Publications by authors named "Martin Isabelle"

47 Publications

Congenital immobility and stiffness related to biallelic variants.

Neurol Genet 2020 Dec 24;6(6):e520. Epub 2020 Sep 24.

Département de Génétique (R.B., S.W., B.K., S.C.-B., M.-C.V., L.B., D.H., J.B., A.A., C.M.), Hôpital Armand Trousseau & Groupe Hospitalier Pitié-Salpêtrière, and Unité de Neuropédiatrie et Pathologie du Développement (D.D., M.M., D.R., A.I., T.B.V.), Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris; Centre de Référence des Maladies Neurogénétiques (D.D., D.R.); Centre de Référence Anomalies du Développement et Syndromes Malformatifs (S.W., C.M.); Hôpital de Pédiatrie et de Rééducation (K.M.), Bullion; INSERM UMR 1141 (D.R.), Paris; Réanimation Néonatale et Pédiatrique (P.-L.L.), and Service de Néonatologie (F.K., I.M.), Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris; Centre de Référence Déficience Intellectuelles de Causes Rares (D.H., A.A., T.B.V., C.M.); and INSERM (C.M.), U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Epinière, Paris, France.

Objective: To delineate the phenotype associated with biallelic variants.

Methods: We describe 2 new patients with -related disorder diagnosed by whole-exome sequencing and compare their phenotype to 6 previous patients.

Results: Patients 1 and 2 had a similar distinctive phenotype comprising congenital stiffness of limbs, absent spontaneous movements, weak sucking, and hypoventilation. Both had absent brainstem evoked auditory responses (BEARs). Patient 1 carried the homozygous p.(His357Argfs*15) variant in . In the light of the finding in patient 1, a second reading of exome data for patient 2 revealed the novel homozygous p.(Gly128Val) variant.

Conclusions: Analysis of the phenotypes of these 2 patients and of the 6 previous cases showed that biallelic mutations are responsible for a unique congenital encephalopathy likely comprising absent BEAR, different from hyperekplexia and other conditions with neonatal hypertonia.
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http://dx.doi.org/10.1212/NXG.0000000000000520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577533PMC
December 2020

Raman spectroscopy to differentiate between fresh tissue samples of glioma and normal brain: a comparison with 5-ALA-induced fluorescence-guided surgery.

J Neurosurg 2020 Oct 2:1-11. Epub 2020 Oct 2.

2Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford.

Objective: Raman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It is nondestructive and no sample preparation is required. The aim of this study was to evaluate the ability of Raman spectroscopy to differentiate between glioma and normal brain when using fresh biopsy samples and, in the case of glioblastomas, to compare the performance of Raman spectroscopy to predict the presence or absence of tumor with that of 5-aminolevulinic acid (5-ALA)-induced fluorescence.

Methods: A principal component analysis (PCA)-fed linear discriminant analysis (LDA) machine learning predictive model was built using Raman spectra, acquired ex vivo, from fresh tissue samples of 62 patients with glioma and 11 glioma-free brain samples from individuals undergoing temporal lobectomy for epilepsy. This model was then used to classify Raman spectra from fresh biopsies from resection cavities after functional guided, supramaximal glioma resection. In cases of glioblastoma, 5-ALA-induced fluorescence at the resection cavity biopsy site was recorded, and this was compared with the Raman spectral model prediction for the presence of tumor.

Results: The PCA-LDA predictive model demonstrated 0.96 sensitivity, 0.99 specificity, and 0.99 accuracy for differentiating tumor from normal brain. Twenty-three resection cavity biopsies were taken from 8 patients after supramaximal resection (6 glioblastomas, 2 oligodendrogliomas). Raman spectroscopy showed 1.00 sensitivity, 1.00 specificity, and 1.00 accuracy for predicting tumor versus normal brain in these samples. In the glioblastoma cases, where 5-ALA-induced fluorescence was used, the performance of Raman spectroscopy was significantly better than the predictive value of 5-ALA-induced fluorescence, which showed 0.07 sensitivity, 1.00 specificity, and 0.24 accuracy (p = 0.0009).

Conclusions: Raman spectroscopy can accurately classify fresh tissue samples into tumor versus normal brain and is superior to 5-ALA-induced fluorescence. Raman spectroscopy could become an important intraoperative tool used in conjunction with 5-ALA-induced fluorescence to guide extent of resection in glioma surgery.
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http://dx.doi.org/10.3171/2020.5.JNS20376DOI Listing
October 2020

Compositional boundary layers trigger liquid unmixing in a basaltic crystal mush.

Nat Commun 2019 10 23;10(1):4821. Epub 2019 Oct 23.

Institut für Mineralogie, Leibniz Universität Hannover, Callinstr. 3, 30167, Hannover, Germany.

