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1,691 results on '"Clarke, I."'

6. Accretion-driven core collapse and the collisional formation of massive stars

Author

Bonnell, C. Clarke I.

Subjects
Astrophysics
Abstract

We consider the conditions required for a cluster core to shrink, by adiabatic accretion of gas from the surrounding cluster, to densities such that stellar collisions are a likely outcome. We show that the maximum densities attained, and hence the viability of collisions, depends on a competition between core shrinkage (driven by accretion) and core puffing up (driven by relaxation effects). The expected number of collisions scales as $N_{core}^{5/3} \tilde v^2$ where $N_{core}$ is the number of stars in the cluster core and $\tilde v$ is the free fall velocity of the parent cluster (gas reservoir). Thus whereas collisions are very unlikely in a relatively low mass, low internal velocity system such as the Orion Nebula Cluster, they become considerably more important at the mass and velocity scale characteristic of globular clusters. Thus stellar collisions in response to accretion induced core shrinkage remains a viable prospect in more massive clusters, and may contribute to the production of intermediate mass black holes in these systems., Comment: MNRAS accepted

Published
2008

9. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Author

Mack, SC, Witt, H, Piro, RM, Gu, L, Zuyderduyn, S, Stütz, AM, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, DTW, Sill, M, Pugh, TJ, Ryzhova, M, Wani, KM, Shih, DJH, Head, R, Remke, M, Bailey, SD, Zichner, T, Faria, CC, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, AM, Northcott, PA, Peacock, J, Bertrand, KC, Agnihotri, S, Cavalli, FMG, Clarke, I, Nethery-Brokx, K, Creasy, CL, Verma, SK, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, MA, Roberts, SS, Fults, D, Massimi, L, Cho, YJ, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, AE, von Deimling, A, Witt, O, Scherer, SW, Fan, X, Muraszko, KM, Kool, M, Pomeroy, SL, Gupta, N, Phillips, J, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, PN, Weiss, WA, Jabado, N, Rutka, JT, Bouffet, E, Korbel, JO, Lupien, M, Aldape, KD, Bader, GD, Eils, R, Lichter, P, Dirks, PB, Pfister, SM, Korshunov, A, and Taylor, MD

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Cancer, Neurosciences, Cancer Genomics, Animals, Brain Neoplasms, CpG Islands, DNA Methylation, Embryonic Stem Cells, Ependymoma, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Regulation, Neoplastic, Gene Silencing, Histones, Humans, Infant, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Phenotype, Polycomb Repressive Complex 2, Prognosis, Rhombencephalon, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Published
2014

10. Jules Verne Roundtable

Author

Gunn, James, Clarke, I. F., Alkon, Paul, Freedman, Carl, Bozzetto, Roger, Rottensteiner, Franz, and Ruddick, Nicholas

Published
2005

13. Clinical Improvement After Lumbar Fusion: Using PROMIS to Assess Recovery Kinetics.

Author

Shaikh, Hashim J. F., Cady-McCrea, Clarke I., Menga, Emmanuel N., Haddas, Ram, Molinari, Robert N., Mesfin, Addisu, Rubery, Paul T., and Puvanesarajah, Varun

Subjects
*SPINAL surgery, *SPINAL fusion, *LUMBAR vertebrae, *LOGISTIC regression analysis
Abstract

Study Design. Retrospective review of a single institution cohort. Objective. The goal of this study is to identify features that predict delayed achievement of minimum clinically important difference (MCID) following elective lumbar spine fusion using PatientReported Outcomes Measurement Information System (PROMIS) surveys. Summary of Background Data. Preoperative prediction of delayed recovery following lumbar spine fusion surgery is challenging. While many studies have examined factors impacting the achievement of MCID for patient-reported outcomes in similar cohorts, few studies have assessed predictors of early functional improvement. Methods. We retrospectively reviewed patients undergoing elective one-level posterior lumbar fusion for degenerative pathology. Patients were subdivided into two groups based on achievement of MCID for each respective PROMIS domain either before six months (“early responders”) or after six months (“late responders”) following surgical intervention. Multivariable logistic regression analysis was used to determine features associated with odds of achieving distribution-based MCID before or after six months follow up. Results. 147 patients were included. The average age was 64.3± 13.0 years. At final follow-up, 57.1% of patients attained MCID for PI and 72.8% for PF. However, 42 patients (49.4%) reached MCID for PI by six months, compared to 44 patients (41.1%) for PF. Patients with severe symptoms had the highest probability of attaining MCID for PI (OR 10.3; P=0.001) and PF (OR 10.4; P=0.001) Preoperative PROMIS symptomology did not predict early achievement of MCID for PI or PF. Patients who received concomitant iliac crest autograft during their lumbar fusion had increased odds of achieving MCID for PI (OR 8.56; P=0.001) before six months. Conclusion. Our study demonstrated that the majority of patients achieved MCID following elective one-level lumbar spine fusion at long-term follow-up, although less than half achieved this clinical benchmark for each PROMIS metric by six months. We also found that preoperative impairment was not associated with when patients would achieve MCID. Further prospective investigations are warranted to characterize the trajectory of clinical improvement and identify the risk factors associated with poor outcomes more accurately. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Clinical Improvement After Lumbar Fusion

