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Objective: This study investigated mobile health enabled surveillance in ototoxicity. Method: This was a longitudinal study of 32 participants receiving chemotherapy. Baseline and exit audiograms that included conventional and extended high frequency audiometry were recorded within the patient's treatment venue using a validated mobile health audiometer. Results: Average hearing thresholds at baseline were within the normal range (81.2 per cent left; 93.8 per cent right), reducing at exit testing (71.9 per cent left; 78.1 per cent right). Half of participants presented with a threshold shift according to ototoxicity monitoring criteria. The frequencies affected the most were between 4000 and 16 000 Hz, with left ears significantly more affected than right ears. Noise levels exceeded the maximum permissible ambient noise levels in up to 43.8 per cent of low frequencies (250–1000 Hz). Conclusion: Mobile health supported audiometry proved to be an efficacious tool for ototoxicity monitoring at the treatment venue. Changes in hearing ability over time could be tracked, improving surveillance in patients with full treatment schedules. [ABSTRACT FROM AUTHOR]

Aim The aims of this population genetics study of the common juniper across Eurasia were to (1) assess the contribution of southern mountain ranges to the post-glacial recolonization of high latitudes and (2) test whether recent expansion or high gene flow could explain the low genetic differentiation in Northern Eurasia. Location Northern Eurasia and mountain regions of Central Europe and Asia. Methods Six hundred and twenty-two individuals were sampled in 42 populations. Two chloroplast DNA (cp DNA) fragments were investigated ( trnT- trnL and 16S- trnA). Analyses of the distribution of haplotypes across the continent included a suite of phylogeographical and phylogenetic tests. Putative geographical distribution in the past was reconstructed using environmental niche modelling. Results Eighty-four haplotypes clustered into four main clades ( GL1- GL4). The largest clade, GL3, corresponds to populations from the Alps, northern Europe, Western Caucasus and Siberia. These populations were moderately differentiated (28%) compared to the total range (76%) and Fu's Fs statistic was negative, indicating a population expansion. Some haplotypes within GL3 form subclades with a restricted geographical distribution, suggesting a local origin of the mutation and limited dispersal. In line with these findings, modelling of ecological niches found no significant reduction in the expected range during the LGM. Remarkably, populations from the eastern part of North Caucasus, the Himalayas, Tien Shan and south Siberia were distinctly different from populations in the rest of the range. Main conclusions As in Siberian larch species, the pattern of genetic diversity at cp DNA across the natural range of J. communis suggests that colonization of northern Europe and Siberia started from a limited area and predated the last glaciation. It is likely that juniper survived the subsequent glacial epoch at high latitudes in cryptic refugia serving as secondary centres of recolonization. Southern mountain refugia contribution to the recolonization of high latitudes was, at best, limited. [ABSTRACT FROM AUTHOR]

Background:This study compared vestibulocollic reflex and vestibulo-ocular reflex functioning in subjects with and without human immunodeficiency virus. It also described test results throughout progression of the disease and compared the results of human immunodeficiency virus positive subjects who were receiving antiretroviral therapies with those not receiving this treatment.Methods:Subjects comprised 53 adults with human immunodeficiency virus (mean age 38.5 ± 4.4 years) and 38 without human immunodeficiency virus (mean age 36.9 ± 8.2 years). Clinical examinations included cervical vestibular-evoked myogenic potential and bithermal caloric testing.Results:Abnormal cervical vestibular-evoked myogenic potential and caloric results were significantly higher in the human immunodeficiency virus positive group (p = 0.001), with an odds ratio of 10.2. Vestibulocollic reflex and vestibulo-ocular reflex involvement increased with progression of the disease. There were more abnormal test results in subjects receiving antiretroviral therapies (66.7 per cent) than in those not receiving antiretroviral therapies (63.6 per cent), but this difference was insignificant.Conclusion:Human immunodeficiency virus seems to influence vestibulocollic reflex pathways. Combining cervical vestibular-evoked myogenic potential and caloric testing may be useful to detect early neurological involvement in human immunodeficiency virus positive subjects. [ABSTRACT FROM PUBLISHER]

Introduction:Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear.Objective:To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome.Method:Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched.Results:We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study.Discussion:We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance.Conclusion:Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life. [ABSTRACT FROM PUBLISHER]