The separation of immiscible liquids has significant implications for magma evolution and the formation of magmatic ore deposits. We combine high-resolution imaging and electron probe microanalysis with the first use of atom probe tomography on tholeiitic basaltic glass from Hawaii, the Snake River Plain, and Iceland, to investigate the onset of unmixing of basaltic liquids into Fe-rich and Si-rich conjugates. We examine the relationships between unmixing and crystal growth, and the evolution of a nanoemulsion in a crystal mush. We identify the previously unrecognised role played by compositional boundary layers in promoting unmixing around growing crystals at melt-crystal interfaces. Our findings have important implications for the formation of immiscible liquid in a crystal mush, the interpretations of compositional zoning in crystals, and the role of liquid immiscibility in controlling magma physical properties.
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http://dx.doi.org/10.1038/s41467-019-12694-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811629PMC
October 2019

Rapid intraoperative molecular genetic classification of gliomas using Raman spectroscopy.

Neurooncol Adv 2019 May-Dec;1(1):vdz008. Epub 2019 May 28.

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, UK.

Background: The molecular genetic classification of gliomas, particularly the identification of isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterize its molecular composition. No sample processing is required allowing for rapid analysis of tissue. The aim of this study was to evaluate the ability of Raman spectroscopy to rapidly identify the common molecular genetic subtypes of diffuse glioma in the neurosurgical setting using fresh biopsy tissue. In addition, classification models were built using cryosections, formalin-fixed paraffin-embedded (FFPE) sections and LN-18 (IDH-mutated and wild-type parental cell) glioma cell lines.

Methods: Fresh tissue, straight from neurosurgical theatres, underwent Raman analysis and classification into astrocytoma, IDH-wild-type; astrocytoma, IDH-mutant; or oligodendroglioma. The genetic subtype was confirmed on a parallel section using immunohistochemistry and targeted genetic sequencing.

Results: Fresh tissue samples from 62 patients were collected (36 astrocytoma, IDH-wild-type; 21 astrocytoma, IDH-mutated; 5 oligodendroglioma). A principal component analysis fed linear discriminant analysis classification model demonstrated 79%-94% sensitivity and 90%-100% specificity for predicting the 3 glioma genetic subtypes. For the prediction of IDH mutation alone, the model gave 91% sensitivity and 95% specificity. Seventy-nine cryosections, 120 FFPE samples, and LN18 cells were also successfully classified. Meantime for Raman data collection was 9.5 min in the fresh tissue samples, with the process from intraoperative biopsy to genetic classification taking under 15 min.

Conclusion: These data demonstrate that Raman spectroscopy can be used for the rapid, intraoperative, classification of gliomas into common genetic subtypes.
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http://dx.doi.org/10.1093/noajnl/vdz008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777649PMC
May 2019

Standardization of complex biologically derived spectrochemical datasets.

Nat Protoc 2019 05 5;14(5):1546-1577. Epub 2019 Apr 5.

School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK.

Spectroscopic techniques such as Fourier-transform infrared (FTIR) spectroscopy are used to study interactions of light with biological materials. This interaction forms the basis of many analytical assays used in disease screening/diagnosis, microbiological studies, and forensic/environmental investigations. Advantages of spectrochemical analysis are its low cost, minimal sample preparation, non-destructive nature and substantially accurate results. However, an urgent need exists for repetition and validation of these methods in large-scale studies and across different research groups, which would bring the method closer to clinical and/or industrial implementation. For this to succeed, it is important to understand and reduce the effect of random spectral alterations caused by inter-individual, inter-instrument and/or inter-laboratory variations, such as variations in air humidity and CO levels, and aging of instrument parts. Thus, it is evident that spectral standardization is critical to the widespread adoption of these spectrochemical technologies. By using calibration transfer procedures, in which the spectral response of a secondary instrument is standardized to resemble the spectral response of a primary instrument, different sources of variation can be normalized into a single model using computational-based methods, such as direct standardization (DS) and piecewise direct standardization (PDS); therefore, measurements performed under different conditions can generate the same result, eliminating the need for a full recalibration. Here, we have constructed a protocol for model standardization using different transfer technologies described for FTIR spectrochemical applications. This is a critical step toward the construction of a practical spectrochemical analysis model for daily routine analysis, where uncertain and random variations are present.
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http://dx.doi.org/10.1038/s41596-019-0150-xDOI Listing
May 2019

Choosing appropriate size of I-Gel for initial success insertion: a prospective comparative study.

Anaesth Crit Care Pain Med 2019 08 15;38(4):353-356. Epub 2018 Oct 15.

Anaesthetic and intensive care department, hôpital Cochin, Paris Descartes university, 75014 Paris, France.

Purpose: The optimal size of the I-Gel remains unclear since the manufacturer's weight-based formula (size 3 for weight < 50 kg, size 4 for weight 50-90 kg, and size 5 for weight > 90 kg) for the laryngeal mask airway I-Gel is not evidence-based. We hypothesised that sex may also guide the choice of I-Gel size.

