bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurofibromatosis-associated lung disease: a case series and literature review
Authors: Zamora A. C. , Collard H. R. , Wolters P. J. , Webb W. R. , King T. E.
Published: July 2006

An association of neurofibromatosis with diffuse lung disease (NF-DLD) has been described, but its true prevalence and characteristics remain unclear. The objective of the present study was to define diffuse lung disease in patients with neurofibromatosis.

A retrospective case series and literature review in a tertiary care academic medical centre is reported in which medical records, chest radiographs and high-resolution computed tomography (HRCT) scans were reviewed.

A total of 55 adult patients with neurofibromatosis were identified, three of whom had NF-DLD. A literature review revealed 16 articles reporting 61 additional cases, yielding a total of 64 NF-DLD cases. The mean age of patients was 50 yrs. Males outnumbered females; most reported dyspnoea. Of the 16 subjects with documented smoking histories, 12 were ever-smokers. Eight patients had HRCT scan results demonstrating ground-glass opacities (37%), bibasilar reticular opacities (50%), bullae (50%), cysts (25%) and emphysema (25%); none had honeycombing. A group of 14 patients had surgical biopsy results that showed findings of interstitial fibrosis (100%) and interstitial inflammation (93%).

In conclusion, neurofibromatosis with diffuse lung disease is a definable clinical entity, characterised by upper lobe cystic and bullous disease and lower lobe fibrosis. Its relationship to smoking remains unclear.
Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses
Authors: Noakes P. S. , Hale J. , Thomas R. , Lane C. , Devadason S. G. , Prescott S. L.
Published: July 2006

Infants of smokers have much higher rates of respiratory infection, asthma and airway disease. The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness.

In a prospective birth cohort, the cord blood immune responses of neonates of smoking and nonsmoking mothers were compared. Maternal and cord serum cotinine were measured to confirm the level of cigarette smoke exposure. Neonatal cytokine responses were assessed to optimal doses of TLR2, TLR3, TLR4 and TLR9 ligands.

Cotinine levels confirmed maternal reporting of cigarette smoking in pregnancy, with significantly higher cotinine levels in maternal and cord blood compared with the nonsmoking group. Infants of smoking mothers showed significantly attenuated innate TLR-mediated responses compared with infants of nonsmokers.

The current findings indicate that in addition to effects on developing airways, maternal smoking also has significant immunological effects in pregnancy, which could contribute to the well recognised, subsequent increased risk of respiratory infections and asthma. These effects appear to be mediated through effects on toll-like receptor-mediated innate response pathways, which also promote regulatory pathways in the inhibition of allergic immune responses in the postnatal period, suggesting that other environmental interactions are highly relevant to the “hygiene hypothesis”.
Driving ability in sleep apnoea patients before and after CPAP treatment: evaluation on a road safety platform
Authors: Mazza S. , Pépin J-L. , Naëgelé B. , Rauch E. , Deschaux C. , Ficheux P. , Lévy P.
Published: July 2006

Sleepiness is considered to be the major cause of increased traffic accidents in patients with obstructive sleep apnoea syndrome (OSAS). Until now, OSAS patients′ driving ability has been assessed using driving simulators, but no assessment in a more natural driving environment has been carried out to date.

The aim of the present study was to evaluate driving parameters in OSAS and in controls on a road safety platform, and to compare them with attentional in-laboratory measures before and after continuous positive airway pressure treatment.

The parameters measured were: reaction time; distance to stop and number of collisions on the platform; maintenance of wakefulness; and sustained, selective and divided attention in laboratory.

Patients exhibited much longer reaction times than controls, leading to a lengthening of the vehicle′s stopping distance of 8.8 m at 40 km·h-1and to twice the number of collisions. Patients did not demonstrate objective sleepiness or selective and sustained attention deficits. Divided attention deficits were found. However, they did not allow the prediction of real driving impairment. After CPAP treatment, there was no longer any difference between patients and controls regarding driving and attention performances.

Driving abilities are significantly impaired in obstructive sleep apnoea syndrome. After continuous positive airway pressure treatment, deficits were normalised. This stresses the importance of evaluating attentional parameters in apnoeic patients and of offering continuous positive airway pressure treatment even to non-sleepy subjects.
GSTM1andGSTP1and respiratory health in asthmatic children exposed to ozone
Authors: Romieu I. , Ramirez-Aguilar M. , Sienra-Monge J. J. , Moreno-Macías H. , del Rio-Navarro B. E. , David G. , Marzec J. , Hernández-Avila M. , London S.
Published: July 2006

Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals. Genetic factors may influence interindividual variation in ozone response. The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress,i.e.glutathioneS-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics.

A total of 151 asthmatic children, who were participants in a randomised controlled trial of antioxidant vitamin supplementation in Mexico City, were studied. Children were genotyped using PCR methods and followed from October 1998–April 2000.