Author

Shaikh, Hashim J.F., primary, Cady-McCrea, Clarke I., additional, Menga, Emmanuel N., additional, Haddas, Ram, additional, Molinari, Robert N., additional, Mesfin, Addisu, additional, Rubery, Paul T., additional, and Puvanesarajah, Varun, additional

Published
2023
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19. Clinical Improvement After Lumbar Fusion

Author

Hashim J.F. Shaikh, Clarke I. Cady-McCrea, Emmanuel N. Menga, Ram Haddas, Robert N. Molinari, Addisu Mesfin, Paul T. Rubery, and Varun Puvanesarajah

Subjects
Orthopedics and Sports Medicine, Neurology (clinical)
Published
2023
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22. Distal Ventral Iliac Pathway for Spinopelvic Fixation: Technique Description and Case Series

Author

Richard A. Tallarico, William F. Lavelle, Clarke I. Cady-McCrea, and Zachary R. Visco

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Soft tissue, medicine.disease, New Technology, Surgery, Degenerative disease, Blood loss, Deformity, medicine, Fluoroscopy, Pelvic fixation, Orthopedics and Sports Medicine, Clinical significance, medicine.symptom, business, Lumbosacral joint
Abstract

Background Pelvic fixation improves the stability of spinal instrumentation and can be used in high-grade degenerative disease, trauma, deformity, and destabilizing invasive pathologies, such as infection and tumor. Classic techniques for spinopelvic fixation include traditional iliac screws and S2-Alar-Iliac screws. We present a case series describing the distal ventral iliac pathway (DVIP) for spinopelvic fixation and discuss surgical indications and merits of this technique. We describe the use of the DVIP for spinopelvic fixation in the setting of degenerative and traumatic pathologies, compare this technique with existing approaches, and summarize literature to support this approach. Methods One hundred twenty-eight cases of DVIP screws were identified at 1 academic medical center, and 3 cases were chosen as representative examples for technique demonstration. Results Patient ages ranged from 19 to 81 (mean 62) years. Intraoperative and postoperative complications include 12 incidental durotomies, 3 suprafascial infections, and 2 compressive hematomas. There were 22 instances of hardware failure and 8 instances of pseudoarthrosis. Overall, 26 patients underwent revision surgery. Mean estimated blood loss, operative time, and time under fluoroscopy were 1959 mL, 386 minutes, and 3.19 minutes, respectively. Conclusions The DVIP is both safe and effective as a treatment for patients with degenerative and traumatic lumbosacral pathology. Spinopelvic fixation provides improved soft tissue coverage and fewer hardware complications at minimum of 1 year follow up. This case series demonstrates a novel surgical technique for spinopelvic fixation in the setting of numerous spinal pathologies. Level of Evidence 4. Clinical Relevance This surgical technique is less technically challenging than current approaches, minimizes radiation exposure, and obviates the need for horizontal connector rods. In addition, in highly destabilizing pathologies, this technique also allows for multiple screw placement within the ilium, while maintaining the ability to connect to a single rod construct. This technique is safe, technically approachable, and broadly applicable to an array of spinopelvic pathologies.

Published
2021
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37. Taxonomy of the Caliciviruses

Author

Green, K. Y., Ando, T., Balayan, M. S., Berke, T., Clarke, I. N., Estes, M. K., Matson, D. O., Nakata, S., Neill, J. D., Studdert, M. J., and Thiel, H-J.