Methods: Insertion success rates of the I-Gel chosen according to the weight-based formula were prospectively recorded and compared with those of a patients' cohort ventilated with an I-Gel chosen according to the sex-based formula recorded. Two periods of 18 months were randomised in three independent hospitals in France to study each choice strategy. Patients requiring I-Gel size change were compared with those who where successfully ventilated with the initially chosen device. Complications linked to the I-Gel and factors for changing the size of the I-Gel were also recorded and analysed.

Results: Data from 900 patients were prospectively collected in the three participating centres. The overall initial ventilation was inadequate in 80 cases, including 7% (n = 31) in the weight-based group and 3% (n = 13) in the sex-based group (P = 0.01). In the weight-based group, changing size of I-Gel was successful in 28 (90%) cases. In the sex-based group, changing size of I-Gel was useful in 1 case only. Endotracheal tube insertion was necessary in 15 cases despite changing I-Gel size, including 3 cases in the weight-based group and 12 cases in the sex-based group. Ease of insertion and postoperative pharyngo-laryngeal problems were similar between groups with or without changing size of I-Gel.

Conclusion: Adequate ventilation is achieved most of the time using size selection for the I-Gel laryngeal mask airway according to the manufacturer's weight-based formula. However, our results suggest that the sex-based formula in healthy, anaesthetised, adult patients may also be appropriate for I-Gel size choice.
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http://dx.doi.org/10.1016/j.accpm.2018.08.003DOI Listing
August 2019

An update on the use of Raman spectroscopy in molecular cancer diagnostics: current challenges and further prospects.

Expert Rev Mol Diagn 2018 03 17;18(3):245-258. Epub 2018 Feb 17.

a Department of Upper GI Surgery , Gloucestershire Royal Hospital , Gloucester.

Introduction: Cancer is responsible for an extraordinary burden of disease, affecting 90.5 million people worldwide in 2015. Outcomes for these patients are improved when the disease is diagnosed at an early, or even precancerous, stage. Raman spectroscopy is demonstrating results that show its ability to detect the molecular changes that are diagnostic of precancerous and cancerous tissue. This review highlights the new advances occurring in this domain. Areas covered: PubMed searches were undertaken to identify new research in the utilisation of Raman spectroscopy in cancer diagnostics. The areas in which Raman spectroscopy is showing promise are covered, including improving the accuracy of identifying precancerous changes, using the technology in real time, in vivo modalities, the search for a biomarker to aid potential screening and predicting the response of the cancer to the treatment regimen. Expert commentary: Many of the examples in this review are focused on Barrett's oesophagus and oesophageal adenocarcinoma as this is my area of expertise and perfectly exemplifies where Raman spectroscopy could be utilised in clinical practise. The authors discuss the areas where they believe current knowledge is lacking and how Raman spectroscopy could answer the dilemmas that are still faced in the management of cancer.
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http://dx.doi.org/10.1080/14737159.2018.1439739DOI Listing
March 2018

Developments in optical imaging for gastrointestinal surgery.

Future Oncol 2017 Nov 10;13(26):2363-2382. Epub 2017 Nov 10.

Biophotonics Research Unit, Gloucestershire Royal Hospital, Great Western Road, Gloucester, UK, GL1 3NN.

To improve outcomes for patients with cancer, in terms of both survival and a reduction in the morbidity and mortality that results from surgical resection and treatment, there are two main areas that require improvement. Accurate early diagnosis of the cancer, at a stage where curative and, ideally, minimally invasive treatment is achievable, is desired as well as identification of tumor margins, lymphatic and distant disease, enabling complete, but not unnecessarily extensive, resection. Optical imaging is making progress in achieving these aims. This review discusses the principles of optical imaging, focusing on fluorescence and spectroscopy, and the current research that is underway in GI tract carcinomas.
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http://dx.doi.org/10.2217/fon-2017-0181DOI Listing
November 2017

The prescription of antiplatelet medication in a very elderly population: An observational study in 15 141 ambulatory subjects.

Int J Clin Pract 2017 Dec 21;71(12). Epub 2017 Sep 21.

Pôle Personnes Âgées, Hospital of Champmaillot, University Hospital, Dijon, France.

Objective: Despite the frequent use of antiplatelet medication (AM) in the elderly patients, very few studies have investigated its prescription. We describe AM prescription through retrospective study in ambulatory elderly patients.

Method: All subjects aged over 80 years with a medical prescription delivered in March 2015 and affiliated to the Mutualité Sociale Agricole de Bourgogne. Subjects with prescriptions for AM were compared with those without.