Increases in reported breathing difficulty were associated with ozone exposure in children withGSTM1null (8%, 95% confidence interval (CI) 1–15%, per 20-ppb increase in 1-h maximum daily average over 7 days) orGSTP1Valine/Valine (Val/Val) genotypes (14%, 95% CI 5–25%). In children with bothGSTM1null andGSTP1Val/Val genotypes, the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater (21%, 95% CI 5–39%).GSTP1genotypes were not significantly associated with ozone-related lung function changes.

In conclusion, asthmatic children with glutathioneS-transferase M1 null and glutathioneS-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure.
An oral selective M3 cholinergic receptor antagonist in COPD
Authors: Lu S. , Parekh D. D. , Kuznetsova O. , Green S. A. , Tozzi C. A. , Reiss T. F.
Published: July 2006

Cholinergic antagonists have been used since the early 1900s as bronchodilators for chronic obstructive pulmonary disease (COPD). The present study investigated whether an oral muscarinic M3-selective anticholinergic agent (OrM3) would provide an improved therapeutic advantage compared with an inhaled anticholinergic agent in patients with COPD.

A 6-week, multicentre, randomised, placebo- and active-controlled, parallel-group study was performed at 56 sites in the USA. In total, 412 male and female patients (aged 35–86 yrs) with a clinical history consistent with COPD were randomised to receive OrM3 0.5, 2, 3 or 4 mg orally once daily, ipratropium bromide 36 μg by inhalation four times daily or placebo.

OrM3 demonstrated a significant dose-related improvement in serial forced expiratory volume in one second and a trend for dose-related improvement in patient-reported symptoms compared with placebo. However, at a dose that provided efficacy less than that of ipratropium, the incidence of dose-related, mechanism-based side-effects for OrM3 exceeded those observed for ipratropium.

In patients with chronic obstructive pulmonary disease, the oral M3-selective agent did not offer a therapeutic advantage over inhaled ipratropium. These results do not support the hypothesis that high selectivity for muscarinic M3 receptors over airway neuronal M2 receptors will represent a more effective therapy than current inhaled anticholinergics in obstructive airway disease.
The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer
Authors: Lam B. , Wong M. P. , Fung S. L. , Lam D. C. L. , Wong P. C. , Mok T. Y. W. , Lam F. M. , Ip M. S. M. , Ooi C. G. C. , Lam W. K.
Published: July 2006

The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer.

Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination.

Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91versus58%) at detecting these lesions, but less specific (26versus50%).

A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.
TENOR risk score predicts healthcare in adults with severe or difficult-to-treat asthma
Authors: Miller M. K. , Lee J. H. , Blanc P. D. , Pasta D. J. , Gujrathi S. , Barron H. , Wenzel S. E. , Weiss S. T.
Published: July 2006

The aim of the present study was to predict which patients with severe or difficult-to-treat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management.

Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline.

Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index ≥35 kg·m-2; post-bronchodilator per cent predicted forced vital capacity <70%; history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0–18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12- to 18-months follow-up among the same cohort (c-index: 0.77).

The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.
Incidence of asthma and net change in symptoms in relation to changes in obesity
Authors: Chinn S. , Downs S. H. , Anto J. M. , Gerbase M. W. , Leynaert B. , de Marco R. , Janson C. , Jarvis D. , Künzli N. , Sunyer J. , Svanes C. , Zemp E. , Ackermann-Liebrich U. , Burney P.
Published: July 2006

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline.

Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group.

Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25–3.20; excess net change 2.8%, 0.4–5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males.

The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.
Participation of the PI-3K/Akt-NF-κB signaling pathways in hypoxia-induced mitogenic factor-stimulated Flk-1 expression in endothelial cells
Authors: Tong Qiangsong , Zheng Liduan , Lin Li , Li Bo , Wang Danming , Huang Chuanshu , Matuschak George M , Li Dechun
Published: July 2006

Background

Hypoxia-induced mitogenic factor (HIMF), a lung-specific growth factor, promotes vascular tubule formation in a matrigel plug model. We initially found that HIMF enhances vascular endothelial growth factor (VEGF) expression in lung epithelial cells. In present work, we tested whether HIMF modulates expression of fetal liver kinase-1 (Flk-1) in endothelial cells, and dissected the possible signaling pathways that link HIMF to Flk-1 upregulation.

Methods

Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, Flk-1 expression was examined by immunohistochemistry and Western blot. The promoter-luciferase reporter assay and real-time RT-PCR were performed to examine the effects of HIMF on Flk-1 expression in mouse endothelial cell line SVEC 4–10. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK, and IκBα were examined by luciferase assay and Western blot, respectively.