Abstract: Buffer structures and edge termination have a decisive influence on the static and dynamic characteristics of free-wheeling diodes. In this paper the influence of buffer structures at the cathode side, the influence of the design of the edge termination and of a resistive zone at the anode side are analysed with respect to the ruggedness of free-wheeling diodes. Therefore, we investigated the device behaviour by means of numerical device simulation concerning the formation of current filamentation and the correlated shape of the electrical field distribution. The considered edge termination of the diodes was planar junction termination extensions and a beveled edge. Various buffer structures, a Gaussian buffer and a buried n-doped layer of increased doping called epitaxy level buffer are compared with a reference diode without any buffer structure. [Copyright &y& Elsevier]

The effects of different buffer structures on the avalanche and post avalanche behaviour of high voltage silicon diodes under high reverse current conditions has been investigated. After the onset of avalanche, when the diodes are reverse biased, branches both with positive and negative differential resistance may occur in the device characteristics and depend sensitively on the doping profile of the buffer layer. By numerical device simulation the influence of relevant bulk doping and various buffer profiles on these static reverse characteristics are analysed to understand, clarify and illustrate the breakdown behaviour of high voltage pin-diodes. Based upon these considerations an effective restriction of the electric field maximum at the nn+-junction at the cathode side of the diode can be achieved by adapting the doping gradient of the buffer profile. [ABSTRACT FROM AUTHOR]

The article presents a commentary on the study "Association genetics in Pinus taeda L. II. Carbon isotope discrimination," by S. C. González-Martínez and colleagues. According to the author, the paper provides partly an answer to the query about the strong clinical and ecotypic variation in the growth traits of forest trees since the first genetic markers became available. The researchers, accordingly, show how two particular nucleotide changes influence drought tolerance in pines.

Objective:To characterise auditory involvement secondary to excessive craniotubular bone growth in individuals with sclerosteosis in South Africa.Methods:This cross-sectional study assessed the auditory profile of 10 participants with sclerosteosis. An auditory test battery was used and results for each ear were recorded using descriptive and comparative analyses.Results:All participants presented with bilateral, mixed hearing losses. Of the 20 ears, hearing loss was moderate in 5 per cent (n = 1), severe in 55 per cent (n = 11) and profound in 40 per cent (n = 8). Air–bone gaps were smaller in older participants, although the difference was not statistically significant (p > 0.05). Computed tomography scans indicated pervasive abnormalities of the external auditory canal, tympanic membrane, middle-ear space, ossicles, oval window, round window and internal auditory canal. Narrowed internal auditory canals corresponded to poor speech discrimination, indicative of retrocochlear pathology and absent auditory brainstem response waves.Conclusion:Progressive abnormal bone formation in sclerosteosis involves the middle ear, the round and oval windows of the cochlea, and the internal auditory canal. The condition compromises conductive, sensory and neural auditory pathways, which results in moderate to profound, mixed hearing loss. [ABSTRACT FROM PUBLISHER]

Developing "climate smart forestry" (CSF) indicators in mountain forest regions requires collection and evaluation of local data and their attributes. Genetic resources are listed among the core indicators for forest biological diversity. This study is a report on the evaluation of the standing genetic diversity within and across 12 pure beech stands (Fagus sylvatica L.) established within the CLIMO (CLImate Smart Forestry in MOuntain Regions) project, using nuclear microsatellite markers. The sampling sites were set along the species' distribution range, including the Balkan region and extending towards the Iberian Peninsula. Cores or leaves from 20 to 23 old, mature trees per plot were sampled for DNA analysis. Genetic diversity indices were high across the range (HE = 0.74−0.81) with the highest in the Bosnian Mountains. Genetic divergence increased significantly with the geographical distance (Mantel test: r = 0.81, p < 0.001). Most of the stands exhibited an excess of heterozygotes, with the highest value at the Hungarian site (HO/HE = 1.177), where beech persists close to the eastern xeric limit of the species' distribution. STRUCTURE revealed within-region differentiation in the Balkan Peninsula, where the Bulgarian stand was the most outstanding. The genetic parameters of each stand could be assessed as a resource for CSF indicators interpreted especially at the local level. [ABSTRACT FROM AUTHOR]