Results: A total of 15 141 ambulatory elderly patients (83-89 years, 61.3% of women) were included and 4412 (29.14%) had a prescription for AM. The latter were more frequently men than those without AM (43% vs 36.93%, P < .0001) and more frequently had chronic comorbidities (77.24% vs 64.65%, P < .0001). Compared with ambulatory subjects without AM, those with AM more frequently had coronary heart disease (35.15% vs 14.49%), severe hypertension (30% vs 25.65%), diabetes (27.42% vs 20.64%), peripheral arterial diseases (16.28% vs 5.96%) and disabling stroke (9% vs 5.56% (all P < .0001). In addition, they had more prescriptions of beta-blockers (45.24% vs 36.90%), angiotensin conversion enzyme inhibitor (31.35% vs 25.44%), calcium channel blockers (33.34% vs 27.90%), nitrate derivatives (10.6% vs 6.03%) or hypolipidemic agents (HA; 49.81% vs 29.72%) (all P < .0001) than those without AM.

Conclusion: In this study, which is very interested for its size and the advanced age of the subjects, long-course AM was prescribed in one third of ambulatory elderly patients. Coronary heart disease, severe hypertension and diabetes were more frequent in AM subjects. However, the low percentage of declared strokes was surprising. We provide additional data to doctors following subjects with AM.
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http://dx.doi.org/10.1111/ijcp.13020DOI Listing
December 2017

Three-Dimensional Nanoscale Mapping of State-of-the-Art Field-Effect Transistors (FinFETs).

Microsc Microanal 2017 10 31;23(5):916-925. Epub 2017 Aug 31.

Department of NanoEngineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

The semiconductor industry has seen tremendous progress over the last few decades with continuous reduction in transistor size to improve device performance. Miniaturization of devices has led to changes in the dopants and dielectric layers incorporated. As the gradual shift from two-dimensional metal-oxide semiconductor field-effect transistor to three-dimensional (3D) field-effect transistors (finFETs) occurred, it has become imperative to understand compositional variability with nanoscale spatial resolution. Compositional changes can affect device performance primarily through fluctuations in threshold voltage and channel current density. Traditional techniques such as scanning electron microscope and focused ion beam no longer provide the required resolution to probe the physical structure and chemical composition of individual fins. Hence advanced multimodal characterization approaches are required to better understand electronic devices. Herein, we report the study of 14 nm commercial finFETs using atom probe tomography (APT) and scanning transmission electron microscopy-energy-dispersive X-ray spectroscopy (STEM-EDS). Complimentary compositional maps were obtained using both techniques with analysis of the gate dielectrics and silicon fin. APT additionally provided 3D information and allowed analysis of the distribution of low atomic number dopant elements (e.g., boron), which are elusive when using STEM-EDS.
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http://dx.doi.org/10.1017/S1431927617012491DOI Listing
October 2017

Developing Raman spectroscopy as a diagnostic tool for label-free antigen detection.

J Biophotonics 2018 02 7;11(2). Epub 2017 Aug 7.

Department of Cell and Developmental Biology, University College London, London, UK.

For several decades, a multitude of studies have documented the ability of Raman spectroscopy (RS) to differentiate between tissue types and identify pathological changes to tissues in a range of diseases. Furthermore, spectroscopists have illustrated that the technique is capable of detecting disease-specific alterations to tissue before morphological changes become apparent to the pathologist. This study draws comparisons between the information that is obtainable using RS alongside immunohistochemistry (IHC), since histological examination is the current GOLD standard for diagnosing a wide range of diseases. Here, Raman spectral maps were generated using formalin-fixed, paraffin-embedded colonic tissue sections from healthy patients and spectral signatures from principal components analysis (PCA) were compared with several IHC markers to confirm the validity of their localizations. PCA loadings identified a number of signatures that could be assigned to muscle, DNA and mucin glycoproteins and their distributions were confirmed with antibodies raised against anti-Desmin, anti-Ki67 and anti-MUC2, respectively. The comparison confirms that there is excellent correlation between RS and the IHC markers used, demonstrating that the technique is capable of detecting compositional changes in tissue in a label-free manner, eliminating the need for antibodies.
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http://dx.doi.org/10.1002/jbio.201700028DOI Listing
February 2018

Automated cytological detection of Barrett's neoplasia with infrared spectroscopy.

J Gastroenterol 2018 Feb 13;53(2):227-235. Epub 2017 May 13.

Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, GL1 3NN, UK.

Background: Development of a nonendoscopic test for Barrett's esophagus would revolutionize population screening and surveillance for patients with Barrett's esophagus. Swallowed cell collection devices have recently been developed to obtain cytology brushings from the esophagus: automated detection of neoplasia in such samples would enable large-scale screening and surveillance.

Methods: Fourier transform infrared (FTIR) spectroscopy was used to develop an automated tool for detection of Barrett's esophagus and Barrett's neoplasia in esophageal cell samples. Cytology brushings were collected at endoscopy, cytospun onto slides and FTIR images were measured. An automated cell recognition program was developed to identify individual cells on the slide.