Results

Intratracheal instillation of HIMF protein resulted in a significant increase of Flk-1 production in lung tissues. Stimulation of SVEC 4–10 cells by HIMF resulted in increased phosphorylation of IKK and IκBα, leading to activation of NF-κB. Blocking NF-κB signaling pathway by dominant-negative mutants of IKK and IκBα suppressed HIMF-induced Flk-1 upregulation. Mutation or deletion of NF-κB binding site within Flk-1 promoter also abolished HIMF-induced Flk-1 expression in SVEC 4–10 cells. Furthermore, HIMF strongly induced phosphorylation of Akt. A dominant-negative mutant of PI-3K, Δp85, as well as PI-3K inhibitor LY294002, blocked HIMF-induced NF-κB activation and attenuated Flk-1 production.

Conclusion

These results suggest that HIMF upregulates Flk-1 expression in endothelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis.
PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs
Authors: Pitre Sylvain , Dehne Frank , Chan Albert , Cheetham Jim , Duong Alex , Emili Andrew , Gebbia Marinella , Greenblatt Jack , Jessulat Mathew , Krogan Nevan , Luo Xuemei , Golshani Ashkan
Published: July 2006

Background

Identification of protein interaction networks has received considerable attention in the post-genomic era. The currently available biochemical approaches used to detect protein-protein interactions are all time and labour intensive. Consequently there is a growing need for the development of computational tools that are capable of effectively identifying such interactions.

Results

Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins. PIPE showed a sensitivity of 61% for detecting any yeast protein interaction with 89% specificity and an overall accuracy of 75%. This rate of success is comparable to those associated with the most commonly used biochemical techniques. Using PIPE, we identified a novel interaction between YGL227W (vid30) and YMR135C (gid8) yeast proteins. This lead us to the identification of a novel yeast complex that here we term vid30 complex (vid30c). The observed interaction was confirmed by tandem affinity purification (TAP tag), verifying the ability of PIPE to predict novel protein-protein interactions. We then used PIPE analysis to investigate the internal architecture of vid30c. It appeared from PIPE analysis that vid30c may consist of a core and a secondary component. Generation of yeast gene deletion strains combined with TAP tagging analysis indicated that the deletion of a member of the core component interfered with the formation of vid30c, however, deletion of a member of the secondary component had little effect (if any) on the formation of vid30c. Also, PIPE can be used to analyse yeast proteins for which TAP tagging fails, thereby allowing us to predict protein interactions that are not included in genome-wide yeast TAP tagging projects.

Conclusion

PIPE analysis can predict yeast protein-protein interactions. Also, PIPE analysis can be used to study the internal architecture of yeast protein complexes. The data also suggests that a finite set of short polypeptide signals seem to be responsible for the majority of the yeast protein-protein interactions.
Increased large conductance calcium-activated potassium (BK) channel expression accompanied by STREX variant downregulation in the developing mouse CNS
Authors: MacDonald Stephen H-F , Ruth Peter , Knaus Hans-Guenther , Shipston Michael J
Published: July 2006

Background

Large conductance calcium- and voltage activated potassium (BK) channels are important determinants of neuronal excitability through effects on action potential duration, frequency and synaptic efficacy. The pore- forming subunits are encoded by a single gene, KCNMA1, which undergoes extensive alternative pre mRNA splicing. Different splice variants can confer distinct properties on BK channels. For example, insertion of the 58 amino acid stress-regulated exon (STREX) insert, that is conserved throughout vertebrate evolution, encodes channels with distinct calcium sensitivity and regulation by diverse signalling pathways compared to the insertless (ZERO) variant. Thus, expression of distinct splice variants may allow cells to differentially shape their electrical properties during development. However, whether differential splicing of BK channel variants occurs during development of the mammalian CNS has not been examined.

Results

Using quantitative real-time polymerase chain reaction (RT-PCR) Taqman™ assays, we demonstrate that total BK channel transcripts are up regulated throughout the murine CNS during embryonic and postnatal development with regional variation in transcript levels. This upregulation is associated with a decrease in STREX variant mRNA expression and an upregulation in ZERO variant expression.

Conclusion

As BK channel splice variants encode channels with distinct functional properties the switch in splicing from the STREX phenotype to ZERO phenotype during embryonic and postnatal CNS development may provide a mechanism to allow BK channels to control distinct functions at different times of mammalian brain development.
Why are physicians not persuaded by scientific evidence? A grounded theory interview study
Authors: Sekimoto Miho , Imanaka Yuichi , Kitano Nobuko , Ishizaki Tatsuro , Takahashi Osamu
Published: July 2006

Background

The government-led "evidence-based guidelines for cataract treatment" labelled pirenoxine and glutathione eye drops, which have been regarded as the standard care for cataracts in Japan, as lacking evidence of effectiveness, causing great upset among ophthalmologists and professional ophthalmology societies. This study investigated the reasons why such "scientific evidence of treatment effectiveness" is not easily accepted by physicians, and thus, why they do not change their clinical practices to reflect such evidence.

