Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

We assessed short-term treatment results of younger patients with varus malalignment and chronic anterior cruciate ligament deficiency. Forty-one patients (mean, 32 years; range, 16 to 47) underwent a high tibial osteotomy. Because of giving way symptoms, 14 also had a lateral iliotibial band extraarticular procedure at the time of the osteotomy and 16 had an intraarticular anterior cruciate ligament allograft reconstruction after the osteotomy. All returned for followup (mean, 58 months; range, 23 to 86), which included KT-1000 arthrometer testing and evaluation by our knee rating system. Statistically significant (P < 0.05) improvements were found in the mean overall rating scores for pain, swelling, and giving way. Preoperatively, 30 (73%) had pain with activities of daily living or with any sports activity; 11 (27%) could perform only light sports activities without pain. At followup, 32 patients (78%) had no pain with activities of daily living or light sports. Ten of 15 patients with advanced medial tibiofemoral arthrosis (subchondral bone exposure) had significant improvements in symptoms. Patient satisfaction was high: 88% stated they would undergo the procedure again and 78% felt their knee condition was improved. Patients who had the allograft reconstruction had significantly lower (P < 0.05) anterior-posterior displacements at followup than those who had the extraarticular procedure. We concluded that osteotomy should be performed early in the disease process for younger athletes who experience symptoms with activity. It may be unrealistic, however, to expect continuation of sports beyond light recreational, given the joint arthrosis that is usually present and the high in vivo joint loadings with athletes. Anterior cruciate ligament reconstruction should be considered when giving way previously occurred and the patient plans to resume athletics. However, patients with advanced arthrosis can avoid anterior cruciate ligament surgery by reducing athletic activities.

Motivation: Major tumor sequencing projects have been conducted in the past few years to identify genes that contain ‘driver’ somatic mutations in tumor samples. These genes have been defined as those for which the non-silent mutation rate is significantly greater than a background mutation rate estimated from silent mutations. Several methods have been used for estimating the background mutation rate.Results: We propose a new method for identifying cancer driver genes, which we believe provides improved accuracy. The new method accounts for the functional impact of mutations on proteins, variation in background mutation rate among tumors and the redundancy of the genetic code. We reanalyzed sequence data for 623 candidate genes in 188 non-small cell lung tumors using the new method. We found several important genes like PTEN, which were not deemed significant by the previous method. At the same time, we determined that some genes previously reported as drivers were not significant by the new analysis because mutations in these genes occurred mainly in tumors with large background mutation rates.Availability: The software is available at: http://linus.nci.nih.gov/Data/YounA/software.zipContact: rsimon@mail.nih.govSupplementary information: Supplementary data are available at Bioinformatics online.

The impact of OSA on neurocognitive performance is small for many individuals with this condition and is most related to the severity of hypoxemia.