The use of admixed human populations to scan the genome for chromosomal segments affecting complex phenotypic traits has proved a powerful analytical tool. However, its potential in other organisms has not yet been evaluated. Here, we use DNA microsatellites to assess the feasibility of this approach in hybrid zones between two members of the ‘model tree’ genus Populus: Populus alba (white poplar) and Populus tremula (European aspen). We analyzed samples of both species and a Central European hybrid zone (N=544 chromosomes) for a genome-wide set of 19 polymorphic DNA microsatellites. Our results indicate that allele frequency differentials between the two species are substantial (mean δ=0.619±0.067). Background linkage disequilibrium (LD) in samples of the parental gene pools is moderate and should respond to sampling schemes that minimize drift and account for rare alleles. LD in hybrids decays with increasing number of backcross generations as expected from theory and approaches background levels of the parental gene pools in advanced generation backcrosses. Introgression from P. tremula into P. alba varies strongly across marker loci. For several markers, alleles from P. tremula are slightly over-represented relative to neutral expectations, whereas a single locus exhibits evidence of selection against P. tremula genotypes. We interpret our results in terms of the potential for admixture mapping in these two ecologically divergent Populus species, and we validate a modified approach of studying genotypic clines in ‘mosaic’ hybrid zones.Heredity (2007) 98, 74–84. doi:10.1038/sj.hdy.6800898; published online 20 September 2006 [ABSTRACT FROM AUTHOR]

The renewed interest in the use of hybrid zones for studying speciation calls for the identification and study of hybrid zones across a wide range of organisms, especially in long-lived taxa for which it is often difficult to generate interpopulation variation through controlled crosses. Here, we report on the extent and direction of introgression between two members of the‘model tree’ genusPopulus:Populus alba(white poplar) andPopulus tremula(European aspen), across a large zone of sympatry located in the Danube valley. We genotyped 93 hybrid morphotypes and samples from four parental reference populations from within and outside the zone of sympatry for a genome-wide set of 20 nuclear microsatellites and eight plastid DNA restriction site polymorphisms. Our results indicate that introgression occurs preferentially fromP. tremulatoP. albaviaP. tremulapollen. This unidirectional pattern is facilitated by high levels of pollen vs. seed dispersal inP. tremula(pollen/seed flow = 23.9) and by great ecological opportunity in the lowland floodplain forest in proximity toP. albaseed parents, which maintains gene flow in the direction ofP. albadespite smaller effective population sizes (N e) in this species (P. alba N e c.500–550;P. tremula N e c.550–700). Our results indicate that hybrid zones will be valuable tools for studying the genetic architecture of the barrier to gene flow between these two ecologically divergentPopulusspecies. [ABSTRACT FROM AUTHOR]

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph+ chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-a therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-a ± low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-a dose applied (P<0.000005). MF progressed during low-dose therapy (3 × 5 × 106?IU/week), but was prevented from progression when applying high dose (5 × 106?IU/m2/per day). MF disappeared when high-dose interferon-a was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-a on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-a with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-a. MF appears to be a significant early indicator of ineffective therapy in CML.Leukemia (2004) 18, 1460-1467. doi:10.1038/sj.leu.2403451 Published online 29 July 2004 [ABSTRACT FROM AUTHOR]

Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph+ CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-a, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-a and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.Leukemia (2003) 17, 2444-2453. doi:10.1038/sj.leu.2403172 Published online 16 October 2003 [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) in older patients has not been studied well. To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged ?60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon a (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years. In all, 45 patients were treated with Bu, 63 with HU, and 91 with IFN. The 5-year survival was 38% in patients ?60 years and 47% in patients <60 years (P<0.001). Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077). Calculation of age-adjusted, relative survival confirmed these results. Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients. We conclude that the course of CML is not different in the elderly. They require lower IFN doses, achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity.Leukemia (2003) 17, 1820-1826. doi:10.1038/sj.leu.2403042 [ABSTRACT FROM AUTHOR]