Methods

We conducted a qualitative study based on grounded theory to explore physicians' awareness of "scientific evidence" and evidence-supported treatment in relation to pirenoxine and glutathione eye drops, and to identify current barriers to the implementation of evidence-based policies in clinical practice. Interviews were conducted with 35 ophthalmologists and 3 general practitioners on their prescribing behaviours, perceptions of eye drop effectiveness, attitudes toward the eye drop guideline recommendations, and their perceptions of "scientific evidence."

Results

Although few physicians believed that eye drops are remarkably effective, the majority of participants reported that they prescribed eye drops to patients who asked for them, and that such patients accounted for a considerable proportion of those with cataracts. Physicians seldom attempted to explain to patients the limitations of effectiveness or to encourage them to stop taking the eye drops. Physicians also acknowledged the benefits of prescribing such drugs, which ultimately outweighed any uncertainty of their effectiveness. These benefits included economic incentives and a desire to be appreciated by patients. Changes in clinical practice were considered to bring little benefit to physicians or patients. Government approval, rarity of side effects, and low cost of the drops also encouraged prescription.

Conclusion

Physicians occasionally provide treatment without expecting remarkable therapeutic effectiveness, as exemplified by the use of eye drops. This finding highlights that scientific evidence alone cannot easily change physicians' clinical practices, unless evidence-based practices are accepted by the general public and supported by health policy.
Assessment of skeletal muscle fatigue of road maintenance workers based on heart rate monitoring and myotonometry
Authors: Roja Zenija , Kalkis Valdis , Vain Arved , Kalkis Henrijs , Eglite Maija
Published: July 2006

Objective

This research work is dedicated to occupational health problems caused by ergonomic risks. The research object was road building industry, where workers have to work very intensively, have long work hours, are working in forced/constrained work postures and overstrain during the work specific parts of their bodies. The aim of this study was to evaluate the work heaviness degree and to estimate the muscle fatigue of workers after one week work cycle. The study group consisted of 10 road construction and maintenance workers and 10 pavers aged between 20 and 60 years.

Methods

Physical load were analyzed by measuring heart rate (HR), work postures (OWAS) and perceived exertion (RPE). Assessments of the muscles strain and functional state (tone) were carried out using myotonometric (MYO) measurements. The reliability of the statistical processing of heart rate monitoring and myotonometry data was determined using correlating analysis.

Results

This study showed that that road construction and repairing works should be considered as a hard work according to average metabolic energy consumption 8.1 ± 1.5 kcal/min; paving, in its turn, was a moderately hard work according to 7.2 ± 1.1 kcal/min. Several muscle tone levels were identified allowing subdivision of workers into three conditional categories basing on muscle tone and fatigue: I – absolute muscle relaxation and ability to relax; II – a state of equilibrium, when muscles are able to adapt to the work load and are partly able to relax; and III – muscle fatigue and increased tone. It was also found out that the increase of muscle tone and fatigue mainly depend on workers physical preparedness and length of service, and less – on their age.

Conclusion

We have concluded that a complex ergonomic analysis consisting of heart rate monitoring, assessment of compulsive working postures and myotonometry is appropriate to assess the work heaviness degree and can provide prognosis of occupational pathology or work-related musculoskeletal disorders for the workers under different workload conditions. These results can also be used when deciding on necessary rest time and its periodicity.
Fine scale structural variants distinguish the genomes of Drosophila melanogaster and D. pseudoobscura
Authors: Macdonald Stuart J , Long Anthony D
Published: July 2006

Background

A primary objective of comparative genomics is to identify genomic elements of functional significance that contribute to phenotypic diversity. Complex changes in genome structure (insertions, duplications, rearrangements, translocations) may be widespread, and have important effects on organismal diversity. Any survey of genomic variation is incomplete without an assessment of structural changes.

Results

We re-examine the genome sequences of the diverged species Drosophila melanogaster and D. pseudoobscura to identify fine-scale structural features that distinguish the genomes. We detect 95 large insertion/deletion events that occur within the introns of orthologous gene pairs, the majority of which represent insertion of transposable elements. We also identify 143 microinversions below 5 kb in size. These microinversions reside within introns or just upstream or downstream of genes, and invert conserved DNA sequence. The sequence conservation within microinversions suggests they may be enriched for functional genetic elements, and their position with respect to known genes implicates them in the regulation of gene expression. Although we found a distinct pattern of GC content across microinversions, this was indistinguishable from the pattern observed across blocks of conserved non-coding sequence.

