429 research outputs found
Nemo: a computational tool for analyzing nematode locomotion
The nematode Caenorhabditis elegans responds to an impressive range of
chemical, mechanical and thermal stimuli and is extensively used to investigate
the molecular mechanisms that mediate chemosensation, mechanotransduction and
thermosensation. The main behavioral output of these responses is manifested as
alterations in animal locomotion. Monitoring and examination of such
alterations requires tools to capture and quantify features of nematode
movement. In this paper, we introduce Nemo (nematode movement), a
computationally efficient and robust two-dimensional object tracking algorithm
for automated detection and analysis of C. elegans locomotion. This algorithm
enables precise measurement and feature extraction of nematode movement
components. In addition, we develop a Graphical User Interface designed to
facilitate processing and interpretation of movement data. While, in this
study, we focus on the simple sinusoidal locomotion of C. elegans, our approach
can be readily adapted to handle complicated locomotory behaviour patterns by
including additional movement characteristics and parameters subject to
quantification. Our software tool offers the capacity to extract, analyze and
measure nematode locomotion features by processing simple video files. By
allowing precise and quantitative assessment of behavioral traits, this tool
will assist the genetic dissection and elucidation of the molecular mechanisms
underlying specific behavioral responses.Comment: 12 pages, 2 figures. accepted by BMC Neuroscience 2007, 8:8
The formation of professional identity in medical students: considerations for educators
<b>Context</b> Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.<p></p>
<b>Objectives</b> This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.<p></p>
<b>Implications</b> A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.<p></p>
<b>Conclusions</b> Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education
Dimensionality and dynamics in the behavior of C. elegans
A major challenge in analyzing animal behavior is to discover some underlying
simplicity in complex motor actions. Here we show that the space of shapes
adopted by the nematode C. elegans is surprisingly low dimensional, with just
four dimensions accounting for 95% of the shape variance, and we partially
reconstruct "equations of motion" for the dynamics in this space. These
dynamics have multiple attractors, and we find that the worm visits these in a
rapid and almost completely deterministic response to weak thermal stimuli.
Stimulus-dependent correlations among the different modes suggest that one can
generate more reliable behaviors by synchronizing stimuli to the state of the
worm in shape space. We confirm this prediction, effectively "steering" the
worm in real time.Comment: 9 pages, 6 figures, minor correction
Intra-tumoural extra-cellular pH: a useful parameter of response to chemotherapy in syngeneic tumour lines
Reliable surrogate markers of response to anticancer therapy remain a desirable tool for preclinical modelling and clinical practice in oncology. Clinical evaluation is relatively unreliable when attempting to assess rapidly and prospectively the outcome of treatment. Fluxes in released or circulating tumour marker levels are a useful but inconsistent marker of cytotoxic response. Serial measurement of circulating tumour cells appears to have some utility as a surrogate marker, but assay systems are expensive, and many cancers are not associated with the presence of circulating tumour cells. Because tissue breakdown is associated with release of nucleic acids and other cellular products, we reasoned that serial measurement of intra-tumoural pH may correlate with the extent of tumour lysis, and thus with outcomes of cytotoxic chemotherapy. Doxorubicin-sensitive and doxorubicin-resistant sublines of P388 murine monocytic leukaemia in C57BL/6 mice were treated with increasing concentrations of doxorubicin. Tumours were serially measured by conventional bi-dimensional methods and pH was sampled using a bevelled tip electrode. Mean and median pH changes were statistically different in responsive and resistant tumours, and amplitude of change correlated with long-term responses to doxorubicin. Serial sampling of pH in tumour masses may provide a useful surrogate of long-term response to chemotherapy
Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.
