is an important mediator of secondary neurological injury after traumatic brain injury (TBI). Endocannabinoids, endogenously produced arachidonate based lipids, have recently emerged as powerful anti-inflammatory compounds, yet the molecular and cellular mechanisms underlying these effects are poorly defined. Endocannabinoids are physiological ligands for two known cannabinoid receptors, CB1R and CB2R. In the present study, we hypothesized that selective activation of CB2R attenuates neuroinflammation and reduces neurovascular injury after TBI. Using a murine controlled cortical impact (CCI) model of TBI, we observed a dramatic upregulation of CB2R within infiltrating myeloid cells beginning at 72 h. Administration of the selective CB2R agonist, GP1a (1-5 mg/kg), attenuated pro-inflammatory M1 macrophage polarization, increased anti-inflammatory M2 polarization, reduced edema development, enhanced cerebral blood flow, and improved neurobehavioral outcomes after TBI. In contrast, the CB2R antagonist, AM630, worsened outcomes. Taken together, our findings support the development of selective CB2R agonists as a therapeutic strategy to improve TBI outcomes while avoiding the psychoactive effects of CB1R activation.

Spectrally resolved single-molecule electrometry.

Escape-time electrometry is a recently developed experimental technique that offers the ability to measure the effective electrical charge of a single biomolecule in solution with sub-elementary charge precision. The approach relies on measuring the average escape-time of a single charged macromolecule or molecular species transiently confined in an electrostatic fluidic trap. Comparing the experiments with the predictions of a mean-field model of molecular electrostatics, we have found that the measured effective charge even reports on molecular conformation, e.g., folded or disordered state, and non-uniform charge distribution in disordered proteins or polyelectrolytes. Here we demonstrate the ability to use the spectral dimension to distinguish minute differences in electrical charge between individual molecules or molecular species in a single simultaneous measurement, under identical experimental conditions. Using one spectral channel for referenced measurement, this kind of photophysical distinguishability essentially eliminates the need for accurate knowledge of key experimental parameters, otherwise obtained through intensive characterization of the experimental setup. As examples, we demonstrate the ability to detect small differences (∼5%) in the length of double-stranded DNA fragments as well as single amino acid exchange in an intrinsically disordered protein, prothymosin α.

Echocardiographic and electrocardiographic presentations of patients with endomyocardial biopsy-proven cardiac amyloidosis.

OBJECTIVE: Cardiac amyloidosis is under diagnosed and its prevalence is unknown. This is a retrospective, nonrandomised, single centre study of patients with endomyocardial biopsy-proven cardiac amyloidosis focusing on their echocardiographic and electrocardiogram (ECG) presentations. This is the first case series in Malaysia on this subject. METHODS: We identified all of our endomyocardial biopsyproven cardiac amyloidosis patients from January 2010 to January 2018 and reviewed their medical records. All patients echocardiographic and ECG findings reviewed and analysed comparing to basic mean population value. RESULTS: In total there are 13 biopsy-proven cardiac amyloidosis patients. All of the biopsies shows light chain (AL) amyloid. Majority of the patients (8, 61.5%) is male, and most of our patients (8, 61.5%) is Chinese. All seven patients on whom we performed deformation imaging have apical sparing pattern on longitudinal strain echocardiogram. Mean ejection fraction is 49.3%, (SD=7.9). All patients have concentric left ventricular hypertrophy and right ventricular hypertrophy. Diastolic dysfunction was present in all of our patients with nine out of 13 patients (69.2%) having restrictive filling patterns (E/A ≥2.0 E/e' ≥15). On electrocardiogram, 12 (92%) patients have prolonged PR interval (median 200ms, IQR 76.50ms) and 9 (69.2%) patients have pseudoinfarct pattern. CONCLUSION: Echocardiography plays an important role in diagnosing cardiac amyloidosis. The findings of concentric left ventricular hypertrophy with preserved ejection fraction without increased in loading condition should alert the clinician towards its possibility. This is further supported by right ventricular hypertrophy and particularly longitudinal strain imaging showing apical sparing pattern.