Results: Cytology review and contemporaneous histology was used to inform a training dataset containing 141 cells from 17 patients. A classification model was constructed by principal component analysis fed linear discriminant analysis, then tested by leave-one-sample-out cross validation. With application of this training model to whole slide samples, a threshold voting system was used to classify samples according to their constituent cells. Across the entire dataset of 115 FTIR maps from 66 patients, whole samples were classified with sensitivity and specificity respectively as follows: normal squamous cells 79.0% and 81.1%, nondysplastic Barrett's esophagus cells 31.3% and 100%, and neoplastic Barrett's esophagus cells 83.3% and 62.7%.

Conclusions: Analysis of esophageal cell samples can be performed with FTIR spectroscopy with reasonable sensitivity for Barrett's neoplasia, but with poor specificity with the current technique.
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http://dx.doi.org/10.1007/s00535-017-1344-zDOI Listing
February 2018

The 50 distal amino acids of the 2A homing protein of Grapevine fanleaf virus elicit a hypersensitive reaction on Nicotiana occidentalis.

Mol Plant Pathol 2018 03 15;19(3):731-743. Epub 2017 May 15.

Université de Strasbourg, CNRS, IBMP UPR 2357, Strasbourg, 67000, France.

Avirulence factors are critical for the arm's race between a virus and its host in determining incompatible reactions. The response of plants to viruses from the genus Nepovirus in the family Secoviridae, including Grapevine fanleaf virus (GFLV), is well characterized, although the nature and characteristics of the viral avirulence factor remain elusive. By using infectious clones of GFLV strains F13 and GHu in a reverse genetics approach with wild-type, assortant and chimeric viruses, the determinant of necrotic lesions caused by GFLV-F13 on inoculated leaves of Nicotiana occidentalis was mapped to the RNA2-encoded protein 2A , particularly to its 50 C-terminal amino acids. The necrotic response showed hallmark characteristics of a genuine hypersensitive reaction, such as the accumulation of phytoalexins, reactive oxygen species, pathogenesis-related protein 1c and hypersensitivity-related (hsr) 203J transcripts. Transient expression of the GFLV-F13 protein 2A fused to an enhanced green fluorescent protein (EGFP) tag in N. occidentalis by agroinfiltration was sufficient to elicit a hypersensitive reaction. In addition, the GFLV-F13 avirulence factor, when introduced in GFLV-GHu, which causes a compatible reaction on N. occidentalis, elicited necrosis and partially restricted the virus. This is the first identification of a nepovirus avirulence factor that is responsible for a hypersensitive reaction in both the context of virus infection and transient expression.
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http://dx.doi.org/10.1111/mpp.12558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637978PMC
March 2018

Mirrored stainless steel substrate provides improved signal for Raman spectroscopy of tissue and cells.

J Raman Spectrosc 2017 Jan 29;48(1):119-125. Epub 2016 Jul 29.

Department of Cell and Developmental Biology University College London London UK.

Raman spectroscopy (RS) is a powerful technique that permits the non-destructive chemical analysis of cells and tissues without the need for expensive and complex sample preparation. To date, samples have been routinely mounted onto calcium fluoride (CaF) as this material possesses the desired mechanical and optical properties for analysis, but CaF is both expensive and brittle and this prevents the technique from being routinely adopted. Furthermore, Raman scattering is a weak phenomenon and CaF provides no means of increasing signal. For RS to be widely adopted, particularly in the clinical field, it is crucial that spectroscopists identify an alternative, low-cost substrate capable of providing high spectral signal to noise ratios with good spatial resolution. Results show that these desired properties are attainable when using mirrored stainless steel as a Raman substrate. When compared with CaF, data show that stainless steel has a low background signal and provides an average signal increase of 1.43 times during tissue analysis and 1.64 times when analyzing cells. This result is attributed to a double-pass of the laser beam through the sample where the photons from the source laser and the forward scattered Raman signal are backreflected and retroreflected from the mirrored steel surface and focused towards collection optics. The spatial resolution on stainless steel is at least comparable to that on CaF and it is not compromised by the reflection of the laser. Steel is a fraction of the cost of CaF and the reflection and focusing of photons improve signal to noise ratios permitting more rapid mapping. The low cost of steel coupled with its Raman signal increasing properties and robust durability indicates that steel is an ideal substrate for biological and clinical RS as it possesses key advantages over routinely used CaF. © 2016 The Authors. Published by John Wiley & Sons Ltd.
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http://dx.doi.org/10.1002/jrs.4980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256423PMC
January 2017

Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts.

Sci Rep 2016 Feb 17;6:21006. Epub 2016 Feb 17.

Mathematics, Statistics, Physics, and Computer Science, University of British Columbia Okanagan, 3333 University Way, Kelowna, British Columbia, V1V 1V7, Canada.