The reliability of routine BCR-ABL RT-nested-PCR was evaluated in 1453 B-lineage ALL or hybrid leukemia at initial diagnosis by RT-nested-PCR. All BCR-ABL-positive (n = 642) and 176 BCR-ABL-negative samples underwent a second RT-PCR. In 518 patients, karyotyping and/or FISH was compared to the BCR-ABL status. The second RT-PCR revealed in 155/642 initially positive samples a divergent result (153 BCR-ABL-negative, two other transcripts) that in most cases turned out to be caused by contaminations in the first RT-nested-PCR. Confirmatory RT-PCR detected 2/176 false negative first RT-nested-PCR results. Thirty-nine specimens remained ambiguous despite different RT-PCR approaches. As far as cytogenetic evaluation and FISH is available (n = 23), the majority but not all patients with an ambiguous RT-PCR result were Ph-negative (n = 18). RT-nested-PCR and cytogenetics yielded in 346 of 383 evaluable samples a concordant result. Differing results are given and account in part to the lower sensitivity of karyotyping. Taken together, confirmed RT-PCR detected BCR-ABL fusion transcripts consistently in 487 out of 1453 ALL samples (c-ALL: 43%, pre-B ALL: 34%, pro-B ALL: 5%, B-ALL: 0%, hybrid leukemia: 5/11). Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance. [ABSTRACT FROM AUTHOR]

The reliability of routine BCR-ABL RT-nested-PCR was evaluated in 1453 B-lineage ALL or hybrid leukemia at initial diagnosis by RT-nested-PCR. All BCR-ABL-positive (n = 642) and 176 BCR-ABL-negative samples underwent a second RT-PCR. In 518 patients, karyotyping and/or FISH was compared to the BCR-ABL status. The second RT-PCR revealed in 155/642 initially positive samples a divergent result (153 BCR-ABL-negative, two other transcripts) that in most cases turned out to be caused by contaminations in the first RT-nested-PCR. Confirmatory RT-PCR detected 2/176 false negative first RT-nested-PCR results. Thirty-nine specimens remained ambiguous despite different RT-PCR approaches. As far as cytogenetic evaluation and FISH is available (n = 23), the majority but not all patients with an ambiguous RT-PCR result were Ph-negative (n = 18). RT-nested-PCR and cytogenetics yielded in 346 of 383 evaluable samples a concordant result. Differing results are given and account in part to the lower sensitivity of karyotyping. Taken together, confirmed RT-PCR detected BCR-ABL fusion transcripts consistently in 487 out of 1453 ALL samples (c-ALL: 43%, pre-B ALL: 34%, pro-B ALL: 5%, B-ALL: 0%, hybrid leukemia: 5/11). Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance. [ABSTRACT FROM AUTHOR]

Purpose : The detection of long-term persistent chromosome aberrations in circulating haemopoietic stem cells after accidental radiation exposure. Materialand methods : Peripheral blood samples fromhighly exposed persons were collected 7-25 years after the radiation accidents in Moscow (1971), Kazan (1975) and Chernobyl (1996). Haemopoietic blood stem cells were analysed when investigating individual colonies derived from haemopoietic progenitor cells: burst-forming units-erythroid (BFU-E), granulocytemacrophage-colony-forming cells (GM-CFC) and multipotent granulocyte-erythrocyte-macrophage-megakaryocyte-colonyforming cells (GEMM-CFC). Colony formation was obtained in methylcellulose cultures. Chromosome preparations in single colonies were performed using a microtechnique. Results : Nine patients were investigated at 1 to 4 follow-up time points after radiation exposure. Three hundred and thirty-four single colonies were analyzed resulting in 1375 mitoses. It was found that colonies showed chromosome aberrations (ChA) up to 25 years after radiation exposure by classical cytogenetics and by fluorescence in situ hybridization (FISH). Stable aberrations were detected in 21% of colonies. They were clonal in 19% of colonies, i.e. the same abnormality was found in all cells derived from a single colony. In 2% of colonies ChA were stable but non-clonal; unstable ChA were not observed. Conclusions : The results indicate that blood-derived haemopoietic stem cells may serve as a biological indicator to detect radiation-induced ChA. Since they are considered to be in dynamic and functional exchange with stem cells in the medullary sites of blood cell formation such as bone marrow, the use of blood stem cells as a marker of radiation effects should be explored to assess the repair status of the stem cell pool as such. [ABSTRACT FROM AUTHOR]

A correction to the article "Admixture in European Populus Hybrid Zones Makes Feasible the Mapping of Loci that Contribute to Reproductive Isolation and Trait Differences" that was published in the September 20, 2006 issue is presented.