BACKGROUND: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. CASE PRESENTATION: A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1. CONCLUSION: This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights
The RR Lyrae Distance Scale
We review seven methods of measuring the absolute magnitude M_V of RR Lyrae
stars in light of the Hipparcos mission and other recent developments. We focus
on identifying possible systematic errors and rank the methods by relative
immunity to such errors. For the three most robust methods, statistical
parallax, trigonometric parallax, and cluster kinematics, we find M_V (at
[Fe/H] = -1.6) of 0.77 +/- 0.13, 0.71 +/- 0.15, 0.67 +/- 0.10. These methods
cluster consistently around 0.71 +/- 0.07. We find that Baade-Wesselink and
theoretical models both yield a broad range of possible values (0.45-0.70 and
0.45-0.65) due to systematic uncertainties in the temperature scale and input
physics. Main-sequence fitting gives a much brighter M_V = 0.45 +/- 0.04 but
this may be due to a difference in the metallicity scales of the cluster giants
and the calibrating subdwarfs. White-dwarf cooling-sequence fitting gives 0.67
+/- 0.13 and is potentially very robust, but at present is too new to be fully
tested for systematics. If the three most robust methods are combined with
Walker's mean measurement for 6 LMC clusters, V_{0,LMC} = 18.98 +/- 0.03 at
[Fe/H] = -1.9, then mu_{LMC} = 18.33 +/- 0.08.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles',
A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21
pages including 1 table; uses Kluwer's crckapb.sty LaTeX style file, enclose
A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials.
Background The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according to CTCAE, v4.03, to identify variables associated with EAs and their prognostic significance in a phase I population.Methods A retrospective chart review was performed of 1088 cases in 82 phase I clinical trials consecutively treated from 2011 to 2015 at the Drug Development Unit of the Royal Marsden Hospital. Cox regression analysis was performed to examine the relationship between overall survival (OS) and baseline characteristics, treating the occurrence of grade III/IV EAs as a time-varying covariate.Results The most common emergent EAs (all grades) were as follows: hyponatraemia 62%, hypokalaemia 40%, hypophosphataemia 32%, hypomagnesaemia 17% and hypocalcaemia 12%. Grade III/IV EAs occurred in 19% of cases. Grade III/IV EAs occurred during the dose-limiting toxicity window in 8.46% of cases. Diarrhoea was associated with hypomagnesaemia at all grades (p < 0.001), hyponatraemia at all grades (p = 0.006) and with G3/G4 hypokalaemia (p = 0.02). Baseline hypoalbuminaemia and hyponatraemia were associated with a higher risk of developing other EAs during the trial in the univariate analysis. Patients who developed grade III/IV EAs during follow-up had an inferior median OS (26 weeks vs 37 weeks, hazard ratio = 1.61; p < 0.001).Conclusion This is the first study to demonstrate the clinical significance of baseline hypoalbuminaemia and hyponatraemia, which are predictors of development of other EAs in phase I patients. Grade III/IV EAs are adverse prognostic factors of OS independent of serum albumin levels
Review for the generalist: evaluation of low back pain in children and adolescents
Back pain is common in children and adolescents. Most cases of back pain are non-specific and self-limiting. In children and adolescents, pain is usually related to the posterior elements of the spine and disc-related problems are rare. Serious pathology, including malignancy and infection needs to be excluded. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the immature skeleton. Diagnostic imaging is useful in the evaluation of a child or adolescent with low back pain and can help guide management. This article will review common causes of back pain in the pediatric population
Personality, personnel selection, and job performance
Job Performance: The term job performance can
either refer to the objective or subjective outcomes
one achieves in a specific job (e.g., the profit of a
sales persons, the number of publications of a
scientist, the number of successful operations of
a surgeon) or to work-related activities (e.g., writing
an article, conducting specific surgical acts).
In the majority of research on this topic, job performance
as an outcome is used.
Personnel selection: Personnel selection
refers to the process of selecting the best
employees for specific jobs.
Introduction
One major application of personality research is in
the area of personnel selection. The key question
in this area is to which extent personality can
predict how well a candidate will perform on the
job he or she is applying for. Most scholars in this
area acknowledge that personality has predictive
validity for job performance. In line with this,
personality assessment is part of the selection
procedure in many organizations
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