Conclusion

Drosophila has long been known as a genus harboring a variety of large inversions that disrupt chromosome colinearity. Here we demonstrate that microinversions, many of which are below 1 kb in length, located in/near genes may also be an important source of genetic variation in Drosophila. Further examination of other Drosophila genome sequences will likely identify an array of novel microinversion events.
Holocene environmental change inferred from a high-resolution pollen record, Lake Zhuyeze, arid China
Authors: Chen Fa-Hu , Cheng Bo , Zhao Yan , Zhu Yan , Madsen David B.
Published: July 2006

A high-resolution pollen record, c. 50 yr/sample, from terminal lake sediments in the Shiyang River drainage basin on the present margin of the summer monsoon was used to reconstruct vegetation and climate history during the Holocene. Forest trees from mountainous areas of the drainage, including Sabina, Picea and Pinus, dominated pollen assemblages in the early Holocene (11.6-7.1 cal. ka). In the mid-Holocene (7.1-3.8 cal. ka) desert and steppe shrubs and herbs around the lake, including Nitraria, Poaceae, Compositae and Artemisia, were dominant. The late Holocene (3.8-0 cal. ka) was again dominated by alternation of Pinus-Sabina tree pollen and desert-steppe pollen. The early Holocene forest expansion in the mountains and subsequent increase in the river transport of tree pollen corresponds with maximum precipitation during the East Asian summer monsoon maximum. The timing of these changes in our record from arid China is different from that of East China, where the Holocene monsoon maximum appeared in the middle Holocene. This difference indicates that the extent and development of summer monsoon circulation in the Holocene was complex. Changes in the pollen record appear to show pervasive and persistent centennial-to millennial-scale oscillations throughout both wet and dry periods of the Holocene. Our results imply the continental interior was sensitive to changing moisture conditions and responsive to Holocene climatic events.
Late Quaternary river evolution of floodplain pockets along Mulloon Creek, New South Wales, Australia
Authors: Johnston Peter , Brierley Gary
Published: July 2006

Valley confinement along upper-middle reaches of Mulloon Creek, in the upper Shoalhaven catchment of southern New South Wales, Australia, restricts floodplain development to a series of distinct pockets. These pockets comprise a downstream-thinning wedge of vertically accreted fine-grained deposits atop basal gravels. Some time before 12 500 years ago a bedload-dominated river was transformed into a suspended load system. In the mid-late Holocene, swamps developed in the middle-lower part of each floodplain pocket. Within a few decades of European settlement of this region (circa AD 1820), discontinuous watercourses in some floodplain pockets had incised to form a low-sinuosity gravel-bed channel. Wedge-shaped units of post-incisional alluvium that thicken downstream overlie the swamp and floodplain deposits in the downstream part of these pockets. In the downstream-most pocket, incision commenced prior to colonization, while upstream swamps retain a continuous swamp across the valley floor. The late Quaternary evolution of this variant of discontinuous watercourse is summarized in a schematic model.
Multicentury glacier fluctuations in the Swiss Alps during the Holocene
Authors: Joerin Ulrich E. , Stocker Thomas F. , Schlüchter Christian
Published: July 2006

Subfossil remains of wood and peat from six Swiss glaciers found in proglacial fluvial sediments indicate that glaciers were smaller than the 1985 reference level and climatic conditions allowed vegetation growth in now glaciated basins. An extended data set of Swiss glacier recessions consisting of 143 radiocarbon dates is presented to improve the chronology of glacier fluctuations. A comparison with other archives and dated glacier advances suggests 12 major recession periods occurring at 9850- 9600, 9300-8650, 8550-8050, 7700-7550, 7450-6550, 6150-5950, 5700-5500, 5200-4400, 4300-3400, 2800-2700, 2150-1850, 1400-1200 cal. yr BP. It is proposed that major glacier fluctuations occurred on a multicentennial scale with a changing pattern during the course of the Holocene. After the Younger Dryas, glaciers receded to a smaller extent and prolonged recessions occurred repeatedly, culminating around 7 cal. kyr BP. After a transition around 6 cal. kyr BP weak fluctuations around the present level dominated. After 3.6 cal. kyr BP less frequent recessions interrupted the trend to advanced glaciers peaking with the prominent ‘Little Ice Age’. This trend is in line with a continuous decrease of summer insolation during the Holocene.
Pattern and timing of sediment infill at glacier-fed Mud Lake: implications for lateglacial and Holocene environments in the Monashee Mountain region of British Columbia, Canada
Authors: Hodder K. R. , Desloges J. R. , Gilbert R.
Published: July 2006

