Non-auditory Influences on the Auditory Periphery

Once thought to be predominantly the domain of cortex, multisensory integration has now been found at numerous sub-cortical locations in the auditory pathway. Prominent ascending and descending connection within the pathway suggest that the system may utilize non-auditory activity to help filter incoming sounds as they first enter the ear. Active mechanisms in the periphery, particularly the outer hair cells (OHCs) of the cochlea and middle ear muscles (MEMs), are capable of modulating the sensitivity of other peripheral mechanisms involved in the transduction of sound into the system. Through indirect mechanical coupling of the OHCs and MEMs to the eardrum, motion of these mechanisms can be recorded as acoustic signals in the ear canal. Here, we utilize this recording technique to describe three different experiments that demonstrate novel multisensory interactions occurring at the level of the eardrum. 1) In the first experiment, measurements in humans and monkeys performing a saccadic eye movement task to visual targets indicate that the eardrum oscillates in conjunction with eye movements. The amplitude and phase of the eardrum movement, which we dub the Oscillatory Saccadic Eardrum Associated Response or OSEAR, depended on the direction and horizontal amplitude of the saccade and occurred in the absence of any externally delivered sounds. 2) For the second experiment, we use an audiovisual cueing task to demonstrate a dynamic change to pressure levels in the ear when a sound is expected versus when one is not. Specifically, we observe a drop in frequency power and variability from 0.1 to 4kHz around the time when the sound is expected to occur in contract to a slight increase in power at both lower and higher frequencies. 3) For the third experiment, we show that seeing a speaker say a syllable that is incongruent with the accompanying audio can alter the response patterns of the auditory periphery, particularly during the most relevant moments in the speech stream. These visually influenced changes may contribute to the altered percept of the speech sound. Collectively, we presume that these findings represent the combined effect of OHCs and MEMs acting in tandem in response to various non-auditory signals in order to manipulate the receptive properties of the auditory system. These influences may have a profound, and previously unrecognized, impact on how the auditory system processes sounds from initial sensory transduction all the way to perception and behavior. Moreover, we demonstrate that the entire auditory system is, fundamentally, a multisensory system.

Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland

OBJECTIVES This study compared the profile of intentional drug overdoses (IDOs) presenting to emergency departments in Ireland and in the Western Trust Area of Northern Ireland between 2007 and 2012. Specifically the study aimed to compare characteristics of the patients involved, to explore the factors associated with repeated IDO and to report the prescription rates of common drug types in the population. METHODS We utilised data from two comparable registries which monitor the incidence of hospital-treated self-harm, recording data from deliberate self-harm presentations involving an IDO to all hospital emergency departments for the period 1 January 2007 to 31 December 2012. RESULTS Between 2007 and 2012 the registries recorded 56,494 self-harm presentations involving an IDO. The study showed that hospital-treated IDO was almost twice as common in Northern Ireland than in Ireland (278 vs 156/100,000, respectively). CONCLUSIONS Despite the overall difference in the rates of IDO, the profile of such presentations was remarkably similar in both countries. Minor tranquillisers were the drugs most commonly involved in IDOs. National campaigns are required to address the availability and misuse of minor tranquillisers, both prescribed and non-prescribed.

Can a Broader Education Narrow the Gap? Evidence on Non-Academic Features of Schooling

Empirical studies of education programs and systems, by nature, rely upon use of student outcomes that are measurable. Often, these come in the form of test scores. However, in light of growing evidence about the long-run importance of other student skills and behaviors, the time has come for a broader approach to evaluating education. This dissertation undertakes experimental, quasi-experimental, and descriptive analyses to examine social, behavioral, and health-related mechanisms of the educational process. My overarching research question is simply, which inside- and outside-the-classroom features of schools and educational interventions are most beneficial to students in the long term? Furthermore, how can we apply this evidence toward informing policy that could effectively reduce stark social, educational, and economic inequalities?

The first study of three assesses mechanisms by which the Fast Track project, a randomized intervention in the early 1990s for high-risk children in four communities (Durham, NC; Nashville, TN; rural PA; and Seattle, WA), reduced delinquency, arrests, and health and mental health service utilization in adolescence through young adulthood (ages 12-20). A decomposition of treatment effects indicates that about a third of Fast Track’s impact on later crime outcomes can be accounted for by improvements in social and self-regulation skills during childhood (ages 6-11), such as prosocial behavior, emotion regulation and problem solving. These skills proved less valuable for the prevention of mental and physical health problems.

