With the advent of computerized tomography (CT), an increasing number of patients with only minimal neurological symptoms and no signs of brain herniation are found to harbor subacute or chronic extradural hematomas (EH's). The authors present the cases of 11 symptomatic but neurologically normal children with medium to large EH's managed by close observation. These EH's were discovered 4 hours to 6 days after injury; three were in the posterior fossa, seven over the frontoparietal convexity, and one in the temporal fossa. These clots were followed by serial CT scans. Nine children recovered without surgery from 4 to 18 days after injury, and all had evidence on CT of spontaneous clot resorption. Of these nine EH's, five clots displayed volume expansion from 5 to 16 days after injury before final resorption occurred. Expansion correlated with persistence or increase in symptoms, whereas resorption correlated with improvement. Two patients showed gradual uncal herniation on Days 6 and 8, respectively, presumably during the "expansile phase" of their clots. Both had emergency craniotomy and recovered without morbidity. It is hypothesized that the resorption dynamics of the subacute or chronic EH are similar to that of the chronic subdural hematoma, with predictable volume changes, and the outcome of each lesion depends on the interplay between the patient's intracranial pressure buffering capacity and the rate of volume change. If subtle signs of brain dysfunction are adopted to signal the failure of conservative treatment and the need for craniotomy, these patients may be safely, and many successfully, managed without surgery. Factors that influence outcome of medical treatment include the size, location, configuration, and the rapidity of accumulation of the clot, the presence of associated intradural lesions, the extracranial decompression of blood through skull diastases, and the age of the patient. These factors, the criteria for patient selection, and the indications for immediate operative intervention are discussed.

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a "driver" phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosinesubstrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.STAT3 activation | driver mutations | phosphatase mutations T yrosine phosphorylation regulates a multitude of cellular processes by coordinately activating and inactivating signaling proteins. Aberrations of protein tyrosine phosphorylation and signaling are a hallmark for oncogenic events found in most human cancers. The phosphorylation/dephosphorylation of tyrosine residues on signaling proteins is directly mediated by protein tyrosine kinases and phosphatases. Although many cellular factors are known to dynamically control the activity of these enzymes, genetic alterations of kinases and phosphatases in human cancers lead to perturbations in the levels of tyrosine phosphorylated proteins, uncontrolled cell growth, and tumor formation. Although activating mutations of tyrosine kinases have been extensively studied (1, 2), cancer-associated mutations of tyrosine phosphatases remain incompletely understood, partly due to the lack of comprehensive genomic analysis of these large arrays of phosphatases, as well as their largely unknown and often ambiguous actions in normal physiology and cancer biology.Among the 107 known protein tyrosine phosphatases, the receptor protein tyrosine phosphatases (RPTPs) represent the largest family of the human tyrosine phosphatome, comprising 21 family members (3). These RPTPs are believed to be crucial for the regulation of inter-as well as intracellular signaling due to the cell-surface localization of RPTPs. Selected members of the RPTP family have been reported to function as tumor suppressors, where gene mutation, deletion, or methylation may contribute to the cancer phenotype (3).STAT3 is an oncogene, and constitutive STAT3 activation is a hallmark of human cancers. Activating STAT3 mutations are rare in all cancers studied to date, including head and neck squamous cell carcinoma (HNSCC) (4). Although activating mutations of upst...

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External ventricular drainage is an important therapeutic adjunct in neurosurgical practice. Unfortunately, this procedure has been associated with a significant incidence of ventriculitis. A major source for many of these infections has been bacterial contamination of the tract of the ventricular catheter, at the site where it enters the scalp. To prevent this problem, the authors have devised a new ventriculostomy technique that involves tunneling the ventricular catheter through the scalp, between the dermis and the galea. One hundred consecutive procedures in 66 patients are analyzed in this paper. The average duration of drainage was 6.2 days. There were no infections subsequent to the insertion of the ventricular catheter in this group of patients.

Accurate chemical shifts for the atoms in molecular mechanics (MD) trajectories can be obtained from quantum mechanical (QM) calculations that depend solely on the coordinates of the atoms in the localized regions surrounding atoms of interest. If these coordinates are correct and the sample size is adequate, the ensemble average of these chemical shifts should be equal to the chemical shifts obtained from NMR spectroscopy. If this is not the case, the coordinates must be incorrect. We have utilized this fact to quantify the errors associated with the backbone atoms in MD simulations of proteins. A library of regional conformers containing 169,499 members was constructed from 6 model proteins. The chemical shifts associated with the backbone atoms in each of these conformers was obtained from QM calculations using density functional theory at the B3LYP level with a 6-311+G(2d,p) basis set. Chemical shifts were assigned to each backbone atom in each MD simulation frame using a template matching approach. The ensemble average of these chemical shifts was compared to chemical shifts from NMR spectroscopy. A large systematic error was identified that affected the 1H atoms of the peptide bonds involved in hydrogen bonding with water molecules or peptide backbone atoms. This error was highly sensitive to changes in electrostatic parameters. Smaller errors affecting the 13Ca and 15N atoms were also detected. We believe these errors could be useful as metrics for comparing the force-fields and parameter sets used in MD simulation because they are directly tied to errors in atomic coordinates.