The Holocene sedimentary infill of proglacial Mud Lake, British Columbia, Canada, was investigated using 3.5 kHz acoustic sub-bottom profiling and sediment samples. The sediment infill is a mixture of silt and clay and is divided into five stratigraphic units: massive silt (Unit 1), weakly laminated silt with very fine sand beds (Unit 2), weakly laminated silt with rippled beds of fine sand (Unit 3), weakly laminated clay with very fine sand laminations (Unit 4) and silt-clay varves (Unit 5). Acoustic reflectors correlate with stratigraphic unit boundaries. Annual accumulation rates were estimated for six age/depth intervals: prior to 9.6 kyr cal. BP, accumulation rates were very high - on the order of several centimetres per year. Early to middle Holocene sediment inputs (9.6-3.6 kyr cal. BP) were variable but low, ranging from 0.3 mm/yr to 1.2 mm/yr. The late Holocene (most recent 3.6 kyr) shows annual accumulation rates that generally exceed 2 mm/yr. Surface sediment reveals a mean of 4.3 mm/yr over the last 20 years. These results are consistent with regional Holocene chronologies and long-term paraglacial succession: (1) maximum sediment and meltwater availability and minimum stabilization by vegetation following Fraser deglaciation replaced by (2) less meltwater and sediment availability during the Hypsithermal, and (3) more stabilized sediment during the early and mid Holocene. Renewal of glacial activity, particularly in the late Neoglacial, has led to increased rates of accumulation in Mud Lake. Despite the contrasting geologic setting of Mud Lake in the Omineca belt, contemporary sediment yield is consistent with the trend of sediment yield with glacier cover in lakes of the adjacent Foreland belt.
Radiocarbon-dated peat and wood remains from the Finnish Subarctic: evidence of treeline and landscape history
Authors: Holtmeier Friedrich-Karl , Broll Gabriele
Published: July 2006

Seven peat and 40 dead wood remains (mountain birch) were sampled within and above the present treeline ecotone on two mountains (Rodjanoaivi, Koahppeloaivi/Staloskaidi) along the Tenojoki in northernmost Finnish Lapland. The oldest peat samples (‘summit peats’) date back to about 2000 yr BP. They accumulated during cool and increasingly humid climatic conditions. The other peat samples taken from wind-eroded peat remains on convex topography 60-100 m above the present tree limit are about 700-1300 years old. These peat layers developed during a phase of increasing Sphagnum peat formation. An eroded peat-covered Podzol that had developed under former tree stands with dwarfshrub vegetation in the understorey also reflects this climatic change. The oldest birch wood samples date from the same period. These and the many younger samples are evidence for a general treeline decline since the Holocene climatic optimum until present. As a result of the decline of the upper forest stands, the alpine zone has extended downslope and wind erosion has increased considerably in the former and present treeline ecotone, removing most of the peaty layers and top soils from wind-exposed topography. Whilst the cooling climate was the main factor triggering treeline retreat, episodic mass-outbreaks of the autumnal moth ( Epirrita autumnata), particularly when coincident with cold summers, must also be taken into consideration as a factor that enhanced or accelerated treeline decline during this period. As is evidenced by the wood samples, forest decline continued into modern times when overgrazing by reindeer ( Rangifer tarandus) became an additional factor enhancing wind erosion and affecting the regeneration of birch in the present treeline ecotone.
The WinGeol Lamination Tool: new software for rapid, semi-automated analysis of laminated climate archives
Authors: Meyer Michael C. , Faber Robert , Spötl Christoph
Published: July 2006

Geological and biological archives showing an annually laminated internal structure are currently top priority in palaeoclimate research, as they are recognized as very high-resolution archives of environmental change. Also, the annual origin of laminations can be validated by absolute age dating or by using instrumental data for the most recent period. Microscopic laminae may span several hundreds to thousands of years and frequently reveal a high degree of internal growth variability. Quantitative examination of laminations using transmitted-light or epifluorescence microscopy is thus a tedious task and may be partly automated. We developed a software (WinGeol Lamination Tool) using C + + capable of semi-automatically detecting and measuring individual lamina thicknesses in archives showing large internal growth variability. The Lamination Tool enables the operator to efficiently and quantitatively examine laminae down to the micron scale and it was successfully tested on a variety of annually banded samples.
How does cholesterol affect the way Hedgehog works?
Authors: Wendler Franz , Franch-Marro Xavier , Vincent Jean-Paul
Published: July 2006

Members of the Hedgehog (Hh) family of proteins are conserved morphogens that spread and modulate cell fates in target tissue. Mature Hh carries two lipid adducts, a palmitoyl group at the N terminus and cholesterol at the C terminus. Recent findings have addressed how these lipid modifications affect the function and transport of Hh in Drosophila. In contrast to the palmitoyl adduct, cholesterol appears not to be essential for signalling. However, the absence of the cholesterol adduct affects the spread of Hh within tissues. As we discuss here, the exact nature of this effect is controversial.
Efficient prediction of siRNAs with siRNArules 1.0: An open-source JAVA approach to siRNA algorithms
Authors: Holen Torgeir
Published: July 2006