The second study contributes new evidence on how non-instructional investments – such as increased spending on school social workers, guidance counselors, and health services – affect multiple aspects of student performance and well-being. Merging several administrative data sources spanning the 1996-2013 school years in North Carolina, I use an instrumental variables approach to estimate the extent to which local expenditure shifts affect students’ academic and behavioral outcomes. My findings indicate that exogenous increases in spending on non-instructional services not only reduce student absenteeism and disciplinary problems (important predictors of long-term outcomes) but also significantly raise student achievement, in similar magnitude to corresponding increases in instructional spending. Furthermore, subgroup analyses suggest that investments in student support personnel such as social workers, health services, and guidance counselors, in schools with concentrated low-income student populations could go a long way toward closing socioeconomic achievement gaps.

The third study examines individual pathways that lead to high school graduation or dropout. It employs a variety of machine learning techniques, including decision trees, random forests with bagging and boosting, and support vector machines, to predict student dropout using longitudinal administrative data from North Carolina. I consider a large set of predictor measures from grades three through eight including academic achievement, behavioral indicators, and background characteristics. My findings indicate that the most important predictors include eighth grade absences, math scores, and age-for-grade as well as early reading scores. Support vector classification (with a high cost parameter and low gamma parameter) predicts high school dropout with the highest overall validity in the testing dataset at 90.1 percent followed by decision trees with boosting and interaction terms at 89.5 percent.

Effects of vermicomposted spent mushroom compost on growing medium characteristics, plant growth, yield and abiotic stress tolerance

Treatment of agricultural biodegradable wastes and by-products can be carried out using composting or vermicomposting, or a combination of both treatment methods, to create a growing medium amendment suitable for horticultural use. When compared to traditional compost-maturation, vermicompost-maturation resulted in a more mature growing medium amendment i.e. lower C/N and pH, with increased nutrient content and improved plant growth response, increasing lettuce shoot fresh and dry weight by an average of 15% and 14%, respectively. Vermicomposted horse manure compost was used as a growing medium amendment for lettuce and was found to significantly increase lettuce shoot and root growth, and chlorophyll content. When used as a growing medium amendment for tomato fruit production, vermicomposted spent mushroom compost increased shoot growth and marketable yield, and reduced blossom end rot in two independent studies. Vermicompost addition to peat-based growing media increased marketable yield by an average of 21%. Vermicompost also improved tomato fruit quality parameters such as acidity and sweetness. Fruit sweetness, as measured using Brix value, was significantly increased in fruits grown with 10% or 20% vermicompost addition by 0.2 in truss one and 0.3 in truss two. Fruit acidity (% citric acid) was significantly increased in plants grown with vermicompost by an average of 0.65% in truss one and 0.68% in truss two. These changes in fruit chemical parameters resulted in a higher tomato fruit overall acceptability rating as determined by a consumer acceptance panel. When incorporated into soil, vermicomposted spent mushroom compost increased plant growth and reduced plant stress under conditions of cold stress, but not salinity or heat stress. The addition of 20% vermicompost to cold-stressed plants increased plant growth by an average of 30% and increased chlorophyll fluorescence by an average of 21%. Compared to peat-based growing medium, vermicompost had consistently higher nutrient content, pH, electrical conductivity and bulk density, and when added to a peat-based growing medium, vermicomposted spent mushroom compost altered the microbial community. Vermicompost amendment increased the microbial activity of the growing medium when incorporated initially, and this increased microbial activity was observed for up to four months after incorporation when plants were grown in it. Vermicomposting was shown to be a suitable treatment method for agricultural biodegradable wastes and by-products, with the resulting vermicompost having suitable physical, chemical and biological properties, and resulting in increased plant growth, marketable yield and yield quality, when used as an amendment in peat-based growing medium.