Published
2000

43. Cement-Augmented and Dual-Headed Posterior Screw Reconstruction After Corpectomy for Metastatic Tumor Resection

Author

Michael A. Galgano, Jennifer C. Gilbert, and Clarke I. Cady-McCrea

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Tumor resection, Metastatic tumor, Resection, Posterior stabilization, Pedicle Screws, Medicine, Humans, Corpectomy, Pedicle screw, Aged, Spinal Neoplasms, business.industry, Bone Cements, Laminectomy, Middle Aged, Plastic Surgery Procedures, Decompression, Surgical, Surgery, Female, Neurology (clinical), Radiology, business, Surgical interventions
Abstract

Background Metastatic spinal tumors have a well-documented deleterious effect on the overall strength of the bony spine. Surgical interventions must address not only removal of the tumor itself, but the integrity of reconstructive hardware constructs as well. Methods We present a series of 8 patients with metastatic spine tumors who were successfully treated with tumor resection and reconstruction of residual 3-column defect with cement-augmented fenestrated pedicle screws and dual-rod posterior stabilization. Results All patients demonstrated resolution of their presenting neurologic symptoms. Conclusions This series supports the use of the aforementioned constructs in conjunction to provide added stability and reduce hardware failure when treating a diversity of spinal tumors.

Published
2021

47. C2 quad-screws facilitate 4-rod fixation across the cervico-thoracic junction

Author

Clarke I. Cady-McCrea and Michael A. Galgano

Subjects
Cervical pathology, medicine.medical_specialty, business.industry, Thoracic spine, Electronic medical record, Spinal tumor, Posterior instrumentation, Surgery, 03 medical and health sciences, Spinal deformity, 0302 clinical medicine, Blood loss, 030220 oncology & carcinogenesis, Cervical spine, Cervicothoracic junction, Medicine, Operative time, Cervical spine deformity, Neurology (clinical), Technical Notes, business, 030217 neurology & neurosurgery, Fixation (histology), Cervico-thoracic junction
Abstract

Background: Cervical spine deformity is a potentially devitalizing problem. Contemporary techniques for repair and reconstruction include fusion using rods of tapered diameter alone, or quadruple-rod constructs in which primary rods are joined to floating accessory rods by connectors. Here, we present how we utilized a quadruple-rod construct to perform five C2 to thoracic spine fusions. Methods: Our hospital electronic medical record revealed five patients who underwent the four rod C2-thoracic spine fixation. Patients ranged in age from 14-years-old to 78-years-old. The mean operative time was 715.8 min (range 549–987 min), and average estimated blood loss was 878 cc (range 40–1800 cc). Results: None of the five patients sustained any intraoperative complications, and none demonstrated progressive kyphotic deformity over the average follow-up interval of 8 months. Conclusion: We successfully treated five patients with degenerative or oncologic cervical pathology requiring fixation across the cervicothoracic junction utilizing a 4-rod C2-cervicothoracic fusion technique.

Published
2020

48. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy

Author

Yeo, GSH, Chao, DHM, Siegert, A-M, Koerperich, ZM, Ericson, MD, Simonds, SE, Larson, CM, Luquet, S, Clarke, I, Sharma, S, Clement, K, Cowley, MA, Haskell-Luevano, C, Van der Ploeg, L, Adan, RAH, Yeo, GSH, Chao, DHM, Siegert, A-M, Koerperich, ZM, Ericson, MD, Simonds, SE, Larson, CM, Luquet, S, Clarke, I, Sharma, S, Clement, K, Cowley, MA, Haskell-Luevano, C, Van der Ploeg, L, and Adan, RAH

Abstract

BACKGROUND: Over the past 20 years, insights from human and mouse genetics have illuminated the central role of the brain leptin-melanocortin pathway in controlling mammalian food intake, with genetic disruption resulting in extreme obesity, and more subtle polymorphic variations influencing the population distribution of body weight. At the end of 2020, the U.S. Food and Drug Administration (FDA) approved setmelanotide, a melanocortin 4 receptor agonist, for use in individuals with severe obesity due to either pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. SCOPE OF REVIEW: Herein, we chart the melanocortin pathway's history, explore its pharmacology, genetics, and physiology, and describe how a neuropeptidergic circuit became an important druggable obesity target. MAJOR CONCLUSIONS: Unravelling the genetics of the subset of severe obesity has revealed the importance of the melanocortin pathway in appetitive control; coupling this with studying the molecular pharmacology of compounds that bind melanocortin receptors has brought a new obesity drug to the market. This process provides a drug discovery template for complex disorders, which for setmelanotide took 25 years to transform from a single gene into an approved drug.

Published
2021

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