White matter damage after traumatic brain injury: A role for damage associated molecular patterns.

Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5'-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors, including toll-like receptor and purinergic receptors, play in progressive neurological injury after TBI is detailed. Finally, we provide support for the notion that resident and infiltrating macrophages are critical cellular targets linking acute DAMP release with adaptive immune responses and chronic injury after TBI. The therapeutic potential of targeting DAMPs and barriers to clinical translational, in the context of TBI patient management, are discussed.

A simple model for electrical charge in globular macromolecules and linear polyelectrolytes in solution.

We present a model for calculating the net and effective electrical charge of globular macromolecules and linear polyelectrolytes such as proteins and DNA, given the concentration of monovalent salt and pH in solution. The calculation is based on a numerical solution of the non-linear Poisson-Boltzmann equation using a finite element discretized continuum approach. The model simultaneously addresses the phenomena of charge regulation and renormalization, both of which underpin the electrostatics of biomolecules in solution. We show that while charge regulation addresses the true electrical charge of a molecule arising from the acid-base equilibria of its ionizable groups, charge renormalization finds relevance in the context of a molecule's interaction with another charged entity. Writing this electrostatic interaction free energy in terms of a local electrical potential, we obtain an "interaction charge" for the molecule which we demonstrate agrees closely with the "effective charge" discussed in charge renormalization and counterion-condensation theories. The predictions of this model agree well with direct high-precision measurements of effective electrical charge of polyelectrolytes such as nucleic acids and disordered proteins in solution, without tunable parameters. Including the effective interior dielectric constant for compactly folded molecules as a tunable parameter, the model captures measurements of effective charge as well as published trends of pKa shifts in globular proteins. Our results suggest a straightforward general framework to model electrostatics in biomolecules in solution. In offering a platform that directly links theory and experiment, these calculations could foster a systematic understanding of the interrelationship between molecular 3D structure and conformation, electrical charge and electrostatic interactions in solution. The model could find particular relevance in situations where molecular crystal structures are not available or rapid, reliable predictions are desired.

Reducing the surface roughness of dental acrylic resins by using an eggshell abrasive material.

STATEMENT OF PROBLEM: Excessive surface roughness of denture base resins adversely impacts oral health. PURPOSE: The purpose of this in vitro study was to examine the abrasive potential of eggshell powder in reducing the surface roughness of denture base resins. MATERIAL AND METHODS: Thirty poly(methyl methacrylate) specimens were fabricated and polished with eggshell powders of different particle sizes and with pumice. The average surface roughness (Ra) after polishing was measured with a profilometer. Scanning electron microscope and optical electron microscope techniques were used to assess the surface roughness morphology of the specimens. ANOVA was used to analyze the Ra values. The Tukey honest significant differences and Bonferroni tests were used to identify differences between the 2 abrasive materials (α=.05). RESULTS: Significant differences in the Ra values were observed between the fine and medium eggshell powder abrasives (P<.05). Similarly, significant differences were found between pumice and the fine eggshell powder abrasives (P<.001). No significant differences were found between pumice and the medium eggshell powder abrasive (P>.05). Specimens polished with pumice had the highest Ra values, whereas specimens polished with the fine eggshell powder abrasive had the lowest Ra values. CONCLUSIONS: By connecting the Ra values to the threshold limit value of 0.2 µm, eggshell powder abrasive finished denture acrylic resin surfaces better than pumice.

What is the publication rate for presentations given at the British Academic Conference in Otolaryngology (BACO)?