Identification des grands utilisateurs de soins de santé chez les patients souffrant de la douleur chronique non cancéreuse et suivis en soins de première ligne

Contexte: La douleur chronique non cancéreuse (DCNC) génère des retombées économiques et sociétales importantes. L’identification des patients à risque élevé d’être de grands utilisateurs de soins de santé pourrait être d’une grande utilité; en améliorant leur prise en charge, il serait éventuellement possible de réduire leurs coûts de soins de santé. Objectif: Identifier les facteurs prédictifs bio-psycho-sociaux des grands utilisateurs de soins de santé chez les patients souffrant de DCNC et suivis en soins de première ligne. Méthodologie: Des patients souffrant d’une DCNC modérée à sévère depuis au moins six mois et bénéficiant une ordonnance valide d’un analgésique par un médecin de famille ont été recrutés dans des pharmacies communautaires du territoire du Réseau universitaire intégré de santé (RUIS), de l’Université de Montréal entre Mai 2009 et Janvier 2010. Ce dernier est composé des six régions suivantes : Mauricie et centre du Québec, Laval, Montréal, Laurentides, Lanaudière et Montérégie. Les caractéristiques bio-psycho-sociales des participants ont été documentées à l’aide d’un questionnaire écrit et d’une entrevue téléphonique au moment du recrutement. Les coûts directs de santé ont été estimés à partir des soins et des services de santé reçus au cours de l’année précédant et suivant le recrutement et identifiés à partir de la base de données de la Régie d’Assurance maladie du Québec, RAMQ (assureur publique de la province du Québec). Ces coûts incluaient ceux des hospitalisations reliées à la douleur, des visites à l’urgence, des soins ambulatoires et de la médication prescrite pour le traitement de la douleur et la gestion des effets secondaires des analgésiques. Les grands utilisateurs des soins de santé ont été définis comme étant ceux faisant partie du quartile le plus élevé de coûts directs annuels en soins de santé dans l’année suivant le recrutement. Des modèles de régression logistique multivariés et le critère d’information d’Akaike ont permis d’identifier les facteurs prédictifs des coûts directs élevés en soins de santé. Résultats: Le coût direct annuel médian en soins de santé chez les grands utilisateurs de soins de santé (63 patients) était de 7 627 CAD et de 1 554 CAD pour les utilisateurs réguliers (188 patients). Le modèle prédictif final du risque d’être un grand utilisateur de soins de santé incluait la douleur localisée au niveau des membres inférieurs (OR = 3,03; 95% CI: 1,20 - 7,65), la réduction de la capacité fonctionnelle liée à la douleur (OR = 1,24; 95% CI: 1,03 - 1,48) et les coûts directs en soins de santé dans l’année précédente (OR = 17,67; 95% CI: 7,90 - 39,48). Les variables «sexe», «comorbidité», «dépression» et «attitude envers la guérison médicale» étaient également retenues dans le modèle prédictif final. Conclusion: Les patients souffrant d’une DCNC au niveau des membres inférieurs et présentant une détérioration de la capacité fonctionnelle liée à la douleur comptent parmi ceux les plus susceptibles d’être de grands utilisateurs de soins et de services. Le coût direct en soins de santé dans l’année précédente était également un facteur prédictif important. Améliorer la prise en charge chez cette catégorie de patients pourrait influencer favorablement leur état de santé et par conséquent les coûts assumés par le système de santé.

On the Current Mismatch of English Education in China and Its Possible Improvement in Pedagogy for Chinese College non-English Majors

By reviewing the current mismatch of English education in China,the paper argues the content of English curriculum and instruction in China need guide students to learn the difference between Chinese and English,examine Chinese learners’ English that are incorporated with typical Chinese language characteristics.

Geomicrobiology, bulk sediment characteristics and pore water chemistry of sediment cores from Laguna Potrok Aike, southern Patagonia