External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.
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http://dx.doi.org/10.1038/srep21006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756358PMC
February 2016

Multiscale Self-Assembly of Silicon Quantum Dots into an Anisotropic Three-Dimensional Random Network.

Nano Lett 2016 Mar 12;16(3):1942-8. Epub 2016 Feb 12.

Department of Physics, Middle East Technical University , 06800, Ankara, Turkey.

Multiscale self-assembly is ubiquitous in nature but its deliberate use to synthesize multifunctional three-dimensional materials remains rare, partly due to the notoriously difficult problem of controlling topology from atomic to macroscopic scales to obtain intended material properties. Here, we propose a simple, modular, noncolloidal methodology that is based on exploiting universality in stochastic growth dynamics and driving the growth process under far-from-equilibrium conditions toward a preplanned structure. As proof of principle, we demonstrate a confined-but-connected solid structure, comprising an anisotropic random network of silicon quantum-dots that hierarchically self-assembles from the atomic to the microscopic scales. First, quantum-dots form to subsequently interconnect without inflating their diameters to form a random network, and this network then grows in a preferential direction to form undulated and branching nanowire-like structures. This specific topology simultaneously achieves two scale-dependent features, which were previously thought to be mutually exclusive: good electrical conduction on the microscale and a bandgap tunable over a range of energies on the nanoscale.
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http://dx.doi.org/10.1021/acs.nanolett.5b05158DOI Listing
March 2016

Patient Preferences for Treatment of Basal Cell Carcinoma: Importance of Cure and Cosmetic Outcome.

Acta Derm Venereol 2016 Mar;96(3):355-60

Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.

Treatment options for localized resectable basal cell carcinoma (BCC) include micrographically controlled surgery, simple excision, curettage, laser ablation, cryosurgery, imiquimod, 5-fluorouracil, photodynamic therapy and radiotherapy. The aim of this study was to assess the preferences of patients with BCC for outcome (cure and recurrence rate, cosmetic outcome, risk of temporary and permanent complications) and process attributes (type of therapy, treatment location, anaesthesia, method of wound closure, duration of wound healing, out-of-pocket costs) of these treatments with conjoint analysis. Participants (n = 124) attached greatest importance to recurrence rate (relative importance score (RIS) = 17.28), followed by cosmetic outcome (RIS = 16.90) and cure rate (RIS = 15.02). Participants with BCC on the head or neck were particularly interested in cosmetic outcome. Those with a recurrence were willing to trade risk of recurrence, treatment location and duration of wound healing for a better cosmetic result. In summary, participants particularly valued cure and cosmetic outcome, although preferences varied with individual and tumour-associated characteristics.
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http://dx.doi.org/10.2340/00015555-2273DOI Listing
March 2016

Radiation-Induced Glycogen Accumulation Detected by Single Cell Raman Spectroscopy Is Associated with Radioresistance that Can Be Reversed by Metformin.

PLoS One 2015 17;10(8):e0135356. Epub 2015 Aug 17.

Trev and Joyce Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460) and breast (MCF7) tumor cells compared to prostate (LNCaP) tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135356PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539228PMC
May 2016

A Raman spectroscopic study of cell response to clinical doses of ionizing radiation.

Appl Spectrosc 2015 1;69(2):193-204. Epub 2015 Jan 1.

University of Victoria, Department of Physics and Astronomy, PO Box 1700 STN CSC, Victoria, British Columbia V8W 2Y2, Canada.

The drive toward personalized radiation therapy (RT) has created significant interest in determining patient-specific tumor and normal tissue responses to radiation. Raman spectroscopy (RS) is a non-invasive and label-free technique that can detect radiation response through assessment of radiation-induced biochemical changes in tumor cells. In the current study, single-cell RS identified specific radiation-induced responses in four human epithelial tumor cell lines: lung (H460), breast (MCF-7, MDA-MB-231), and prostate (LNCaP), following exposure to clinical doses of radiation (2-10 Gy). At low radiation doses (2 Gy), H460 and MCF-7 cell lines showed an increase in glycogen-related spectral features, and the LNCaP cell line showed a membrane phospholipid-related radiation response. In these cell lines, only spectral information from populations receiving 10 Gy or less was required to identify radiation-related features using principal component analysis (PCA). In contrast, the MDA-MB-231 cell line showed a significant increase in protein relative to nucleic acid and lipid spectral features at doses of 6 Gy or higher, and high-dose information (30, 50 Gy) was required for PCA to identify this biological response. The biochemical nature of the radiation-related changes occurring in cells exposed to clinical doses was found to segregate by status of p53 and radiation sensitivity. Furthermore, the utility of RS to identify a biological response in human tumor cells exposed to therapeutic doses of radiation was found to be governed by the extent of the biochemical changes induced by a radiation response and is therefore cell line specific. The results of this study demonstrate the utility and effectiveness of single-cell RS to identify and measure biological responses in tumor cells exposed to standard radiotherapy doses.
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http://dx.doi.org/10.1366/14-07561DOI Listing
November 2015

[An innovative approach to support for the elderly].

