Purpose: Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value.Patients and Methods: We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy.Results: Similar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis.Conclusion: Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.

To evaluate symptoms, clinical findings, and etiological factors in external ear canal cholesteatoma (EECC). Retrospective evaluation of clinical records of all consecutive patients with EECC in the period 1979 to 2005 in a tertiary referral centre. Main outcome measures were incidence rates, classification according to causes, symptoms, extensions in the ear canal including adjacent structures, and possible etiological factors. Forty-five patients were identified with 48 EECC. Overall incidence rate was 0.30 cases per year per 100,000 inhabitants. Twenty-five cases were primary, while 23 cases were secondary: postoperative (n = 9), postinflammatory (n = 5), postirradiatory (n = 7), and posttraumatic (n = 2). Primary EECC showed a right/left ratio of 12/13 and presented with otalgia (n = 15), itching (n = 5), occlusion (n = 4), hearing loss (n = 3), fullness (n = 2), and otorrhea (n = 1). Similar symptoms were found in secondary EECC, but less pronounced. In total the temporomandibular joint was exposed in 11 cases, while the mastoid and middle ear was invaded in six and three cases, respectively. In one primary case the facial nerve was exposed and in a posttraumatic case the atticus and antrum were invaded. In primary EECC 48% of cases reported mechanical trauma. EECC is a rare condition with inconsistent and silent symptoms, whereas the extent of destruction may be pronounced. Otalgia was the predominant symptom and often related to extension into nearby structures. Whereas the aetiology of secondary EECC can be explained, the origin of primary EECC remains uncertain; smoking and minor trauma of the ear canal may predispose.

For an individual with tetraplegia assistive robotic arms provide a potentially invaluable opportunity for rehabilitation. However, there is a lack of available control methods to allow these individuals to fully control the assistive arms. Here we show that it is possible for an individual with tetraplegia to use the tongue to fully control all 14 movements of an assistive robotic arm in a three dimensional space using a wireless intraoral control system, thus allowing for numerous activities of daily living. We developed a tongue-based robotic control method incorporating a multi-sensor inductive tongue interface. One abled-bodied individual and one individual with tetraplegia performed a proof of concept study by controlling the robot with their tongue using direct actuator control and endpoint control, respectively. After 30 min of training, the able-bodied experimental participant tongue controlled the assistive robot to pick up a roll of tape in 80% of the attempts. Further, the individual with tetraplegia succeeded in fully tongue controlling the assistive robot to reach for and touch a roll of tape in 100% of the attempts and to pick up the roll in 50% of the attempts. Furthermore, she controlled the robot to grasp a bottle of water and pour its contents into a cup; her first functional action in 19 years. To our knowledge, this is the first time that an individual with tetraplegia has been able to fully control an assistive robotic arm using a wireless intraoral tongue interface. The tongue interface used to control the robot is currently available for control of computers and of powered wheelchairs, and the robot employed in this study is also commercially available. Therefore, the presented results may translate into available solutions within reasonable time.

Purpose: Individuals with tetraplegia depend on alternative interfaces in order to control computers and other electronic equipment. Current interfaces are often limited in the number of available control commands, and may compromise the social identity of an individual due to their undesirable appearance. The purpose of this study was to implement an alternative computer interface, which was fully embedded into the oral cavity and which provided multiple control commands. Methods: The development of a wireless, intraoral, inductive tongue computer was described. The interface encompassed a 10-key keypad area and a mouse pad area. This system was embedded wirelessly into the oral cavity of the user. The functionality of the system was demonstrated in two tetraplegic individuals and two able-bodied individuals Results: The system was invisible during use and allowed the user to type on a computer using either the keypad area or the mouse pad. The maximal typing rate was 1.8 s for repetitively typing a correct character with the keypad area and 1.4 s for repetitively typing a correct character with the mouse pad area. Conclusion: The results suggest that this inductive tongue computer interface provides an esthetically acceptable and functionally efficient environmental control for a severely disabled user.

Middle ear pressure (MEP) is actively regulated by both the Eustachian tube and the mastoid air cell system. MEP is a highly significant factor involved in many clinical conditions related to otitis media. Basic knowledge on its overall regulation remains insufficient, but the Eustachian tube and mastoid gas exchange are important factors. The main focus has been aimed at the tube; however, evidence points to the mastoid as equally important. More detailed methods are demanded to study their complementary functions. A catheter was inserted into the mastoid of 12 human volunteers (patients for parotidectomy). This enabled monitoring MEP directly, and experiments were performed with volume displacements of +/-50, 100, and 200 microl resulting in a range of overpressure and underpressure. The following counter-regulation was recorded over 10 minutes. In some cases, MEP counter-regulation presented as Eustachian tube openings with steep and fast pressure changes toward 0 Pa, whereas in others, gradual and slow pressure changes presented related to the mastoid; these changes sometimes crossed 0 Pa into opposite pressures. In many cases, combinations of these distinct mechanisms were found. The human mastoid as well as the Eustachian tube was capable of active counter-regulation of the MEP in short-term experimental pressure changes in healthy ears. Thus, these 2 systems seemed to function in a complementary way, where the mastoid was related to continuous regulation of smaller pressures, whereas the tube was related to intermittent regulation of higher pressures.