Authigenic minerals can form in the water column and sediments of lakes, either abiotically or mediated by biological activity. Such minerals have been used as paleosalinity and paleoproductivity indicators and reflect trophic state and early diagenetic conditions. They are also considered potential indicators of past and perhaps ongoing microbial activity within sediments. Authigenic concretions, including vivianite, were described in late glacial sediments of Laguna Potrok Aike, a maar lake in southernmost Argentina. Occurrence of iron phosphate implies specific phosphorus sorption behavior and a reducing environment, with methane present. Because organic matter content in these sediments was generally low during glacial times, there must have been alternative sources of phosphorus and biogenic methane. Identifying these sources can help define past trophic state of the lake and diagenetic processes in the sediments. We used scanning electron microscopy, phosphorus speciation in bulk sediment, pore water analyses, in situ ATP measurements, microbial cell counts, and measurements of methane content and its carbon isotope composition (d13C CH4) to identify components of and processes in the sediment. The multiple approaches indicated that volcanic materials in the catchment are important suppliers of iron, sulfur and phosphorus. These elements influence primary productivity and play a role in microbial metabolism during early diagenesis. Authigenic processes led to the formation of pyrite framboids and revealed sulfate reduction. Anaerobic oxidation of methane and shifts in pore water ion concentration indicated microbial influence with depth. This study documents the presence of active microbes within the sediments and their relationship to changing environmental conditions. It also illustrates the substantial role played by microbes in the formation of Laguna Potrok Aike concretions. Thus, authigenic minerals can be used as biosignatures in these late Pleistocene maar sediments.

(Table 1) Clay and non-clay mineral composition of dirty ice samples from across the Arctic

Extensive dirty ice patches with up to 7 kg/m**2 sediment concentrations in layers of up to 10 cm thickness were encountered in 2005 and 2007 in numerous areas across the central Arctic. The Fe grain fingerprint determination of sources for these sampled dirty ice floes indicated both Russian and Canadian sources, with the latter dominating. The presence of benthic shells and sea weeds along with thick layers (2-10 cm) of sediment covering 5-10 m2 indicates an anchor ice entrainment origin as opposed to suspension freezing for some of these floes. The anchor ice origin might explain the dominance of Canadian sources where only narrow flaw leads occur that would not favor suspension freezing as an entrainment process. Expandable clays, commonly used as an indicator of a Kara Sea origin for dirty sea ice, are present in moderately high percentages (>20%) in many circum-Arctic source areas, including the Arctic coasts of North America. Some differences between the Russian and the North American coastal areas are found in clay mineral abundance, primarily the much higher abundance of chlorite in North America and the northern Barents Sea as opposed to the rest of the Russian Arctic. However, sea ice clay mineralogy matched many source areas, making it difficult to use as a provenance tool by itself. The bulk mineralogy (clay and non-clay) does not match specific sources possibly due to reworking of the sediment in dirty floes through summer melting or the failure to characterize all possible source areas.

Seawater carbonate chemistry, structural and chemical characteristics of the seagrass Thalassia testudinum in an situ CO2 enrichment experiment

Seagrasses commonly display carbon-limited photosynthetic rates. Thus, increases in atmospheric pCO2, and consequentially oceanic CO2(aq) concentrations, may prove beneficial. While addressed in mesocosms, these hypotheses have not been tested in the field with manipulative experimentation. This study examines the effects of in situ CO2(aq) enrichment on the structural and chemical characteristics of the tropical seagrass, Thalassia testudinum. CO2(aq) availability was manipulated for 6 months in clear, open-top chambers within a shallow seagrass meadow in the Florida Keys (USA), reproducing forecasts for the year 2100. Structural characteristics (leaf area, leaf growth, shoot mass, and shoot density) were unresponsive to CO2(aq) enrichment. However, leaf nitrogen and phosphorus content declined on average by 11 and 21 %, respectively. Belowground, non-structural carbohydrates increased by 29 %. These results indicate that increased CO2(aq) availability may primarily alter the chemical composition of seagrasses, influencing both the nutrient status and resilience of these systems.

Imputing accelerometer non-wear time when assessing children's moderate-to-vigorous physical activity