Soins Gerontol 2012 Sep-Oct(97):14-6

Cadre de santé, hôpital Saint-Nicolas, Angers, France.

In order to improve the care conditions of elderly patients at the Saint-Nicolas hospital in Angers, two health care techniques have been developed: the diffusion of essential oils and a relaxing massage. We have evaluated their effect on patients and their caregivers and a certain number of advantages have been demonstrated.
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December 2012

[Sleep complaints and disorders in residential home patients taking hypnotic drugs].

Geriatr Psychol Neuropsychiatr Vieil 2012 Jun;10(2):159-63

Clinique de gérontologie, Centre hospitalier régional et universitaire (CHRU) de Lille.

Objective: To analyze sleep of residential home patients taking hypnotic drugs.

Patients And Method: This prospective, observational and multicentric study was performed a given day in nursing homes. Residents over than 65, having MMSE ≥ 15 and coherence A or B (for the AGGIR scale) were included. Aphasic residents or having acute pathology were excluded. Sleep complain was expressed by the resident himself and sleep disorder was observed by care givers. Sleep qualitative (complain versus disorder, difficulty to fall asleep and night awakenings) and quantitative (sleep duration) aspects were compared to residents who take or not hypnotic treatments.

Results: 635 residents were included. 28.2% of the residents expressed sleep complains whereas care givers reported that only 11.4% of resident presented real sleep disorders (p<0.001). Compared to the residents who take hypnotic drugs (55.6%), residents without such treatment had shown less sleep complaints (31.2 versus 24.8%; p<0.05), less difficulties to fall asleep (38.6 versus 26.5%; p<0.001), and less night awakenings (69.5 versus 60.9%; p<0.05). No sleep duration difference was found according to hypnotic drugs.

Discussion: Institutionalized geriatric patients who take hypnotic drugs seem to have a significant lower quality of sleep.
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http://dx.doi.org/10.1684/pnv.2012.0348DOI Listing
June 2012

Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France).

BMC Health Serv Res 2012 Mar 12;12:59. Epub 2012 Mar 12.

Unité de Maladies Infectieuses, Pôle Médecine, Hôpital COCHIN, Paris, France.

Background: Treatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population.

Methods: We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively.

Results: Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians.

Conclusions: Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.
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http://dx.doi.org/10.1186/1472-6963-12-59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325848PMC
March 2012

Internet gambling, substance use, and delinquent behavior: an adolescent deviant behavior involvement pattern.

Psychol Addict Behav 2012 Jun 20;26(2):364-70. Epub 2012 Feb 20.

Department of Special Education, Université du Québec à Trois-Rivières, Québec, Canada.

Internet gambling among adolescents is a growing phenomenon that has received little attention to date. This study examines associations between Internet gambling and the severity of gambling, substance use (SU), and delinquent behavior among 1,870 Quebec students aged 14 to 18. The results show a higher proportion of Internet-gambling (IG) students reporting problematic substance use and delinquency, compared with nongamblers (NG) and non-Internet gamblers (NIG). Furthermore, a higher proportion of at-risk and probable pathological gamblers are found among IG compared with NIG. A moderating effect (Baron & Kenny, 1986) of the gambler categories (NIG, IG) was found in the relationship between the associated problems and the severity of gambling. Among IG, the severity of delinquency and of substance use contributes to explaining gambling severity whereas, among NIG, the severity of delinquency is the only factor that significantly contributes to such an explanation. Discussion of the results is based on Jessor, Donovan, and Costa's (1991) general deviance syndrome theory.
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http://dx.doi.org/10.1037/a0027079DOI Listing
June 2012

Dual-channel imaging system for singlet oxygen and photosensitizer for PDT.

Biomed Opt Express 2011 Apr 15;2(5):1233-42. Epub 2011 Apr 15.

A two-channel optical system has been developed to provide spatially resolved simultaneous imaging of singlet molecular oxygen ((1)O(2)) phosphorescence and photosensitizer (PS) fluorescence produced by the photodynamic process. The current imaging system uses a spectral discrimination method to differentiate the weak (1)O(2) phosphorescence that peaks near 1.27 μm from PS fluorescence that also occurs in this spectral region. The detection limit of (1)O(2) emission was determined at a concentration of 500 nM benzoporphyrin derivative monoacid (BPD) in tissue-like phantoms, and these signals observed were proportional to the PS fluorescence. Preliminary in vivo images with tumor laden mice indicate that it is possible to obtain simultaneous images of (1)O(2) and PS tissue distribution.
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http://dx.doi.org/10.1364/BOE.2.001233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087579PMC
April 2011

Residential trajectory and HIV high-risk behaviors among Montréal street youth--a reciprocal relationship.