OBJECTIVES: The publication rate of some large academic meetings such as the American Academy of Otolaryngology-Head and Neck Surgery has been reported as 32%. We aimed to compare the rate of publication at the British Academic Conference in Otolaryngology (BACO) to allow surveillance of research activity in the United Kingdom (UK). DESIGN AND SETTING: The abstract records of both BACO 2009 and 2012 were examined. The MEDLINE database was searched using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and an iterative approach. We recorded time to publication as well as the authors' region and journal. MAIN OUTCOME MEASURES: publication rate by conference, region and journal. RESULTS: Twice the number of presentations were made at BACO 2012 (n = 814) compared to BACO 2009 (n = 387). Absolute numbers of publications were 158 in 2012 and 92 in 2009. Overall, the publication rate dropped from 24% overall in 2009 to 19% in 2012. This difference in proportions was not significant (P = 0.08). The number of abstracts accepted for BACO 2012 doubled from BACO 2009 in nearly every subspecialty category, except the general/training category, which trebled. For both conferences, head and neck was the largest subspecialty abstract category, as well as the largest subspecialty publication category. CONCLUSIONS: This study showed that the majority of abstracts presented at BACO 2009 and 2012 did not progress to publication. The rate of publication was similar to that seen in other general ENT meetings but do not compare favourably to the 69% rate seen for presentations made at the Otorhinolaryngological Research Society (ORS). The large increase in accepted abstracts at BACO 2012 may reflect growing competition for entry to specialist training.

An analysis of the fate of 917 manuscripts rejected from Clinical Otolaryngology.

OBJECTIVES: The fate of all manuscripts rejected from the journal Clinical Otolaryngology (CO) over a three-year period was investigated. The aim was to review publication rate, delay and the impact factors of the journals that the papers went on to be published in. DESIGN: In total, 917 papers were rejected from CO between 2011 and 2013. The fate of these manuscripts was determined by searching for the corresponding author's surname, and if necessary keywords from the manuscript title, in both PubMed and Google Scholar. MAIN OUTCOME MEASURES: The main outcome measures recorded were as follows: the subsequent publication of the article, delay to publication and journal of publication. RESULTS: In all, 511 papers were subsequently published in journals, representing 55.7% of all rejected manuscripts. The average delay was 15.1 months (standard deviation [sd] = 8.8). The impact factor of CO was found to be higher than the average of the journals that accepted the rejected manuscripts in all 3 years. Only 41 (8%) papers were published in journals with a higher impact factor than CO. Of all subsequently accepted manuscripts, 60 (11.7%) were found only on Google Scholar (and not on PubMed). CONCLUSIONS: Rejection from CO certainly does not prevent subsequent publication, although the papers tend to be published after a lengthy delay and in journals with a lower impact factor than CO. When performing literature searches, it is important to search more than one database to ensure as many of the relevant articles are found as possible.

Characterising brain network topologies: A dynamic analysis approach using heat kernels.

Network theory provides a principled abstraction of the human brain: reducing a complex system into a simpler representation from which to investigate brain organisation. Recent advancement in the neuroimaging field is towards representing brain connectivity as a dynamic process in order to gain a deeper understanding of how the brain is organised for information transport. In this paper we propose a network modelling approach based on the heat kernel to capture the process of heat diffusion in complex networks. By applying the heat kernel to structural brain networks, we define new features which quantify change in heat propagation. Identifying suitable features which can classify networks between cohorts is useful towards understanding the effect of disease on brain architecture. We demonstrate the discriminative power of heat kernel features in both synthetic and clinical preterm data. By generating an extensive range of synthetic networks with varying density and randomisation, we investigate heat diffusion in relation to changes in network topology. We demonstrate that our proposed features provide a metric of network efficiency and may be indicative of organisational principles commonly associated with, for example, small-world architecture. In addition, we show the potential of these features to characterise and classify between network topologies. We further demonstrate our methodology in a clinical setting by applying it to a large cohort of preterm babies scanned at term equivalent age from which diffusion networks were computed. We show that our heat kernel features are able to successfully predict motor function measured at two years of age (sensitivity, specificity, F-score, accuracy = 75.0, 82.5, 78.6, and 82.3%, respectively).