BACKGROUND: Moderate-to-vigorous physical activity (MVPA) is an important determinant of children’s physical health, and is commonly measured using accelerometers. A major limitation of accelerometers is non-wear time, which is the time the participant did not wear their device. Given that non-wear time is traditionally discarded from the dataset prior to estimating MVPA, final estimates of MVPA may be biased. Therefore, alternate approaches should be explored. OBJECTIVES: The objectives of this thesis were to 1) develop and describe an imputation approach that uses the socio-demographic, time, health, and behavioural data from participants to replace non-wear time accelerometer data, 2) determine the extent to which imputation of non-wear time data influences estimates of MVPA, and 3) determine if imputation of non-wear time data influences the associations between MVPA, body mass index (BMI), and systolic blood pressure (SBP). METHODS: Seven days of accelerometer data were collected using Actical accelerometers from 332 children aged 10-13. Three methods for handling missing accelerometer data were compared: 1) the “non-imputed” method wherein non-wear time was deleted from the dataset, 2) imputation dataset I, wherein the imputation of MVPA during non-wear time was based upon socio-demographic factors of the participant (e.g., age), health information (e.g., BMI), and time characteristics of the non-wear period (e.g., season), and 3) imputation dataset II wherein the imputation of MVPA was based upon the same variables as imputation dataset I, plus organized sport information. Associations between MVPA and health outcomes in each method were assessed using linear regression. RESULTS: Non-wear time accounted for 7.5% of epochs during waking hours. The average minutes/day of MVPA was 56.8 (95% CI: 54.2, 59.5) in the non-imputed dataset, 58.4 (95% CI: 55.8, 61.0) in imputed dataset I, and 59.0 (95% CI: 56.3, 61.5) in imputed dataset II. Estimates between datasets were not significantly different. The strength of the relationship between MVPA with BMI and SBP were comparable between all three datasets. CONCLUSION: These findings suggest that studies that achieve high accelerometer compliance with unsystematic patterns of missing data can use the traditional approach of deleting non-wear time from the dataset to obtain MVPA measures without substantial bias.

Spatio-temporal characteristics of Agulhas leakage: a model inter-comparison study

Investigating the variability of Agulhas leakage, the volume transport of water from the Indian Ocean to the South Atlantic Ocean, is highly relevant due to its potential contribution to the Atlantic Meridional Overturning Circulation as well as the global circulation of heat and salt and hence global climate. Quantifying Agulhas leakage is challenging due to the non-linear nature of this process; current observations are insufficient to estimate its variability and ocean models all have biases in this region, even at high resolution . An Eulerian threshold integration method is developed to examine the mechanisms of Agulhas leakage variability in six ocean model simulations of varying resolution. This intercomparison, based on the circulation and thermo- haline structure at the Good Hope line, a transect to the south west of the southern tip of Africa, is used to identify features that are robust regardless of the model used and takes into account the thermohaline biases of each model. When determined by a passive tracer method, 60 % of the magnitude of Agulhas leakage is captured and more than 80 % of its temporal fluctuations, suggesting that the method is appropriate for investigating the variability of Agulhas leakage. In all simulations but one, the major driver of variability is associated with mesoscale features passing through the section. High resolution (<1/10 deg.) hindcast models agree on the temporal (2–4 cycles per year) and spatial (300–500 km) scales of these features corresponding to observed Agulhas Rings. Coarser resolution models (<1/4 deg.) reproduce similar time scale of variability of Agulhas leakage in spite of their difficulties in representing the Agulhas rings properties. A coarser resolution climate model (2 deg.) does not resolve the spatio-temporal mechanism of variability of Agulhas leakage. Hence it is expected to underestimate the contribution of Agulhas Current System to climate variability.

Spatio-temporal characteristics of Agulhas leakage: a model inter-comparison study

Investigating the variability of Agulhas leakage, the volume transport of water from the Indian Ocean to the South Atlantic Ocean, is highly relevant due to its potential contribution to the Atlantic Meridional Overturning Circulation as well as the global circulation of heat and salt and hence global climate. Quantifying Agulhas leakage is challenging due to the non-linear nature of this process; current observations are insufficient to estimate its variability and ocean models all have biases in this region, even at high resolution . An Eulerian threshold integration method is developed to examine the mechanisms of Agulhas leakage variability in six ocean model simulations of varying resolution. This intercomparison, based on the circulation and thermo- haline structure at the Good Hope line, a transect to the south west of the southern tip of Africa, is used to identify features that are robust regardless of the model used and takes into account the thermohaline biases of each model. When determined by a passive tracer method, 60 % of the magnitude of Agulhas leakage is captured and more than 80 % of its temporal fluctuations, suggesting that the method is appropriate for investigating the variability of Agulhas leakage. In all simulations but one, the major driver of variability is associated with mesoscale features passing through the section. High resolution (<1/10 deg.) hindcast models agree on the temporal (2–4 cycles per year) and spatial (300–500 km) scales of these features corresponding to observed Agulhas Rings. Coarser resolution models (<1/4 deg.) reproduce similar time scale of variability of Agulhas leakage in spite of their difficulties in representing the Agulhas rings properties. A coarser resolution climate model (2 deg.) does not resolve the spatio-temporal mechanism of variability of Agulhas leakage. Hence it is expected to underestimate the contribution of Agulhas Current System to climate variability.