RNAi interference and siRNA have become useful tools for investigation of gene function. However, the discovery that not all siRNA are equally efficient made necessary screens or design algorithms to obtain high activity siRNA candidates. Several algorithms have been published, but they remain inefficient, obscure, or commercially restricted. This article describes an open-source JAVA program that is surprisingly efficient at predicting active siRNAs (Pearson correlation coefficient r = 0.52, n = 526 siRNAs). Furthermore, this version 1.0 sets the stage for further improvement of the free code by the open-source community (http://sourceforge.net/).
ppGalNAc-T13: A New Molecular Marker of Bone Marrow Involvement in Neuroblastoma
Authors: Berois Nora , Blanc Etienne , Ripoche Hugues , Mergui Xénia , Trajtenberg Felipe , Cantais Sabrina , Barrois Michel , Dessen Philippe , Kågedal Bertil , Bénard Jean , Osinaga Eduardo , Raguénez Gilda
Published: July 2006

Background: To identify new molecular markers of bone marrow dissemination in human neuroblastoma (NB), we studied the transcriptome profiles of malignant neuroblasts established from the human MYCN-amplified IGR-N-91 model.

Methods: This experimental model includes human neuroblastoma cells derived from a subcutaneous stage 4 disease, myocardium (Myoc) and bone marrow (BM) metastatic cells.

Results: Gene expression profiles obtained with Agilent oligo microarrays revealed a set of 107 differentially expressed genes in the metastatic neuroblasts. This set included up-regulated genes involved in chemoresistance, cell motility, neuronal structure/signaling, and the recently characterized GALNT13 gene encoding a glycosyltransferase that initiates mucin-type O-glycosylation. Because the glycosylation process is involved in the progression of primary tumor to metastatic disease, we investigated whether the most strongly up-regulated gene, GALNT13, might be a marker of bone marrow involvement in stage 4 NB patients. Importantly, in the BM of healthy adults no GALNT13 transcript was detected with analysis by quantitative (n = 3) and nested reverse transcription-PCR (n = 4) assays. In contrast, GALNT13 transcripts were detected in 23/23 cytologically involved BM samples obtained at diagnosis of stage 4 NB patients and in 5/27 cytologically noninvolved BM samples obtained from patients with stage 1–4 and 4S and treated stage 4 NB. The quantitative measurements of tyrosine hydroxylase (TH), ganglioside D2 synthase, dopa decarboxylase, and GALNT13 transcript values were compared in the same NB patients, and the results showed that GALNT13 expression was most highly correlated to poor clinical outcome at diagnosis.

Conclusion: We propose ppGalNAc-T13 as a new informative marker for the molecular diagnosis of BM involvement and the follow-up of minimal residual disease in NB patients.
Do the Survivin (BIRC5) Splice Variants Modulate or Add to the Prognostic Value of Total Survivin in Breast Cancer?
Authors: Span Paul N , Tjan-Heijnen Vivianne CG , Heuvel Joop JTM , de Kok Jacques B , Foekens John A , Sweep Fred CGJ
Published: July 2006

Background: A total of 4 additional splice variants (survivin-ΔEx3, survivin 2α, survivin-2B, and survivin-3B) have been described for survivin [baculoviral IAP repeat-containing protein (BIRC-5), approved gene symbol BIRC5], which has been implicated in both inhibition of apoptosis and regulation in mitosis in many tumor types. In this study, we assessed whether the survivin splice variants modulate or add to the prognostic value of total survivin in breast cancer.

Methods: With quantitative reverse transcription-PCR, we measured mRNA concentrations of survivin and all variants in tumor tissue from 275 patients with breast cancer and associated these with clinicopathologic characteristics and relapse-free survival.

Results: Total survivin, survivin-ΔEx3, and survivin 2α mRNA levels were associated with young age and ductal histology. Total survivin and survivin-ΔEx3 were highest in samples with advanced histological grade, whereas patients with 4–9 involved lymph nodes expressed less survivin-2B mRNA than those with 1–3 involved nodes. All variants were higher in tumors negative for steroid hormone receptors. Total survivin, survivin 2α, and survivin-3B were associated with poor relapse-free survival in univariate analyses. Survivin 2α and survivin-3B added to the prognostic value of total survivin in multivariate analyses. In addition, the prognostic value of total survivin was evident only in the presence of higher expression levels of these 2 variants.

Conclusions: All variants of survivin exhibited particular associations with clinicopathologic characteristics (age, histology, grade, and steroid hormone receptor status) of breast cancer patients. Survival analyses suggest a modulating role of survivin 2α and survivin-3B on the biological function of total survivin.
Invasion Patterns along Elevation and Urbanization Gradients in Hawaiian Streams
Authors: Brasher Anne M. D. , Luton Corene D. , Goodbred Steven L. , Wolff Reuben H.
Published: July 2006