J Urban Health 2011 Aug;88(4):767-78

Direction de santé publique, Montréal, Canada.

Evidence has linked residential instability and engagement in high-risk behaviors. This paper longitudinally examines the relationship between changes in residential stability and changes in HIV risk behaviors among Montréal street youth (SY). Between April 2006 and May 2007, 419 SY (18-25 years old) were recruited in a cohort study. SY (using Montréal street youth agencies services) were eligible if they had had at least one 24-hour episode of homelessness in the previous 30 days. Baseline and follow-up interviews, carried out every 3 months, included completion of a questionnaire (based on Life History Calendar Technique) assessing daily sleeping arrangements since the last interview, and monthly sexual and drug use behaviors. Using mixed-effects logistic regression method, we examined the association between various risk behaviors and residential stability, reached when a youth resided in any of the following settings for a whole month: own place; friends'/partner's/parent's place; any types of housing service (excluding emergency shelters). Analyses were carried out controlling for gender, age, education level, lifetime duration of homelessness, childhood sexual trauma, and lifetime mental health disorders. As of January 2009, 360 SY (79% boys) had completed at least one follow-up interview, representing 4,889 months of follow-up. Residential stability was significantly associated with the following: sex exchange (adjusted odd ratio [AOR], 0.25; 95% confidence interval [CI], 0.14-0.37), drug injection (AOR, 0.55; CI, 0.33-0.76), daily alcohol consumption (AOR, 0.58; CI, 0.42-0.74), polydrug consumption (AOR, 0.61; CI, 0.50-0.73), polydrug consumption excluding marijuana (AOR, 0.55; CI, 0.45-0.65), and multiple sex partners (≥3 partners; AOR, 0.57; CI, 0.40-0.74). Our results suggest a reciprocal relationship between residential instability and HIV risk behaviors. This calls for more integrated services combining both individual and structural-level interventions to improve the health of street youth.
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http://dx.doi.org/10.1007/s11524-011-9574-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157499PMC
August 2011

Correlation mapping: rapid method for identification of histological features and pathological classification in mid infrared spectroscopic images of lymph nodes.

J Biomed Opt 2010 Mar-Apr;15(2):026030

Cranfield Health, Gloucestershire Hospitals NHS Foundation Trust, Biophotonics Research Group, Gloucester, GL1 3NN United Kingdom.

In this work, a novel technique for rapid image analysis of Fourier transform infrared (FTIR) data obtained from human lymph nodes is explored. It uses the mathematical principle of orthogonality as a method to quickly and efficiently obtain tissue and pathology information from a spectral image cube. It requires less computational power and time compared to most forms of cluster analysis. The values obtained from different tissue and pathology types allows for discrimination of noncancerous from cancerous lymph nodes. It involves the calculation of the dot product between reference spectra and individual spectra from across the tissue image. These provide a measure of the correlation between individual spectra and the reference spectra, and each spectrum or pixel in the image is given a color representing the reference most closely correlating with it. The correlation maps are validated with the tissue and pathology features identified by an expert pathologist from corresponding hematoxylin and eosin stained tissue sections. Although this novel technique requires further study to properly test and validate this tool, with inclusion of more lymph node hyperspectral datasets (containing a greater variety of tissue states), it demonstrates significant clinical potential for pathology diagnosis.
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http://dx.doi.org/10.1117/1.3386061DOI Listing
September 2010

Association study of the ubiquitin conjugating enzyme gene UBE2H in sporadic ALS.

Amyotroph Lateral Scler 2009 Oct-Dec;10(5-6):432-5

INSERM U930, Université François Rabelais Tours, Montpellier, France.

Ubiquitin inclusions represent a cytopathological hallmark of ALS. The ubiquitin-dependent protein degradation pathway may also be involved in the pathophysiology of SOD1 mutated ALS cases as demonstrated in transgenic animals. UBE2H is an ubiquitin conjugating enzyme known to act on histones and cytoskeletal proteins, both involved in the degenerative pathway of the motor neuron. We screened the whole coding sequence of the UBE2H gene in 24 sporadic ALS (SALS) patients using single strand conformation polymorphism (SSCP). All variants detected by SSCP were analysed by genomic DNA sequencing. We found one known polymorphism (rs12539800) and two new synonymous single nucleotide polymorphisms (SNP) (nG78A and nG501A). The allele distribution of the rs12539800 (A336G) SNP were tested for association in 252 SALS patients and 357 controls. The allele and genotype distributions were identical in the two groups. The UBE2H gene is not implicated in SALS; however, the ubiquitin pathway is worthy of further investigation in ALS.
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http://dx.doi.org/10.3109/17482960802444972DOI Listing
February 2010
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