Receptive Vocabulary of CLIL and Non-CLIL Primary and Secondary School Learners

CLIL instruction has been reported to be beneficial for foreign language vocabulary learning since CLIL students show higher vocabulary profiles than students of their same age in traditional EFL contexts. However, to our knowledge, the receptive vocabulary knowledge of CLIL and non-CLIL learners at the end of primary and secondary education has not been examined yet. Hence, this study aims at comparing the receptive vocabulary size 79 CLIL primary learners with the receptive vocabulary knowledge of 331 non-CLIL learners at the end of primary and secondary school. Sex-based differences were also analysed. The 2k Vocabulary Levels Test (VLT) was used for the purposes of the study. Results revealed that learners’ receptive vocabulary sizes lie within the most frequent 1000 words, non-CLIL secondary school students throw better results than primary students but the differences between the secondary group and the CLIL group are not statistically significant. As for sex-based differences, we found no significant differences among the groups. These findings led us to believe that the CLIL approach offers a benefit for vocabulary acquisition since CLIL learners have been exposed to the foreign language for a shorter period of time and the results are quite similar to their non-CLIL secondary school partners.

Molecular characteristics and gene segment usage in IGH gene rearrangements in multiple myeloma.

BACKGROUND AND OBJECTIVES: Analysis of IgH rearrangements in B-cell malignancies has provided clinical researchers with a wide range of information during the last few years. However, only a few studies have contributed to the characterization of these features in multiple myeloma (MM), and they have been focused on the analysis of the expressed IgH allele only. Comparison between the expressed and the non-functional IgH alleles allows further characterizion of the selection processes to which pre-myeloma cells are submitted. DESIGN AND METHODS: We analyzed a cohort of 84 untreated MM patients in order to characterize their functional VDJH and non-functional DJH rearrangements. The pattern of mutations and gene segment usage for both types of rearrangements was analyzed by polymerase chain reaction and sequencing. RESULTS: VH3 and VH1 family members were over- and under-represented, respectively. VH3-30 and VH3-15 segments were the most frequently used, whereas VH4-34 was found only in non-functional or heavily mutated VDJH rearrangements. DH2 and DH3 family members were over-represented in both VDJH and DJH repertoires, while the DH1 family was under-represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2-21 gene segments were found to be over-represented in the functional repertoire while segments commonly used by less mature B-cell malignancies, such as DH6-19 or DH3-3, were under-represented. INTERPRETATION AND CONCLUSIONS: Data reported here help to identify the clonogenic MM cell as a post-germinal center B cell that has undergone selection processes during the germinal center reaction.

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone.

Leukemic B-chronic lymphoproliferative disorders (B-CLPDs) are generally believed to derive from a monoclonal B cell; biclonality has only occasionally been reported. In this study, we have explored the incidence of B-CLPD cases with 2 or more B-cell clones and established both the phenotypic differences between the coexisting clones and the clinicobiologic features of these patients. In total, 53 B-CLPD cases with 2 or more B-cell clones were studied. Presence of 2 or more B-cell clones was suspected by immunophenotype and confirmed by molecular/genetic techniques in leukemic samples (n = 42) and purified B-cell subpopulations (n = 10). Overall, 4.8% of 477 consecutive B-CLPDs had 2 or more B-cell clones, their incidence being especially higher among hairy cell leukemia (3 of 13), large cell lymphoma (2 of 10), and atypical chronic lymphocytic leukemia (CLL) (4 of 29). In most cases the 2 B-cell subsets displayed either different surface immunoglobulin (sIg) light chain (n = 37 of 53) or different levels of the same sIg (n = 9 of 53), usually associated with other phenotypic differences. Compared with monoclonal cases, B-CLL patients with 2 or more clones had lower white blood cell (WBC) and lymphocyte counts, more frequently displayed splenomegaly, and required early treatment. Among these, the cases in which a CLL clone coexisted with a non-CLL clone were older and more often displayed B symptoms, a monoclonal component, and diffuse infiltration of bone marrow and required early treatment more frequently than cases with monoclonal CLL or 2 CLL clones.