Hawaii's extreme isolation has resulted in a native stream fauna characterized by high endemism and unusual life history characteristics. With the rapid increase in the human population, the viability of Hawaiian stream ecosystems is threatened by development and the associated habitat alteration. Thirty‐eight sites on three islands (Oahu, Kauai, and Hawaii) were sampled to determine how habitat alteration resulting from urbanization and development was associated with the establishment of introduced species. Undeveloped sites had higher streamflow velocities, more riffles, lower embeddedness, deeper water, larger substrate, and lower water temperature than developed sites. Developed sites additionally had more pools and greater sparseness of riparian canopy cover. Overall, 23 fish species from 11 families and 5 crustacean species from 3 families were collected. Of these, 16 fish species and 3 crustacean species were introduced. Developed sites had on average almost twice as many species as undeveloped sites and were dominated by introduced species. Low‐elevation sites were the most developed and supported the highest number of introduced species. However, species composition at some relatively undeveloped sites was impacted by downstream habitat alteration, since all native species must pass through the lower reaches to complete their life cycles. With increasing urbanization and development, the habitat features required by native species are disappearing and streams are becoming more suitable for generalist introduced species, which are typically better adapted for altered habitats than are native species. As development pressures in tropical island ecosystems increase worldwide, this will become an increasingly important issue globally. An understanding of which habitats are most likely to support nonnative species provides information necessary for developing a management strategy to protect aquatic ecosystems from invasive nonnative species.
Comparison of Life History Traits between First‐Generation Hatchery and Wild Upper Yakima River Spring Chinook Salmon
Authors: Knudsen Curtis M. , Schroder Steve L. , Busack Craig A. , Johnston Mark V. , Pearsons Todd N. , Bosch William J. , Fast David E.
Published: July 2006

Life history traits in hatchery and wild spring Chinook salmon Oncorhynchus tshawytscha from the upper Yakima River were compared to determine whether locally adapted traits had diverged after one generation of state‐of‐the‐art artificial propagation. Sex composition in wild‐ and hatchery‐origin fish differed in three of four brood years (P ≤ 0.01). The proportion of hatchery males, primarily age 3, increased from 38% to 49% over time. Conversely, the sex composition of wild fish did not exhibit a similar linear trend. Most hatchery‐ and wild‐origin fish reached maturity at age 4 (≥76%), followed in magnitude by ages 3 and 5. Wild mean age at maturation demonstrated no significant trend over time, while hatchery mean age at maturation declined (P = 0.05). Mean lengths of 3–5‐year‐old hatchery fish were shorter than those of wild fish of the same age (differences of 2.7 cm for age 3, 1.7 cm for age 4, and 1.9 cm for age 5). Likewise, body weights of hatchery fish were lower than those of wild fish (differences of 0.3 kg for age 3, 0.3 kg for age 4, and 0.6 kg for age 5), representing a change in body size of between 0.5 and 1.0 standard deviation (SD). Median arrival timing of hatchery and wild fish at a broodstock collection site just downstream of ancestral spawning grounds showed no consistent difference. However, the median arrival date of age‐3 fish was 19–20 d later than that for fish of ages 4 and 5 (P < 0.01). Mean spawn timing of hatchery fish was significantly earlier (5.1 d) than that of wild fish in a “common‐garden” experiment (P < 0.05). We estimate that fitness could be reduced by as much as 1–5% for traits diverging from their optima by 0.5–1.0 SD. The degree of genetic determination of the divergence is unknown, but future monitoring will help clarify this. Perhaps the most important conclusion of our study is that even a hatchery program designed to minimize differences between hatchery and wild fish did not produce fish that were identical to wild fish.
Assessment of Patients’ Level of Satisfaction with Cleft Treatment Using the Cleft Evaluation Profile
Authors: Noor Siti Noor Fazliah Mohd , Musa Sabri
Published: July 2006

Objectives:

Determination of the psychosocial status and assessment of the level of satisfaction in Malaysian cleft palate patients and their parents.

Design:

Cross-sectional study.

Participants and Methods:

Sixty cleft lip and palate patients (12 to 17 years of age) from Hospital Universiti Sains Malaysia and their parents were selected. The questionnaires used were the Child Interview Schedule, the Parents Interview Schedule, and the Cleft Evaluation Profile (CEP), administered via individual interviews.

Results:

Patients were teased because of their clefts and felt their self-confidence was affected by the cleft condition. They were frequently teased about cleft-related features such as speech, teeth, and lip appearance. Parents also reported that their children were being teased because of their clefts and that their children's self-confidence was affected by the clefts. Both showed a significant level of satisfaction with the treatment provided by the cleft team. There was no significant difference between the responses of the patients and their parents. The features that were found to be most important for the patients and their parents, in decreasing order of priority, were teeth, nose, lips, and speech.

Conclusions:

Cleft lip and/or palate patients were teased because of their clefts, and it affected their self-confidence. The Cleft Evaluation Profile is a reliable and useful tool to assess patients’ level of satisfaction with treatment received for cleft lip and/or palate and can identify the types of cleft-related features that are most important for the patients.